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Sample records for random phase encoding

  1. Review of Random Phase Encoding in Volume Holographic Storage

    Directory of Open Access Journals (Sweden)

    Wei-Chia Su

    2012-09-01

    Full Text Available Random phase encoding is a unique technique for volume hologram which can be applied to various applications such as holographic multiplexing storage, image encryption, and optical sensing. In this review article, we first review and discuss diffraction selectivity of random phase encoding in volume holograms, which is the most important parameter related to multiplexing capacity of volume holographic storage. We then review an image encryption system based on random phase encoding. The alignment of phase key for decryption of the encoded image stored in holographic memory is analyzed and discussed. In the latter part of the review, an all-optical sensing system implemented by random phase encoding and holographic interconnection is presented.

  2. Optical double image security using random phase fractional Fourier domain encoding and phase-retrieval algorithm

    Science.gov (United States)

    Rajput, Sudheesh K.; Nishchal, Naveen K.

    2017-04-01

    We propose a novel security scheme based on the double random phase fractional domain encoding (DRPE) and modified Gerchberg-Saxton (G-S) phase retrieval algorithm for securing two images simultaneously. Any one of the images to be encrypted is converted into a phase-only image using modified G-S algorithm and this function is used as a key for encrypting another image. The original images are retrieved employing the concept of known-plaintext attack and following the DRPE decryption steps with all correct keys. The proposed scheme is also used for encryption of two color images with the help of convolution theorem and phase-truncated fractional Fourier transform. With some modification, the scheme is extended for simultaneous encryption of gray-scale and color images. As a proof-of-concept, simulation results have been presented for securing two gray-scale images, two color images, and simultaneous gray-scale and color images.

  3. 3D Multisource Full‐Waveform Inversion using Dynamic Random Phase Encoding

    KAUST Repository

    Boonyasiriwat, Chaiwoot

    2010-10-17

    We have developed a multisource full‐waveform inversion algorithm using a dynamic phase encoding strategy with dual‐randomization—both the position and polarity of simultaneous sources are randomized and changed every iteration. The dynamic dual‐randomization is used to promote the destructive interference of crosstalk noise resulting from blending a large number of common shot gathers into a supergather. We compare our multisource algorithm with various algorithms in a numerical experiment using the 3D SEG/EAGE overthrust model and show that our algorithm provides a higher‐quality velocity tomogram than the other methods that use only monorandomization. This suggests that increasing the degree of randomness in phase encoding should improve the quality of the inversion result.

  4. Multiple-wavelength double random phase encoding with CCD-plane sparse-phase multiplexing for optical information verification.

    Science.gov (United States)

    Chen, Wen

    2015-12-20

    A novel method is proposed by using multiple-wavelength double random phase encoding (MW-DRPE) with CCD-plane sparse-phase multiplexing for optical information verification. Two different strategies are applied to conduct sparse-phase multiplexing in the CCD plane. The results demonstrate that large capacity can be achieved for optical multiple-image verification. The proposed optical verification strategy is implemented based on optical encoding, and the keys generated by optical encryption can further guarantee the safety of the designed optical multiple-image verification system. The proposed method provides a novel alternative for DRPE-based optical information verification.

  5. Fractional Fourier transform-based optical encryption with treble random phase-encoding

    Science.gov (United States)

    Xin, Yi; Tao, Ran; Wang, Yue

    2008-03-01

    We propose a new architecture of optical encryption technique using the fractional Fourier transform with three statistically independent random phase masks. Compared with the existing double-phase encoding method in the fractional Fourier-domain, the proposed extra phase mask in the last fractional Fourier domain makes the architecture symmetrical, and additive processing to the encrypted image can be turned into complex stationary white noise after decryption, and enlarge the key space without any degradation of its robustness to blind decryption. This property can be utilized to improve the quality of the recover image. Simulation results have verified the validity.

  6. Optical image transformation and encryption by phase-retrieval-based double random-phase encoding and compressive ghost imaging

    Science.gov (United States)

    Yuan, Sheng; Yang, Yangrui; Liu, Xuemei; Zhou, Xin; Wei, Zhenzhuo

    2018-01-01

    An optical image transformation and encryption scheme is proposed based on double random-phase encoding (DRPE) and compressive ghost imaging (CGI) techniques. In this scheme, a secret image is first transformed into a binary image with the phase-retrieval-based DRPE technique, and then encoded by a series of random amplitude patterns according to the ghost imaging (GI) principle. Compressive sensing, corrosion and expansion operations are implemented to retrieve the secret image in the decryption process. This encryption scheme takes the advantage of complementary capabilities offered by the phase-retrieval-based DRPE and GI-based encryption techniques. That is the phase-retrieval-based DRPE is used to overcome the blurring defect of the decrypted image in the GI-based encryption, and the CGI not only reduces the data amount of the ciphertext, but also enhances the security of DRPE. Computer simulation results are presented to verify the performance of the proposed encryption scheme.

  7. Information hiding based on double random-phase encoding and public-key cryptography.

    Science.gov (United States)

    Sheng, Yuan; Xin, Zhou; Alam, Mohammed S; Xi, Lu; Xiao-Feng, Li

    2009-03-02

    A novel information hiding method based on double random-phase encoding (DRPE) and Rivest-Shamir-Adleman (RSA) public-key cryptosystem is proposed. In the proposed technique, the inherent diffusion property of DRPE is cleverly utilized to make up the diffusion insufficiency of RSA public-key cryptography, while the RSA cryptosystem is utilized for simultaneous transmission of the cipher text and the two phase-masks, which is not possible under the DRPE technique. This technique combines the complementary advantages of the DPRE and RSA encryption techniques and brings security and convenience for efficient information transmission. Extensive numerical simulation results are presented to verify the performance of the proposed technique.

  8. Double image encryption based on random phase encoding in the fractional Fourier domain.

    Science.gov (United States)

    Tao, Ran; Xin, Yi; Wang, Yue

    2007-11-26

    A novel image encryption method is proposed by utilizing random phase encoding in the fractional Fourier domain to encrypt two images into one encrypted image with stationary white distribution. By applying the correct keys which consist of the fractional orders, the random phase masks and the pixel scrambling operator, the two primary images can be recovered without cross-talk. The decryption process is robust against the loss of data. The phase-based image with a larger key space is more sensitive to keys and disturbances than the amplitude-based image. The pixel scrambling operation improves the quality of the decrypted image when noise perturbation occurs. The novel approach is verified by simulations.

  9. Optical information authentication via compressed sensing and double random phase encoding

    Science.gov (United States)

    Chen, Junxin; Bao, Nan; Zhu, Zhi-liang

    2017-10-01

    This paper presents a novel information authentication scheme via compressed sensing and double random phase encoding. Two alternative architectures have been investigated, in which significantly compressed data with micro percentage is sufficient for authentication. At the decoder end, a noise-like image with no leakage of the plaintext is recovered and subsequently authenticated using a nonlinear optical correlation approach. The authentication effectiveness, noise resistance and security performance of the proposed scheme have been experimentally validated. This work was supported by the Fundamental Research Funds for the Central Universities (N162410002-4, N151904002), the National Natural Science Foundation of China (No. 61374178).

  10. Biometrics based key management of double random phase encoding scheme using error control codes

    Science.gov (United States)

    Saini, Nirmala; Sinha, Aloka

    2013-08-01

    In this paper, an optical security system has been proposed in which key of the double random phase encoding technique is linked to the biometrics of the user to make it user specific. The error in recognition due to the biometric variation is corrected by encoding the key using the BCH code. A user specific shuffling key is used to increase the separation between genuine and impostor Hamming distance distribution. This shuffling key is then further secured using the RSA public key encryption to enhance the security of the system. XOR operation is performed between the encoded key and the feature vector obtained from the biometrics. The RSA encoded shuffling key and the data obtained from the XOR operation are stored into a token. The main advantage of the present technique is that the key retrieval is possible only in the simultaneous presence of the token and the biometrics of the user which not only authenticates the presence of the original input but also secures the key of the system. Computational experiments showed the effectiveness of the proposed technique for key retrieval in the decryption process by using the live biometrics of the user.

  11. Fractional Fourier domain optical image hiding using phase retrieval algorithm based on iterative nonlinear double random phase encoding.

    Science.gov (United States)

    Wang, Xiaogang; Chen, Wen; Chen, Xudong

    2014-09-22

    We present a novel image hiding method based on phase retrieval algorithm under the framework of nonlinear double random phase encoding in fractional Fourier domain. Two phase-only masks (POMs) are efficiently determined by using the phase retrieval algorithm, in which two cascaded phase-truncated fractional Fourier transforms (FrFTs) are involved. No undesired information disclosure, post-processing of the POMs or digital inverse computation appears in our proposed method. In order to achieve the reduction in key transmission, a modified image hiding method based on the modified phase retrieval algorithm and logistic map is further proposed in this paper, in which the fractional orders and the parameters with respect to the logistic map are regarded as encryption keys. Numerical results have demonstrated the feasibility and effectiveness of the proposed algorithms.

  12. Securing image information using double random phase encoding and parallel compressive sensing with updated sampling processes

    Science.gov (United States)

    Hu, Guiqiang; Xiao, Di; Wang, Yong; Xiang, Tao; Zhou, Qing

    2017-11-01

    Recently, a new kind of image encryption approach using compressive sensing (CS) and double random phase encoding has received much attention due to the advantages such as compressibility and robustness. However, this approach is found to be vulnerable to chosen plaintext attack (CPA) if the CS measurement matrix is re-used. Therefore, designing an efficient measurement matrix updating mechanism that ensures resistance to CPA is of practical significance. In this paper, we provide a novel solution to update the CS measurement matrix by altering the secret sparse basis with the help of counter mode operation. Particularly, the secret sparse basis is implemented by a reality-preserving fractional cosine transform matrix. Compared with the conventional CS-based cryptosystem that totally generates all the random entries of measurement matrix, our scheme owns efficiency superiority while guaranteeing resistance to CPA. Experimental and analysis results show that the proposed scheme has a good security performance and has robustness against noise and occlusion.

  13. Robustness of double random phase encoding spread-space spread-spectrum image watermarking technique

    Science.gov (United States)

    Liu, Shi; Hennelly, Bryan M.; Sheridan, John T.

    2013-09-01

    In this paper the robustness of a recently proposed image watermarking scheme is investigated, namely the Double Random Phase Encoding spread-space spread-spectrum watermarking (DRPE SS-SS) technique. In the DRPE SS-SS method, the watermark is in the form of a digital barcode image which is numerically encrypted using a simulation of the optical DRPE process. This produces a random complex image, which is then processed to form a real valued random image with a low number of quantization levels. This signal is added to the host image. Extraction of the barcode, involves applying an inverse DRPE process to the watermarked image followed by a low pass filter. This algorithm is designed to utilize the capability of the DRPE to reversibly spread the energy of the watermarking information in both the space and spatial frequency domains, and the energy of the watermark in any spatial or spatial frequency bin is very small. The common geometric transformations and signal processing operations are performed using both the informed and the blind detections for different barcode widths and different quantization levels. The results presented indicate that the DRPE SS-SS method is robust to scaling, JPEG compression distortion, cropping, low pass and high pass filtering. It is also demonstrated that the bigger the barcode width is, the lower the false positive rate will be.

  14. Combining double random phase encoding for color image watermarking in quaternion gyrator domain

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    Shao, Zhuhong; Duan, Yuping; Coatrieux, Gouenou; Wu, Jiasong; Meng, Jinyu; Shu, Huazhong

    2015-05-01

    Quaternion representation of color image has attracted great attention due to its capability to treat holistically the three color channels. In a more general way, it has successfully been used in multi-channel signal processing applications over the past few decades. In this study, a joint encryption/watermarking system with more security based on double random phase encoding (DRPE) in quaternion gyrator transform domain is addressed. In the proposed scheme, an RGB-scale watermark image together with a grayscale watermark image or not is encoded into a quaternion matrix and encrypted through the DRPE, the encrypted data is then fused into the middle coefficients of the quaternion gyrator-transformed host image. In the process of extracting watermarks, it is impossible to retrieve them without authorized keys. Compared with the three channels independently processing approach implemented in fractional Fourier domain, the proposed algorithm achieves lower complexity by reason of avoiding repetitive operations. Experimental results have demonstrated the feasibility of the proposed algorithm and its superior performance in terms of noise robustness.

  15. A Multispectral Photon-Counting Double Random Phase Encoding Scheme for Image Authentication

    Directory of Open Access Journals (Sweden)

    Faliu Yi

    2014-05-01

    Full Text Available In this paper, we propose a new method for color image-based authentication that combines multispectral photon-counting imaging (MPCI and double random phase encoding (DRPE schemes. The sparsely distributed information from MPCI and the stationary white noise signal from DRPE make intruder attacks difficult. In this authentication method, the original multispectral RGB color image is down-sampled into a Bayer image. The three types of color samples (red, green and blue color in the Bayer image are encrypted with DRPE and the amplitude part of the resulting image is photon counted. The corresponding phase information that has nonzero amplitude after photon counting is then kept for decryption. Experimental results show that the retrieved images from the proposed method do not visually resemble their original counterparts. Nevertheless, the original color image can be efficiently verified with statistical nonlinear correlations. Our experimental results also show that different interpolation algorithms applied to Bayer images result in different verification effects for multispectral RGB color images.

  16. Fly Photoreceptors Encode Phase Congruency.

    Directory of Open Access Journals (Sweden)

    Uwe Friederich

    Full Text Available More than five decades ago it was postulated that sensory neurons detect and selectively enhance behaviourally relevant features of natural signals. Although we now know that sensory neurons are tuned to efficiently encode natural stimuli, until now it was not clear what statistical features of the stimuli they encode and how. Here we reverse-engineer the neural code of Drosophila photoreceptors and show for the first time that photoreceptors exploit nonlinear dynamics to selectively enhance and encode phase-related features of temporal stimuli, such as local phase congruency, which are invariant to changes in illumination and contrast. We demonstrate that to mitigate for the inherent sensitivity to noise of the local phase congruency measure, the nonlinear coding mechanisms of the fly photoreceptors are tuned to suppress random phase signals, which explains why photoreceptor responses to naturalistic stimuli are significantly different from their responses to white noise stimuli.

  17. Phase-Image Encryption Based on 3D-Lorenz Chaotic System and Double Random Phase Encoding

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    Sharma, Neha; Saini, Indu; Yadav, AK; Singh, Phool

    2017-12-01

    In this paper, an encryption scheme for phase-images based on 3D-Lorenz chaotic system in Fourier domain under the 4f optical system is presented. The encryption scheme uses a random amplitude mask in the spatial domain and a random phase mask in the frequency domain. Its inputs are phase-images, which are relatively more secure as compared to the intensity images because of non-linearity. The proposed scheme further derives its strength from the use of 3D-Lorenz transform in the frequency domain. Although the experimental setup for optical realization of the proposed scheme has been provided, the results presented here are based on simulations on MATLAB. It has been validated for grayscale images, and is found to be sensitive to the encryption parameters of the Lorenz system. The attacks analysis shows that the key-space is large enough to resist brute-force attack, and the scheme is also resistant to the noise and occlusion attacks. Statistical analysis and the analysis based on correlation distribution of adjacent pixels have been performed to test the efficacy of the encryption scheme. The results have indicated that the proposed encryption scheme possesses a high level of security.

  18. Holographically Encoded Volume Phase Masks

    Science.gov (United States)

    2015-07-13

    optics ,” Nat. Photonics 4, 188–193 (2010). 26. H. Kogelnik, “Coupled wave theory for thick volume holograms ,” Bell System Tech. J. 45(9), 2909–2944...phase masks Marc SeGall, Ivan Divliansky,* Clémence Jollivet, Axel Schülzgen, and Leonid B. Glebov University of Central Florida, College of Optics and...satisfying the Bragg condition of the hologram . Moreover, this approach enables the capability to encode and multiplex several phase masks into a single

  19. Reading Neural Encodings using Phase Space Methods

    OpenAIRE

    Abarbanel, Henry D. I.; Tumer, Evren C.

    2003-01-01

    Environmental signals sensed by nervous systems are often represented in spike trains carried from sensory neurons to higher neural functions where decisions and functional actions occur. Information about the environmental stimulus is contained (encoded) in the train of spikes. We show how to "read" the encoding using state space methods of nonlinear dynamics. We create a mapping from spike signals which are output from the neural processing system back to an estimate of the analog input sig...

  20. Composite pulses for RF phase encoded MRI: A simulation study.

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    Salajeghe, Somaie; Babyn, Paul; Sarty, Gordon E

    2017-02-01

    In B1 encoded MRI, a realistic non-linear phase RF encoding coil will generate an inhomogeneous B1 field that leads to spatially dependent flip angles. The non-linearity of the B1 phase gradient can be compensated for in the reconstruction, but B1 inhomogeneity remains a problem. The effect of B1 inhomogeneity on tip angles for conventional, B0 encoded MRI, may be minimized using composite pulses. The objective of this study was to explore the feasibility of using composite pulses with non-linear RF phase encoding coils and to identify the most appropriate composite pulse scheme. RF encoded signals were simulated via the Bloch equation for various symmetric, asymmetric and antisymmetric composite pulses. The simulated signals were reconstructed using a constrained least squares method. Root mean square reconstruction errors varied from 6% (for an asymmetric composite pulse) to 9.7% (for an antisymmetric composite pulse). An asymmetric composite pulse scheme created images with fewer artifacts than other composite pulse schemes in inhomogeneous B0 and B1 fields making it the best choice for decreasing the effects of spatially varying flip angles. This is contrary to the conclusion that antisymmetric composite pulses are the best ones to use for spin echo sequences in conventional, B0 encoded, MRI. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  1. Inline SAW RFID tag using time position and phase encoding.

    Science.gov (United States)

    Härmä, Sanna; Arthur, Wesley G; Hartmann, Clinton S; Maev, Roman G; Plessky, Victor P

    2008-08-01

    Surface acoustic wave (SAW) radio-frequency identification (RFID) tags are encoded according to partial reflections of an interrogation signal by short metal reflectors. The standard encryption method involves time position encoding that uses time delays of response signals. However, the data capacity of a SAW RFID tag can be significantly enhanced by extracting additional phase information from the tag responses. In this work, we have designed, using FEM-BEM simulations, and fabricated, on 128 degrees -LiNbO3, inline 2.44-GHz SAW RFID tag samples that combine time position and phase encoding. Each reflective echo has 4 possible time positions and a phase of 0 degrees , -90 degrees , -180 degrees , or -270 degrees. This corresponds to 16 different states, i.e., 4 bits of data, per code reflector. In addition to the enhanced data capacity, our samples also exhibit a low loss level of -38 dB for code reflections.

  2. Theory of multisource crosstalk reduction by phase-encoded statics

    KAUST Repository

    Schuster, Gerard T.

    2011-03-01

    Formulas are derived that relate the strength of the crosstalk noise in supergather migration images to the variance of time, amplitude and polarity shifts in encoding functions. A supergather migration image is computed by migrating an encoded supergather, where the supergather is formed by stacking a large number of encoded shot gathers. Analysis reveals that for temporal source static shifts in each shot gather, the crosstalk noise is exponentially reduced with increasing variance of the static shift and the square of source frequency. This is not too surprising because larger time shifts lead to less correlation between traces in different shot gathers, and so should tend to reduce the crosstalk noise. Analysis also reveals that combining both polarity and time statics is a superior encoding strategy compared to using either polarity statics or time statics alone. Signal-to-noise (SNR) estimates show that for a standard migration image and for an image computed by migrating a phase-encoded supergather; here, G is the number of traces in a shot gather, I is the number of stacking iterations in the supergather and S is the number of encoded/blended shot gathers that comprise the supergather. If the supergather can be uniformly divided up into Q unique sub-supergathers, then the resulting SNR of the final image is, which means that we can enhance image quality but at the expense of Q times more cost. The importance of these formulas is that they provide a precise understanding between different phase encoding strategies and image quality. Finally, we show that iterative migration of phase-encoded supergathers is a special case of passive seismic interferometry. We suggest that the crosstalk noise formulas can be helpful in designing optimal strategies for passive seismic interferometry and efficient extraction of Green\\'s functions from simulated supergathers. © 2011 The Authors Geophysical Journal International © 2011 RAS.

  3. DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer Library Synthesis.

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    MacConnell, Andrew B; McEnaney, Patrick J; Cavett, Valerie J; Paegel, Brian M

    2015-09-14

    The promise of exploiting combinatorial synthesis for small molecule discovery remains unfulfilled due primarily to the "structure elucidation problem": the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation. Here we present DNA-encoded solid-phase synthesis (DESPS), comprising parallel compound synthesis in organic solvent and aqueous enzymatic ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding language design yielded 148 thermodynamically optimized sequences with Hamming string distance ≥ 3 and total read length bases for facile sequencing. Ligation is efficient (70% yield), specific, and directional over 6 encoding positions. A series of isomers served as a testbed for DESPS's utility in split-and-pool diversification. Single-bead quantitative PCR detected 9 × 10(4) molecules/bead and sequencing allowed for elucidation of each compound's synthetic history. We applied DESPS to the combinatorial synthesis of a 75,645-member OBOC library containing scaffold, stereochemical and regiochemical diversity using mixed-scale resin (160-μm quality control beads and 10-μm screening beads). Tandem DNA sequencing/MALDI-TOF MS analysis of 19 quality control beads showed excellent agreement (ppt) between DNA sequence-predicted mass and the observed mass. DESPS synergistically unites the advantages of solid-phase synthesis and DNA encoding, enabling single-bead structural elucidation of complex compounds and synthesis using reactions normally considered incompatible with unprotected DNA. The widespread availability of inexpensive oligonucleotide synthesis, enzymes, DNA sequencing, and PCR make

  4. Binary encoded computer generated holograms for temporal phase shifting.

    Science.gov (United States)

    Amphawan, Angela

    2011-11-07

    The trend towards real-time optical applications predicates the need for real-time interferometry. For real-time interferometric applications, rapid processing of computer generated holograms is crucial as the intractability of rapid phase changes may compromise the input to the system. This paper introduces the design of a set of binary encoded computer generated holograms (CGHs) for real-time five-frame temporal phase shifting interferometry using a binary amplitude spatial light modulator. It is suitable for portable devices with constraints in computational power. The new set of binary encoded CGHs is used for measuring the phase of the generated electric field for a real-time selective launch in multimode fiber. The processing time for the new set of CGHs was reduced by up to 65% relative to the original encoding scheme. The results obtained from the new interferometric technique are in good agreement with the results obtained by phase shifting by means of a piezo-driven flat mirror.

  5. Fourier Phase Domain Steganography: Phase Bin Encoding Via Interpolation

    Science.gov (United States)

    Rivas, Edward

    2007-04-01

    In recent years there has been an increased interest in audio steganography and watermarking. This is due primarily to two reasons. First, an acute need to improve our national security capabilities in light of terrorist and criminal activity has driven new ideas and experimentation. Secondly, the explosive proliferation of digital media has forced the music industry to rethink how they will protect their intellectual property. Various techniques have been implemented but the phase domain remains a fertile ground for improvement due to the relative robustness to many types of distortion and immunity to the Human Auditory System. A new method for embedding data in the phase domain of the Discrete Fourier Transform of an audio signal is proposed. Focus is given to robustness and low perceptibility, while maintaining a relatively high capacity rate of up to 172 bits/s.

  6. Investigation of digital hologram watermarking with double binary phase encoding

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    Zhou, Xiaohong; Chen, Linsen; Shao, Jie

    2005-02-01

    We propose a new method of digital watermarking with double binary optical phase encoding technique. Design procedures base on iterative Fourier transform algorithm (IFTA). The combination of two binary phase structures, in which one is used to encode the hidden image, and the other as encryption phase key, is inserted as watermark into the host image. The affections of phase levels of binary phase holograms on the quality of extracting watermark from the watermarked image have been analyzed, and results show that the 2/2 phase level combination is the best scheme of watermarking than other multiple combinations. The principle of encrypting the private key has been presented. This method can effectively increase the security of digital hologram watermarking and support the hard output of the watermarked image. The watermark is robust against hard output. We analysis the influence on the quality of extracted image after the processing of printing and scanning. We also develop the software tool for the watermarking process. The experimental results are given.

  7. Digital ultrasonically encoded (DUE) optical focusing into random media

    CERN Document Server

    Tay, Jian Wei; Suzuki, Yuta; Wang, Lihong V

    2013-01-01

    Focusing light into opaque random or scattering media such as biological tissue is a much sought-after goal for biomedical applications such as photodynamic therapy, optical manipulation, and photostimulation. However, focusing with conventional lenses is restricted to one transport mean free path in scattering media, limiting both optical penetration depth and resolution. Focusing deeper is possible by using optical phase conjugation or wavefront shaping to compensate for the scattering. For practical applications, wavefront shaping offers the advantage of a robust optical system that is less sensitive to optical misalignment. Here, the phase of the incident light is spatially tailored using a phase-shifting array to pre-compensate for scattering. The challenge, then, is to determine the phase pattern which allows light to be optimally delivered to the target region. Optimization algorithms are typically employed for this purpose, with visible particles used as targets to generate feedback. However, using th...

  8. Encoding Sequential Information in Semantic Space Models: Comparing Holographic Reduced Representation and Random Permutation

    OpenAIRE

    Recchia, Gabriel; Sahlgren, Magnus; Kanerva, Pentti; Jones, Michael N.

    2015-01-01

    Circular convolution and random permutation have each been proposed as neurally plausible binding operators capable of encoding sequential information in semantic memory. We perform several controlled comparisons of circular convolution and random permutation as means of encoding paired associates as well as encoding sequential information. Random permutations outperformed convolution with respect to the number of paired associates that can be reliably stored in a single memory trace. Perform...

  9. Three-dimensional shape measurement using color random binary encoding pattern projection

    Science.gov (United States)

    Zhou, Pei; Zhu, Jiangping; Su, Xianyu; Jing, Hailong; Zhang, Xing

    2017-10-01

    Acquiring the three-dimensional (3-D) surface geometry of objects with a full-frame resolution is of great concern in many applications. This paper reports a 3-D measurement scheme based on single-frame pattern projection in the combination of random binary encoding and color encoding. Three random binary encoding patterns generated by a computer embedded in three channels of a color pattern lead to a color binary encoding pattern. Two color cameras with a stereo-vision arrangement simultaneously capture the measured scene under the proposed encoding structured illumination. From captured images, three encoding images are extracted and analyzed using the extended spatial-temporal correlation algorithm for 3-D reconstruction. Theoretical explanation and analysis concerning the encoding principle and reconstruction algorithm, followed by experiments for reconstructing 3-D geometry of stationary and dynamic scenes show the feasibility and practicality of the proposed method.

  10. Artificial neural networks using complex numbers and phase encoded weights.

    Science.gov (United States)

    Michel, Howard E; Awwal, Abdul Ahad S

    2010-04-01

    The model of a simple perceptron using phase-encoded inputs and complex-valued weights is proposed. The aggregation function, activation function, and learning rule for the proposed neuron are derived and applied to Boolean logic functions and simple computer vision tasks. The complex-valued neuron (CVN) is shown to be superior to traditional perceptrons. An improvement of 135% over the theoretical maximum of 104 linearly separable problems (of three variables) solvable by conventional perceptrons is achieved without additional logic, neuron stages, or higher order terms such as those required in polynomial logic gates. The application of CVN in distortion invariant character recognition and image segmentation is demonstrated. Implementation details are discussed, and the CVN is shown to be very attractive for optical implementation since optical computations are naturally complex. The cost of the CVN is less in all cases than the traditional neuron when implemented optically. Therefore, all the benefits of the CVN can be obtained without additional cost. However, on those implementations dependent on standard serial computers, CVN will be more cost effective only in those applications where its increased power can offset the requirement for additional neurons.

  11. Encoding Sequential Information in Semantic Space Models: Comparing Holographic Reduced Representation and Random Permutation

    Directory of Open Access Journals (Sweden)

    Gabriel Recchia

    2015-01-01

    Full Text Available Circular convolution and random permutation have each been proposed as neurally plausible binding operators capable of encoding sequential information in semantic memory. We perform several controlled comparisons of circular convolution and random permutation as means of encoding paired associates as well as encoding sequential information. Random permutations outperformed convolution with respect to the number of paired associates that can be reliably stored in a single memory trace. Performance was equal on semantic tasks when using a small corpus, but random permutations were ultimately capable of achieving superior performance due to their higher scalability to large corpora. Finally, “noisy” permutations in which units are mapped to other units arbitrarily (no one-to-one mapping perform nearly as well as true permutations. These findings increase the neurological plausibility of random permutations and highlight their utility in vector space models of semantics.

  12. Encoding sequential information in semantic space models: comparing holographic reduced representation and random permutation.

    Science.gov (United States)

    Recchia, Gabriel; Sahlgren, Magnus; Kanerva, Pentti; Jones, Michael N

    2015-01-01

    Circular convolution and random permutation have each been proposed as neurally plausible binding operators capable of encoding sequential information in semantic memory. We perform several controlled comparisons of circular convolution and random permutation as means of encoding paired associates as well as encoding sequential information. Random permutations outperformed convolution with respect to the number of paired associates that can be reliably stored in a single memory trace. Performance was equal on semantic tasks when using a small corpus, but random permutations were ultimately capable of achieving superior performance due to their higher scalability to large corpora. Finally, "noisy" permutations in which units are mapped to other units arbitrarily (no one-to-one mapping) perform nearly as well as true permutations. These findings increase the neurological plausibility of random permutations and highlight their utility in vector space models of semantics.

  13. Information Encoding on a Pseudo Random Noise Radar Waveform

    Science.gov (United States)

    2013-03-01

    antenna under test AWG arbitrary waveform generator AWGN additive white Gaussian noise BPSK binary phase shift keying CDMA code division multiple...focused on the orthogonal frequency-division multiplexing (OFDM) and code division multiple access ( CDMA ) waveforms. The Ohio State University has...components into a single unit allows for a more mobile compact platform. The plan is diagrammed in Figure 3.5. Figure 3.5: Planned modifications to

  14. Encoding Sequential Information in Vector Space Models of Semantics: Comparing Holographic Reduced Representation and Random Permutation

    OpenAIRE

    Recchia, Gabriel; Jones, Michael; Sahlgren, Magnus; Kanerva, Pentti

    2010-01-01

    Encoding information about the order in which words typically appear has been shown to improve the performance of high-dimensional semantic space models. This requires an encoding operation capable of binding together vectors in an order-sensitive way, and efficient enough to scale to large text corpora. Although both circular convolution and random permutations have been enlisted for this purpose in semantic models, these operations have never been systematically compared. In Experiment 1 we...

  15. Comment on "Secure quantum private information retrieval using phase-encoded queries"

    Science.gov (United States)

    Shi, Run-hua; Mu, Yi; Zhong, Hong; Zhang, Shun

    2016-12-01

    In this Comment, we reexamine the security of phase-encoded quantum private query (QPQ). We find that the current phase-encoded QPQ protocols, including their applications, are vulnerable to a probabilistic entangle-and-measure attack performed by the owner of the database. Furthermore, we discuss how to overcome this security loophole and present an improved cheat-sensitive QPQ protocol without losing the good features of the original protocol.

  16. Phase Transitions on Random Lattices: How Random is Topological Disorder?

    Science.gov (United States)

    Barghathi, Hatem; Vojta, Thomas

    2015-03-01

    We study the effects of topological (connectivity) disorder on phase transitions. We identify a broad class of random lattices whose disorder fluctuations decay much faster with increasing length scale than those of generic random systems, yielding a wandering exponent of ω = (d - 1) / (2 d) in d dimensions. The stability of clean critical points is thus governed by the criterion (d + 1) ν > 2 rather than the usual Harris criterion dν > 2 , making topological disorder less relevant than generic randomness. The Imry-Ma criterion is also modified, allowing first-order transitions to survive in all dimensions d > 1 . These results explain a host of puzzling violations of the original criteria for equilibrium and nonequilibrium phase transitions on random lattices. We discuss applications, and we illustrate our theory by computer simulations of random Voronoi and other lattices. This work was supported by the NSF under Grant Nos. DMR-1205803 and PHYS-1066293. We acknowledge the hospitality of the Aspen Center for Physics.

  17. Random-phase metasurfaces at optical wavelengths

    DEFF Research Database (Denmark)

    Pors, Anders; Ding, Fei; Chen, Yiting

    2016-01-01

    of an optically thick gold film overlaid by a subwavelength thin glass spacer and an array of gold nanobricks, we design and realize random-phase metasurfaces at a wavelength of 800 nm. Optical characterisation of the fabricated samples convincingly demonstrates the diffuse scattering of reflected light...

  18. Polarization states encoded by phase modulation for high bit rate quantum key distribution

    Science.gov (United States)

    Liu, Xiaobao; Tang, Zhilie; Liao, Changjun; Lu, Yiqun; Zhao, Feng; Liu, Songhao

    2006-10-01

    We present implementation of quantum cryptography with polarization code by wave-guide type phase modulator. At four different low input voltages of the phase modulator, coder encodes pulses into four different polarization states, 45°, 135° linearly polarized or right, left circle polarized, while the decoder serves as the complementary polarizers.

  19. Spatiotemporal oscillatory dynamics during the encoding and maintenance phases of a visual working memory task.

    Science.gov (United States)

    Heinrichs-Graham, Elizabeth; Wilson, Tony W

    2015-08-01

    Many electrophysiology studies have examined neural oscillatory activity during the encoding, maintenance, and/or retrieval phases of various working memory tasks. Together, these studies have helped illuminate the underlying neural dynamics, although much remains to be discovered and some findings have not replicated in subsequent work. In this study, we examined the oscillatory dynamics that serve visual working memory operations using high-density magnetoencephalography (MEG) and advanced time-frequency and beamforming methodology. Specifically, we recorded healthy adults while they performed a high-load, Sternberg-type working memory task, and focused on the encoding and maintenance phases. We found significant 9-16 Hz desynchronizations in the bilateral occipital cortices, left dorsolateral prefrontal cortex (DLPFC), and left superior temporal areas throughout the encoding phase. Our analysis of the dynamics showed that the left DLPFC and superior temporal desynchronization became stronger as a function of time during the encoding period, and was sustained throughout most of the maintenance phase until sharply decreasing in the milliseconds preceding retrieval. In contrast, desynchronization in occipital areas became weaker as a function of time during encoding and eventually evolved into a strong synchronization during the maintenance period, consistent with previous studies. These results provide clear evidence of dynamic network-level processes during the encoding and maintenance phases of working memory, and support the notion of a dynamic pattern of functionally-discrete subprocesses within each working memory phase. The presence of such dynamic oscillatory networks may be a potential source of inconsistent findings in this literature, as neural activity within these networks changes dramatically with time. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Random phase textures: theory and synthesis.

    Science.gov (United States)

    Galerne, Bruno; Gousseau, Yann; Morel, Jean-Michel

    2011-01-01

    This paper explores the mathematical and algorithmic properties of two sample-based texture models: random phase noise (RPN) and asymptotic discrete spot noise (ADSN). These models permit to synthesize random phase textures. They arguably derive from linearized versions of two early Julesz texture discrimination theories. The ensuing mathematical analysis shows that, contrarily to some statements in the literature, RPN and ADSN are different stochastic processes. Nevertheless, numerous experiments also suggest that the textures obtained by these algorithms from identical samples are perceptually similar. The relevance of this study is enhanced by three technical contributions providing solutions to obstacles that prevented the use of RPN or ADSN to emulate textures. First, RPN and ADSN algorithms are extended to color images. Second, a preprocessing is proposed to avoid artifacts due to the nonperiodicity of real-world texture samples. Finally, the method is extended to synthesize textures with arbitrary size from a given sample.

  1. GPU accelerated iterative SENSE reconstruction of radial phase encoded whole-heart MRI

    DEFF Research Database (Denmark)

    Sørensen, Thomas Sangild; Prieto, Claudia; Atkinson, David

    2010-01-01

    Isotropic whole-heart imaging has become an important protocol in simplifying cardiac MRI. The acquisition time can however be a prohibiting factor. To reduce acquisition times a 3D scheme combining Cartesian sampling in the readout direction with radial sampling in the phase encoding plane was r...... time can be brought to a clinically acceptable level using commodity graphics hardware (GPUs)....

  2. The application of random phase filter in the image recognition

    Science.gov (United States)

    Yang, Xiujuan; Zhong, Mei; Shao, Zhufeng

    2016-03-01

    We define one kind of new correlation, i.e. random phase correlation, which based on the Random Fourier Transform (RFT). An optical pattern recognition system, random phase filtering, is given according to random phase correlation. Furthermore its electro-optical setup is given for the application in image recognition. By the numerical simulation on computer, when the, we have found the proposed random phase filter can recognize the small change of object image and has higher recognition capability comparing of other three conventional correlators, the classical marched filter, the phase-only filter and the pure phase correlator.

  3. Sex and menstrual cycle phase at encoding influence emotional memory for gist and detail.

    Science.gov (United States)

    Nielsen, Shawn E; Ahmed, Imran; Cahill, Larry

    2013-11-01

    Sex influences on emotional memory have received increasing interest over the past decade. However, only a subset of this previous work explored the influence of sex on memory for central information (gist) and peripheral detail in emotional versus neutral contexts. Here we examined the influence of sex and menstrual cycle phase at encoding on memory for either an emotional or neutral story, specifically with respect to the retention of gist and peripheral detail. Healthy naturally cycling women and men viewed a brief, narrated, three-phase story containing neutral or emotionally arousing elements. One week later, participants received a surprise free recall test for story elements. The results indicate that naturally cycling women in the luteal (high hormone) phase of the menstrual cycle at encoding show enhanced memory for peripheral details, but not gist, when in the emotional compared with neutral stories (pemotional compared with neutral stories. Men show enhanced memory for gist, but not peripheral details, in the emotional versus neutral stories (pdifferences in attention or arousal; luteal women, follicular women, and men performed similarly on measures of attention (fixation time percentage) and arousal (pupil diameter changes) during the most arousing phase of the emotional story. These findings suggest that sex and menstrual cycle phase at encoding influence long term memory for different types of emotional information. Published by Elsevier Inc.

  4. Wavelet filtered shifted phase-encoded joint transform correlation for face recognition

    Science.gov (United States)

    Moniruzzaman, Md.; Alam, Mohammad S.

    2017-05-01

    A new wavelet-filtered-based Shifted- phase-encoded Joint Transform Correlation (WPJTC) technique has been proposed for efficient face recognition. The proposed technique uses discrete wavelet decomposition for preprocessing and can effectively accommodate various 3D facial distortions, effects of noise, and illumination variations. After analyzing different forms of wavelet basis functions, an optimal method has been proposed by considering the discrimination capability and processing speed as performance trade-offs. The proposed technique yields better correlation discrimination compared to alternate pattern recognition techniques such as phase-shifted phase-encoded fringe-adjusted joint transform correlator. The performance of the proposed WPJTC has been tested using the Yale facial database and extended Yale facial database under different environments such as illumination variation, noise, and 3D changes in facial expressions. Test results show that the proposed WPJTC yields better performance compared to alternate JTC based face recognition techniques.

  5. Generalized Encoding CRDSA: Maximizing Throughput in Enhanced Random Access Schemes for Satellite

    Directory of Open Access Journals (Sweden)

    Manlio Bacco

    2014-12-01

    Full Text Available This work starts from the analysis of the literature about the Random Access protocols with contention resolution, such as Contention Resolution Diversity Slotted Aloha (CRDSA, and introduces a possible enhancement, named Generalized Encoding Contention Resolution Diversity Slotted Aloha (GE-CRDSA. The GE-CRDSA aims at improving the aggregated throughput when the system load is less than 50%, playing on the opportunity of transmitting an optimal combination of information and parity packets frame by frame. This paper shows the improvement in terms of throughput, by performing traffic estimation and adaptive choice of information and parity rates, when a satellite network undergoes a variable traffic load profile.

  6. BLIPPED (BLIpped Pure Phase EncoDing) high resolution MRI with low amplitude gradients

    Science.gov (United States)

    Xiao, Dan; Balcom, Bruce J.

    2017-12-01

    MRI image resolution is proportional to the maximum k-space value, i.e. the temporal integral of the magnetic field gradient. High resolution imaging usually requires high gradient amplitudes and/or long spatial encoding times. Special gradient hardware is often required for high amplitudes and fast switching. We propose a high resolution imaging sequence that employs low amplitude gradients. This method was inspired by the previously proposed PEPI (π Echo Planar Imaging) sequence, which replaced EPI gradient reversals with multiple RF refocusing pulses. It has been shown that when the refocusing RF pulse is of high quality, i.e. sufficiently close to 180°, the magnetization phase introduced by the spatial encoding magnetic field gradient can be preserved and transferred to the following echo signal without phase rewinding. This phase encoding scheme requires blipped gradients that are identical for each echo, with low and constant amplitude, providing opportunities for high resolution imaging. We now extend the sequence to 3D pure phase encoding with low amplitude gradients. The method is compared with the Hybrid-SESPI (Spin Echo Single Point Imaging) technique to demonstrate the advantages in terms of low gradient duty cycle, compensation of concomitant magnetic field effects and minimal echo spacing, which lead to superior image quality and high resolution. The 3D imaging method was then applied with a parallel plate resonator RF probe, achieving a nominal spatial resolution of 17 μm in one dimension in the 3D image, requiring a maximum gradient amplitude of only 5.8 Gauss/cm.

  7. Sex and menstrual cycle phase at encoding influence emotional memory for gist and detail

    OpenAIRE

    Nielsen, Shawn E.; Ahmed, Imran; Cahill, Larry

    2013-01-01

    Sex influences on emotional memory have received increasing interest over the past decade. However, only a subset of this previous work explored the influence of sex on memory for central information (gist) and peripheral detail in emotional versus neutral contexts. Here we examined the influence of sex and menstrual cycle phase at encoding on memory for either an emotional or neutral story, specifically with respect to the retention of gist and peripheral detail. Healthy naturally cycling wo...

  8. Phase recovering algorithms for extended objects encoded in digitally recorded holograms

    Directory of Open Access Journals (Sweden)

    Peng Z.

    2010-06-01

    Full Text Available The paper presents algorithms to recover the optical phase of digitally encoded holograms. Algorithms are based on the use of a numerical spherical reconstructing wave. Proof of the validity of the concept is performed through an experimental off axis digital holographic set-up. Two-color digital holographic reconstruction is also investigated. Application of the color set-up and algorithms concerns the simultaneous two-dimensional deformation measurement of an object submitted to a mechanical loading.

  9. Real-Time RGB-D Camera Relocalization via Randomized Ferns for Keyframe Encoding.

    Science.gov (United States)

    Glocker, Ben; Shotton, Jamie; Criminisi, Antonio; Izadi, Shahram

    2015-05-01

    Recovery from tracking failure is essential in any simultaneous localization and tracking system. In this context, we explore an efficient keyframe-based relocalization method based on frame encoding using randomized ferns. The method enables automatic discovery of keyframes through online harvesting in tracking mode, and fast retrieval of pose candidates in the case when tracking is lost. Frame encoding is achieved by applying simple binary feature tests which are stored in the nodes of an ensemble of randomized ferns. The concatenation of small block codes generated by each fern yields a global compact representation of camera frames. Based on those representations we define the frame dissimilarity as the block-wise hamming distance (BlockHD). Dissimilarities between an incoming query frame and a large set of keyframes can be efficiently evaluated by simply traversing the nodes of the ferns and counting image co-occurrences in corresponding code tables. In tracking mode, those dissimilarities decide whether a frame/pose pair is considered as a novel keyframe. For tracking recovery, poses of the most similar keyframes are retrieved and used for reinitialization of the tracking algorithm. The integration of our relocalization method into a hand-held KinectFusion system allows seamless continuation of mapping even when tracking is frequently lost.

  10. Temporal lobe cortical electrical stimulation during the encoding and retrieval phase reduces false memories.

    Directory of Open Access Journals (Sweden)

    Paulo S Boggio

    Full Text Available A recent study found that false memories were reduced by 36% when low frequency repetitive transcranial magnetic stimulation (rTMS was applied to the left anterior temporal lobe after the encoding (study phase. Here we were interested in the consequences on a false memory task of brain stimulation throughout the encoding and retrieval task phases. We used transcranial direct current stimulation (tDCS because it has been shown to be a useful tool to enhance cognition. Specifically, we examined whether tDCS can induce changes in a task assessing false memories. Based on our preliminary results, three conditions of stimulation were chosen: anodal left/cathodal right anterior temporal lobe (ATL stimulation ("bilateral stimulation"; anodal left ATL stimulation (with a large contralateral cathodal electrode--referred as "unilateral stimulation" and sham stimulation. Our results showed that false memories were reduced significantly after the two active conditions (unilateral and bilateral stimulation as compared with sham stimulation. There were no significant changes in veridical memories. Our findings show that false memories are reduced by 73% when anodal tDCS is applied to the anterior temporal lobes throughout the encoding and retrieval stages, suggesting a possible strategy for improving certain aspects of learning.

  11. A spectral phase encoded time spreading optical code division multiple access testbed

    Science.gov (United States)

    Cong, Wei

    Spectral phase-encode time-spreading (SPECTS) is a promising technique for optical code-division multiple-access (O-CDMA) networks. In SPECTS O-CDMA, users are multiplexed and distinguished with unique phase codes impressed on the spectrum of ultra-short optical signal pulses. The encoding and decoding processes are implemented with grating/lens zero-dispersion pulse-shapers using spatial light phase modulators (SLPMs) in the Fourier plane. The SLPMs add the encoding or decoding O-CDMA phase codes on the spectrum which is spatially spread and then recombined by the grating(s) and lens(es). In this dissertation, we demonstrate a SPECTS O-CDMA network testbed with large throughputs and high performances. Two types of fiber-pigtailed bulk-optic pulseshapers, 1-D transparent-mode and 2-D reflective-mode, are constructed to be used as SPECTS O-CDMA encoders and decoders in the testbed. In order to support a large number of users, the testbed includes up to eight SPECTS O-CDMA encoding channels and one decoding channel. With the combination of time-slotting and polarization-multiplexing operations, the maximum throughput achieved on the testbed is 32 users (8 O-CDMA channel x 2 time slots x 2 polarizations) at 10 Gb/s/user. Two nonlinear detecting techniques (thresholding and gating) for coherent SPECTS O-CDMA are discussed in the dissertation. A nonlinear thresholder and a nonlinear optical loop mirror (NOLM) time gate are built in the testbed; each uses a 500-m highly nonlinear fiber(HNLF). An "O-CDMA receiver" including the NOLM and the thresholder followed by an optical-electrical (O-E) converter can distinguish the intended user by demultiplexing the time-slotted signal and then suppressing the multi-user interference (MUI). In the bit-error-rate (BER) statistics experiments, the "O-CDMA receiver" can detect the intended user's signal with error-free or low BER performance in various testbed structures. Network-layer application experiments including video

  12. Stimulus number, duration and intensity encoding in randomly connected attractor networks with synaptic depression

    Directory of Open Access Journals (Sweden)

    Paul eMiller

    2013-05-01

    Full Text Available Randomly connected recurrent networks of excitatory groups of neurons can possess a multitude of attractor states. When the internal excitatory synapses of these networks are depressing, the attractor states can be destabilized with increasing input. This leads to an itinerancy, where with either repeated transient stimuli, or increasing duration of a single stimulus, the network activity advances through sequences of attractor states. We find that the resulting network state, which persists beyond stimulus offset, can encode the number of stimuli presented via a distributed representation of neural activity with non-monotonic tuning curves for most neurons. Increased duration of a single stimulus is encoded via different distributed representations, so unlike an integrator, the network distinguishes separate successive presentations of a short stimulus from a single presentation of a longer stimulus with equal total duration. Moreover, different amplitudes of stimulus cause new, distinct activity patterns, such that changes in stimulus number, duration and amplitude can be distinguished from each other. These properties of the network depend on dynamic depressing synapses, as they disappear if synapses are static. Thus short-term synaptic depression allows a network to store separately the different dynamic properties of a spatially constant stimulus.

  13. Nonlinear higher quasiparticle random phase approximation

    Science.gov (United States)

    Smetana, Adam; Šimkovic, Fedor; Štefánik, Dušan; Krivoruchenko, Mikhail

    2017-10-01

    We develop a new approach to describe nuclear states of multiphonon origin, motivated by the necessity for a more accurate description of matrix elements of neutrinoless double-beta decay. Our approach is an extension of the Quasiparticle Random Phase Approximation (QRPA), in which nonlinear phonon operators play an essential role. Before applying the nonlinear higher QRPA (nhQRPA) to realistic problems, we test its efficiency with exactly solvable models. The first considered model is equivalent to a harmonic oscillator. The nhQRPA solutions follow from the standard QRPA equation, but for nonlinear phonon operators defined for each individual excited state separately. The second exactly solvable model is the proton-neutron Lipkin model that describes successfully not only energy spectrum of nuclei, but also beta-decay transitions. Again, we reproduce exactly the numerical solutions in the nhQRPA framework. We show in particular that truncation of the nonlinear phonon operators leads to an approximation similar to the self-consistent second QRPA, given the phonon operators are defined with a constant term. The test results demonstrate that the proposed nhQRPA is a promising tool for a realistic calculation of energy spectra and nuclear transitions.

  14. Nuclear magnetic resonance diffusion pore imaging: Experimental phase detection by double diffusion encoding.

    Science.gov (United States)

    Demberg, Kerstin; Laun, Frederik Bernd; Windschuh, Johannes; Umathum, Reiner; Bachert, Peter; Kuder, Tristan Anselm

    2017-02-01

    Diffusion pore imaging is an extension of diffusion-weighted nuclear magnetic resonance imaging enabling the direct measurement of the shape of arbitrarily formed, closed pores by probing diffusion restrictions using the motion of spin-bearing particles. Examples of such pores comprise cells in biological tissue or oil containing cavities in porous rocks. All pores contained in the measurement volume contribute to one reconstructed image, which reduces the problem of vanishing signal at increasing resolution present in conventional magnetic resonance imaging. It has been previously experimentally demonstrated that pore imaging using a combination of a long and a narrow magnetic field gradient pulse is feasible. In this work, an experimental verification is presented showing that pores can be imaged using short gradient pulses only. Experiments were carried out using hyperpolarized xenon gas in well-defined pores. The phase required for pore image reconstruction was retrieved from double diffusion encoded (DDE) measurements, while the magnitude could either be obtained from DDE signals or classical diffusion measurements with single encoding. The occurring image artifacts caused by restrictions of the gradient system, insufficient diffusion time, and by the phase reconstruction approach were investigated. Employing short gradient pulses only is advantageous compared to the initial long-narrow approach due to a more flexible sequence design when omitting the long gradient and due to faster convergence to the diffusion long-time limit, which may enable application to larger pores.

  15. Security enhanced optical encryption system by random phase key and permutation key.

    Science.gov (United States)

    He, Mingzhao; Tan, Qiaofeng; Cao, Liangcai; He, Qingsheng; Jin, Guofan

    2009-12-07

    Conventional double random phase encoding (DRPE) encrypts plaintext to white noise-like ciphertext which may attract attention of eavesdroppers, and recent research reported that DRPE is vulnerable to various attacks. Here we propose a security enhanced optical encryption system that can hide the existence of secret information by watermarking. The plaintext is encrypted using iterative fractional Fourier transform with random phase key, and ciphertext is randomly permuted with permutation key before watermarking. Cryptanalysis shows that linearity of the security system has been broken and the permutation key prevent the attacker from accessing the ciphertext in various attacks. A series of simulations have shown the effectiveness of this system and the security strength is enhanced for invisibility, nonlinearity and resistance against attacks.

  16. MR imaging of ore for heap bioleaching studies using pure phase encode acquisition methods

    Science.gov (United States)

    Fagan, Marijke A.; Sederman, Andrew J.; Johns, Michael L.

    2012-03-01

    Various MRI techniques were considered with respect to imaging of aqueous flow fields in low grade copper ore. Spin echo frequency encoded techniques were shown to produce unacceptable image distortions which led to pure phase encoded techniques being considered. Single point imaging multiple point acquisition (SPI-MPA) and spin echo single point imaging (SESPI) techniques were applied. By direct comparison with X-ray tomographic images, both techniques were found to be able to produce distortion-free images of the ore packings at 2 T. The signal to noise ratios (SNRs) of the SESPI images were found to be superior to SPI-MPA for equal total acquisition times; this was explained based on NMR relaxation measurements. SESPI was also found to produce suitable images for a range of particles sizes, whereas SPI-MPA SNR deteriorated markedly as particles size was reduced. Comparisons on a 4.7 T magnet showed significant signal loss from the SPI-MPA images, the effect of which was accentuated in the case of unsaturated flowing systems. Hence it was concluded that SESPI was the most robust imaging method for the study of copper ore heap leaching hydrology.

  17. Ordering and phase transitions in random-field Ising systems

    Science.gov (United States)

    Maritan, Amos; Swift, Michael R.; Cieplak, Marek; Chan, Moses H. W.; Cole, Milton W.; Banavar, Jayanth R.

    1991-01-01

    An exact analysis of the Ising model with infinite-range interactions in a random field and a local mean-field theory in three dimensions is carried out leading to a phase diagram with several coexistence surfaces and lines of critical points. The results show that the phase diagram depends crucially on whether the distribution of random fields is symmetric or not. Thus, Ising-like phase transitions in a porous medium (the asymmetric case) are in a different universality class from the conventional random-field model (symmetric case).

  18. Ultrasonic Backscatter Imaging by Shear-Wave-Induced Echo Phase Encoding of Target Locations

    Science.gov (United States)

    McAleavey, Stephen

    2011-01-01

    We present a novel method for ultrasound backscatter image formation wherein lateral resolution of the target is obtained by using traveling shear waves to encode the lateral position of targets in the phase of the received echo. We demonstrate that the phase modulation as a function of shear wavenumber can be expressed in terms of a Fourier transform of the lateral component of the target echogenicity. The inverse transform, obtained by measurements of the phase modulation over a range of shear wave spatial frequencies, yields the lateral scatterer distribution. Range data are recovered from time of flight as in conventional ultrasound, yielding a B-mode-like image. In contrast to conventional ultrasound imaging, where mechanical or electronic focusing is used and lateral resolution is determined by aperture size and wavelength, we demonstrate that lateral resolution using the proposed method is independent of the properties of the aperture. Lateral resolution of the target is achieved using a stationary, unfocused, single-element transducer. We present simulated images of targets of uniform and non-uniform shear modulus. Compounding for speckle reduction is demonstrated. Finally, we demonstrate image formation with an unfocused transducer in gelatin phantoms of uniform shear modulus. PMID:21244978

  19. Hacking on decoy-state quantum key distribution system with partial phase randomization

    Science.gov (United States)

    Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

    2014-04-01

    Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.

  20. Experimental demonstration of quantum digital signatures using phase-encoded coherent states of light.

    Science.gov (United States)

    Clarke, Patrick J; Collins, Robert J; Dunjko, Vedran; Andersson, Erika; Jeffers, John; Buller, Gerald S

    2012-01-01

    Digital signatures are frequently used in data transfer to prevent impersonation, repudiation and message tampering. Currently used classical digital signature schemes rely on public key encryption techniques, where the complexity of so-called 'one-way' mathematical functions is used to provide security over sufficiently long timescales. No mathematical proofs are known for the long-term security of such techniques. Quantum digital signatures offer a means of sending a message, which cannot be forged or repudiated, with security verified by information-theoretical limits and quantum mechanics. Here we demonstrate an experimental system, which distributes quantum signatures from one sender to two receivers and enables message sending ensured against forging and repudiation. Additionally, we analyse the security of the system in some typical scenarios. Our system is based on the interference of phase-encoded coherent states of light and our implementation utilizes polarization-maintaining optical fibre and photons with a wavelength of 850 nm.

  1. Multiple-image authentication with a cascaded multilevel architecture based on amplitude field random sampling and phase information multiplexing.

    Science.gov (United States)

    Fan, Desheng; Meng, Xiangfeng; Wang, Yurong; Yang, Xiulun; Pan, Xuemei; Peng, Xiang; He, Wenqi; Dong, Guoyan; Chen, Hongyi

    2015-04-10

    A multiple-image authentication method with a cascaded multilevel architecture in the Fresnel domain is proposed, in which a synthetic encoded complex amplitude is first fabricated, and its real amplitude component is generated by iterative amplitude encoding, random sampling, and space multiplexing for the low-level certification images, while the phase component of the synthetic encoded complex amplitude is constructed by iterative phase information encoding and multiplexing for the high-level certification images. Then the synthetic encoded complex amplitude is iteratively encoded into two phase-type ciphertexts located in two different transform planes. During high-level authentication, when the two phase-type ciphertexts and the high-level decryption key are presented to the system and then the Fresnel transform is carried out, a meaningful image with good quality and a high correlation coefficient with the original certification image can be recovered in the output plane. Similar to the procedure of high-level authentication, in the case of low-level authentication with the aid of a low-level decryption key, no significant or meaningful information is retrieved, but it can result in a remarkable peak output in the nonlinear correlation coefficient of the output image and the corresponding original certification image. Therefore, the method realizes different levels of accessibility to the original certification image for different authority levels with the same cascaded multilevel architecture.

  2. Effect of Phase-Encoding Reduction on Geometric Distortion and BOLD Signal Changes in fMRI

    Directory of Open Access Journals (Sweden)

    Golestan karami

    2013-03-01

    Full Text Available Introduction Echo-planar imaging (EPI is a group of fast data acquisition methods commonly used in fMRI studies. It acquires multiple image lines in k-space after a single excitation, which leads to a very short scan time. A well-known problem with EPI is that it is more sensitive to distortions due to the used encoding scheme. Source of distortion is inhomogeneity in the static B0 field that causes more geometric distortion in phase encoding direction. This inhomogeneity is induced mainly by the magnetic susceptibility differences between various structures within the object placed inside the scanner, often at air-tissue or bone-tissue interfaces. Methods of reducing EPI distortion are mainly based on decreasing steps of the phase encoding. Reducing steps of phase encoding can be applied by reducing field of view, slice thickness, and/or the use of parallel acquisition technique. Materials and Methods We obtained three data acquisitions with different FOVs including: conventional low resolution, conventional high resolution, and zoomed high resolution EPIs. Moreover we used SENSE technique for phase encoding reduction. All experiments were carried out on three Tesla scanners (Siemens, TIM, and Germany equipped with 12 channel head coil. Ten subjects participated in the experiments. Results The data were processed by FSL software and were evaluated by ANOVA. Distortion was assessed by obtaining low displacement voxels map, and calculated from a field map image. Conclusion We showed that image distortion can be reduced by decreasing slice thickness and phase encoding steps. Distortion reduction in zoomed technique resulted the lowest level, but at the cost of signal-to-noise loss. Moreover, the SENSE technique was shown to decrease the amount of image distortion, efficiently.

  3. Implementation of the direct evaluation of strains using a phase analysis code for random patterns

    CERN Document Server

    Molimard, Jérôme

    2011-01-01

    A new approach for decoding directly strains from surfaces encoded with random patterns has been developed and validated. It is based on phase analysis of small region of interest. Here we adapt to random patterns new concepts proposed by Badulescu (2009) on the grid method. First metrological results are encouraging: resolution is proportional to strain level, being 9% of the nominal value, for a spatial resolution of 9 pixels (ZOI 64 \\times 64 pixels2). Random noise has to be carefully controlled. A numerical example shows the relevance of the approach. Then, first application on a carbon fiber reinforced composite is developed. Fabric intertwining is studied using a tensile test. Over-strains are clearly visible, and results connect well with the previous studies

  4. A Novel Encoded Excitation Scheme in a Phased Array for The Improving Data Acquisition Rate

    Directory of Open Access Journals (Sweden)

    César Gutiérrez-Fernández

    2013-12-01

    Full Text Available One of the challenges of phased array (PA ultrasonic imaging systems is their limited capability to deal with real-time applications, such as echocardiography and obstetrics. In its most basic outline, these systems require emitting and receiving with the entire array for each image line to be acquired; therefore, with many image lines, a higher acquisition time and a lower frame rate. This constraint requires one to find alternatives to reduce the total number of emissions needed to obtain the whole image. In this work, we propose a new PA scheme based on the Code Division Multiple Access (CDMA technique, where a different code is assigned to each steering direction, allowing the array to emit in several directions simultaneously. However, the use of encoding techniques produces a reduction of the image contrast because of the interferences between codes. To solve this, a new scheme based on merging several images is proposed, allowing the system to get close to the theoretical maximum frame rate, as well as to limit the loss of contrast, intrinsic to the technique.

  5. Regulation of the Escherichia coli rmf gene encoding the ribosome modulation factor: growth phase- and growth rate-dependent control.

    OpenAIRE

    Yamagishi, M.; Matsushima, H; Wada, A.; Sakagami, M.; Fujita, N.; Ishihama, A

    1993-01-01

    Ribosome modulation factor (RMF) is a protein specifically associated with 100S ribosome dimers which start to accumulate in Escherichia coli cells upon growth transition from exponential to stationary phase. The structural gene, rmf, encoding the 55 amino acid residues RMF protein has been cloned from the 21.8 min region of the E. coli genome and sequenced. While rmf was silent in rapidly growing exponential phase cells, a high level of transcription took place concomitantly with the growth ...

  6. Phase transitions for information diffusion in random clustered networks

    Science.gov (United States)

    Lim, Sungsu; Shin, Joongbo; Kwak, Namju; Jung, Kyomin

    2016-09-01

    We study the conditions for the phase transitions of information diffusion in complex networks. Using the random clustered network model, a generalisation of the Chung-Lu random network model incorporating clustering, we examine the effect of clustering under the Susceptible-Infected-Recovered (SIR) epidemic diffusion model with heterogeneous contact rates. For this purpose, we exploit the branching process to analyse information diffusion in random unclustered networks with arbitrary contact rates, and provide novel iterative algorithms for estimating the conditions and sizes of global cascades, respectively. Showing that a random clustered network can be mapped into a factor graph, which is a locally tree-like structure, we successfully extend our analysis to random clustered networks with heterogeneous contact rates. We then identify the conditions for phase transitions of information diffusion using our method. Interestingly, for various contact rates, we prove that random clustered networks with higher clustering coefficients have strictly lower phase transition points for any given degree sequence. Finally, we confirm our analytical results with numerical simulations of both synthetically-generated and real-world networks.

  7. Single-random-phase holographic encryption of images

    Science.gov (United States)

    Tsang, P. W. M.

    2017-02-01

    In this paper, a method is proposed for encrypting an optical image onto a phase-only hologram, utilizing a single random phase mask as the private encryption key. The encryption process can be divided into 3 stages. First the source image to be encrypted is scaled in size, and pasted onto an arbitrary position in a larger global image. The remaining areas of the global image that are not occupied by the source image could be filled with randomly generated contents. As such, the global image as a whole is very different from the source image, but at the same time the visual quality of the source image is preserved. Second, a digital Fresnel hologram is generated from the new image, and converted into a phase-only hologram based on bi-directional error diffusion. In the final stage, a fixed random phase mask is added to the phase-only hologram as the private encryption key. In the decryption process, the global image together with the source image it contained, can be reconstructed from the phase-only hologram if it is overlaid with the correct decryption key. The proposed method is highly resistant to different forms of Plain-Text-Attacks, which are commonly used to deduce the encryption key in existing holographic encryption process. In addition, both the encryption and the decryption processes are simple and easy to implement.

  8. Random phase-free computer-generated hologram

    CERN Document Server

    Shimobaba, Tomoyoshi

    2015-01-01

    Addition of random phase to the object light is required in computer-generated holograms (CGHs) to widely diffuse the object light and to avoid its concentration on the CGH; however, this addition causes considerable speckle noise in the reconstructed image. For improving the speckle noise problem, techniques such as iterative phase retrieval algorithms and multi-random phase method are used; however, they are time consuming and are of limited effectiveness. Herein, we present a simple and computationally inexpensive method that drastically improves the image quality and reduces the speckle noise by multiplying the object light with the virtual convergence light. Feasibility of the proposed method is shown using simulations and optical reconstructions; moreover, we apply it to lens-less zoom-able holographic projection. The proposed method is useful for the speckle problems in holographic applications.

  9. Enhanced wavefront reconstruction by random phase modulation with a phase diffuser

    DEFF Research Database (Denmark)

    Almoro, Percival F; Pedrini, Giancarlo; Gundu, Phanindra Narayan

    2011-01-01

    propagation in free space. The presentation of this technique is carried out using two setups. In the first setup, a diffuser plate is placed at the image plane of a metallic test object. The benefit of randomizing the phase of the object wave is the enhanced intensity recording due to high dynamic range...... of the diffusely scattered beam. The use of demagnification optics will also allow the investigations of relatively large objects. In the second setup, a transparent object is illuminated using a wavefront with random phase and constant amplitude by positioning the phase diffuser close to the object. The benefit...

  10. Double random phase spread spectrum spread space technique for secure parallel optical multiplexing with individual encryption key

    Science.gov (United States)

    Hennelly, B. M.; Javidi, B.; Sheridan, J. T.

    2005-09-01

    A number of methods have been recently proposed in the literature for the encryption of 2-D information using linear optical systems. In particular the double random phase encoding system has received widespread attention. This system uses two Random Phase Keys (RPK) positioned in the input spatial domain and the spatial frequency domain and if these random phases are described by statistically independent white noises then the encrypted image can be shown to be a white noise. Decryption only requires knowledge of the RPK in the frequency domain. The RPK may be implemented using a Spatial Light Modulators (SLM). In this paper we propose and investigate the use of SLMs for secure optical multiplexing. We show that in this case it is possible to encrypt multiple images in parallel and multiplex them for transmission or storage. The signal energy is effectively spread in the spatial frequency domain. As expected the number of images that can be multiplexed together and recovered without loss is proportional to the ratio of the input image and the SLM resolution. Many more images may be multiplexed with some loss in recovery. Furthermore each individual encryption is more robust than traditional double random phase encoding since decryption requires knowledge of both RPK and a lowpass filter in order to despread the spectrum and decrypt the image. Numerical simulations are presented and discussed.

  11. Phase shifting interferometry from two normalized interferograms with random tilt phase-shift.

    Science.gov (United States)

    Liu, Fengwei; Wu, Yongqian; Wu, Fan

    2015-07-27

    We propose a novel phase shifting interferometry from two normalized interferograms with random tilt phase-shift. The determination of tilt phase-shift is performed by extracting the tilted phase-shift plane from the phase difference of two normalized interferograms, and with the calculated tilt phase-shift value the phase distribution can be retrieved from the two normalized frames. By analyzing the distribution of phase difference and utilizing special points fitting method, the tilted phase-shift plane is extracted in three different cases, which relate to different magnitudes of tilts. Proposed method has been applied to simulations and experiments successfully and the satisfactory results manifest that proposed method is of high accuracy and high speed compared with the three step iterative method. Additionally, both open and closed fringe can be analyzed with proposed method. What's more, it cannot only eliminate the small tilt-shift error caused by slight vibration in phase-shifting interferometry, but also detect the large tilt phase-shift in phase-tilting interferometry. Thus, it will relaxes the requirements on the accuracy of phase shifter, and the costly phase shifter may even be useless by applying proposed method in high amplitude vibrated circumstance to achieve high-precision analysis.

  12. Peak velocity measurements in tortuous arteries with phase contrast magnetic resonance imaging: the effect of multidirectional velocity encoding.

    Science.gov (United States)

    Schubert, Tilman; Bieri, Oliver; Pansini, Michele; Stippich, Christoph; Santini, Francesco

    2014-04-01

    Blood flow velocity measurement with phase contrast magnetic resonance imaging (PC-MRI) is widely applied in clinical routine imaging. Usually, velocity and volumetric flow measurements are performed using unidirectional encoding of the through-plane velocity with a 2-dimensional (2D) acquisition. Single-slice acquisitions and measurements with unidirectional encoding, however, may lead to significant errors, especially in tortuous vessels, but might benefit from higher signal-to-noise ratios (SNRs). To evaluate the impact of volumetric acquisition and multidirectional velocity encoding, blood velocity measurements were performed at 3 locations in the distal internal carotid artery with a 3-dimensional, 3-directional time-resolved phase contrast (PC) sequence (4-dimensional [4D]) and a 2D acquisition with 3-directional (2D-3dir) and through-plane velocity encoding (2D-tp) derived from the same sequence. Twenty carotid arteries of 10 healthy volunteers (24-37 years) were evaluated. For each volunteer, 1 4D acquisition and 3 2D 3-directional PC measurements were placed according to a time-of-flight angiography. Unidirectionally encoded through-plane velocities were derived from the multidirectionally encoded 2D scan by discarding the in-plane components. Regions of interest were identified on the slab after postprocessing and visualization for the 4D data set as well as directly on the digital imaging and communications in medicine images for the 2D measurement. Blood flow velocity, volumetric flow, and SNRs were measured at carotid segments C4, C5, and C7 on both sides obtaining 20 values per vessel location. The quantities were tested for significant differences between each modality at all 3 locations with paired t tests. At the segments C5 and C7, the highest peak velocities (PVs) were measured with the 4D sequence, followed by 2D-3dir and 2D tp. The PV differences between the sequences were significant (P measured with 2D-tp. The mean PV value of the 4D sequence

  13. Relativistic Quasiparticle Random Phase Approximation in Deformed Nuclei

    OpenAIRE

    Pena Arteaga, Daniel

    2008-01-01

    Covariant density functional theory is used to study the influence of electromagnetic radiation on deformed superfluid nuclei. The relativistic Hartree-Bogoliubov equations and the resulting diagonalization problem of the quasiparticle random phase approximation are solved for axially symmetric systems in a fully self-consistent way by a newly developed parallel code. Three different kinds of high precision energy functionals are investigated and special care is taken for the decoupling of th...

  14. Reconstruction of a random phase dynamics network from observations

    Science.gov (United States)

    Pikovsky, A.

    2018-01-01

    We consider networks of coupled phase oscillators of different complexity: Kuramoto-Daido-type networks, generalized Winfree networks, and hypernetworks with triple interactions. For these setups an inverse problem of reconstruction of the network connections and of the coupling function from the observations of the phase dynamics is addressed. We show how a reconstruction based on the minimization of the squared error can be implemented in all these cases. Examples include random networks with full disorder both in the connections and in the coupling functions, as well as networks where the coupling functions are taken from experimental data of electrochemical oscillators. The method can be directly applied to asynchronous dynamics of units, while in the case of synchrony, additional phase resettings are necessary for reconstruction.

  15. Profilometry of discontinuous solids by means of co-phased demodulation of projected fringes with RGB encoding

    Science.gov (United States)

    Padilla, J. M.; Servin, M.; Garnica, G.

    2015-05-01

    Here we describe a 2-projectors and 1-camera setup for profilometry of discontinuous solids by means of co-phased demodulation of projected fringes and red, green, and blue (RGB) multichannel operation. The dual projection configuration for this profilometer is proposed to solve efficiently specular regions and self-occluding shadows due to discontinuities, which are the main drawbacks for a 1-projector 1-camera configuration. This is because the regions where shadows and specular reflections are generated, and the fringe contrast drops to zero, are in general different for each projection direction; thus, the resulting fringe patterns will have complementary phase information. Multichannel RGB operation allows us to work simultaneously with both projectors and to record independently the complementary fringe patterns phase-modulated by the 3D profile of the object under study. In other words, color encoding/decoding reduces the acquisition time respect to one-at-a-time grayscale operation and, in principle, enables the study of dynamic phenomena. The co-phased demodulation method implemented in this work benefits from the complex (analytic) nature of the output signals estimated with most phase demodulation methods (such as the Fourier method, and temporal phaseshifting algorithms). This allowed us to straightforwardly generate a single phase-map well-defined for the entire area of interest. Finally we assessed our proposed profilometry setup by measuring a fractured spherical cap made of (uncoated) expanded polystyrene. The results were satisfactory but in the authors' opinion this must be considered a preliminary report.

  16. Regulation of the Escherichia coli rmf gene encoding the ribosome modulation factor: growth phase- and growth rate-dependent control.

    Science.gov (United States)

    Yamagishi, M; Matsushima, H; Wada, A; Sakagami, M; Fujita, N; Ishihama, A

    1993-02-01

    Ribosome modulation factor (RMF) is a protein specifically associated with 100S ribosome dimers which start to accumulate in Escherichia coli cells upon growth transition from exponential to stationary phase. The structural gene, rmf, encoding the 55 amino acid residues RMF protein has been cloned from the 21.8 min region of the E. coli genome and sequenced. While rmf was silent in rapidly growing exponential phase cells, a high level of transcription took place concomitantly with the growth transition to stationary phase. Under slow growth conditions, rmf was expressed even in exponential phase and there was an inverse relationship between the expression of rmf and the cell growth rate. Thus, the expression profile of rmf is contrary to those of genes for ribosomal components and ribosome-associated proteins constituting the translational apparatus. The katF gene product, a stationary phase-specific sigma factor, was not required for the expression of rmf. Disruption of rmf resulted in loss of ribosome dimers and reduction of cell viability during stationary phase.

  17. Single pulse TMS-induced modulations of resting brain neurodynamics encoded in EEG phase.

    Science.gov (United States)

    Stamoulis, Catherine; Oberman, Lindsay M; Praeg, Elke; Bashir, Shahid; Pascual-Leone, Alvaro

    2011-06-01

    Integration of electroencephalographic (EEG) recordings and transcranial magnetic stimulation (TMS) provides a useful framework for quantifying stimulation-induced modulations of neural dynamics. Amplitude and frequency modulations by different TMS protocols have been previously investigated, but the study of stimulation-induced effects on EEG phase has been more limited. We examined changes in resting brain dynamics following single TMS pulses, focusing on measures in the phase domain, to assess their sensitivity to stimulation effects. We observed a significant, approximately global increase in EEG relative phase following prolonged (>20 min) single-pulse TMS. In addition, we estimated higher rates of phase fluctuation from the slope of estimated phase curves, and higher numbers of phase resetting intervals following TMS over motor cortex, particularly in frontal and centro-parietal/parietal channels. Phase changes were only significantly different from their pre-TMS values at the end of the stimulation session, which suggests that prolonged single-pulse TMS may result in cumulative changes in neural activity reflected in the phase of the EEG. This is a novel result, as prior studies have reported only transient stimulation-related effects in the amplitude and frequency domains following single-pulse TMS.

  18. Relativistic quasiparticle random phase approximation in deformed nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Pena Arteaga, D.

    2007-06-25

    Covariant density functional theory is used to study the influence of electromagnetic radiation on deformed superfluid nuclei. The relativistic Hartree-Bogolyubov equations and the resulting diagonalization problem of the quasiparticle random phase approximation are solved for axially symmetric systems in a fully self-consistent way by a newly developed parallel code. Three different kinds of high precision energy functionals are investigated and special care is taken for the decoupling of the Goldstone modes. This allows the microscopic investigation of Pygmy and scissor resonances in electric and magnetic dipole fields. Excellent agreement with recent experiments is found and new types of modes are predicted for deformed systems with large neutron excess. (orig.)

  19. Accelerated three-dimensional cine phase contrast imaging using randomly undersampled echo planar imaging with compressed sensing reconstruction.

    Science.gov (United States)

    Basha, Tamer A; Akçakaya, Mehmet; Goddu, Beth; Berg, Sophie; Nezafat, Reza

    2015-01-01

    The aim of this study was to implement and evaluate an accelerated three-dimensional (3D) cine phase contrast MRI sequence by combining a randomly sampled 3D k-space acquisition sequence with an echo planar imaging (EPI) readout. An accelerated 3D cine phase contrast MRI sequence was implemented by combining EPI readout with randomly undersampled 3D k-space data suitable for compressed sensing (CS) reconstruction. The undersampled data were then reconstructed using low-dimensional structural self-learning and thresholding (LOST). 3D phase contrast MRI was acquired in 11 healthy adults using an overall acceleration of 7 (EPI factor of 3 and CS rate of 3). For comparison, a single two-dimensional (2D) cine phase contrast scan was also performed with sensitivity encoding (SENSE) rate 2 and approximately at the level of the pulmonary artery bifurcation. The stroke volume and mean velocity in both the ascending and descending aorta were measured and compared between two sequences using Bland-Altman plots. An average scan time of 3 min and 30 s, corresponding to an acceleration rate of 7, was achieved for 3D cine phase contrast scan with one direction flow encoding, voxel size of 2 × 2 × 3 mm(3) , foot-head coverage of 6 cm and temporal resolution of 30 ms. The mean velocity and stroke volume in both the ascending and descending aorta were statistically equivalent between the proposed 3D sequence and the standard 2D cine phase contrast sequence. The combination of EPI with a randomly undersampled 3D k-space sampling sequence using LOST reconstruction allows a seven-fold reduction in scan time of 3D cine phase contrast MRI without compromising blood flow quantification. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Affine cryptosystem of double-random-phase encryption based on the fractional Fourier transform.

    Science.gov (United States)

    Xin, Zhou; Sheng, Yuan; Sheng-wei, Wang; Jian, Xie

    2006-11-20

    An affine mapping mathematical expression of the double-random-phase encryption technique has been deduced utilizing the matrix form of discrete fractional Fourier transforms. This expression clearly describes the encryption laws of the double-random-phase encoding techniques based on both the fractional Fourier transform and the ordinary Fourier transform. The encryption process may be regarded as a substantial optical realization of the affine cryptosystem. It has been illustrated that the encryption process converts the original image into a white Gaussian noise with a zero-mean value. Also, the decryption process converts the data deviations of the encrypted image into white Gaussian noises, regardless of the type of data deviations. These noises superimpose on the decrypted image and degrade the signal-to-noise ratio. Numerical simulations have been implemented for the different types of noises introduced into the encrypted image, such as the white noise with uniform distribution probability, the white noise with Gaussian distribution probability, colored noise, and the partial occlusion of the encrypted image.

  1. Transcript accumulation from the rpoS gene encoding a stationary-phase sigma factor in Pseudomonas chlororaphis strain O6 is regulated by the polyphosphate kinase gene.

    Science.gov (United States)

    Kim, H J; Yang, K Y; Cho, B H; Kim, K Y; Lee, M C; Kim, Y H; Anderson, A J; Kim, Y C

    2007-03-01

    Polyphosphate levels are modulated by the actions of polyphosphate kinase, encoded by ppk, and exopolyphosphatase, encoded by ppx. The genes ppk and ppx are adjacent to each other in the genome of the root colonizer, Pseudomonas chlororaphis O6. A ppk-deficient mutant was more sensitive to oxidative stress than the wild-type and the ppx mutant. Transcripts from ppx increased as cultures matured from mid- to late-logarithmic and stationary phases, whereas abundance was greater for ppk in the late-logarithmic phase than in the stationary phase. Transcript accumulation from the rpoS gene, encoding the stationary-phase sigma factor RpoS, was decreased in the mid- and late-logarithmic and stationary phases in the ppk mutant. Thus, ppk regulates rpoS transcript accumulation in P. chlororaphis 06. However, mutations in either the ppk or ppx genes had no effect on induction of systemic resistance in plants colonized by P. chlororaphis O6.

  2. Localization of cortical phase and amplitude dynamics during visual working memory encoding and retention.

    Science.gov (United States)

    Palva, Satu; Kulashekhar, Shrikanth; Hämäläinen, Matti; Palva, J Matias

    2011-03-30

    Several studies show that the amplitudes of human brain oscillations are modulated during the performance of visual working memory (VWM) tasks in a load-dependent manner. Less is known about the dynamics and identities of the cortical regions in which these modulations take place, and hence their functional significance has remained unclear. We used magnetoencephalography and electroencephalography together with minimum norm estimate-based source modeling to study the dynamics of ongoing brain activity during a parametric VWM task. Early stimulus processing and memory encoding were associated with a memory load-dependent spread of neuronal activity from occipital to temporal, parietal, and frontal cortical regions. During the VWM retention period, the amplitudes of oscillations in theta/alpha- (5-9 Hz), high-alpha- (10-14 Hz), beta- (15-30 Hz), gamma- (30-50 Hz), and high-gamma- (50-150 Hz) frequency bands were suppressed below baseline levels, and yet, in frontoparietal regions, load dependently strengthened. However, in occipital and occipitotemporal structures, only beta, gamma, and high-gamma amplitudes were robustly strengthened by memory load. Individual behavioral VWM capacity was predicted by both the magnitude of the N1 evoked response component in early visual regions and by the amplitudes of frontoparietal high-alpha and high-gamma band oscillations. Thus, both early stimulus processing and late retention period activities may influence the behavioral outcome in VWM tasks. These data support the notion that beta- and gamma-band oscillations support the maintenance of object representations in VWM whereas alpha-, beta-, and gamma-band oscillations together contribute to attentional and executive processing.

  3. Improvement of phase-contrast flow measurements. Opposite directional flow-encoding technique to eliminate the influence of the maxwell term phase errors

    Energy Technology Data Exchange (ETDEWEB)

    Yukawa, Osamu [Hiroshima General Hospital (Japan)

    2001-02-01

    A new method termed the opposite directional flow-encoding (ODFE) technique is proposed to increase the accuracy and the reproducibility of phase-contrast flow measurements by correcting the non-linear background of velocity images induced by concomitant magnetic fields (Maxwell terms). In this technique, the volume flow rate is calculated from the difference of two region of interest (ROI) values derived from two velocity images obtained by reversing the flow-encoding direction. To evaluate the technique, various phantom experiments were carried out and volume blood flow rates of internal carotid arteries (ICAs) were measured in four volunteers. The technique could measure the volume flow rates of the phantom with higher accuracy (mean absolute percentage error =1.04%) and reproducibility (coefficient of variation =1.18%) than conventional methods. Flow measurements with the technique was not significantly affected by ROI size variation, measuring position, and flow obliquity not exceeding 30 deg. The volume flow rates in the ICAs of a volunteer were measured with high reproducibility (coefficient of variation =2.89% on the right, 1.48% on the left), and the flow measurement was not significantly affected by ROI size variation. The ODFE technique can minimize the effect of the non-linear background due to Maxwell terms. The technique allows use of ROIs of approximate size including the flow signal and provides accurate and objective phase-contrast flow measurements. (author)

  4. Improvement of the image quality of random phase--free holography using an iterative method

    CERN Document Server

    Shimobaba, Tomoyoshi; Endo, Yutaka; Hirayama, Ryuji; Hiyama, Daisuke; Hasegawa, Satoki; Nagahama, Yuki; Sano, Marie; Oikawa, Minoru; Sugie, Takashige; Ito, Tomoyoshi

    2015-01-01

    Our proposed method of random phase-free holography using virtual convergence light can obtain large reconstructed images exceeding the size of the hologram, without the assistance of random phase. The reconstructed images have low-speckle noise in the amplitude and phase-only holograms (kinoforms); however, in low-resolution holograms, we obtain a degraded image quality compared to the original image. We propose an iterative random phase-free method with virtual convergence light to address this problem.

  5. A Fast Variant of 1H Spectroscopic U-FLARE Imaging Using Adjusted Chemical Shift Phase Encoding

    Science.gov (United States)

    Ebel, Andreas; Dreher, Wolfgang; Leibfritz, Dieter

    2000-02-01

    So far, fast spectroscopic imaging (SI) using the U-FLARE sequence has provided metabolic maps indirectly via Fourier transformation (FT) along the chemical shift (CS) dimension and subsequent peak integration. However, a large number of CS encoding steps Nω is needed to cover the spectral bandwidth and to achieve sufficient spectral resolution for peak integration even if the number of resonance lines is small compared to Nω and even if only metabolic images are of interest and not the spectra in each voxel. Other reconstruction algorithms require extensive prior knowledge, starting values, and/or model functions. An adjusted CS phase encoding scheme (APE) can be used to overcome these drawbacks. It incorporates prior knowledge only about the resonance frequencies present in the sample. Thus, Nω can be reduced by a factor of 4 for many 1H in vivo studies while no spectra have to be reconstructed, and no additional user interaction, prior knowledge, starting values, or model function are required. Phantom measurements and in vivo experiments on rat brain have been performed at 4.7 T to test the feasibility of the method for proton SI.

  6. Analytic interatomic forces in the random phase approximation

    CERN Document Server

    Ramberger, Benjamin; Kresse, Georg

    2016-01-01

    We discuss that in the random phase approximation (RPA) the first derivative of the energy with respect to the Green's function is the self-energy in the GW approximation. This relationship allows to derive compact equations for the RPA interatomic forces. We also show that position dependent overlap operators are elegantly incorporated in the present framework. The RPA force equations have been implemented in the projector augmented wave formalism, and we present illustrative applications, including ab initio molecular dynamics simulations, the calculation of phonon dispersion relations for diamond and graphite, as well as structural relaxations for water on boron nitride. The present derivation establishes a concise framework for forces within perturbative approaches and is also applicable to more involved approximations for the correlation energy.

  7. Cramer-Rao Bounds for M-PSK Packets with Random Phase

    Science.gov (United States)

    Drake, Jeffrey

    1999-01-01

    In this paper, we derive new Cramer-Rao bounds (CRBs) for the estimation of phase from a block of random M-PSK (M=8) symbols for the case where the phase to be estimated is a random variable(r.v.). Existing bounds for 2 and 4-PSK which model the phase as non-random are extended to obtain a new 8-PSK CRB. The new bound which models the phase as a r.v. is compared to the new 8-PSK bound which models the phase as non-random. With 8-PSK we see clearly that use of the random phase CRB more accurately models the behavior if the phase, as normally happens, is supposed to be constrained to the interval [-pi/M,pi/M).

  8. Relativistic continuum random phase approximation in spherical nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Daoutidis, Ioannis

    2009-10-01

    Covariant density functional theory is used to analyze the nuclear response in the external multipole fields. The investigations are based on modern functionals with zero range and density dependent coupling constants. After a self-consistent solution of the Relativistic Mean Field (RMF) equations for the nuclear ground states multipole giant resonances are studied within the Relativistic Random Phase Approximation (RRPA), the small amplitude limit of the time-dependent RMF. The coupling to the continuum is treated precisely by calculating the single particle Greens-function of the corresponding Dirac equation. In conventional methods based on a discretization of the continuum this was not possible. The residual interaction is derived from the same RMF Lagrangian. This guarantees current conservation and a precise decoupling of the Goldstone modes. For nuclei with open shells pairing correlations are taken into account in the framework of BCS theory and relativistic quasiparticle RPA. Continuum RPA (CRPA) presents a robust method connected with an astonishing reduction of the numerical effort as compared to conventional methods. Modes of various multipolarities and isospin are investigated, in particular also the newly discovered Pygmy modes in the vicinity of the neutron evaporation threshold. The results are compared with conventional discrete RPA calculations as well as with experimental data. We find that the full treatment of the continuum is essential for light nuclei and the study of resonances in the neighborhood of the threshold. (orig.)

  9. Phase reconstruction from velocity-encoded MRI measurements – A survey of sparsity-promoting variational approaches

    KAUST Repository

    Benning, Martin

    2014-01-01

    In recent years there has been significant developments in the reconstruction of magnetic resonance velocity images from sub-sampled k-space data. While showing a strong improvement in reconstruction quality compared to classical approaches, the vast number of different methods, and the challenges in setting them up, often leaves the user with the difficult task of choosing the correct approach, or more importantly, not selecting a poor approach. In this paper, we survey variational approaches for the reconstruction of phase-encoded magnetic resonance velocity images from sub-sampled k-space data. We are particularly interested in regularisers that correctly treat both smooth and geometric features of the image. These features are common to velocity imaging, where the flow field will be smooth but interfaces between the fluid and surrounding material will be sharp, but are challenging to represent sparsely. As an example we demonstrate the variational approaches on velocity imaging of water flowing through a packed bed of solid particles. We evaluate Wavelet regularisation against Total Variation and the relatively recent second order Total Generalised Variation regularisation. We combine these regularisation schemes with a contrast enhancement approach called Bregman iteration. We verify for a variety of sampling patterns that Morozov\\'s discrepancy principle provides a good criterion for stopping the iterations. Therefore, given only the noise level, we present a robust guideline for setting up a variational reconstruction scheme for MR velocity imaging. © 2013 Elsevier Inc. All rights reserved.

  10. Spin pumping driven auto-oscillator for phase-encoded logic—device design and material requirements

    Science.gov (United States)

    Rakheja, S.; Kani, N.

    2017-05-01

    In this work, we propose a spin nano-oscillator (SNO) device where information is encoded in the phase (time-shift) of the output oscillations. The spin current required to set up the oscillations in the device is generated through spin pumping from an input nanomagnet that is precessing at RF frequencies. We discuss the operation of the SNO device, in which either the in-plane (IP) or out-of-plane (OOP) magnetization oscillations are utilized toward implementing ultra-low-power circuits. Using physical models of the nanomagnet dynamics and the spin transport through non-magnetic channels, we quantify the reliability of the SNO device using a "scaling ratio". Material requirements for the nanomagnet and the channel to ensure correct logic functionality are identified using the scaling ratio metric. SNO devices consume (2-5)× lower energy compared to CMOS devices and other spin-based devices with similar device sizes and material parameters. The analytical models presented in this work can be used to optimize the performance and scaling of SNO devices in comparison to CMOS devices at ultra-scaled technology nodes.

  11. Cloning and sequencing of cDNA encoding haptoglobin, an acute phase protein in Syrian hamster, Mesacricetus auratus.

    Science.gov (United States)

    Yamamoto, K; Matsui, I; Nakatani, T; Matsuura, K; Sinohara, H

    1998-02-01

    One of the most prominent acute phase proteins in Syrian hamster (Mesacricetus auratus) was identified as haptoglobin and cDNA encoding this protein was sequenced. The deduced amino acid sequence of the mature protein is 83.6, 80.5, 79.6, and 76.1% identical to those of mouse, rat, human (1 s isoform), and dog homologues, respectively. As compared with six known members of this family, including human haptoglobin-related protein, hamster haptoglobin had 11 unique substitutions and one unique codon deletion, that is, the corresponding residues have been conserved in all other members. This indicates that hamster haptoglobin gene has accumulated these unique mutations after the time of cricetid-murid split while the ancestral sequence has been conserved in all other species examined. Hamster haptoglobin, however, contains nine cysteine residues, all of which are found in conserved positions in primate and rodent homologues. Molecular phylogenetic trees of alpha- and beta-chains show that the alpha-chain is more divergent than the beta-chain and that the difference in genetic distance between canine and hamster alpha-chains is much greater than that of corresponding beta-chains.

  12. Depth-encoded dual beam phase-resolved Doppler OCT for Doppler-angle-independent flow velocity measurement

    Science.gov (United States)

    Qian, Jie; Cheng, Wei; Cao, Zhaoyuan; Chen, Xinjian; Mo, Jianhua

    2017-02-01

    Phase-resolved Doppler optical coherence tomography (PR-D-OCT) is a functional OCT imaging technique that can provide high-speed and high-resolution depth-resolved measurement on flow in biological materials. However, a common problem with conventional PR-D-OCT is that this technique often measures the flow motion projected onto the OCT beam path. In other words, it needs the projection angle to extract the absolute velocity from PR-D-OCT measurement. In this paper, we proposed a novel dual-beam PR-D-OCT method to measure absolute flow velocity without separate measurement on the projection angle. Two parallel light beams are created in sample arm and focused into the sample at two different incident angles. The images produced by these two beams are encoded to different depths in single B-scan. Then the Doppler signals picked up by the two beams together with the incident angle difference can be used to calculate the absolute velocity. We validated our approach in vitro on an artificial flow phantom with our home-built 1060 nm swept source OCT. Experimental results demonstrated that our method can provide an accurate measurement of absolute flow velocity with independency on the projection angle.

  13. Random fractional Fourier transform.

    Science.gov (United States)

    Liu, Zhengjun; Liu, Shutian

    2007-08-01

    We propose a novel random fractional Fourier transform by randomizing the transform kernel function of the conventional fractional Fourier transform. The random fractional Fourier transform inherits the excellent mathematical properties from the fractional Fourier transform and can be easily implemented in optics. As a primary application the random fractional Fourier transform can be directly used in optical image encryption and decryption. The double phase encoding image encryption schemes can thus be modeled with cascaded random fractional Fourier transformers.

  14. Deep Learning the Quantum Phase Transitions in Random Two-Dimensional Electron Systems

    Science.gov (United States)

    Ohtsuki, Tomoki; Ohtsuki, Tomi

    2016-12-01

    Random electron systems show rich phases such as Anderson insulator, diffusive metal, quantum Hall and quantum anomalous Hall insulators, Weyl semimetal, as well as strong/weak topological insulators. Eigenfunctions of each matter phase have specific features, but owing to the random nature of systems, determining the matter phase from eigenfunctions is difficult. Here, we propose the deep learning algorithm to capture the features of eigenfunctions. Localization-delocalization transition, as well as disordered Chern insulator-Anderson insulator transition, is discussed.

  15. Suppressing Respiration Effects when Geometric Distortion Is Corrected Dynamically by Phase Labeling for Additional Coordinate Encoding (PLACE) during Functional MRI.

    Science.gov (United States)

    Faraji-Dana, Zahra; Tam, Fred; Chen, J Jean; Graham, Simon J

    2016-01-01

    Echo planar imaging (EPI) suffers from geometric distortions caused by magnetic field inhomogeneities, which can be time-varying as a result of small amounts of head motion that occur over seconds and minutes during fMRI experiments, also known as "dynamic geometric distortion". Phase Labeling for Additional Coordinate Encoding (PLACE) is a promising technique for geometric distortion correction without reduced temporal resolution and in principle can be used to correct for motion-induced dynamic geometric distortion. PLACE requires at least two EPI images of the same anatomy that are ideally acquired with no variation in the magnetic field inhomogeneities. However, head motion and lung ventilation during the respiratory cycle can cause changes in magnetic field inhomogeneities within the EPI pair used for PLACE. In this work, we exploited dynamic off-resonance in k-space (DORK) and averaging to correct the within EPI pair magnetic field inhomogeneities; and hence proposed a combined technique (DORK+PLACE+averaging) to mitigate dynamic geometric distortion in EPI-based fMRI while preserving the temporal resolution. The performance of the combined DORK, PLACE and averaging technique was characterized through several imaging experiments involving test phantoms and six healthy adult volunteers. Phantom data illustrate reduced temporal standard deviation of fMRI signal intensities after use of combined dynamic PLACE, DORK and averaging compared to the standard processing and static geometric distortion correction. The combined technique also substantially improved the temporal standard deviation and activation maps obtained from human fMRI data in comparison to the results obtained by standard processing and static geometric distortion correction, highlighting the utility of the approach.

  16. Shaping the spectrum of random-phase radar waveforms

    Science.gov (United States)

    Doerry, Armin W.; Marquette, Brandeis

    2017-05-09

    The various technologies presented herein relate to generation of a desired waveform profile in the form of a spectrum of apparently random noise (e.g., white noise or colored noise), but with precise spectral characteristics. Hence, a waveform profile that could be readily determined (e.g., by a spoofing system) is effectively obscured. Obscuration is achieved by dividing the waveform into a series of chips, each with an assigned frequency, wherein the sequence of chips are subsequently randomized. Randomization can be a function of the application of a key to the chip sequence. During processing of the echo pulse, a copy of the randomized transmitted pulse is recovered or regenerated against which the received echo is correlated. Hence, with the echo energy range-compressed in this manner, it is possible to generate a radar image with precise impulse response.

  17. Double blind randomized phase II study with radiation + 5-fluorouracil ± celecoxib for resectable rectal cancer

    National Research Council Canada - National Science Library

    Debucquoy, Annelies; Roels, Sarah; Goethals, Laurence; Libbrecht, Louis; Cutsem, Eric Van; Geboes, Karel; Penninckx, Freddy; D’Hoore, André; McBride, William H; Haustermans, Karin

    2009-01-01

    To assess the feasibility and efficacy of the COX-2 inhibitor celecoxib in conjunction with preoperative chemoradiation for patients with locally advanced rectal cancer in a double blind randomized phase II study...

  18. Variance of phase fluctuations of waves propagating through a random medium

    Science.gov (United States)

    Chu, Nelson C.; Kong, Jin AU; Yueh, Simon H.; Nghiem, Son V.; Fleischman, Jack G.; Ayasli, Serpil; Shin, Robert T.

    1992-01-01

    As an electromagnetic wave propagates through a random scattering medium, such as a forest, its energy is attenuated and random phase fluctuations are induced. The magnitude of the random phase fluctuations induced is important in estimating how well a Synthetic Aperture Radar (SAR) can image objects within the scattering medium. The two-layer random medium model, consisting of a scattering layer between free space and ground, is used to calculate the variance of the phase fluctuations induced between a transmitter located above the random medium and a receiver located below the random medium. The scattering properties of the random medium are characterized by a correlation function of the random permittivity fluctuations. The effective permittivity of the random medium is first calculated using the strong fluctuation theory, which accounts for large permittivity fluctuations of the scatterers. The distorted Born approximation is used to calculate the first-order scattered field. A perturbation series for the phase of the received field in the Rytov approximation is then introduced and the variance of the phase fluctuations is also calculated assuming that the transmitter and receiver are in the paraxial limit of the random medium, which allows an analytic solution to be obtained. Results are compared using the paraxial approximation, scalar Green's function formulation, and dyadic Green's function formulation. The effects studied are the dependence of the variance of the phase fluctuations on receiver location in lossy and lossless regions, medium thickness, correlation length and fractional volume of scatterers, depolarization of the incident wave, ground layer permittivity, angle of incidence, and polarization.

  19. Speeding up image quality improvement in random phase-free holograms using ringing artifact characteristics.

    Science.gov (United States)

    Nagahama, Yuki; Shimobaba, Tomoyoshi; Kakue, Takashi; Masuda, Nobuyuki; Ito, Tomoyoshi

    2017-05-01

    A holographic projector utilizes holography techniques. However, there are several barriers to realizing holographic projections. One is deterioration of hologram image quality caused by speckle noise and ringing artifacts. The combination of the random phase-free method and the Gerchberg-Saxton (GS) algorithm has improved the image quality of holograms. However, the GS algorithm requires significant computation time. We propose faster methods for image quality improvement of random phase-free holograms using the characteristics of ringing artifacts.

  20. Divided Attention Can Enhance Early-Phase Memory Encoding: The Attentional Boost Effect and Study Trial Duration

    Science.gov (United States)

    Mulligan, Neil W.; Spataro, Pietro

    2015-01-01

    Divided attention during encoding typically produces marked reductions in later memory. The attentional boost effect (ABE) is a surprising variation on this phenomenon. In this paradigm, each study stimulus (e.g., a word) is presented along with a target or a distractor (e.g., different colored circles) in a detection task. Later memory is better…

  1. Three Phase Power Imbalance Decomposition into Systematic Imbalance and Random Imbalance

    DEFF Research Database (Denmark)

    Kong, Wangwei; Ma, Kang; Wu, Qiuwei

    2017-01-01

    is calculated based on the systematic imbalance component to guide phase swapping. Case studies demonstrate that 72.8% of 782 low voltage substations have systematic imbalance components. The degree of power imbalance results reveal the maximum need for phase swapping and the random imbalance components reveal...

  2. A Randomized Double-Blind Crossover Study of Phase-Shift Sound Therapy for Tinnitus

    NARCIS (Netherlands)

    Heijneman, Karin M.; de Kleine, Emile; van Dijk, Pim

    Objective. The purpose of this study was to compare the efficacy of the treatment of tinnitus with a phase-shifting pure tone to that of the same tone treatment without phase shifting. Study Design. A double-blind crossover randomized controlled trial. Setting. This study was conducted at the

  3. Exosomes released in vitro from Epstein-Barr virus (EBV)-infected cells contain EBV-encoded latent phase mRNAs.

    Science.gov (United States)

    Canitano, Andrea; Venturi, Giulietta; Borghi, Martina; Ammendolia, Maria Grazia; Fais, Stefano

    2013-09-01

    EBV is a human herpesvirus associated with a number of malignancies. Both lymphoblastoid cell lines (LCLs), and EBV-infected nasopharyngeal carcinoma (NPC) cells have been demonstrated to release exosomes containing the EBV-encoded latent membrane protein 1 (LMP1), and mature micro-RNAs (EBV-miRNAs). Here we analyze the EBV protein and nucleic acid content of exosomes from different EBV-infected cells (LCL, 721 and Daudi) and we show for the first time that exosomes released from LCLs and 721 also contain EBV-encoded latent phase mRNAs. This confirms and strengthens exosomes pathogenetic potential, and might provide insights for development of novel diagnostic and therapeutic strategies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial.

    Science.gov (United States)

    Fouda, Abdelrahman Y; Newsome, Andrea S; Spellicy, Samantha; Waller, Jennifer L; Zhi, Wenbo; Hess, David C; Ergul, Adviye; Edwards, David J; Fagan, Susan C; Switzer, Jeffrey A

    2017-10-01

    Minocycline is under investigation as a neurovascular protective agent for stroke. This study evaluated the pharmacokinetic, anti-inflammatory, and safety profile of minocycline after intracerebral hemorrhage. This study was a single-site, randomized controlled trial of minocycline conducted from 2013 to 2016. Adults ≥18 years with primary intracerebral hemorrhage who could have study drug administered within 24 hours of onset were included. Patients received 400 mg of intravenous minocycline, followed by 400 mg minocycline oral daily for 4 days. Serum concentrations of minocycline after the last oral dose and biomarkers were sampled to determine the peak concentration, half-life, and anti-inflammatory profile. A total of 16 consecutive eligible patients were enrolled, with 8 randomized to minocycline. Although the literature supports a time to peak concentration (Tmax) of 1 hour for oral minocycline, the Tmax was estimated to be at least 6 hours in this cohort. The elimination half-life (available on 7 patients) was 17.5 hours (SD±3.5). No differences were observed in inflammatory biomarkers, hematoma volume, or perihematomal edema. Concentrations remained at neuroprotective levels (>3 mg/L) throughout the dosing interval in 5 of 7 patients. In intracerebral hemorrhage, a 400 mg dose of minocycline was safe and achieved neuroprotective serum concentrations. However, oral administration led to delayed absorption in these critically ill patients and should not be used when rapid, high concentrations are desired. Given the safety and pharmacokinetic profile of minocycline in intracerebral hemorrhage and promising data in the treatment of ischemic stroke, intravenous minocycline is an excellent candidate for a prehospital treatment trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01805895. © 2017 American Heart Association, Inc.

  5. Phase correction for three-dimensional (3D) diffusion-weighted interleaved EPI using 3D multiplexed sensitivity encoding and reconstruction (3D-MUSER).

    Science.gov (United States)

    Chang, Hing-Chiu; Hui, Edward S; Chiu, Pui-Wai; Liu, Xiaoxi; Chen, Nan-Kuei

    2017-09-23

    Three-dimensional (3D) multiplexed sensitivity encoding and reconstruction (3D-MUSER) algorithm is proposed to reduce aliasing artifacts and signal corruption caused by inter-shot 3D phase variations in 3D diffusion-weighted echo planar imaging (DW-EPI). 3D-MUSER extends the original framework of multiplexed sensitivity encoding (MUSE) to a hybrid k-space-based reconstruction, thereby enabling the correction of inter-shot 3D phase variations. A 3D single-shot EPI navigator echo was used to measure inter-shot 3D phase variations. The performance of 3D-MUSER was evaluated by analyses of point-spread function (PSF), signal-to-noise ratio (SNR), and artifact levels. The efficacy of phase correction using 3D-MUSER for different slab thicknesses and b-values were investigated. Simulations showed that 3D-MUSER could eliminate artifacts because of through-slab phase variation and reduce noise amplification because of SENSE reconstruction. All aliasing artifacts and signal corruption in 3D interleaved DW-EPI acquired with different slab thicknesses and b-values were reduced by our new algorithm. A near-whole brain single-slab 3D DTI with 1.3-mm isotropic voxel acquired at 1.5T was successfully demonstrated. 3D phase correction for 3D interleaved DW-EPI data is made possible by 3D-MUSER, thereby improving feasible slab thickness and maximum feasible b-value. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  6. Equilibrium phase diagram of a randomly pinned glass-former.

    Science.gov (United States)

    Ozawa, Misaki; Kob, Walter; Ikeda, Atsushi; Miyazaki, Kunimasa

    2015-06-02

    We use computer simulations to study the thermodynamic properties of a glass-former in which a fraction c of the particles has been permanently frozen. By thermodynamic integration, we determine the Kauzmann, or ideal glass transition, temperature [Formula: see text] at which the configurational entropy vanishes. This is done without resorting to any kind of extrapolation, i.e., [Formula: see text] is indeed an equilibrium property of the system. We also measure the distribution function of the overlap, i.e., the order parameter that signals the glass state. We find that the transition line obtained from the overlap coincides with that obtained from the thermodynamic integration, thus showing that the two approaches give the same transition line. Finally, we determine the geometrical properties of the potential energy landscape, notably the T- and c dependence of the saddle index, and use these properties to obtain the dynamic transition temperature [Formula: see text]. The two temperatures [Formula: see text] and [Formula: see text] cross at a finite value of c and indicate the point at which the glass transition line ends. These findings are qualitatively consistent with the scenario proposed by the random first-order transition theory.

  7. Phase microscopy of technical and biological samples through random phase modulation with a difuser

    DEFF Research Database (Denmark)

    Almoro, Percival; Pedrini, Giancarlo; Gundu, Phanindra Narayan

    2010-01-01

    A technique for phase microscopy using a phase diffuser and a reconstruction algorithm is proposed. A magnified specimen wavefront is projected on the diffuser plane that modulates the wavefront into a speckle field. The speckle patterns at axially displaced planes are sampled and used in an iter...

  8. UA(1) breaking and phase transition in chiral random matrix model

    OpenAIRE

    Sano, T.; Fujii, H.; Ohtani, M

    2009-01-01

    We propose a chiral random matrix model which properly incorporates the flavor-number dependence of the phase transition owing to the \\UA(1) anomaly term. At finite temperature, the model shows the second-order phase transition with mean-field critical exponents for two massless flavors, while in the case of three massless flavors the transition turns out to be of the first order. The topological susceptibility satisfies the anomalous \\UA(1) Ward identity and decreases gradually with the temp...

  9. Deterministic matrices matching the compressed sensing phase transitions of Gaussian random matrices

    Science.gov (United States)

    Monajemi, Hatef; Jafarpour, Sina; Gavish, Matan; Donoho, David L.; Ambikasaran, Sivaram; Bacallado, Sergio; Bharadia, Dinesh; Chen, Yuxin; Choi, Young; Chowdhury, Mainak; Chowdhury, Soham; Damle, Anil; Fithian, Will; Goetz, Georges; Grosenick, Logan; Gross, Sam; Hills, Gage; Hornstein, Michael; Lakkam, Milinda; Lee, Jason; Li, Jian; Liu, Linxi; Sing-Long, Carlos; Marx, Mike; Mittal, Akshay; Monajemi, Hatef; No, Albert; Omrani, Reza; Pekelis, Leonid; Qin, Junjie; Raines, Kevin; Ryu, Ernest; Saxe, Andrew; Shi, Dai; Siilats, Keith; Strauss, David; Tang, Gary; Wang, Chaojun; Zhou, Zoey; Zhu, Zhen

    2013-01-01

    In compressed sensing, one takes samples of an N-dimensional vector using an matrix A, obtaining undersampled measurements . For random matrices with independent standard Gaussian entries, it is known that, when is k-sparse, there is a precisely determined phase transition: for a certain region in the (,)-phase diagram, convex optimization typically finds the sparsest solution, whereas outside that region, it typically fails. It has been shown empirically that the same property—with the same phase transition location—holds for a wide range of non-Gaussian random matrix ensembles. We report extensive experiments showing that the Gaussian phase transition also describes numerous deterministic matrices, including Spikes and Sines, Spikes and Noiselets, Paley Frames, Delsarte-Goethals Frames, Chirp Sensing Matrices, and Grassmannian Frames. Namely, for each of these deterministic matrices in turn, for a typical k-sparse object, we observe that convex optimization is successful over a region of the phase diagram that coincides with the region known for Gaussian random matrices. Our experiments considered coefficients constrained to for four different sets , and the results establish our finding for each of the four associated phase transitions. PMID:23277588

  10. Generation of sound by Alfven waves with random phases in the solar atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Petrukhin, N.S.; Fainshtein, S.M.

    1976-11-01

    The problem of the excitation of sound by Alfven waves meeting in the solar plasma is discussed. Kinetic equations for the interacting waves are derived and analyzed on the assumption that the Alfven waves have random phases. Estimates are given which show the possibility of the generation of LF-pulsations in the solar atmosphere.

  11. Nanostructure-property relations for phase-change random access memory (PCRAM) line cells

    NARCIS (Netherlands)

    Kooi, B. J.; Oosthoek, J. L. M.; Verheijen, M. A.; Kaiser, M.; Jedema, F. J.; Gravesteijn, D. J.

    2012-01-01

    Phase-change random access memory (PCRAM) cells have been studied extensively using electrical characterization and rather limited by detailed structure characterization. The combination of these two characterization techniques has hardly been exploited and it is the focus of the present work.

  12. Phase I study of liposome-DNA complexes encoding the interleukin-2 gene in dogs with osteosarcoma lung metastases.

    Science.gov (United States)

    Dow, Steven; Elmslie, Robyn; Kurzman, Ilene; MacEwen, Gregory; Pericle, Federica; Liggitt, Denny

    2005-08-01

    Systemic gene delivery using cationic liposome-DNA complexes (LDCs) has been shown to elicit potent antitumor activity in mice with tumor metastases to the lungs. However, intravenous gene delivery for treatment of established cancer has not been evaluated previously in a spontaneous, large animal model. We therefore evaluated the safety, toxicity, and efficacy of intravenous gene delivery, using LDCs in dogs with established tumor metastases. Twenty dogs with chemotherapy-resistant osteosarcoma metastases to the lungs received a series of intravenous infusions of cationic liposomes and plasmid DNA encoding the canine interleukin-2 (IL-2) cDNA. Effects of intravenous gene delivery on immune activation, clinical and hematologic parameters, tumor responses, and survival times were assessed. We found that slow intravenous administration of IL-2 LDCs resulted in detectable IL-2 transgene expression in lung tissues of dogs. Repeated intravenous infusions of LDCs were well tolerated by dogs with lung tumor metastases and elicited systemic immune activation, as reflected by fever, leukogram changes, monocyte activation, and increased natural killer cell activity. Three of 20 dogs experienced partial or complete regression of lung metastases after infusion of IL-2 LDCs. Overall survival times were significantly increased in treated dogs compared with historical control animals with the same stage of disease. We conclude that repeated intravenous infusion of LDCs in cancerbearing dogs is safe and well tolerated at low doses and may be capable of eliciting antitumor activity in some animals with advanced tumor metastases.

  13. Deep Learning the Quantum Phase Transitions in Random Electron Systems: Applications to Three Dimensions

    Science.gov (United States)

    Ohtsuki, Tomi; Ohtsuki, Tomoki

    2017-04-01

    Three-dimensional random electron systems undergo quantum phase transitions and show rich phase diagrams. Examples of the phases are the band gap insulator, Anderson insulator, strong and weak topological insulators, Weyl semimetal, and diffusive metal. As in the previous paper on two-dimensional quantum phase transitions [J. Phys. Soc. Jpn. 85, 123706 (2016)], we use an image recognition algorithm based on a multilayered convolutional neural network to identify which phase the eigenfunction belongs to. The Anderson model for localization-delocalization transition, the Wilson-Dirac model for topological insulators, and the layered Chern insulator model for Weyl semimetal are studied. The situation where the standard transfer matrix approach is not applicable is also treated by this method.

  14. Stochastic modeling for starting-time of phase evolution of random seismic ground motions

    Directory of Open Access Journals (Sweden)

    Yongbo Peng

    2014-01-01

    Full Text Available In response to the challenge inherent in classical high-dimensional models of random ground motions, a family of simulation methods for non-stationary seismic ground motions was developed previously through employing a wave-group propagation formulation with phase spectrum model built up on the frequency components' starting-time of phase evolution. The present paper aims at extending the formulation to the simulation of non-stationary random seismic ground motions. The ground motion records associated with N—S component of Northridge Earthquake at the type-II site are investigated. The frequency components' starting-time of phase evolution of is identified from the ground motion records, and is proved to admit the Gamma distribution through data fitting. Numerical results indicate that the simulated random ground motion features zero-mean, non-stationary, and non-Gaussian behaviors, and the phase spectrum model with only a few starting-times of phase evolution could come up with a sound contribution to the simulation.

  15. Bayesian phase II adaptive randomization by jointly modeling time-to-event efficacy and binary toxicity.

    Science.gov (United States)

    Lei, Xiudong; Yuan, Ying; Yin, Guosheng

    2011-01-01

    In oncology, toxicity is typically observable shortly after a chemotherapy treatment, whereas efficacy, often characterized by tumor shrinkage, is observable after a relatively long period of time. In a phase II clinical trial design, we propose a Bayesian adaptive randomization procedure that accounts for both efficacy and toxicity outcomes. We model efficacy as a time-to-event endpoint and toxicity as a binary endpoint, sharing common random effects in order to induce dependence between the bivariate outcomes. More generally, we allow the randomization probability to depend on patients' specific covariates, such as prognostic factors. Early stopping boundaries are constructed for toxicity and futility, and a superior treatment arm is recommended at the end of the trial. Following the setup of a recent renal cancer clinical trial at M. D. Anderson Cancer Center, we conduct extensive simulation studies under various scenarios to investigate the performance of the proposed method, and compare it with available Bayesian adaptive randomization procedures.

  16. NOGA-guided analysis of regional myocardial perfusion abnormalities treated with intramyocardial injections of plasmid encoding vascular endothelial growth factor A-165 in patients with chronic myocardial ischemia: subanalysis of the EUROINJECT-ONE multicenter double-blind randomized study

    DEFF Research Database (Denmark)

    Gyongyosi, Mariann; Khorsand, Aliasghar; Zamini, Sholeh

    2005-01-01

    BACKGROUND: The aim of this substudy of the EUROINJECT-ONE double-blind randomized trial was to analyze changes in myocardial perfusion in NOGA-defined regions with intramyocardial injections of plasmid encoding plasmid human (ph)VEGF-A(165) using an elaborated transformation algorithm. METHODS A...

  17. Role of an encapsulating layer for reducing resistance drift in phase change random access memory

    Directory of Open Access Journals (Sweden)

    Bo Jin

    2014-12-01

    Full Text Available Phase change random access memory (PCRAM devices exhibit a steady increase in resistance in the amorphous phase upon aging and this resistance drift phenomenon directly affects the device reliability. A stress relaxation model is used here to study the effect of a device encapsulating layer material in addressing the resistance drift phenomenon in PCRAM. The resistance drift can be increased or decreased depending on the biaxial moduli of the phase change material (YPCM and the encapsulating layer material (YELM according to the stress relationship between them in the drift regime. The proposed model suggests that the resistance drift can be effectively reduced by selecting a proper material as an encapsulating layer. Moreover, our model explains that reducing the size of the phase change material (PCM while fully reset and reducing the amorphous/crystalline ratio in PCM help to improve the resistance drift, and thus opens an avenue for highly reliable multilevel PCRAM applications.

  18. What makes a phase transition? Analysis of the random satisfiability problem

    Science.gov (United States)

    Zweig, Katharina A.; Palla, Gergely; Vicsek, Tamás

    2010-04-01

    In the last 30 years it was found that many combinatorial systems undergo phase transitions. One of the most important examples of these can be found among the random k-satisfiability problems (often referred to as k-SAT), asking whether there exists an assignment of Boolean values satisfying a Boolean formula composed of clauses with k random variables each. The random 3-SAT problem is reported to show various phase transitions at different critical values of the ratio of the number of clauses to the number of variables. The most famous of these occurs when the probability of finding a satisfiable instance suddenly drops from 1 to 0. This transition is associated with a rise in the hardness of the problem, but until now the correlation between any of the proposed phase transitions and the hardness is not totally clear. In this paper we will first show numerically that the number of solutions universally follows a lognormal distribution, thereby explaining the puzzling question of why the number of solutions is still exponential at the critical point. Moreover we provide evidence that the hardness of the closely related problem of counting the total number of solutions does not show any phase transition-like behavior. This raises the question of whether the probability of finding a satisfiable instance is really an order parameter of a phase transition or whether it is more likely to just show a simple sharp threshold phenomenon. More generally, this paper aims at starting a discussion where a simple sharp threshold phenomenon turns into a genuine phase transition.

  19. Phase-space representation and polarization domains of random electromagnetic fields.

    Science.gov (United States)

    Castaneda, Roman; Betancur, Rafael; Herrera, Jorge; Carrasquilla, Juan

    2008-08-01

    The phase-space representation of stationary random electromagnetic fields is developed by using electromagnetic spatial coherence wavelets. The propagation of the field's power and states of spatial coherence and polarization results from correlations between the components of the field vectors at pairs of points in space. Polarization domains are theoretically predicted as the structure of the field polarization at the observation plane. In addition, the phase-space representation provides a generalization of the Poynting theorem. Theoretical predictions are examined by numerically simulating the Young experiment with electromagnetic waves. The experimental implementation of these results is a current subject of research.

  20. Viterbi Tracking of Randomly Phase-Modulated Data (and Related Topics).

    Science.gov (United States)

    1982-08-10

    space I-ir, vr). were a random sequence on the unit circle C or equiva- Discretization of this bounded interval leads to a finite-state lently on the...and the symbol phase, arg ak. Also, of Recall ’k is defined on the circle C . Therefore, for clarity course, for PSK symbol sets only one symbol...x)) on [-V,w] g,(R(x)) Wropped on M-4 the Circle C . M*4 (c) (d) Fig. 5. Density functions of phase increment before and after folding. dix). It

  1. Security authentication with a three-dimensional optical phase code using random forest classifier: an overview

    Science.gov (United States)

    Markman, Adam; Carnicer, Artur; Javidi, Bahram

    2017-05-01

    We overview our recent work [1] on utilizing three-dimensional (3D) optical phase codes for object authentication using the random forest classifier. A simple 3D optical phase code (OPC) is generated by combining multiple diffusers and glass slides. This tag is then placed on a quick-response (QR) code, which is a barcode capable of storing information and can be scanned under non-uniform illumination conditions, rotation, and slight degradation. A coherent light source illuminates the OPC and the transmitted light is captured by a CCD to record the unique signature. Feature extraction on the signature is performed and inputted into a pre-trained random-forest classifier for authentication.

  2. PAH1-encoded phosphatidate phosphatase plays a role in the growth phase- and inositol-mediated regulation of lipid synthesis in Saccharomyces cerevisiae.

    Science.gov (United States)

    Pascual, Florencia; Soto-Cardalda, Aníbal; Carman, George M

    2013-12-13

    In the yeast Saccharomyces cerevisiae, the synthesis of phospholipids in the exponential phase of growth occurs at the expense of the storage lipid triacylglycerol. As exponential phase cells progress into the stationary phase, the synthesis of triacylglycerol occurs at the expense of phospholipids. Early work indicates a role of the phosphatidate phosphatase (PAP) in this metabolism; the enzyme produces the diacylglycerol needed for the synthesis of triacylglycerol and simultaneously controls the level of phosphatidate for the synthesis of phospholipids. Four genes (APP1, DPP1, LPP1, and PAH1) encode PAP activity in yeast, and it has been unclear which gene is responsible for the synthesis of triacylglycerol throughout growth. An analysis of lipid synthesis and composition, as well as PAP activity in various PAP mutant strains, showed the essential role of PAH1 in triacylglycerol synthesis throughout growth. Pah1p is a phosphorylated enzyme whose in vivo function is dependent on its dephosphorylation by the Nem1p-Spo7p protein phosphatase complex. nem1Δ mutant cells exhibited defects in triacylglycerol synthesis and lipid metabolism that mirrored those imparted by the pah1Δ mutation, substantiating the importance of Pah1p dephosphorylation throughout growth. An analysis of cells bearing PPAH1-lacZ and PPAH1-DPP1 reporter genes showed that PAH1 expression was induced throughout growth and that the induction in the stationary phase was stimulated by inositol supplementation. A mutant analysis indicated that the Ino2p/Ino4p/Opi1p regulatory circuit and transcription factors Gis1p and Rph1p mediated this regulation.

  3. A randomized double-blind crossover study of phase-shift sound therapy for tinnitus.

    Science.gov (United States)

    Heijneman, Karin M; de Kleine, Emile; van Dijk, Pim

    2012-08-01

    The purpose of this study was to compare the efficacy of the treatment of tinnitus with a phase-shifting pure tone to that of the same tone treatment without phase shifting. A double-blind crossover randomized controlled trial. This study was conducted at the University Medical Center Groningen. Twenty-two patients with predominantly tonal tinnitus underwent both intervention and control treatments. Each treatment consisted of three 30-minute sessions in 1 week. The control treatment was identical to the intervention treatment, except that the stimulus was a pure tone without phase shifting. Questionnaires, tinnitus loudness match, and annoyance and loudness ratings were used to measure treatment effects. Pure-tone treatment and phase-shift treatment had no significant effect on tinnitus according to questionnaires (Tinnitus Handicap Index, Tinnitus Reaction Questionnaire, Hospital Anxiety and Depression Scale, and Maastricht Questionnaire), audiological matching procedures, and loudness and annoyance ratings of tinnitus. Furthermore, phase-shift treatment showed no additional significant improvement in comparison with pure-tone treatment. Changes in questionnaire scores due to pure-tone and the phase-shift treatment were correlated. On average across the group, both treatments failed to demonstrate a significant effect. Both treatments were beneficial for some patients. However, a positive effect was not demonstrated that could be attributed to the periodic shifting of the phase of the stimulus tone.

  4. Luteal Phase Support in the Intrauterine Insemination (IUI) Cycles: A Randomized Double Blind, Placebo Controlled Study.

    OpenAIRE

    Batool Hossein Rashidi; Fatemeh Davari Tanha; Haleh Rahmanpour; Mahya Ghazizadeh

    2014-01-01

    Objective: To evaluate the impact of luteal phase support with vaginal progesterone on pregnancy rates in the intrauterine insemination (IUI) cycles, stimulated with clomiphene citrate and human menopausal gonadotropin (hMG), in sub fertile couples. Materials and methods: This prospective, randomized, double blind study was performed in a tertiary infertility center from March 2011 to January 2012. It consisted of 253 sub fertile couples undergoing ovarian stimulation for IUI cycles. They und...

  5. Single-subject fMRI mapping at 7 T of the representation of fingertips in S1: a comparison of event-related and phase-encoding designs.

    Science.gov (United States)

    Besle, Julien; Sánchez-Panchuelo, Rosa-Maria; Bowtell, Richard; Francis, Susan; Schluppeck, Denis

    2013-05-01

    A desirable goal of functional MRI (fMRI), both clinically and for basic research, is to produce detailed maps of cortical function in individual subjects. Single-subject mapping of the somatotopic hand representation in the human primary somatosensory cortex (S1) has been performed using both phase-encoding and block/event-related designs. Here, we review the theoretical strengths and limits of each method and empirically compare high-resolution (1.5 mm isotropic) somatotopic maps obtained using fMRI at ultrahigh magnetic field (7 T) with phase-encoding and event-related designs in six subjects in response to vibrotactile stimulation of the five fingertips. Results show that the phase-encoding design is more efficient than the event-related design for mapping fingertip-specific responses and in particular allows us to describe a new additional somatotopic representation of fingertips on the precentral gyrus. However, with sufficient data, both designs yield very similar fingertip-specific maps in S1, which confirms that the assumption of local representational continuity underlying phase-encoding designs is largely valid at the level of the fingertips in S1. In addition, it is shown that the event-related design allows the mapping of overlapping cortical representations that are difficult to estimate using the phase-encoding design. The event-related data show a complex pattern of overlapping cortical representations for different fingertips within S1 and demonstrate that regions of S1 responding to several adjacent fingertips can incorrectly be identified as responding preferentially to one fingertip in the phase-encoding data.

  6. Optimization of sparse phase encodings for variable repetition-delay turbo-spin echo (TSE) T1 measurements for preclinical applications

    Science.gov (United States)

    Lee, DongKyu; Han, Sohyun; Cho, HyungJoon

    2017-01-01

    A variable repetition-delay (TR) spin echo sequence with repeated refocusing pulses, i.e., a variable TR turbo-spin echo (TSE), provides an attractive means of acquiring an accurate T1 map information that is free from gradient echo based artifacts such as magnetic field inhomogeneities particularly for ultra-high field (at 7T and above) preclinical applications. However, the applicability of multi-slice TSE sequences is often limited by signal distortion from T2 relaxation due to echo-train acquisitions for short T2 tissues, inter-slice cross talks and magnetization transfer (MT) from repetitive slice-selective 180° pulse, and extended scan times with multiple TR excitations. These TSE shortcomings are difficult to remedy for preclinical applications, where small sizes of target organs usually limit the slice-gap control with restricted parallel imaging capabilities. In this study, compressed-sensing-assisted turbo-spin echo (CS-TSE) acquisitions for variable TR T1 measurements at 7T preclinical scanner were implemented to reduce the echo-trains by sparse phase encodings. Following the sparse signal simulation and sampling scheme optimization, the measured T1 values from CS-TSE and TSE were compared for phantoms, ex vivo, and in vivo subjects. The phantom T1 values from CS-TSE and TSE were identical to those from the inversion recovery spin echo. For both ex vivo and in vivo multi-slice T1 mapping, the shortened echo-trains of CS-TSE relieved the T2 relaxation, reduced the inter-slice interferences of multi-slice acquisition, and made room for additional slice encodings while maintaining a shorter scan time than the conventional TSE at the expense of local image smoothness from CS regularizations.

  7. High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study

    NARCIS (Netherlands)

    Deenik, W.; van der Holt, B.; Verhoef, G. E. G.; Schattenberg, A. V. M. B.; Verdonck, L. F.; Daenen, S. M. G. J.; Zachee, P.; Westveer, P. H. M.; Smit, W. M.; Wittebol, S.; Schouten, H. C.; Lowenberg, B.; Ossenkoppele, G. J.; Cornelissen, J. J.

    A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase

  8. High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia : A prospective randomized phase III study

    NARCIS (Netherlands)

    Deenik, W.; Holt, B. van der; Verhoef, G.E.; Schattenberg, A.V.M.B.; Verdonck, L.F.; Daenen, S.M.G.J.; Zachee, P.; Westveer, P.H.; Smit, W.M.; Wittebol, S.; Schouten, H.C.; Lowenberg, B.; Ossenkoppele, G.J.; Cornelissen, J.J.L.M.

    2007-01-01

    A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase

  9. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia : 2-year follow-up from a randomized phase 3 trial (DASISION)

    NARCIS (Netherlands)

    Kantarjian, Hagop M.; Shah, Neil P.; Cortes, Jorge E.; Baccarani, Michele; Agarwal, Mohan B.; Soledad Undurraga, Maria; Wang, Jianxiang; Kassack Ipina, Juan Julio; Kim, Dong-Wook; Ogura, Michinori; Pavlovsky, Carolina; Junghanss, Christian; Milone, Jorge H.; Nicolini, Franck E.; Robak, Tadeusz; Van Droogenbroeck, Jan; Vellenga, Edo; Bradley-Garelik, M. Brigid; Zhu, Chao; Hochhaus, Andreas

    2012-01-01

    Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n =

  10. Equilibrium phase behavior and maximally random jammed state of truncated tetrahedra.

    Science.gov (United States)

    Chen, Duyu; Jiao, Yang; Torquato, Salvatore

    2014-07-17

    Numerous recent investigations have been devoted to the determination of the equilibrium phase behavior and packing characteristics of hard nonspherical particles, including ellipsoids, superballs, and polyhedra, to name but just a few shapes. Systems of hard nonspherical particles exhibit a variety of stable phases with different degrees of translational and orientational order, including isotropic liquid, solid crystal, rotator and a variety of liquid crystal phases. In this paper, we employ a Monte Carlo implementation of the adaptive-shrinking-cell (ASC) numerical scheme and free-energy calculations to ascertain with high precision the equilibrium phase behavior of systems of congruent Archimedean truncated tetrahedra over the entire range of possible densities up to the maximal nearly space-filling density. In particular, we find that the system undergoes two first-order phase transitions as the density increases: first a liquid-solid transition and then a solid-solid transition. The isotropic liquid phase coexists with the Conway-Torquato (CT) crystal phase at intermediate densities, verifying the result of a previous qualitative study [ J. Chem. Phys. 2011 , 135 , 151101 ]. The freezing- and melting-point packing fractions for this transition are respectively ϕF = 0.496 ± 0.006 and ϕM = 0.591 ± 0.005. At higher densities, we find that the CT phase undergoes another first-order phase transition to one associated with the densest-known crystal, with coexistence densities in the range ϕ ∈ [0.780 ± 0.002, 0.802 ± 0.003]. We find no evidence for stable rotator (or plastic) or nematic phases. We also generate the maximally random jammed (MRJ) packings of truncated tetrahedra, which may be regarded to be the glassy end state of a rapid compression of the liquid. Specifically, we systematically study the structural characteristics of the MRJ packings, including the centroidal pair correlation function, structure factor and orientational pair correlation

  11. In vivo application of sub-second spiral chemical shift imaging (CSI) to hyperpolarized 13C metabolic imaging: comparison with phase-encoded CSI.

    Science.gov (United States)

    Mayer, Dirk; Yen, Yi-Fen; Levin, Yakir S; Tropp, James; Pfefferbaum, Adolf; Hurd, Ralph E; Spielman, Daniel M

    2010-06-01

    A fast spiral chemical shift imaging (CSI) has been developed to address the challenge of the limited acquisition window in hyperpolarized (13)C metabolic imaging. The sequence exploits the sparsity of the spectra and prior knowledge of resonance frequencies to reduce the measurement time by undersampling the data in the spectral domain. As a consequence, multiple reconstructions are necessary for any given data set as only frequency components within a selected bandwidth are reconstructed "in-focus" while components outside that band are severely blurred ("spectral tomosynthesis"). A variable-flip-angle scheme was used for optimal use of the longitudinal magnetization. The sequence was applied to sub-second metabolic imaging of the rat in vivo after injection of hyperpolarized [1-(13)C]-pyruvate on a clinical 3T MR scanner. The comparison with conventional CSI based on phase encoding showed similar signal-to-noise ratio (SNR) and spatial resolution in metabolic maps for the substrate and its metabolic products lactate, alanine, and bicarbonate, despite a 50-fold reduction in scan time for the spiral CSI acquisition. The presented results demonstrate that dramatic reductions in scan time are feasible in hyperpolarized (13)C metabolic imaging without a penalty in SNR or spatial resolution. (c) 2010 Elsevier Inc. All rights reserved.

  12. Core polarization effects in the Hartree--Fock--random phase approximation schemes

    Energy Technology Data Exchange (ETDEWEB)

    Lipparini, E.; Stringari, S.

    1987-02-01

    Core polarization effects in odd nuclei are investigated in the framework of the Hartree--Fock and random phase approximation schemes. The results of the particle vibration coupling model are recovered by linearizing the equations of motion in the interaction Hamiltonian between the external and the core particles. The formalism is used to study the renormalization of diagonal and off-diagonal M1 matrix elements. It is found that M1 polarization effects exhibit a very strong dependence on the range of the force. Copyright 1987 Academic Press, Inc.

  13. Correlations in two-dimensional electron gas: Random-phase approximation with exchange and ladder results

    Science.gov (United States)

    Pederiva, F.; Lipparini, E.; Takayanagi, K.

    1997-12-01

    We have evaluated the density-density response of the two-dimensional electron gas at zero temperature by solving the Dyson equation for the particle-hole Green's function, including exchange Coulomb matrix elements and short-range contributions in the ladder approximation. We study the effect of these correlations on the total energy, compressibility per particle, local field factor G(q), static structure factor and pair-correlation function. Results are compared with the normal random-phase approximation, local field theories and quantum Monte Carlo calculations.

  14. Role of small-norm components in extended random-phase approximation

    Science.gov (United States)

    Tohyama, Mitsuru

    2017-09-01

    The role of the small-norm amplitudes in extended random-phase approximation (RPA) theories such as the particle-particle and hole-hole components of one-body amplitudes and the two-body amplitudes other than two-particle/two-hole components are investigated for the one-dimensional Hubbard model using an extended RPA derived from the time-dependent density matrix theory. It is found that these amplitudes cannot be neglected in strongly interacting regions where the effects of ground-state correlations are significant.

  15. Restoring the Pauli principle in the random phase approximation ground state

    Science.gov (United States)

    Kosov, D. S.

    2017-12-01

    Random phase approximation ground state contains electronic configurations where two (and more) identical electrons can occupy the same molecular spin-orbital violating the Pauli exclusion principle. This overcounting of electronic configurations happens due to quasiboson approximation in the treatment of electron-hole pair operators. We describe the method to restore the Pauli principle in the RPA wavefunction. The proposed theory is illustrated by the calculations of molecular dipole moments and electronic kinetic energies. The Hartree-Fock based RPA, which is corrected for the Pauli principle, gives the results of comparable accuracy with Møller-Plesset second order perturbation theory and coupled-cluster singles and doubles method.

  16. Cryptographic salting for security enhancement of double random phase encryption schemes

    Science.gov (United States)

    Velez Zea, Alejandro; Fredy Barrera, John; Torroba, Roberto

    2017-10-01

    Security in optical encryption techniques is a subject of great importance, especially in light of recent reports of successful attacks. We propose a new procedure to reinforce the ciphertexts generated in double random phase encrypting experimental setups. This ciphertext is protected by multiplexing with a ‘salt’ ciphertext coded with the same setup. We present an experimental implementation of the ‘salting’ technique. Thereafter, we analyze the resistance of the ‘salted’ ciphertext under some of the commonly known attacks reported in the literature, demonstrating the validity of our proposal.

  17. Phase transitions of Ising mixed spin 1 and 3/2 with random crystal field distribution

    Science.gov (United States)

    Sabri, S.; EL Falaki, M.; EL Yadari, M.; Benyoussef, A.; EL Kenz, A.

    2016-10-01

    The thermal and magnetic properties of the mixed spin-1 and spin-3/2 in the presence of the random crystal field are studied within the mean field approach based on the Bogoliubov inequality for the Gibbs free energy. The model exhibits first, second order transitions, a tricritical point, triple point and an isolated critical end point. It is found that the system displays simple and double compensation temperatures, five topologies of the phase diagrams. A re-entrant phenomenon is also discussed and the thermal dependences of total magnetization according to extended Neel classification have been also given.

  18. High energy X-ray phase and dark-field imaging using a random absorption mask.

    Science.gov (United States)

    Wang, Hongchang; Kashyap, Yogesh; Cai, Biao; Sawhney, Kawal

    2016-07-28

    High energy X-ray imaging has unique advantage over conventional X-ray imaging, since it enables higher penetration into materials with significantly reduced radiation damage. However, the absorption contrast in high energy region is considerably low due to the reduced X-ray absorption cross section for most materials. Even though the X-ray phase and dark-field imaging techniques can provide substantially increased contrast and complementary information, fabricating dedicated optics for high energies still remain a challenge. To address this issue, we present an alternative X-ray imaging approach to produce transmission, phase and scattering signals at high X-ray energies by using a random absorption mask. Importantly, in addition to the synchrotron radiation source, this approach has been demonstrated for practical imaging application with a laboratory-based microfocus X-ray source. This new imaging method could be potentially useful for studying thick samples or heavy materials for advanced research in materials science.

  19. Workshop on Strategic Behavior and Phase Transitions in Random and Complex Combinatorial Structures : Extended Abstracts

    CERN Document Server

    Kirousis, Lefteris; Ortiz-Gracia, Luis; Serna, Maria

    2017-01-01

    This book is divided into two parts, the first of which seeks to connect the phase transitions of various disciplines, including game theory, and to explore the synergies between statistical physics and combinatorics. Phase Transitions has been an active multidisciplinary field of research, bringing together physicists, computer scientists and mathematicians. The main research theme explores how atomic agents that act locally and microscopically lead to discontinuous macroscopic changes. Adopting this perspective has proven to be especially useful in studying the evolution of random and usually complex or large combinatorial objects (like networks or logic formulas) with respect to discontinuous changes in global parameters like connectivity, satisfiability etc. There is, of course, an obvious strategic element in the formation of a transition: the atomic agents “selfishly” seek to optimize a local parameter. However, up to now this game-theoretic aspect of abrupt, locally triggered changes had not been e...

  20. A random phased array device for delivery of high intensity focused ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Hand, J W [Radiological Sciences Unit, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London W12 0HS (United Kingdom); Shaw, A; Sadhoo, N; Rajagopal, S [Acoustics Group, National Physical Laboratory, Teddington TW11 0LW (United Kingdom); Dickinson, R J [Department of Bioengineering, Imperial College London, London SW7 2AZ (United Kingdom); Gavrilov, L R [N.N. Andreev Acoustics Institute, 117036 Moscow (Russian Federation)], E-mail: j.hand@imperial.ac.uk

    2009-10-07

    Randomized phased arrays can offer electronic steering of a single focus and simultaneous multiple foci concomitant with low levels of secondary maxima and are potentially useful as sources of high intensity focused ultrasound (HIFU). This work describes laboratory testing of a 1 MHz random phased array consisting of 254 elements on a spherical shell of radius of curvature 130 mm and diameter 170 mm. Acoustic output power and efficiency are measured for a range of input electrical powers, and field distributions for various single- and multiple-focus conditions are evaluated by a novel technique using an infrared camera to provide rapid imaging of temperature changes on the surface of an absorbing target. Experimental results show that the array can steer a single focus laterally to at least {+-}15 mm off axis and axially to more than {+-}15 mm from the centre of curvature of the array and patterns of four and five simultaneous foci {+-}10 mm laterally and axially whilst maintaining low intensity levels in secondary maxima away from the targeted area in good agreement with linear theoretical predictions. Experiments in which pork meat was thermally ablated indicate that contiguous lesions several cm{sup 3} in volume can be produced using the patterns of multiple foci.

  1. Band-phase-randomized Surrogates to assess nonlinearity in non-stationary time series

    CERN Document Server

    Guarin, Diego; Orozco, Alvaro

    2011-01-01

    Testing for nonlinearity is one of the most important preprocessing steps in nonlinear time series analysis. Typically, this is done by means of the linear surrogate data methods. But it is a known fact that the validity of the results heavily depends on the stationarity of the time series. Since most physiological signals are non-stationary, it is easy to falsely detect nonlinearity using the linear surrogate data methods. In this document, we propose a methodology to extend the procedure for generating constrained surrogate time series in order to assess nonlinearity in non-stationary data. The method is based on the band-phase-randomized surrogates, which consists (contrary to the linear surrogate data methods) in randomizing only a portion of the Fourier phases in the high frequency band. Analysis of simulated time series showed that in comparison to the linear surrogate data method, our method is able to discriminate between linear stationarity, linear non-stationary and nonlinear time series. When apply...

  2. Influence of liquid crystalline phases on the tunability of a random laser

    Science.gov (United States)

    Trull, José; Salud, Josep; Diez-Berart, Sergio; López, David O.

    2017-05-01

    In this paper, we report the temperature behavior of an optimized disordered photonic system-based liquid crystal by means of heat capacity and refractive index measurements. The scattering system is formed by a porous borosilicate glass random matrix (about 60%) infiltrated with a smectogenic liquid crystal (about 16%) and a small amount of laser dye (0.1%). The rest of the scattering system is about 24% air, giving rise to a high refractive index contrast scattering system. Such a system has the functionality to change the refractive index contrast with temperature due to the liquid crystal temperature behavior. The system, optically pumped by the second harmonic of a Q -switched Nd:YAG pulsed laser working at 532 nm, exhibits random laser action, the threshold of which depends upon the liquid crystalline mesophase. Temperatures of existence of the smectic-B phase correspond to the most optimized random laser. In such a mesophase, the transport mean free path has been determined as about 16 μm in a coherent backscattering experiment.

  3. Comparison between amniotomy, oxytocin or both for augmentation of labor in prolonged latent phase: a randomized controlled trial

    OpenAIRE

    Shalev Eliezer; Zafran Noah; Kadan Yfat; Garmi Gali; Nachum Zohar; Salim Raed

    2010-01-01

    Abstract Background A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase. Methods Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1), oxytocin (group 2) or both (group 3). A group of women who pr...

  4. Multicenter, randomized, placebo-controlled phase III study of pyridoxalated hemoglobin polyoxyethylene in distributive shock (PHOENIX).

    Science.gov (United States)

    Vincent, Jean-Louis; Privalle, Christopher T; Singer, Mervyn; Lorente, José A; Boehm, Erwin; Meier-Hellmann, Andreas; Darius, Harald; Ferrer, Ricard; Sirvent, Josep-Maria; Marx, Gernot; DeAngelo, Joseph

    2015-01-01

    To compare the effectiveness and safety of the hemoglobin-based nitric oxide scavenger, pyridoxalated hemoglobin polyoxyethylene, against placebo in patients with vasopressor-dependent distributive shock. Multicenter, randomized, placebo-controlled, open-label study. Sixty-one participating ICUs in six European countries (Austria, Belgium, Germany, the Netherlands, Spain, and United Kingdom). All patients admitted with distributive shock, defined as the presence of at least two systemic inflammatory response syndrome criteria, persisting norepinephrine dependence and evidence of organ dysfunction/hypoperfusion despite adequate fluid resuscitation. Patients were randomized to receive 0.25 mL/kg/hr pyridoxalated hemoglobin polyoxyethylene (20 mg Hb/kg/hr) or an equal volume of placebo, infused for up to 150 hours, in addition to conventional vasopressor therapy. The study was stopped after interim analysis showed higher mortality in the pyridoxalated hemoglobin polyoxyethylene group and an increased prevalence of adverse events. At this time, 377 patients had been randomized to pyridoxalated hemoglobin polyoxyethylene (n = 183) or placebo (n = 194). Age, gender, type of patient (medical/surgical), and Acute Physiology and Chronic Health Evaluation II scores were similar between groups. Twenty-eight-day mortality rate was 44.3% in the pyridoxalated hemoglobin polyoxyethylene group versus 37.6% in the placebo group (OR, 1.29; 95% CI, 0.85-1.95; p = 0.227). In patients with higher organ dysfunction scores (Sepsis-related Organ Failure Assessment > 13), mortality rates were significantly higher in the pyridoxalated hemoglobin polyoxyethylene group when compared with those in placebo-treated patients (60.9% vs 39.2%; p = 0.014). Survivors who received pyridoxalated hemoglobin polyoxyethylene had a longer vasopressor-free time (21.3 vs 19.7 d; p = 0.035). In this randomized, controlled phase III trial in patients with vasopressor-dependent distributive shock

  5. Luteal Phase Support in the Intrauterine Insemination (IUI Cycles: A Randomized Double Blind, Placebo Controlled Study.

    Directory of Open Access Journals (Sweden)

    Batool Hossein Rashidi

    2014-12-01

    Full Text Available To evaluate the impact of luteal phase support with vaginal progesterone on pregnancy rates in the intrauterine insemination (IUI cycles, stimulated with clomiphene citrate and human menopausal gonadotropin (hMG, in sub fertile couples.This prospective, randomized, double blind study was performed in a tertiary infertility center from March 2011 to January 2012. It consisted of 253 sub fertile couples undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with clomiphene citrate (100 mg and hMG (75 IU in preparation for the IUI cycle. Study group (n = 127 received luteal phase support in the form of vaginal progesterone (400 mg twice a day, and control group (n = 126 received placebo. Clinical pregnancy and abortion rates were assessed and compared between the two groups.The clinical pregnancy rate was not significantly higher for supported cycles than that for the unsupported ones (15.75% vs. 12.69%, p = 0.3. The abortion rate in the patients with progesterone luteal support compared to placebo group was not statistically different (10% vs. 18.75%, p = 0.45.It seems that luteal phase support with vaginal progesterone was not enhanced the success of IUI cycles outcomes, when clomiphene citrate and hMG were used for ovulation stimulation.

  6. Luteal Phase Support in the Intrauterine Insemination (IUI) Cycles: A Randomized Double Blind, Placebo Controlled Study.

    Science.gov (United States)

    Hossein Rashidi, Batool; Davari Tanha, Fatemeh; Rahmanpour, Haleh; Ghazizadeh, Mahya

    2014-12-01

    To evaluate the impact of luteal phase support with vaginal progesterone on pregnancy rates in the intrauterine insemination (IUI) cycles, stimulated with clomiphene citrate and human menopausal gonadotropin (hMG), in sub fertile couples. This prospective, randomized, double blind study was performed in a tertiary infertility center from March 2011 to January 2012. It consisted of 253 sub fertile couples undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with clomiphene citrate (100 mg) and hMG (75 IU) in preparation for the IUI cycle. Study group (n = 127) received luteal phase support in the form of vaginal progesterone (400 mg twice a day), and control group (n = 126) received placebo. Clinical pregnancy and abortion rates were assessed and compared between the two groups. The clinical pregnancy rate was not significantly higher for supported cycles than that for the unsupported ones (15.75% vs. 12.69%, p = 0.3). The abortion rate in the patients with progesterone luteal support compared to placebo group was not statistically different (10% vs. 18.75%, p = 0.45). It seems that luteal phase support with vaginal progesterone was not enhanced the success of IUI cycles outcomes, when clomiphene citrate and hMG were used for ovulation stimulation.

  7. Statistical mechanics of random geometric graphs: Geometry-induced first-order phase transition.

    Science.gov (United States)

    Ostilli, Massimo; Bianconi, Ginestra

    2015-04-01

    Random geometric graphs (RGGs) can be formalized as hidden-variables models where the hidden variables are the coordinates of the nodes. Here we develop a general approach to extract the typical configurations of a generic hidden-variables model and apply the resulting equations to RGGs. For any RGG, defined through a rigid or a soft geometric rule, the method reduces to a nontrivial satisfaction problem: Given N nodes, a domain D, and a desired average connectivity 〈k〉, find, if any, the distribution of nodes having support in D and average connectivity 〈k〉. We find out that, in the thermodynamic limit, nodes are either uniformly distributed or highly condensed in a small region, the two regimes being separated by a first-order phase transition characterized by a O(N) jump of 〈k〉. Other intermediate values of 〈k〉 correspond to very rare graph realizations. The phase transition is observed as a function of a parameter a∈[0,1] that tunes the underlying geometry. In particular, a=1 indicates a rigid geometry where only close nodes are connected, while a=0 indicates a rigid antigeometry where only distant nodes are connected. Consistently, when a=1/2 there is no geometry and no phase transition. After discussing the numerical analysis, we provide a combinatorial argument to fully explain the mechanism inducing this phase transition and recognize it as an easy-hard-easy transition. Our result shows that, in general, ad hoc optimized networks can hardly be designed, unless to rely to specific heterogeneous constructions, not necessarily scale free.

  8. Pseudo-random-bit-sequence phase modulation for reduced errors in a fiber optic gyroscope.

    Science.gov (United States)

    Chamoun, Jacob; Digonnet, Michel J F

    2016-12-15

    Low noise and drift in a laser-driven fiber optic gyroscope (FOG) are demonstrated by interrogating the sensor with a low-coherence laser. The laser coherence was reduced by broadening its optical spectrum using an external electro-optic phase modulator driven by either a sinusoidal or a pseudo-random bit sequence (PRBS) waveform. The noise reduction measured in a FOG driven by a modulated laser agrees with the calculations based on the broadened laser spectrum. Using PRBS modulation, the linewidth of a laser was broadened from 10 MHz to more than 10 GHz, leading to a measured FOG noise of only 0.00073  deg/√h and a drift of 0.023  deg/h. To the best of our knowledge, these are the lowest noise and drift reported in a laser-driven FOG, and this noise is below the requirement for the inertial navigation of aircraft.

  9. Dielectric matrix formulation of correlation energies in the Random Phase Approximation (RPA): inclusion of exchange effects

    CERN Document Server

    Mussard, Bastien; Jansen, Georg; Angyan, Janos

    2016-01-01

    Starting from the general expression for the ground state correlation energy in the adiabatic connection fluctuation dissipation theorem (ACFDT) framework, it is shown that the dielectric matrix formulation, which is usually applied to calculate the direct random phase approximation (dRPA) correlation energy, can be used for alternative RPA expressions including exchange effects. Within this famework, the ACFDT analog of the second order screened exchange (SOSEX) approximation leads to a logarithmic formula for the correlation energy similar to the direct RPA expression. Alternatively, the contribution of the exchange can be included in the kernel used to evaluate the response functions. In this case the use of an approximate kernel is crucial to simplify the formalism and to obtain a correlation energy in logarithmic form. Technical details of the implementation of these methods are discussed and it is shown that one can take advantage of density fitting or Cholesky decomposition techniques to improve the co...

  10. Insight into organic reactions from the direct random phase approximation and its corrections

    Energy Technology Data Exchange (ETDEWEB)

    Ruzsinszky, Adrienn [Department of Physics, Temple University, Philadelphia, Pennsylvania 19122 (United States); Zhang, Igor Ying; Scheffler, Matthias [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, 14195 Berlin (Germany)

    2015-10-14

    The performance of the random phase approximation (RPA) and beyond-RPA approximations for the treatment of electron correlation is benchmarked on three different molecular test sets. The test sets are chosen to represent three typical sources of error which can contribute to the failure of most density functional approximations in chemical reactions. The first test set (atomization and n-homodesmotic reactions) offers a gradually increasing balance of error from the chemical environment. The second test set (Diels-Alder reaction cycloaddition = DARC) reflects more the effect of weak dispersion interactions in chemical reactions. Finally, the third test set (self-interaction error 11 = SIE11) represents reactions which are exposed to noticeable self-interaction errors. This work seeks to answer whether any one of the many-body approximations considered here successfully addresses all these challenges.

  11. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial

    Science.gov (United States)

    Motzer, Robert J.; Rini, Brian I.; McDermott, David F.; Redman, Bruce G.; Kuzel, Timothy M.; Harrison, Michael R.; Vaishampayan, Ulka N.; Drabkin, Harry A.; George, Saby; Logan, Theodore F.; Margolin, Kim A.; Plimack, Elizabeth R.; Lambert, Alexandre M.; Waxman, Ian M.; Hammers, Hans J.

    2015-01-01

    Purpose Nivolumab is a fully human immunoglobulin G4 programmed death–1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety. Results A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs. Conclusion Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting. PMID:25452452

  12. Asymmetric multiple information cryptosystem based on chaotic spiral phase mask and random spectrum decomposition

    Science.gov (United States)

    Rafiq Abuturab, Muhammad

    2018-01-01

    A new asymmetric multiple information cryptosystem based on chaotic spiral phase mask (CSPM) and random spectrum decomposition is put forwarded. In the proposed system, each channel of secret color image is first modulated with a CSPM and then gyrator transformed. The gyrator spectrum is randomly divided into two complex-valued masks. The same procedure is applied to multiple secret images to get their corresponding first and second complex-valued masks. Finally, first and second masks of each channel are independently added to produce first and second complex ciphertexts, respectively. The main feature of the proposed method is the different secret images encrypted by different CSPMs using different parameters as the sensitive decryption/private keys which are completely unknown to unauthorized users. Consequently, the proposed system would be resistant to potential attacks. Moreover, the CSPMs are easier to position in the decoding process owing to their own centering mark on axis focal ring. The retrieved secret images are free from cross-talk noise effects. The decryption process can be implemented by optical experiment. Numerical simulation results demonstrate the viability and security of the proposed method.

  13. Mavoglurant in Parkinson's patients with l-Dopa-induced dyskinesias: Two randomized phase 2 studies.

    Science.gov (United States)

    Trenkwalder, Claudia; Stocchi, Fabrizio; Poewe, Werner; Dronamraju, Nalina; Kenney, Chris; Shah, Amy; von Raison, Florian; Graf, Ana

    2016-07-01

    Two phase 2 randomized, double-blind studies were designed to evaluate efficacy and safety of immediate-release (study 1) and modified-release (study 2) mavoglurant formulations in PD l-dopa-induced dyskinesia. Patients were randomized to mavoglurant 100-mg or placebo (4:3) groups (study 1) and mavoglurant 200-mg, mavoglurant 150-mg, or placebo (2:1:1) groups (study 2). Primary outcome was antidyskinetic efficacy, as measured by change from baseline to week 12 in modified Abnormal Involuntary Movement Scale total score. Differences in least-squares mean (standard error) change in modified Abnormal Involuntary Movement Scale total score in week 12 did not reach statistical significance in either study (study 1: mavoglurant 100 mg twice a day versus placebo, 1.7 [1.31]; study 2: mavoglurant 150 mg twice a day (-1.3 [1.16]) and 200 mg twice a day (-0.2 [1.03]) versus placebo). Adverse events incidence was higher with mavoglurant than with placebo. Both studies failed to meet the primary objective of demonstrating improvement of dyskinesia with mavoglurant treatment. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  14. Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial

    Science.gov (United States)

    Van Coevorden, Frits; Punt, Cornelis J. A.; Pierie, Jean-Pierre E. N.; Borel-Rinkes, Inne; Ledermann, Jonathan A.; Poston, Graeme; Bechstein, Wolf; Lentz, Marie-Ange; Mauer, Murielle; Folprecht, Gunnar; Van Cutsem, Eric; Ducreux, Michel; Nordlinger, Bernard

    2017-01-01

    Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n  38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases. PMID:28376151

  15. A Locust Phase Change Model with Multiple Switching States and Random Perturbation

    Science.gov (United States)

    Xiang, Changcheng; Tang, Sanyi; Cheke, Robert A.; Qin, Wenjie

    2016-12-01

    Insects such as locusts and some moths can transform from a solitarious phase when they remain in loose populations and a gregarious phase, when they may swarm. Therefore, the key to effective management of outbreaks of species such as the desert locust Schistocercagregaria is early detection of when they are in the threshold state between the two phases, followed by timely control of their hopper stages before they fledge because the control of flying adult swarms is costly and often ineffective. Definitions of gregarization thresholds should assist preventive control measures and avoid treatment of areas that might not lead to gregarization. In order to better understand the effects of the threshold density which represents the gregarization threshold on the outbreak of a locust population, we developed a model of a discrete switching system. The proposed model allows us to address: (1) How frequently switching occurs from solitarious to gregarious phases and vice versa; (2) When do stable switching transients occur, the existence of which indicate that solutions with larger amplitudes can switch to a stable attractor with a value less than the switching threshold density?; and (3) How does random perturbation influence the switching pattern? Our results show that both subsystems have refuge equilibrium points, outbreak equilibrium points and bistable equilibria. Further, the outbreak equilibrium points and bistable equilibria can coexist for a wide range of parameters and can switch from one to another. This type of switching is sensitive to the intrinsic growth rate and the initial values of the locust population, and may result in locust population outbreaks and phase switching once a small perturbation occurs. Moreover, the simulation results indicate that the switching transient patterns become identical after some generations, suggesting that the evolving process of the perturbation system is not related to the initial value after some fixed number of

  16. Long-Term Improvements After Multimodal Rehabilitation in Late Phase After Stroke: A Randomized Controlled Trial.

    Science.gov (United States)

    Bunketorp-Käll, Lina; Lundgren-Nilsson, Åsa; Samuelsson, Hans; Pekny, Tulen; Blomvé, Karin; Pekna, Marcela; Pekny, Milos; Blomstrand, Christian; Nilsson, Michael

    2017-07-01

    Treatments that improve function in late phase after stroke are urgently needed. We assessed whether multimodal interventions based on rhythm-and-music therapy or horse-riding therapy could lead to increased perceived recovery and functional improvement in a mixed population of individuals in late phase after stroke. Participants were assigned to rhythm-and-music therapy, horse-riding therapy, or control using concealed randomization, stratified with respect to sex and stroke laterality. Therapy was given twice a week for 12 weeks. The primary outcome was change in participants' perception of stroke recovery as assessed by the Stroke Impact Scale with an intention-to-treat analysis. Secondary objective outcome measures were changes in balance, gait, grip strength, and cognition. Blinded assessments were performed at baseline, postintervention, and at 3- and 6-month follow-up. One hundred twenty-three participants were assigned to rhythm-and-music therapy (n=41), horse-riding therapy (n=41), or control (n=41). Post-intervention, the perception of stroke recovery (mean change from baseline on a scale ranging from 1 to 100) was higher among rhythm-and-music therapy (5.2 [95% confidence interval, 0.79-9.61]) and horse-riding therapy participants (9.8 [95% confidence interval, 6.00-13.66]), compared with controls (-0.5 [-3.20 to 2.28]); P =0.001 (1-way ANOVA). The improvements were sustained in both intervention groups 6 months later, and corresponding gains were observed for the secondary outcomes. Multimodal interventions can improve long-term perception of recovery, as well as balance, gait, grip strength, and working memory in a mixed population of individuals in late phase after stroke. URL: http//www.ClinicalTrials.gov. Unique identifier: NCT01372059. © 2017 American Heart Association, Inc.

  17. TU-AB-BRA-09: A Novel Method of Generating Ultrafast Volumetric Cine MRI (VC-MRI) Using Prior 4D-MRI and On-Board Phase-Skipped Encoding Acquisition for Radiotherapy Target Localization

    Energy Technology Data Exchange (ETDEWEB)

    Wang, C; Yin, F; Harris, W; Cai, J; Chang, Z; Ren, L [Duke University Medical Center, Durham, NC (United States)

    2016-06-15

    Purpose: To develop a technique generating ultrafast on-board VC-MRI using prior 4D-MRI and on-board phase-skipped encoding k-space acquisition for real-time 3D target tracking of liver and lung radiotherapy. Methods: The end-of-expiration (EOE) volume in 4D-MRI acquired during the simulation was selected as the prior volume. 3 major respiratory deformation patterns were extracted through the principal component analysis of the deformation field maps (DFMs) generated between EOE and all other phases. The on-board VC-MRI at each instant was considered as a deformation of the prior volume, and the deformation was modeled as a linear combination of the extracted 3 major deformation patterns. To solve the weighting coefficients of the 3 major patterns, a 2D slice was extracted from VC-MRI volume to match with the 2D on-board sampling data, which was generated by 8-fold phase skipped-encoding k-space acquisition (i.e., sample 1 phase-encoding line out of every 8 lines) to achieve an ultrafast 16–24 volumes/s frame rate. The method was evaluated using XCAT digital phantom to simulate lung cancer patients. The 3D volume of end-ofinhalation (EOI) phase at the treatment day was used as ground-truth onboard VC-MRI with simulated changes in 1) breathing amplitude and 2) breathing amplitude/phase change from the simulation day. A liver cancer patient case was evaluated for in-vivo feasibility demonstration. Results: The comparison between ground truth and estimated on-board VC-MRI shows good agreements. In XCAT study with changed breathing amplitude, the volume-percent-difference(VPD) between ground-truth and estimated tumor volumes at EOI was 6.28% and the Center-of-Mass-Shift(COMS) was 0.82mm; with changed breathing amplitude and phase, the VPD was 8.50% and the COMS was 0.54mm. The study of liver patient case also demonstrated a promising in vivo feasibility of the proposed method Conclusion: Preliminary results suggest the feasibility to estimate ultrafast VC-MRI for on

  18. A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia.

    Science.gov (United States)

    Misra, Hemant; Bainbridge, James; Berryman, John; Abuchowski, Abraham; Galvez, Kenneth Mauricio; Uribe, Luis Fernando; Hernandez, Angel Luis; Sosa, Nestor Rodolfo

    Treatment of sickle cell anemia is a challenging task and despite the well understood genetic and biochemical pathway of sickle hemoglobin, current therapy continues to be limited to the symptomatic treatment of pain, supplemental oxygen, antibiotics, red blood cell transfusions and hydroxyurea. SANGUINATE is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities. An open-label randomized Phase Ib study was performed in adult sickle cell anemia patients. Two dose levels of SANGUINATE were compared to hydroxyurea in 24 homozygotes for Hb SS. Twelve subjects received either a low dose (160mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. Another 12 subjects received either a high dose (320mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. The primary endpoint was the safety of SANGUINATE versus hydroxyurea in sickle cell anemia patients. Secondary endpoints included determination of the plasma pharmacokinetics and assessment of hematologic measurements. Musculoskeletal related adverse events were the most common. Transient troponin I levels increased in three patients, one of whom had an increase in tricuspid regurgitant velocity; however, no clinical signs were noted. Following an assessment of vital signs, tricuspid regurgitant velocity, electrocardiogram, serum biochemistry, hematology, urinalysis, and analysis of reported adverse events, SANGUINATE was found to be safe in stable sickle cell anemia patients. The clinical trial met its primary objective of demonstrating an acceptable safety profile for SANGUINATE in patients with sickle cell anemia. This trial established the safety of SANGUINATE at both dose levels and permitted its advance to Phase II trials. Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  19. Validation of the k-filtering technique for a signal composed of random-phase plane waves and non-random coherent structures

    Directory of Open Access Journals (Sweden)

    O. W. Roberts

    2014-12-01

    Full Text Available Recent observations of astrophysical magnetic fields have shown the presence of fluctuations being wave-like (propagating in the plasma frame and those described as being structure-like (advected by the plasma bulk velocity. Typically with single-spacecraft missions it is impossible to differentiate between these two fluctuations, due to the inherent spatio-temporal ambiguity associated with a single point measurement. However missions such as Cluster which contain multiple spacecraft have allowed for temporal and spatial changes to be resolved, using techniques such as k filtering. While this technique does not assume Taylor's hypothesis it requires both weak stationarity of the time series and that the fluctuations can be described by a superposition of plane waves with random phases. In this paper we test whether the method can cope with a synthetic signal which is composed of a combination of non-random-phase coherent structures with a mean radius d and a mean separation λ, as well as plane waves with random phase.

  20. Dynamic response of a two-dimensional electron gas: Exact treatment of Coulomb exchange in the random-phase approximation

    Science.gov (United States)

    Takayanagi, K.; Lipparini, E.

    1995-07-01

    The Dyson equation for the particle-hole Green's function, including Coulomb exchange matrix elements, has been solved exactly for a two-dimensional electron gas. Static and dynamic dielectric functions have been calculated and compared with normal random-phase-approximation and recent quantum Monte Carlo results.

  1. Alpha-galactosylceramide in chronic hepatitis B infection: results from a randomized placebo-controlled Phase I/II trial.

    NARCIS (Netherlands)

    Woltman, A.M.; Borg, M.J. Ter; Binda, R.S.; Sprengers, D.; Blomberg, B.M.E. von; Scheper, R.J.; Hayashi, K.; Nishi, N.; Boonstra, A.; Molen, R.G. van der; Janssen, H.L.

    2009-01-01

    BACKGROUND: The glycosphingolipid alpha-galactosylceramide (alpha-GalCer) is known to stimulate invariant natural killer T-cells (iNKTs) and is able to induce powerful antiviral immune responses. The present dose-escalating randomized placebo-controlled Phase I/II trial aimed to investigate

  2. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial.

    Science.gov (United States)

    Rush, A John; Marangell, Lauren B; Sackeim, Harold A; George, Mark S; Brannan, Stephen K; Davis, Sonia M; Howland, Robert; Kling, Mitchel A; Rittberg, Barry R; Burke, William J; Rapaport, Mark H; Zajecka, John; Nierenberg, Andrew A; Husain, Mustafa M; Ginsberg, David; Cooke, Robert G

    2005-09-01

    Vagus nerve stimulation (VNS) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders. An open trial has suggested efficacy. This 10-week, acute, randomized, controlled, masked trial compared adjunctive VNS with sham treatment in 235 outpatients with nonpsychotic major depressive disorder (n = 210) or nonpsychotic, depressed phase, bipolar disorder (n = 25). In the current episode, participants had not responded adequately to between two and six research-qualified medication trials. A two-week, single-blind recovery period (no stimulation) and then 10 weeks of masked active or sham VNS followed implantation. Medications were kept stable. Primary efficacy outcome among 222 evaluable participants was based on response rates (>/=50% reduction from baseline on the 24-item Hamilton Rating Scale for Depression [HRSD(24)]). At 10-weeks, HRSD(24) response rates were 15.2% for the active (n = 112) and 10.0% for the sham (n = 110) groups (p = .251, last observation carried forward [LOCF]). Response rates with a secondary outcome, the Inventory of Depressive Symptomatology - Self-Report (IDS-SR(30)), were 17.0% (active) and 7.3% (sham) (p = .032, LOCF). VNS was well tolerated; 1% (3/235) left the study because of adverse events. This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression.

  3. Broadband diffuse terahertz wave scattering by flexible metasurface with randomized phase distribution.

    Science.gov (United States)

    Zhang, Yin; Liang, Lanju; Yang, Jing; Feng, Yijun; Zhu, Bo; Zhao, Junming; Jiang, Tian; Jin, Biaobing; Liu, Weiwei

    2016-05-26

    Suppressing specular electromagnetic wave reflection or backward radar cross section is important and of broad interests in practical electromagnetic engineering. Here, we present a scheme to achieve broadband backward scattering reduction through diffuse terahertz wave reflection by a flexible metasurface. The diffuse scattering of terahertz wave is caused by the randomized reflection phase distribution on the metasurface, which consists of meta-particles of differently sized metallic patches arranged on top of a grounded polyimide substrate simply through a certain computer generated pseudorandom sequence. Both numerical simulations and experimental results demonstrate the ultralow specular reflection over a broad frequency band and wide angle of incidence due to the re-distribution of the incident energy into various directions. The diffuse scattering property is also polarization insensitive and can be well preserved when the flexible metasurface is conformably wrapped on a curved reflective object. The proposed design opens up a new route for specular reflection suppression, and may be applicable in stealth and other technology in the terahertz spectrum.

  4. Restricted second random phase approximations and Tamm-Dancoff approximations for electronic excitation energy calculations

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Degao; Yang, Yang; Zhang, Peng [Department of Chemistry, Duke University, Durham, North Carolina 27708 (United States); Yang, Weitao, E-mail: weitao.yang@duke.edu [Department of Chemistry and Department of Physics, Duke University, Durham, North Carolina 27708 (United States)

    2014-12-07

    In this article, we develop systematically second random phase approximations (RPA) and Tamm-Dancoff approximations (TDA) of particle-hole and particle-particle channels for calculating molecular excitation energies. The second particle-hole RPA/TDA can capture double excitations missed by the particle-hole RPA/TDA and time-dependent density-functional theory (TDDFT), while the second particle-particle RPA/TDA recovers non-highest-occupied-molecular-orbital excitations missed by the particle-particle RPA/TDA. With proper orbital restrictions, these restricted second RPAs and TDAs have a formal scaling of only O(N{sup 4}). The restricted versions of second RPAs and TDAs are tested with various small molecules to show some positive results. Data suggest that the restricted second particle-hole TDA (r2ph-TDA) has the best overall performance with a correlation coefficient similar to TDDFT, but with a larger negative bias. The negative bias of the r2ph-TDA may be induced by the unaccounted ground state correlation energy to be investigated further. Overall, the r2ph-TDA is recommended to study systems with both single and some low-lying double excitations with a moderate accuracy. Some expressions on excited state property evaluations, such as 〈S{sup ^2}〉 are also developed and tested.

  5. Restricted second random phase approximations and Tamm-Dancoff approximations for electronic excitation energy calculations

    Science.gov (United States)

    Peng, Degao; Yang, Yang; Zhang, Peng; Yang, Weitao

    2014-12-01

    In this article, we develop systematically second random phase approximations (RPA) and Tamm-Dancoff approximations (TDA) of particle-hole and particle-particle channels for calculating molecular excitation energies. The second particle-hole RPA/TDA can capture double excitations missed by the particle-hole RPA/TDA and time-dependent density-functional theory (TDDFT), while the second particle-particle RPA/TDA recovers non-highest-occupied-molecular-orbital excitations missed by the particle-particle RPA/TDA. With proper orbital restrictions, these restricted second RPAs and TDAs have a formal scaling of only O(N4). The restricted versions of second RPAs and TDAs are tested with various small molecules to show some positive results. Data suggest that the restricted second particle-hole TDA (r2ph-TDA) has the best overall performance with a correlation coefficient similar to TDDFT, but with a larger negative bias. The negative bias of the r2ph-TDA may be induced by the unaccounted ground state correlation energy to be investigated further. Overall, the r2ph-TDA is recommended to study systems with both single and some low-lying double excitations with a moderate accuracy. Some expressions on excited state property evaluations, such as < hat{S}2rangle are also developed and tested.

  6. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis

    DEFF Research Database (Denmark)

    Vollmer, T L; Sorensen, P S; Selmaj, K

    2014-01-01

    using EDSS was -31 % [hazard ratio (HR) 0.69, p = 0.063], and using Multiple Sclerosis Functional Composite (MSFC) z-score was -77 % (p = 0.150), vs. placebo. IFNβ-1a reduced ARR 26 % (RR = 0.74, 95 % CI 0.60-0.92, p = 0.007), showed no effect on PBVC loss (+11 %, p = 0.14), and changes in disability......The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS (RRMS), and descriptively compared laquinimod with interferon beta (IFNβ)-1a (Avonex(®) reference arm). RRMS patients age 18-55 years with Expanded Disability Status Scale (EDSS) scores...... months. The primary endpoint was annualized relapse rate (ARR); secondary endpoints included percent brain volume change (PBVC) and 3-month confirmed disability worsening. In all, 1,331 patients were randomized: laquinimod (n = 434), placebo (n = 450), and IFNβ-1a (n = 447). ARR was not significantly...

  7. Innovative measurement of parallelism for parallel transparent plate based on optical scanning holography by using a random-phase pupil.

    Science.gov (United States)

    Luo-Zhi, Zhang; Jian-Ping, Hu; Dao-Ming, Wan; Xing, Zeng; Chun-Miao, Li; Xin, Zhou

    2015-03-20

    A potential method is proposed to measure the parallelism of parallel transparent plate with an advanced lower limit and a convenient process by optical scanning holography (OSH) using a random-phase pupil, which is largely distinct from traditional methods. As a new possible application of OSH, this promising method is demonstrated theoretically and numerical simulations are carried out on a 2  cm×2  cm parallel plate. Discussions are also made on the quality of reconstructed image as well as local mean square error (MSE), which are closely related with the parallelism of sample. These amounts may become the judgments of parallelism, while in most interference methods judgments are paces between two interference fringes. In addition, randomness of random-phase pupil also affects the quality of reconstructed image and local MSE. According to the simulation results, high parallelism usually brings about distinguishable reconstructed information and suppressed local MSE.

  8. Nature of the spin-glass phase in dense packings of Ising dipoles with random anisotropy axes

    Science.gov (United States)

    Alonso, Juan J.; Allés, B.

    2017-09-01

    Using tempered Monte Carlo simulations, we study the the spin-glass phase of dense packings of Ising dipoles pointing along random axes. We consider systems of dipoles (i) placed on the sites of a simple cubic lattice with lattice constant d, and (ii) placed at the center of random close packed spheres of diameter d that occupy 64% of the volume. For both cases, we find a spin-glass phase below a certain temperature T sg. By analysing the data obtained for the overlap parameter, the associated correlation length, as well as the statistics of the overlap distributions of individual samples, we find a behavior consistent with quasi-long-range order in the spin-glass phase, similar to the one previously found in strongly diluted dipolar systems.

  9. Nature of the spin-glass phase in dense packings of Ising dipoles with random anisotropy axes.

    Science.gov (United States)

    Alonso, Juan J; Allés, B

    2017-09-06

    Using tempered Monte Carlo simulations, we study the the spin-glass phase of dense packings of Ising dipoles pointing along random axes. We consider systems of dipoles (i) placed on the sites of a simple cubic lattice with lattice constant d, and (ii) placed at the center of random close packed spheres of diameter d that occupy 64% of the volume. For both cases, we find a spin-glass phase below a certain temperature T sg. By analysing the data obtained for the overlap parameter, the associated correlation length, as well as the statistics of the overlap distributions of individual samples, we find a behavior consistent with quasi-long-range order in the spin-glass phase, similar to the one previously found in strongly diluted dipolar systems.

  10. Trunk Exercises Improve Gait Symmetry in Parkinson Disease: A Blind Phase II Randomized Controlled Trial.

    Science.gov (United States)

    Hubble, Ryan P; Naughton, Geraldine; Silburn, Peter A; Cole, Michael H

    2018-03-01

    Deficits in step-to-step symmetry and trunk muscle activations have been linked to falls in Parkinson disease. Given such symptoms are poorly managed with anti-parkinsonian medications, alternate therapies are needed. This blind phase II randomized controlled trial sought to establish whether exercise can improve step-to-step symmetry in Parkinson disease. Twenty-four Parkinson disease patients with a falls history completed baseline assessments of symptom severity, balance confidence, mobility, and quality of life. Step-to-step symmetry was assessed by deriving harmonic ratios from three-dimensional accelerations collected for the head and trunk. Patients were randomly assigned to either 12 wks of exercise and falls prevention education or falls prevention education only. Both groups repeated the baseline tests 12 and 24 wks after the initial assessment. The Australian and New Zealand Clinical Trials Registry number is ACTRN12613001175763. At 12 wks, the exercise group had statistically significant and clinically relevant improvements in anterior-posterior step-to-step trunk symmetry. In contrast, the education group recorded statistically significant and clinically meaningful reductions in medial-lateral and vertical step-to-step trunk symmetry at 12 wks. Given that step-to-step symmetry improved for the exercise group and declined for the education group after intervention, active interventions seem more suited to increasing independence and quality of life for people with Parkinson disease. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to do the following: (1) Describe the effect deficits in trunk muscle function have on gait in individuals with Parkinson disease; (2) Identify the benefits of targeted trunk exercises on step-to-step symmetry; and (3) Discuss the benefits of improving step-to-step symmetry in individuals with Parkinson

  11. Methadone induction in primary care (ANRS-Methaville: a phase III randomized intervention trial

    Directory of Open Access Journals (Sweden)

    Roux Perrine

    2012-06-01

    Full Text Available Abstract Background In France, the rapid scale-up of buprenorphine, an opioid maintenance treatment (OMT, in primary care for drug users has led to an impressive reduction in HIV prevalence among injecting drug users (IDU but has had no major effect on Hepatitis C incidence. To date, patients willing to start methadone can only do so in a methadone clinic (a medical centre for drug and alcohol dependence (CSAPA or a hospital setting and are referred to primary care physicians after dose stabilization. This study aims to assess the effectiveness of methadone in patients who initiated treatment in primary care compared with those who initiated it in a CSAPA, by measuring abstinence from street opioid use after one year of treatment. Methods/Design The ANRS-Methaville study is a randomized multicenter non-inferiority control trial comparing methadone induction (lasting approximately 2 weeks in primary care and in CSAPA. The model of care chosen for methadone induction in primary care was based on study-specific pre-training of all physicians, exclusion criteria and daily supervision of methadone during the initiation phase. Between January 2009 and January 2011, 10 sites each having one CSAPA and several primary care physicians, were identified to recruit patients to be randomized into two groups, one starting methadone in primary care (n = 147, the other in CSAPA (n = 48. The primary outcome of the study is the proportion of participants abstinent from street opioids after 1 year of treatment i.e. non-inferiority of primary care model in terms of the proportion of patients not using street opioids compared with the proportion observed in those starting methadone in a CSAPA. Discussion The ANRS-Methaville study is the first in France to use an interventional trial to improve access to OMT for drug users. Once the non-inferiority results become available, the Ministry of Health and agency for the safety of health products may change the the

  12. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention.

    Science.gov (United States)

    Chen, Andrew C; Martin, Andrew J; Choy, Bonita; Fernández-Peñas, Pablo; Dalziell, Robyn A; McKenzie, Catriona A; Scolyer, Richard A; Dhillon, Haryana M; Vardy, Janette L; Kricker, Anne; St George, Gayathri; Chinniah, Niranthari; Halliday, Gary M; Damian, Diona L

    2015-10-22

    Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month intervention period, the number of nonmelanoma skin cancers in the 6-month postintervention period, and the safety of nicotinamide. At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (Pnicotinamide was discontinued. Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. (Funded by the National Health and Medical Research Council; ONTRAC Australian New Zealand Clinical Trials

  13. The new INRIM rotating encoder angle comparator (REAC)

    Science.gov (United States)

    Pisani, Marco; Astrua, Milena

    2017-04-01

    A novel angle comparator has been built and tested at INRIM. The device is based on a double air bearing structure embedding a continuously rotating encoder, which is read by two heads: one fixed to the base of the comparator and a second fixed to the upper moving part of the comparator. The phase measurement between the two heads’ signals is proportional to the relative angle suspended between them (and, therefore, the angle between the base and the upper, movable part of the comparator). The advantage of this solution is to reduce the encoder graduation errors and to cancel the cyclic errors due to the interpolation of the encoder lines. By using only two pairs of reading heads, we have achieved an intrinsic accuracy of  ±0.04″ (rectangular distribution) that can be reduced through self-calibration. The residual cyclic errors have shown to be less than 0.01″ peak-to-peak. The random fluctuations are less than 0.01″ rms on a 100 s time interval. A further advantage of the rotating encoder is the intrinsic knowledge of the absolute position without the need of a zeroing procedure. Construction details of the rotating encoder angle comparator (REAC), characterization tests, and examples of practical use are given.

  14. Bicomponent Block Copolymers Derived from One or More Random Copolymers as an Alternative Route to Controllable Phase Behavior

    Energy Technology Data Exchange (ETDEWEB)

    Ashraf, Arman R. [Corporate Research and Development, The Procter and Gamble Company, Cincinnati OH 45224 USA; Ryan, Justin J. [Department of Materials Science and Engineering, North Carolina State University, Raleigh NC 27695 USA; Satkowski, Michael M. [Corporate Research and Development, The Procter and Gamble Company, Cincinnati OH 45224 USA; Lee, Byeongdu [Advanced Photon Source, Argonne National Laboratory, Argonne IL 60439 USA; Smith, Steven D. [Corporate Research and Development, The Procter and Gamble Company, Cincinnati OH 45224 USA; Spontak, Richard J. [Department of Materials Science and Engineering, North Carolina State University, Raleigh NC 27695 USA; Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh NC 27695 USA

    2017-06-29

    Block copolymers have been extensively studied due to their ability to spontaneously self-organize into a wide variety of morphologies that are valuable in energy-, medical- and conservation-related (nano)technologies. While the phase behavior of bicomponent diblock and triblock copolymers is conventionally governed by temperature and individual block masses, we demonstrate that their phase behavior can alternatively be controlled through the use of blocks with random monomer sequencing. Block random copolymers (BRCs), i.e., diblock copolymers wherein one or both blocks is a random copolymer comprised of A and B repeat units, have been synthesized, and their phase behavior, expressed in terms of the order-disorder transition (ODT), has been investigated. Our results establish that, depending on the block composition contrast and molecular weight, BRCs can microphase-separate. We also report that the predicted ODT can be generated at relatively constant molecular weight and temperature with these new soft materials. This sequence-controlled synthetic strategy is extended to thermoplastic elastomeric triblock copolymers differing in chemistry and possessing a random-copolymer midblock.

  15. ATX-101 for reduction of submental fat: A phase III randomized controlled trial.

    Science.gov (United States)

    Humphrey, Shannon; Sykes, Jonathan; Kantor, Jonathan; Bertucci, Vince; Walker, Patricia; Lee, Daniel R; Lizzul, Paul F; Gross, Todd M; Beddingfield, Frederick C

    2016-10-01

    ATX-101, an injectable form of deoxycholic acid, causes adipocytolysis when injected subcutaneously into fat. We sought to evaluate the efficacy and safety of ATX-101. In this phase III trial (REFINE-2), adults dissatisfied with their moderate or severe submental fat (SMF) were randomized to ATX-101 or placebo. Coprimary end points, evaluated at 12 weeks after last treatment, were composite improvements of 1 or more grades and 2 or more grades in SMF observed on both the validated Clinician- and Patient-Reported SMF Rating Scales. Other end points included magnetic resonance imaging-based assessment of submental volume, assessment of psychological impact of SMF, and additional patient-reported outcomes. Among those treated with ATX-101 or placebo (n = 258/treatment group), 66.5% versus 22.2%, respectively, achieved a composite improvement of 1 or more grades (Mantel-Haenszel risk ratio 2.98; 95% confidence interval 2.31-3.85) and 18.6% versus 3.0% achieved a composite improvement of 2 or more grades in SMF (Mantel-Haenszel risk ratio 6.27; 95% confidence interval 2.91-13.52; P ATX-101 were more likely to achieve submental volume reduction confirmed by magnetic resonance imaging, greater reduction in psychological impact of SMF, and satisfaction with treatment (P ATX-101 group and 76.9% in the placebo group were localized to the injection site. Follow-up was limited to 44 weeks. ATX-101 is an alternative treatment for SMF reduction. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  16. Thermochemistry and Geometries for Transition-Metal Chemistry from the Random Phase Approximation.

    Science.gov (United States)

    Waitt, Craig; Ferrara, Nashali M; Eshuis, Henk

    2016-11-08

    Performance of the random phase approximation (RPA) is tested for thermochemistry and geometries of transition-metal chemistry using various benchmarks obtained either computationally or experimentally. Comparison is made to popular (semi)local meta- and hybrid density functionals as well as to the second-order Møller-Plesset perturbation theory (MP2) and its spin-component-scaled derivatives. The benchmark sets include reaction energies, barrier heights, and dissociation energies of prototype bond-activation reactions, dissociation energies for a set of large transition-metal complexes, bond lengths and dissociation energies of metal hydride ions, and bond lengths and angles of a set of closed-shell first-row transition-metal complexes. The emphasis is on first-row transition-metal chemistry, though for energies, elements beyond the first-row are included. Attention is paid to the basis set convergence of RPA. For thermochemistry, RPA performs on par or better than the density functional theory (DFT) functionals presented and is significantly more accurate than MP2. The largest errors are observed in dissociation energies where the electronic environment is altered substantially. For structural parameters, very good results were obtained, and RPA meets the high quality of structures from DFT. In most cases, well-converged structures are obtained with basis sets of triple-zeta quality. MP2 optimized values can often not be obtained and are on average of inferior quality. Though chemical accuracy is not reached, the RPA method is a step forward toward a systematic, parameter-free, all-round method to describe transition-metal chemistry.

  17. Early Aqueous Suppressant Therapy on Hypertensive Phase Following Glaucoma Drainage Device Procedure: A Randomized Prospective Trial.

    Science.gov (United States)

    Law, Simon K; Kornmann, Helen L; Giaconi, JoAnn A; Kwong, Allen; Tran, Eric; Caprioli, Joseph

    2016-03-01

    To prospectively evaluate the effect of early aqueous suppression (therapy) on hypertensive phase (HP) and intraocular pressure (IOP) control after implantation of silicone Ahmed glaucoma valve (AGV). Patients who underwent AGV implantation were randomized to initiate therapy (including β-blockers, α-agonists, or carbonic anhydrase inhibitors) when postoperative IOP>10 mm Hg (low-IOP initiation group) or >17 mm Hg (moderate-IOP initiation group). HP was defined as an IOP>21 mm Hg during the first 6 postoperative months, after an initial IOP reduction to measures included the occurrence of HP and IOP control. Fifty-two eyes (50 patients) underwent AGV implantation. Average follow-up was 21.9±10.7 months. HP was observed in 21 eyes (40.4%) with average peak IOP of 30±8 mm Hg, onset at 32±30 days, and duration of 15±32 days. One year postoperatively, those eyes with HP had higher IOP than eyes that did not develop HP (15.1±5.2, 11.4±4.3, respectively; P=0.021) and required more additional glaucoma surgeries (28.6%, 3.2%, respectively; P=0.013). The peak IOP at week 3 postoperatively in the low-IOP initiation group (26 eyes) was significantly lower than in the moderate-IOP initiation group (26 eyes; 15.7±3.6, 20.6±8.9, respectively; P=0.012). Eyes with therapy started after HP onset had significantly higher postoperative IOP from 2 to 4 months. Therapy initiated before the development of HP was not associated with a higher complication rate. Aqueous suppression initiated in the early postoperative period while IOPs were still in the low-teens and was able to reduce the incidence of IOP spike associated with the HP without an increased complication rate.

  18. Quasiparticle random phase approximation predictions of the gamma-ray strength functions using the Gogny force

    Science.gov (United States)

    Hilaire, Stéphane; Goriely, Stéphane; Péru, Sophie; Lechaftois, François; Deloncle, Isabelle; Martini, Marco

    2017-09-01

    Dipole excitations of nuclei are crucial since they play an important role in nuclear reaction modeling in connection with the photoabsorption and the radiative capture processes. We present here results for the gamma-ray strength function obtained in large-scale axially-symmetric deformed quasiparticle (qp) random phase approximations approach using the finite-range Gogny force, with a particular emphasis on the E1 mode. The convergence with respect to the number of harmonic oscillator shells adopted and the cut-off introduced in the 2-quasiparticle excitation energy space is analyzed. The microscopic nature of our self-consistent Hartree-Fock-Bogoliubov plus QRPA (HFB+QRPA) calculation has unfortunately to be broken, some phenomenological corrections being needed to take into account effects beyond the standard 2-qp QRPA excitations and the coupling between the single-particle and low-lying collective phonon degrees of freedom. The corresponding phenomenological parameters are adjusted on experimental photoabsorption data. In such a procedure, a rather satisfactory description of experimental data is obtained. To study the sensitivity of these phenomenological corrections on the extrapolation, both at low energies and towards exotic neutron-rich nuclei, three different prescriptions are considered. They are shown to lead to rather similar predictions of the E1 strength at low energies as well as for exotic neutron-rich nuclei. The Gogny-HFB+QRPA strength is finally applied to the calculation of radiative neutron capture cross sections and the predictions compared with those obtained with more traditional Lorentzian-type approaches.

  19. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Byrd, John C; Flynn, Joseph M; Kipps, Thomas J; Boxer, Michael; Kolibaba, Kathryn S; Carlile, David J; Fingerle-Rowson, Guenter; Tyson, Nicola; Hirata, Jamie; Sharman, Jeff P

    2016-01-07

    Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at www.clinicaltrials.gov as #NCT01414205. © 2016 by The American Society of Hematology.

  20. Hybrid random walk-linear discriminant analysis method for unwrapping quantitative phase microscopy images of biological samples

    Science.gov (United States)

    Kim, Diane N. H.; Teitell, Michael A.; Reed, Jason; Zangle, Thomas A.

    2015-11-01

    Standard algorithms for phase unwrapping often fail for interferometric quantitative phase imaging (QPI) of biological samples due to the variable morphology of these samples and the requirement to image at low light intensities to avoid phototoxicity. We describe a new algorithm combining random walk-based image segmentation with linear discriminant analysis (LDA)-based feature detection, using assumptions about the morphology of biological samples to account for phase ambiguities when standard methods have failed. We present three versions of our method: first, a method for LDA image segmentation based on a manually compiled training dataset; second, a method using a random walker (RW) algorithm informed by the assumed properties of a biological phase image; and third, an algorithm which combines LDA-based edge detection with an efficient RW algorithm. We show that the combination of LDA plus the RW algorithm gives the best overall performance with little speed penalty compared to LDA alone, and that this algorithm can be further optimized using a genetic algorithm to yield superior performance for phase unwrapping of QPI data from biological samples.

  1. Comparison between amniotomy, oxytocin or both for augmentation of labor in prolonged latent phase: a randomized controlled trial.

    Science.gov (United States)

    Nachum, Zohar; Garmi, Gali; Kadan, Yfat; Zafran, Noah; Shalev, Eliezer; Salim, Raed

    2010-11-07

    A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase. Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1), oxytocin (group 2) or both (group 3). A group of women who progressed spontaneously without intervention composed the control group (group 4). The primary outcome was the duration of time from initiation of augmentation until delivery. A total of 213 women were consented and randomized to group 1 (70 women), group 2 (72 women) and group 3 (71 women). Group 4 was composed from additional 70 women. A mean reduction of 120 minutes in labor duration was observed among group 3 compared to group 1 (p = 0.08) and 180 minutes compared to group 2 and 4 (p = 0.001). Women in group 3 had a shorter length of time from augmentation until the beginning of the active phase and a shorter first stage of labor than group 1 (p = 0.03), group 2 (p = 0.001) and group 4 (p = 0.001). Satisfaction was greater among group 3 and 4. Mode of delivery and neonatal outcome were comparable between the groups. Labor augmentation by combined amniotomy and oxytocin among women with a prolonged latent phase at term seems superior compared to either of them alone.

  2. Least-squares reverse time migration of marine data with frequency-selection encoding

    KAUST Repository

    Dai, Wei

    2013-06-24

    The phase-encoding technique can sometimes increase the efficiency of the least-squares reverse time migration (LSRTM) by more than one order of magnitude. However, traditional random encoding functions require all the encoded shots to share the same receiver locations, thus limiting the usage to seismic surveys with a fixed spread geometry. We implement a frequency-selection encoding strategy that accommodates data with a marine streamer geometry. The encoding functions are delta functions in the frequency domain, so that all the encoded shots have unique nonoverlapping frequency content, and the receivers can distinguish the wavefield from each shot with a unique frequency band. Because the encoding functions are orthogonal to each other, there will be no crosstalk between different shots during modeling and migration. With the frequency-selection encoding method, the computational efficiency of LSRTM is increased so that its cost is comparable to conventional RTM for the Marmousi2 model and a marine data set recorded in the Gulf of Mexico. With more iterations, the LSRTM image quality is further improved by suppressing migration artifacts, balancing reflector amplitudes, and enhancing the spatial resolution. We conclude that LSRTM with frequency-selection is an efficient migration method that can sometimes produce more focused images than conventional RTM. © 2013 Society of Exploration Geophysicists.

  3. Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis

    OpenAIRE

    Constantinescu, Cris S.; Asher, Aliya; Fryze, Waldemar; Kozubski, Wojciech; Wagner, Frank; Aram, Jehan; Tanasescu, Radu; Korolkiewicz, Roman P.; Dirnberger-Hertweck, Maren; Steidl, Stefan; Libretto, Susan E.; Sprenger, Till; Radue, Ernst W.

    2015-01-01

    Objectives: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. Methods: In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infu...

  4. Comparison between amniotomy, oxytocin or both for augmentation of labor in prolonged latent phase: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Shalev Eliezer

    2010-11-01

    Full Text Available Abstract Background A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase. Methods Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1, oxytocin (group 2 or both (group 3. A group of women who progressed spontaneously without intervention composed the control group (group 4. The primary outcome was the duration of time from initiation of augmentation until delivery. Results A total of 213 women were consented and randomized to group 1 (70 women, group 2 (72 women and group 3 (71 women. Group 4 was composed from additional 70 women. A mean reduction of 120 minutes in labor duration was observed among group 3 compared to group 1 (p = 0.08 and 180 minutes compared to group 2 and 4 (p = 0.001. Women in group 3 had a shorter length of time from augmentation until the beginning of the active phase and a shorter first stage of labor than group 1 (p = 0.03, group 2 (p = 0.001 and group 4 (p = 0.001. Satisfaction was greater among group 3 and 4. Mode of delivery and neonatal outcome were comparable between the groups. Conclusion Labor augmentation by combined amniotomy and oxytocin among women with a prolonged latent phase at term seems superior compared to either of them alone.

  5. Is there a spin-glass phase in the random temperature Ising ferromagnet?

    Energy Technology Data Exchange (ETDEWEB)

    Tarjus, Gilles; Dotsenko, Victor [Laboratoire de Physique Theorique des Liquides, UMR 7600, Universite Paris VI, Paris (France)

    2002-02-22

    In this paper we study the phase diagram of the disordered Ising ferromagnet. Within the framework of the Gaussian variational approximation it is shown that in systems with a finite value of the disorder in dimensions D=4 and D<4 the paramagnetic and ferromagnetic phases are separated by a spin-glass phase. The transition from paramagnetic to spin-glass state is continuous (second order), whereas the transition between spin-glass and ferromagnetic states is discontinuous (first order). It is also shown that within the considered approximation there is no replica symmetry breaking in the spin-glass phase. The validity of the Gaussian variational approximation for the present problem is discussed, and we provide a tentative physical interpretation of the results. (author)

  6. Orlistat in clozapine- or olanzapine-treated patients with overweight or obesity: a 16-week open-label extension phase and both phases of a randomized controlled trial.

    Science.gov (United States)

    Tchoukhine, Evgueni; Takala, Pirjo; Hakko, Helinä; Raidma, Mirjam; Putkonen, Hanna; Räsänen, Pirkko; Terevnikov, Viacheslav; Stenberg, Jan-Henry; Eronen, Markku; Joffe, Grigori

    2011-03-01

    To explore long-term effects of orlistat in adult clozapine- or olanzapine-treated patients with DSM-IV-diagnosed schizophrenia and overweight or obesity who tolerate orlistat. Orlistat or placebo was added to clozapine or olanzapine in stable doses in a 16-week randomized controlled trial. Open-label orlistat was added to the antipsychotics during a 16-week extension phase for those completing the double-blind phase. No low-calorie diet or participation in behavioral programs was required. Body weight (primary outcome) and some metabolic parameters were measured prospectively. Analyses were performed for those completing both phases (ie, population differing from that reported earlier). The study was conducted from 2004 through 2005. During the open-label phase, the 44 patients experienced mean ± SD body weight loss of -1.29 ± 3.04 kg, P = .007. During both phases, men (but not women) showed a weight loss of -2.39 ± 5.45 kg, P = .023. Some subgroups showed desirable changes in several metabolic parameters. Prolonged (32 weeks) orlistat treatment yielded no additional benefits as compared to short (16 weeks) treatment. In clozapine- or olanzapine-treated overweight or obese patients able to take orlistat on a long-term basis, the drug, with no concomitant hypocaloric diet or behavioral interventions, caused moderate weight loss only in men. However, some metabolic benefits may be achieved independently of weight changes. In patients who do not respond to orlistat within the first 16 weeks, continuation treatment may provide no additional benefits. controlled-trials.com Identifier: ISRCTN65731856. © Copyright 2011 Physicians Postgraduate Press, Inc.

  7. Phase structure of the O(n) model on a random lattice for n > 2

    DEFF Research Database (Denmark)

    Durhuus, B.; Kristjansen, C.

    1997-01-01

    We show that coarse graining arguments invented for the analysis of multi-spin systems on a randomly triangulated surface apply also to the O(n) model on a random lattice. These arguments imply that if the model has a critical point with diverging string susceptibility, then either γ = +1...... by (γ̃, γ) = (-1/m, 1/m+1), m = 2, 3, . . . We also show that at the critical points with positive string susceptibility exponent the average number of loops on the surface diverges while the average length of a single loop stays finite....

  8. Least-squares reverse time migration of marine data with frequency-selection encoding

    KAUST Repository

    Dai, Wei

    2013-08-20

    The phase-encoding technique can sometimes increase the efficiency of the least-squares reverse time migration (LSRTM) by more than one order of magnitude. However, traditional random encoding functions require all the encoded shots to share the same receiver locations, thus limiting the usage to seismic surveys with a fixed spread geometry. We implement a frequency-selection encoding strategy that accommodates data with a marine streamer geometry. The encoding functions are delta functions in the frequency domain, so that all the en- coded shots have unique non-overlapping frequency content, and the receivers can distinguish the wavefield from each shot with a unique frequency band. Since the encoding functions are orthogonal to each other, there will be no crosstalk between different shots during modeling and migration. With the frequency-selection encoding method, the computational efficiency of LSRTM is increased so that its cost is compara- ble to conventional RTM for both the Marmousi2 model and a marine data set recorded in the Gulf of Mexico. With more iterations, the LSRTM image quality is further improved. We conclude that LSRTM with frequency-selection is an efficient migration method that can sometimes produce more focused images than conventional RTM.

  9. Quasi-Coherent Noise Jamming to LFM Radar Based on Pseudo-random Sequence Phase-modulation

    Directory of Open Access Journals (Sweden)

    N. Tai

    2015-12-01

    Full Text Available A novel quasi-coherent noise jamming method is proposed against linear frequency modulation (LFM signal and pulse compression radar. Based on the structure of digital radio frequency memory (DRFM, the jamming signal is acquired by the pseudo-random sequence phase-modulation of sampled radar signal. The characteristic of jamming signal in time domain and frequency domain is analyzed in detail. Results of ambiguity function indicate that the blanket jamming effect along the range direction will be formed when jamming signal passes through the matched filter. By flexible controlling the parameters of interrupted-sampling pulse and pseudo-random sequence, different covering distances and jamming effects will be achieved. When the jamming power is equivalent, this jamming obtains higher process gain compared with non-coherent jamming. The jamming signal enhances the detection threshold and the real target avoids being detected. Simulation results and circuit engineering implementation validate that the jamming signal covers real target effectively.

  10. Parenteral nutrition at the palliative phase of advanced cancer: the ALIM-K study protocol for a randomized controlled trial.

    Science.gov (United States)

    Pazart, Lionel; Cretin, Elodie; Grodard, Ghislain; Cornet, Cecile; Mathieu-Nicot, Florence; Bonnetain, Franck; Mercier, Mariette; Cuynet, Patrice; Bouleuc, Carole; Aubry, Regis

    2014-09-24

    Malnutrition is a common complication in patients at the palliative stage of cancer. During the curative phase of cancer, optimal enteral or parenteral nutrition intake can reduce morbidity and mortality, and improve quality of life. When the main goal of treatment becomes palliative, introduction of artificial nutrition is controversial. Although scientific societies do not recommend the introduction of artificial nutrition in all cases of malnutrition, especially in hypophagic patients if their life expectancy is shorter than 2 months, considerable differences in the use of parenteral nutrition in nonsurgical oncology practice are noted around the world. One explanation is a paucity of well-conducted randomized controlled trials in these situations, and consequently, the risk/benefit ratio of parenteral nutrition and its impact on quality of life in palliative care remains uncertain. The ALIM-K study is a French national multicenter randomized controlled trial designed to evaluate the effectiveness of parenteral nutrition, versus an exclusive oral-feeding supply, on the quality of life of malnourished patients who have a functional digestive tube and who are at the palliative phase of advanced cancer with a life expectancy of more than 2 months. This article presents the methodologic options chosen for our study, and in particular, the choice of the Zelen method of randomization, the definition of the main end point (quality of life), the choice of comparator (oral feeding), and the inclusion criteria (life expectancy of more than 2 months), which are all critical points in building a randomized controlled trial in the setting of palliative care. This study was registered with the clinical trials database ClinicalTrials.gov on May 27, 2014, under the number NCT02151214.

  11. Empirical forward scattering phase functions from 0.08 to 16 deg. for randomly shaped terrigenous 1-21 microm sediment grains.

    Science.gov (United States)

    Agrawal, Y C; Mikkelsen, Ole A

    2009-05-25

    We present in-water forward scattering phase functions covering the angle range 0.08 to 16 degrees for 19 narrow-sized dispersions of randomly shaped sediment grains. These dispersions cover particle size range from 1 to 20 microns. These phase functions offer a realistic alternative to Mie theory. Qualitatively, (i) the magnitude of phase functions at the smallest angles for equal size spheres and randomly shaped particles are nearly equal; (ii) the oscillations predicted by Mie theory for spheres disappear for random shaped grains, and (iii) the tendency of phase functions of large spheres to merge at large angles is also seen with randomly shaped grains. The data are also provided in tabulated form.

  12. Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: Crossover extension to a randomized, double-blind, Phase III study

    NARCIS (Netherlands)

    M.D. Bronstein (Marcello); Fleseriu, M. (Maria); S.J.C.M.M. Neggers (Bas); A. Colao (Annamaria); Sheppard, M. (Michael); Gu, F. (Feng); Shen, C.-C. (Chiung-Chyi); M.R. Gadelha (Mônica R.); Farrall, A.J. (Andrew J.); Reséndiz, K.H. (Karina Hermosillo); Ruffin, M. (Matthieu); Chen, Y. (YinMiao); P.U. Freda (Pamela)

    2016-01-01

    markdownabstractBackground Many patients with acromegaly do not achieve biochemical control with first-generation somatostatin analogues. A large, multicenter, randomized, Phase III core study demonstrated that pasireotide LAR had significantly superior efficacy over octreotide LAR. This analysis

  13. W-Band Millimeter-Wave Vector Signal Generation Based on Precoding-Assisted Random Photonic Frequency Tripling Scheme Enabled by Phase Modulator

    National Research Council Canada - National Science Library

    Li, Xinying; Xu, Yuming; Xiao, Jiangnan; Yu, Jianjun

    2016-01-01

    We propose W-band photonic millimeter-wave (mm-wave) vector signal generation employing a precoding-assisted random frequency tripling scheme enabled by a single phase modulator cascaded with a wavelength selective switch (WSS...

  14. Generalized optimal design for two-arm, randomized phase II clinical trials with endpoints from the exponential dispersion family.

    Science.gov (United States)

    Jiang, Wei; Mahnken, Jonathan D; He, Jianghua; Mayo, Matthew S

    2016-11-01

    For two-arm randomized phase II clinical trials, previous literature proposed an optimal design that minimizes the total sample sizes subject to multiple constraints on the standard errors of the estimated event rates and their difference. The original design is limited to trials with dichotomous endpoints. This paper extends the original approach to be applicable to phase II clinical trials with endpoints from the exponential dispersion family distributions. The proposed optimal design minimizes the total sample sizes needed to provide estimates of population means of both arms and their difference with pre-specified precision. Its applications on data from specific distribution families are discussed under multiple design considerations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Vernakalant hydrochloride for rapid conversion of atrial fibrillation - A phase 3, randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Roy, D.; Pratt, C.M.; Torp-Pedersen, C.

    2008-01-01

    .6%; P complete atrioventricular block, and cardiogenic shock) occurred in 3 patients. Conclusion - Vernakalant......Background - The present study assessed the efficacy and safety of vernakalant hydrochloride ( RSD1235), a novel compound, for the conversion of atrial fibrillation ( AF). Methods and Results - Patients were randomized in a 2: 1 ratio to receive vernakalant or placebo and were stratified by AF...... was conversion of AF to sinus rhythm for at least 1 minute within 90 minutes of the start of drug infusion in the short-duration AF group. A total of 336 patients were randomized and received treatment (short duration, n = 220; long duration, n = 116). Of the 145 vernakalant patients, 75 (51.7%) in the short...

  16. Phase I Randomized Safety Study of Twice Daily Dosing of Acidform Vaginal Gel: Candidate Antimicrobial Contraceptive

    OpenAIRE

    Keller, Marla J.; Carpenter, Colleen A.; Yungtai Lo; Einstein, Mark H.; Congzhou Liu; David N Fredricks; Herold, Betsy C.

    2012-01-01

    Background Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Methods Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety ...

  17. Phase-space diffusion in turbulent plasmas: The random acceleration problem revisited

    DEFF Research Database (Denmark)

    Pécseli, H.L.; Trulsen, J.

    1991-01-01

    Phase-space diffusion of test particles in turbulent plasmas is studied by an approach based on a conditional statistical analysis of fluctuating electrostatic fields. Analytical relations between relevant conditional averages and higher-order correlations, , and trip...

  18. Safety profile, efficacy, and biodistribution of a bicistronic high-capacity adenovirus vector encoding a combined immunostimulation and cytotoxic gene therapy as a prelude to a phase I clinical trial for glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Puntel, Mariana [Department of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689 (United States); Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689 (United States); Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Ghulam, Muhammad A.K.M. [Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Farrokhi, Catherine [Department of Psychiatry and Behavioral Neurosciences, Cedars Sinai Medical Center, Los Angeles, CA 90048 (United States); VanderVeen, Nathan; Paran, Christopher; Appelhans, Ashley [Department of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689 (United States); Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689 (United States); Kroeger, Kurt M.; Salem, Alireza [Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Lacayo, Liliana [Department of Psychiatry and Behavioral Neurosciences, Cedars Sinai Medical Center, Los Angeles, CA 90048 (United States); Pechnick, Robert N. [Department of Psychiatry and Behavioral Neurosciences, Cedars Sinai Medical Center, Los Angeles, CA 90048 (United States); Department of Psychiatry and Behavioral Neurosciences, David Geffen School of Medicine, University of California, Los Angeles, CA (United States); Kelson, Kyle R.; Kaur, Sukhpreet; Kennedy, Sean [Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Palmer, Donna; Ng, Philip [Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 (United States); and others

    2013-05-01

    Adenoviral vectors (Ads) are promising gene delivery vehicles due to their high transduction efficiency; however, their clinical usefulness has been hampered by their immunogenicity and the presence of anti-Ad immunity in humans. We reported the efficacy of a gene therapy approach for glioma consisting of intratumoral injection of Ads encoding conditionally cytotoxic herpes simplex type 1 thymidine kinase (Ad-TK) and the immunostimulatory cytokine fms-like tyrosine kinase ligand 3 (Ad-Flt3L). Herein, we report the biodistribution, efficacy, and neurological and systemic effects of a bicistronic high-capacity Ad, i.e., HC-Ad-TK/TetOn-Flt3L. HC-Ads elicit sustained transgene expression, even in the presence of anti-Ad immunity, and can encode large therapeutic cassettes, including regulatory elements to enable turning gene expression “on” or “off” according to clinical need. The inclusion of two therapeutic transgenes within a single vector enables a reduction of the total vector load without adversely impacting efficacy. Because clinically the vectors will be delivered into the surgical cavity, normal regions of the brain parenchyma are likely to be transduced. Thus, we assessed any potential toxicities elicited by escalating doses of HC-Ad-TK/TetOn-Flt3L (1 × 10{sup 8}, 1 × 10{sup 9}, or 1 × 10{sup 10} viral particles [vp]) delivered into the rat brain parenchyma. We assessed neuropathology, biodistribution, transgene expression, systemic toxicity, and behavioral impact at acute and chronic time points. The results indicate that doses up to 1 × 10{sup 9} vp of HC-Ad-TK/TetOn-Flt3L can be safely delivered into the normal rat brain and underpin further developments for its implementation in a phase I clinical trial for glioma. - Highlights: ► High capacity Ad vectors elicit sustained therapeutic gene expression in the brain. ► HC-Ad-TK/TetOn-Flt3L encodes two therapeutic genes and a transcriptional switch. ► We performed a dose escalation study at

  19. Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting.

    Science.gov (United States)

    Uc, Ergun Y; Doerschug, Kevin C; Magnotta, Vincent; Dawson, Jeffrey D; Thomsen, Teri R; Kline, Joel N; Rizzo, Matthew; Newman, Sara R; Mehta, Sonya; Grabowski, Thomas J; Bruss, Joel; Blanchette, Derek R; Anderson, Steven W; Voss, Michelle W; Kramer, Arthur F; Darling, Warren G

    2014-07-29

    To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting. Initial design was a 6-month, 2 × 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session. Randomization to group/facility setting was not feasible because of logistical factors. Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%-89.0%), exercising at 46.8% (44.0%-49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinson's Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition. © 2014 American Academy of Neurology.

  20. The gated integration technique for the accurate measurement of the autocorrelation function of speckle intensities scattered from random phase screens

    Science.gov (United States)

    Zhang, Ningyu; Cheng, Chuanfu; Teng, Shuyun; Chen, Xiaoyi; Xu, Zhizhan

    2007-09-01

    A new approach based on the gated integration technique is proposed for the accurate measurement of the autocorrelation function of speckle intensities scattered from a random phase screen. The Boxcar used for this technique in the acquisition of the speckle intensity data integrates the photoelectric signal during its sampling gate open, and it repeats the sampling by a preset number, m. The average analog of the m samplings output by the Boxcar enhances the signal-to-noise ratio by √{m}, because the repeated sampling and the average make the useful speckle signals stable, while the randomly varied photoelectric noise is suppressed by 1/√{m}. In the experiment, we use an analog-to-digital converter module to synchronize all the actions such as the stepped movement of the phase screen, the repeated sampling, the readout of the averaged output of the Boxcar, etc. The experimental results show that speckle signals are better recovered from contaminated signals, and the autocorrelation function with the secondary maximum is obtained, indicating that the accuracy of the measurement of the autocorrelation function is greatly improved by the gated integration technique.

  1. Electric dipole strength and dipole polarizability in 48Ca within a fully self-consistent second random-phase approximation

    Science.gov (United States)

    Gambacurta, D.; Grasso, M.; Vasseur, O.

    2018-02-01

    The second random-phase-approximation model corrected by a subtraction procedure designed to cure double counting, instabilities, and ultraviolet divergences, is employed for the first time to analyze the dipole strength and polarizability in 48Ca. All the terms of the residual interaction are included, leading to a fully self-consistent scheme. Results are illustrated with two Skyrme parametrizations, SGII and SLy4. Those obtained with the SGII interaction are particularly satisfactory. In this case, the low-lying strength below the neutron threshold is well reproduced and the giant dipole resonance is described in a very satisfactory way especially in its spreading and fragmentation. Spreading and fragmentation are produced in a natural way within such a theoretical model by the coupling of 1 particle-1 hole and 2 particle-2 hole configurations. Owing to this feature, we may provide for the electric polarizability as a function of the excitation energy a curve with a similar slope around the centroid energy of the giant resonance compared to the corresponding experimental results. This represents a considerable improvement with respect to previous theoretical predictions obtained with the random-phase approximation or with several ab-initio models. In such cases, the spreading width of the excitation cannot be reproduced and the polarizability as a function of the excitation energy displays a stiff increase around the predicted centroid energy of the giant resonance.

  2. A phase-synchronization and random-matrix based approach to multichannel time-series analysis with application to epilepsy

    Science.gov (United States)

    Osorio, Ivan; Lai, Ying-Cheng

    2011-09-01

    We present a general method to analyze multichannel time series that are becoming increasingly common in many areas of science and engineering. Of particular interest is the degree of synchrony among various channels, motivated by the recognition that characterization of synchrony in a system consisting of many interacting components can provide insights into its fundamental dynamics. Often such a system is complex, high-dimensional, nonlinear, nonstationary, and noisy, rendering unlikely complete synchronization in which the dynamical variables from individual components approach each other asymptotically. Nonetheless, a weaker type of synchrony that lasts for a finite amount of time, namely, phase synchronization, can be expected. Our idea is to calculate the average phase-synchronization times from all available pairs of channels and then to construct a matrix. Due to nonlinearity and stochasticity, the matrix is effectively random. Moreover, since the diagonal elements of the matrix can be arbitrarily large, the matrix can be singular. To overcome this difficulty, we develop a random-matrix based criterion for proper choosing of the diagonal matrix elements. Monitoring of the eigenvalues and the determinant provides a powerful way to assess changes in synchrony. The method is tested using a prototype nonstationary noisy dynamical system, electroencephalogram (scalp) data from absence seizures for which enhanced cortico-thalamic synchrony is presumed, and electrocorticogram (intracranial) data from subjects having partial seizures with secondary generalization for which enhanced local synchrony is similarly presumed.

  3. "HEATPAC" - a phase II randomized study of concurrent thermochemoradiotherapy versus chemoradiotherapy alone in locally advanced pancreatic cancer.

    Science.gov (United States)

    Datta, Niloy Ranjan; Pestalozzi, Bernhard; Clavien, Pierre-Alain; Siebenhüner, Alexander; Puric, Emsad; Khan, Shaka; Mamot, Christoph; Riesterer, Oliver; Knuchel, Jürg; Reiner, Cäcilia Sophie; Bodis, Stephan

    2017-11-21

    Pancreatic cancer has a dismal prognosis with 5-year overall survival rate of around 5%. Although surgery is still the best option in operable cases, majority of the patients who present in locally advanced stages are deemed inoperable. Novel approaches are therefore needed for the management of around 80% of these inoperable locally advanced pancreatic cancers (LAPC). Hyperthermia (39-43 °C) is a potent radiosensitizer and further enhances the action of gemcitabine, also a known radiosensitizer. Thus through triple sensitization, a combination of hyperthermia, radiotherapy and gemcitabine could be expected to improve the therapeutic outcomes in LAPC. This phase II randomized trial, HEATPAC in unresectable LAPC, explores the feasibility and efficacy of concurrent thermochemoradiotherapy (HTCTRT) over chemoradiotherapy (CTRT) alone with pre- and post-intervention FOLFIRINOX at standard dosage and schedule. Following 4 cycles of neoadjuvant FOLFIRINOX, patients with no metastasis and absence of gross peritoneal carcinomatosis would be randomized to either (a) control arm: concurrent CTRT with gemcitabine (400 mg/m2, weekly ×6) or (b) study arm: locoregional hyperthermia (weekly ×6 during radiotherapy) with concurrent CTRT (same as in control arm). All patients would receive simultaneous-integrated boost intensity-modulated radiation therapy to doses of 56Gy and 50.4Gy to the gross and clinical target volumes respectively delivered in 28 fractions over 5.5 weeks. Deep locoregional hyperthermia would be administered weekly and monitored with real-time intraduodenal multisensor thermometry probe. A temperature of 40-43 °C for 60 min would be aimed for each hyperthermia session. On completion of CTRT/HTCTRT, patients of both groups would receive an additional 8 cycles of FOLFIRINOX. The expected 1-year baseline overall survival with CTRT alone is considered as 40%. With HTCTRT, a survival advantage of +20% is expected. Considering α = 0.05 and β = 0

  4. Efficacy of dignity therapy on depression and anxiety in Portuguese terminally ill patients: a phase II randomized controlled trial.

    Science.gov (United States)

    Julião, Miguel; Oliveira, Fátima; Nunes, Baltazar; Vaz Carneiro, António; Barbosa, António

    2014-06-01

    Dignity therapy is a brief psychotherapy developed for patients living with a life-limiting illness. To determine the influence of dignity therapy on depression and anxiety in inpatients with a terminal illness and experiencing a high level of distress in a palliative care unit. A nonblinded phase II randomized controlled trial of 80 patients who were randomly assigned to one of two groups: intervention group (dignity therapy+standard palliative care [SPC]) or control group (SPC alone). The main outcomes were depression and anxiety scores, as measured with the Hospital Anxiety and Depression Scale, and assessed at baseline (T1), day 4 (T2), day 15 (T3), and day 30 (T4) of follow-up. This study is registered with www.controlled-trials.com/ISRCTN34354086. Of the final 80 participants, 41 were randomly assigned to SPC and 39 to dignity therapy. Baseline characteristics were similar between the two groups. Dignity therapy was associated with a decrease in depression scores (median, 95% confidence interval [CI]: -4.00, -6.00 to -2.00, pdepression and anxiety symptoms in end-of-life care. The therapeutic benefit of dignity therapy was sustained over a 30-day period. Having established its efficacy, future trials of dignity therapy may now begin, comparing it with other psychotherapeutic approaches within the context of terminal illness.

  5. Safety and immunogenicity of the recombinant BCG vaccine VPM1002 in a phase 1 open-label randomized clinical trial.

    Science.gov (United States)

    Grode, Leander; Ganoza, Christian A; Brohm, Christiane; Weiner, January; Eisele, Bernd; Kaufmann, Stefan H E

    2013-02-18

    Current vaccination using Mycobacterium bovis bacillus Calmette-Guérin (BCG), fails to prevent pulmonary tuberculosis (TB). New vaccination strategies are essential for reducing the global incidence of TB. We assessed the safety and immunogenicity of VPM1002, a recombinant BCG vaccine candidate. EudraCT (2007-002789-37) and ClinicalTrials.gov (NCT00749034). Healthy volunteers were enrolled in a phase 1 open-label, dose escalation randomized clinical trial, and received one intradermal dose of VPM1002 (Mycobacterium bovis BCG ΔureC::hly Hm(R)) or BCG. Immunogenicity was assessed by interferon-gamma (IFN-γ) production, cellular immune response markers by flow cytometry and serum antibodies against mycobacterial antigens. Eighty volunteers were randomized into two groups according to previous BCG vaccination and mycobacterial exposure (BCG-naïve, n=40 and BCG-immune, n=40). In each group, 30 individuals were vaccinated with VPM1002 (randomized to three escalating doses) and 10 with BCG. VPM1002 was safe and stimulated IFN-γ-producing and multifunctional T cells, as well as antibody-producing B cells in BCG-naïve and BCG-immune individuals. VPM1002 was safe and immunogenic for B-cell and T-cell responses and hence will be brought forward through the clinical trial pipeline. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Phase IV: randomized controlled trial to evaluate lot consistency of trivalent split influenza vaccines in healthy adults.

    Science.gov (United States)

    Song, Joon Young; Cheong, Hee Jin; Lee, Jacob; Wie, Seong-Heon; Park, Kyung-Hwa; Kee, Sae Yoon; Jeong, Hye Won; Kim, Yeon-Sook; Noh, Ji Yun; Choi, Won Suk; Park, Dae Won; Sohn, Jang Wook; Kim, Woo Joo

    2014-01-01

    Influenza vaccines are the primary method for preventing influenza and its complications. Considering the increasing demand for influenza vaccines, vaccine manufacturers are required to establish large-scale production systems. This phase IV randomized trial was conducted to evaluate the lot consistency of trivalent split influenza vaccines regarding immunogenicity and safety. A total of 1,023 healthy adults aged 18-64 y were enrolled in the study. Subjects were randomly assigned in a 1:1 ratio to receive the GC FLU® Prefilled Syringe or the GC FLU® Injection, and they were further randomized to one of 3 lots of each vaccine in a 1:1:1 ratio. In both GC FLU® Injection and GC FLU® Prefilled Syringe groups, immune responses were equivalent between lots for each of the 3 vaccine strains on day 21. The 2-sided 95% CI of GMT ratios between pairs of lots were between 0.67 and 1.5, meeting the equivalence criteria. After vaccination, all 3 criteria of the European Medicines Agency were met in both GC FLU® Injection and GC FLU® Prefilled Syringe groups. The vaccines showed tolerable safety profiles without serious adverse events. The demonstration of lot consistency, robust immunogenic responses and favorable safety profiles support the reliability of mass-manufacturing systems for the GC FLU® Injection and GC FLU® Prefilled Syringe.

  7. Periodically driven random quantum spin chains: real-space renormalization for Floquet localized phases

    Science.gov (United States)

    Monthus, Cécile

    2017-07-01

    When random quantum spin chains are submitted to some periodic Floquet driving, the eigenstates of the time-evolution operator over one period can be localized in real space. For the case of periodic quenches between two Hamiltonians (or periodic kicks), where the time-evolution operator over one period reduces to the product of two simple transfer matrices, we propose a block-self-dual renormalization procedure to construct the localized eigenstates of the Floquet dynamics. We also discuss the corresponding strong disorder renormalization procedure, that generalizes the RSRG-X procedure to construct the localized eigenstates of time-independent Hamiltonians.

  8. Thermodynamics of Phase Transitions and Bipolar Filamentary Switching in Resistive Random-Access Memory

    Science.gov (United States)

    Karpov, V. G.; Niraula, D.; Karpov, I. V.; Kotlyar, R.

    2017-08-01

    We present a phenomenological theory of bipolar filamentary resistive random-access memory describing the commonly observed features of their current-voltage characteristics. Our approach follows the approach of a thermodynamic theory developed earlier for chalcogenide memory and threshold switches and largely independent of their microscopic details. It explains, without adjustable parameters, such features as the domains of filament formation and switching, voltage-independent current in set and current-independent voltage in reset regimes, the relation between the set and reset voltages, filament resistance independent of its length, etc. Furthermore, it expresses the observed features through the material and circuitry parameters, thus paving the way to device improvements.

  9. Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial.

    Science.gov (United States)

    Scheller, Christian; Wienke, Andreas; Tatagiba, Marcos; Gharabaghi, Alireza; Ramina, Kristofer F; Ganslandt, Oliver; Bischoff, Barbara; Zenk, Johannes; Engelhorn, Tobias; Matthies, Cordula; Westermaier, Thomas; Antoniadis, Gregor; Pedro, Maria Teresa; Rohde, Veit; von Eckardstein, Kajetan; Kretschmer, Thomas; Kornhuber, Malte; Steighardt, Jörg; Richter, Michael; Barker, Fred G; Strauss, Christian

    2016-03-01

    A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34-3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dose-dependent hypotension (p nimodipine can be recommended in VS surgery.

  10. Randomized phase II study of TJ-54 (Yokukansan) for postoperative delirium in gastrointestinal and lung malignancy patients.

    Science.gov (United States)

    Sugano, Nobuhiro; Aoyama, Toru; Sato, Tsutomu; Kamiya, Mariko; Amano, Shinya; Yamamoto, Naoto; Nagashima, Takuya; Ishikawa, Yoshihiro; Masudo, Katsuhiko; Taguri, Masataka; Yamanaka, Takeharu; Yamamoto, Yuji; Matsukawa, Hiroshi; Shiraisi, Ryuji; Oshima, Takashi; Yukawa, Norio; Rino, Yasushi; Masuda, Munetaka

    2017-10-01

    The present study evaluated the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies. Patients ≥70 years of age who underwent surgery for gastrointestinal or lung malignancy were eligible for participation in the study. The 186 eligible patients were randomly assigned at a 1:1 ratio to receive TJ-54 or control during their peri-operative care (between 7 days prior to surgery and 4 days following surgery, except for the operation day). The signs and symptoms of delirium were assessed using the Diagnostic and Statistical Manual of Mental Disorders-IV by the investigator during the peri-operative period. A total of 186 eligible gastrointestinal or lung malignancy patients were analyzed (93, TJ-54; 93, control). There were no marked differences between the two randomized groups. The incidence of delirium was 6.5% (6 patients) in the TJ-54 group and 9.7% (9 patients) in the control group, with no significant difference (P=0.419). However, of the patients categorized with a mini-mental state examination (MMSE) score of ≤26, the incidence of postoperative delirium was 9.1% in the TJ-54 group and 26.9% in the control group [risk ratio, 0.338; 95% confidence interval (0.078-1.462), P=0.115]. Treatment with TJ-54 reduced the incidence of postoperative delirium compared with the control group. Although TJ-54 did not demonstrate any contribution to preventing or treating postoperative delirium in patients following surgery for gastrointestinal or lung malignancy, TJ-54 reduced the risk of postoperative delirium in the patients who were classified as MMSE ≤26. Further phase III studies with a larger sample size are required in order to clarify the effects of TJ-54 against postoperative delirium.

  11. Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET: Study protocol for a randomized phase II trial

    Directory of Open Access Journals (Sweden)

    Palma David A

    2012-07-01

    Full Text Available Abstract Background Stereotactic ablative radiotherapy (SABR has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control. Survival outcomes for patients with oligometastatic disease treated with SABR appear promising, but conclusions are limited by patient selection, and the lack of adequate controls in most studies. The goal of this multicenter randomized phase II trial is to assess the impact of a comprehensive oligometastatic SABR treatment program on overall survival and quality of life in patients with up to 5 metastatic cancer lesions, compared to patients who receive standard of care treatment alone. Methods After stratification by the number of metastases (1-3 vs. 4-5, patients will be randomized between Arm 1: current standard of care treatment, and Arm 2: standard of care treatment + SABR to all sites of known disease. Patients will be randomized in a 1:2 ratio to Arm 1:Arm 2, respectively. For patients receiving SABR, radiotherapy dose and fractionation depends on the site of metastasis and the proximity to critical normal structures. This study aims to accrue a total of 99 patients within four years. The primary endpoint is overall survival, and secondary endpoints include quality of life, toxicity, progression-free survival, lesion control rate, and number of cycles of further chemotherapy/systemic therapy. Discussion This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with oligometastatic disease, and will inform the design of a possible phase III study. Trial registration Clinicaltrials.gov identifier: NCT01446744

  12. More evidence on additive antipsychotic effect of adjunctive mirtazapine in schizophrenia: an extension phase of a randomized controlled trial.

    Science.gov (United States)

    Terevnikov, Viacheslav; Stenberg, Jan-Henry; Joffe, Marina; Tiihonen, Jari; Burkin, Mark; Tchoukhine, Evgueni; Joffe, Grigori

    2010-08-01

    Adjunctive mirtazapine improved negative symptoms of schizophrenia in several studies. Recently, we found an improvement also in positive symptoms when mirtazapine was added to first generation antipsychotics (FGAs) in a 6 week randomized controlled trial (RCT). The short duration of that trial was its limitation. This study aimed to explore whether longer treatment is worthwhile. Completers of the RCT (n = 39) received open-label add-on mirtazapine for additional 6 weeks. The Positive and Negative Syndrome Scale (PANSS) total score (primary outcome) and several other clinical parameters were measured prospectively. During the open-label phase, significant improvement was achieved in all parameters, with an effect size of 0.94 (CI 95% = 0.45-1.43) on the primary outcome and an impressive additive antipsychotic effect. Patients who received mirtazapine during both phases demonstrated greater improvement in positive symptoms (29.6% versus 21.2%, p = 0.027) than those who received mirtazapine during open-label extension phase only. These findings support our previous data on the additive antipsychotic effect of mirtazapine in FGAs-treated schizophrenia. Mirtazapine may be effective in other symptom domains, too. Longer duration of mirtazapine treatment may yield additional benefits. If these results will be confirmed in larger studies, add-on mirtazapine may become a feasible option in difficult-to-treat schizophrenia. Copyright 2010 John Wiley & Sons, Ltd.

  13. Second harmonic generation in gallium phosphide microdisks on silicon: from strict \\bar{4} to random quasi-phase matching

    Science.gov (United States)

    Guillemé, P.; Dumeige, Y.; Stodolna, J.; Vallet, M.; Rohel, T.; Létoublon, A.; Cornet, C.; Ponchet, A.; Durand, O.; Léger, Y.

    2017-06-01

    The convergence of nonlinear optical devices and silicon photonics is a key milestone for the practical development of photonic integrated circuits. The associated technological issues often stem from material incompatibility. This is the case of second order nonlinear processes in monolithically integrated III-V semiconductor devices on silicon, where structural defects called antiphase domains strongly impact the optical properties of the material. We theoretically investigate the influence of antiphase domains on second harmonic generation in III-V whispering gallery mode microresonators on silicon and focus on the effects of the antiphase domains’ mean size (i.e. the correlation length of the distribution). We demonstrate that the domain distributions can have opposite effects depending on the nonlinear process under consideration: while antiphase domains negatively impact second harmonic generation under \\bar{4} quasi-phase matching conditions (independent of the correlation length), large conversion efficiencies can arise far from \\bar{4}-quasi-phase matching provided that the APD correlation length remains within an appropriate range, and is still compatible with the spontaneous emergence of such defects in the usual III-V on Si epilayers. Such a build-up can be explained by the occurrence of random quasi-phase matching in the system.

  14. Looking for phase transitions of strongly interacting matter applying new method on basic of Random Matrix Theory

    Energy Technology Data Exchange (ETDEWEB)

    Suleymanov, Mais [CIIT, Islamabad (Pakistan); Shahaliev, Ehtiram [HEPL, JINR, Dubna (Russian Federation)

    2009-07-01

    Over the last 25 years a lot of efforts have been made to search for new phases of strongly interacting matter. Heavy ion collisions are of great importance since they open a way to reproduce these phases in the Earth laboratory. But in this case the volume of information increases sharply as well as the background information. A method was introduced a method on the basic of Random Matrix Theory to study the fluctuations of neutron resonances in compound nuclei which doesn't depend on the background of measurements. To analyze the energetic levels of compound nuclei the function of distances between two energetic levels p(s{sub i}) is defined as the general distributions for probability of all kinds of ensembles. At values of the index of universality {nu}=0 it will change to Poisson type distributions pointing to absence of any correlations in the system and at the values of {nu}=1 it will change to Wigner type behavior directing to some correlation in the studying ensemble. We discuss that the experimental study of the behavior of p(s{sub i}) distribution for secondary particles could give a signal on the phase transitions.

  15. A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children

    DEFF Research Database (Denmark)

    Bélard, Sabine; Issifou, Saadou; Hounkpatin, Aurore B

    2011-01-01

    GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naïve European adults and one in malaria-exposed Gabonese ...... adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials....

  16. Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial.

    Science.gov (United States)

    Butchart, Joseph; Brook, Laura; Hopkins, Vivienne; Teeling, Jessica; Püntener, Ursula; Culliford, David; Sharples, Richard; Sharif, Saif; McFarlane, Brady; Raybould, Rachel; Thomas, Rhodri; Passmore, Peter; Perry, V Hugh; Holmes, Clive

    2015-05-26

    To determine whether the tumor necrosis factor α inhibitor etanercept is well tolerated and obtain preliminary data on its safety in Alzheimer disease dementia. In a double-blind study, patients with mild to moderate Alzheimer disease dementia were randomized (1:1) to subcutaneous etanercept (50 mg) once weekly or identical placebo over a 24-week period. Tolerability and safety of this medication was recorded including secondary outcomes of cognition, global function, behavior, and systemic cytokine levels at baseline, 12 weeks, 24 weeks, and following a 4-week washout period. This trial is registered with EudraCT (2009-013400-31) and ClinicalTrials.gov (NCT01068353). Forty-one participants (mean age 72.4 years; 61% men) were randomized to etanercept (n = 20) or placebo (n = 21). Etanercept was well tolerated; 90% of participants (18/20) completed the study compared with 71% (15/21) in the placebo group. Although infections were more common in the etanercept group, there were no serious adverse events or new safety concerns. While there were some interesting trends that favored etanercept, there were no statistically significant changes in cognition, behavior, or global function. This study showed that subcutaneous etanercept (50 mg/wk) was well tolerated in this small group of patients with Alzheimer disease dementia, but a larger more heterogeneous group needs to be tested before recommending its use for broader groups of patients. This study shows Class I evidence that weekly subcutaneous etanercept is well tolerated in Alzheimer disease dementia. © 2015 American Academy of Neurology.

  17. A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy.

    Science.gov (United States)

    Victor, Ronald G; Sweeney, H Lee; Finkel, Richard; McDonald, Craig M; Byrne, Barry; Eagle, Michelle; Goemans, Nathalie; Vandenborne, Krista; Dubrovsky, Alberto L; Topaloglu, Haluk; Miceli, M Carrie; Furlong, Pat; Landry, John; Elashoff, Robert; Cox, David

    2017-10-24

    To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD). Three hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg·kg(-1)·d(-1), tadalafil 0.6 mg·kg(-1)·d(-1), or placebo. The primary efficacy measure was 6-minute walk distance (6MWD) after 48 weeks. Secondary efficacy measures included North Star Ambulatory Assessment and timed function tests. Performance of Upper Limb (PUL) was a prespecified exploratory outcome. Tadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 ± 9.3 m with placebo, 64.7 ± 9.8 m with low-dose tadalafil (p = 0.307 vs placebo), and 59.1 ± 9.4 m with high-dose tadalafil (p = 0.538 vs placebo). Tadalafil also had no effect on secondary outcomes. In boys >10 years of age, total PUL score and shoulder subscore declined less with low-dose tadalafil than placebo. Adverse events were consistent with the known safety profile of tadalafil and the DMD disease state. Tadalafil did not lessen the decline in ambulatory ability in boys with DMD. Further studies should be considered to confirm the hypothesis-generating upper limb data and to determine whether ambulatory decline can be slowed by initiation of tadalafil before 7 years of age. NCT01865084. This study provides Class I evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old boys with Duchenne muscular dystrophy. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  18. Induction chemotherapy before chemoradiotherapy and surgery for locally advanced rectal cancer. Is it time for a randomized phase III trial?

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, Claus [Frankfurt Univ. (Germany). Klinik fuer Strahlentherapie und Onkologie; Arnold, Dirk [Halle Univ. (Germany). Klinik und Poliklinik fuer Innere Medizin IV; Becker, Heinz; Ghadimi, Michael; Liersch, Torsten [Goettingen Univ. (Germany). Klinik fuer Allgemein- und Visceralchirurgie; Fietkau, Rainer; Sauer, Rolf [Erlangen Univ. (Germany). Strahlenklinik; Graeven, Ullrich [Kliniken Maria Hilf GmbH, Moenchengladbach (Germany). Klinik fuer Haematologie, Onkologie und Gastroenterologie; Hess, Clemens [Goettingen Univ. (Germany). Klinik fuer Strahlentherapie und Radioonkologie; Hofheinz, Ralf [Universitaetsmedizin Mannheim (Germany). III. Medizinische Klinik Haematologie und Internistische Onkologie; Hohenberger, Werner [Erlangen Univ. (Germany). Chirurgische Klinik; Post, Stefan [Universitaetsmedizin Mannheim (Germany). Chirurgische Klinik; Raab, Rudolf [Klinikum Oldenburg (Germany). Klinik fuer Allgemein- und Visceralchirurgie; Wenz, Frederick [Universitaetsmedizin Mannheim (Germany). Klinik fuer Strahlentherapie und Radioonkologie

    2010-12-15

    Background: In the era of preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), the development of distant metastases is the predominant mode of failure in rectal cancer patients today. Integrating more effective systemic therapy into combined modality programs is the challenge. The question that needs to be addressed is how and when to apply systemic treatment with adequate dose and intensity. Material and Methods: This review article focuses on phase II-III trials designed to improve 5-fluorouracil (5-FU)-based combined modality treatment for rectal cancer patients through the inclusion of concurrent, adjuvant or, most recently, induction combination chemotherapy. Computerized bibliographic searches of PubMed were supplemented with hand searches of reference lists and abstracts of ASCO/ASTRO/ESTRO meetings. Results: After preoperative CRT and surgical resection, approximately one third of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients' refusal, or investigator's discretion. In order to be able to apply chemotherapy with sufficient dose and intensity, an innovative approach is to deliver systemic therapy prior to preoperative CRT rather than adjuvant chemotherapy. Emerging evidence from several phase II trials and, recently, randomized phase II trials indicate that induction chemotherapy is feasible, does not compromise CRT or surgical resection, and enables the delivery of chemotherapy in adequate dose and intensity. Although this approach did not increase local efficacy in recent trials (e.g., pathological complete response rates, tumor regression, R0 resection rates, local control), it may help to improve control of distant disease. Conclusion: Whether this improvement in applicability and dose density of chemotherapy will ultimately translate into improved disease-free survival will have to be tested in a larger phase III trial. (orig.)

  19. Teriflunomide added to interferon-β in relapsing multiple sclerosis: a randomized phase II trial.

    Science.gov (United States)

    Freedman, M S; Wolinsky, J S; Wamil, B; Confavreux, C; Comi, G; Kappos, L; Olsson, T P; Miller, A; Benzerdjeb, H; Li, H; Simonson, C; O'Connor, P W

    2012-06-05

    To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-β (IFNβ) in patients with relapsing forms of multiple sclerosis (RMS). A total of 118 patients with RMS were randomly assigned 1:1:1 to receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86 patients entered the 24-week extension. The primary objective was to evaluate safety; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate. Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%, 8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively. The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both teriflunomide groups, with relative risk reductions (RRRs) of 84.6% (p = 0.0005) and 82.8% (p Teriflunomide as add-on therapy to IFNβ had acceptable safety and tolerability and reduced MRI disease activity compared with IFNβ alone. This study provides Class II evidence that teriflunomide, 7 and 14 mg, added to IFNβ, is safe. The T1-Gd lesion burden was significantly reduced with both teriflunomide doses.

  20. Randomized Phase II trial of nintedanib, afatinib and sequential combination in castration-resistant prostate cancer.

    Science.gov (United States)

    Molife, L Rhoda; Omlin, Aurelius; Jones, Rob J; Karavasilis, Vasilios; Bloomfield, David; Lumsden, Graeme; Fong, Peter C; Olmos, David; O'Sullivan, Joe M; Pedley, Ian; Hickish, Tamas; Jenkins, Peter; Thompson, Emilda; Oommen, Nikhil; Wheatley, Duncan; Heath, Catherine; Temple, Graham; Pelling, Katy; de Bono, Johann S

    2014-02-01

    The aim of this article was to evaluate afatinib (BIBW 2992), an ErbB family blocker, and nintedanib (BIBF 1120), a triple angiokinase inhibitor, in castration-resistant prostate cancer patients. Patients were randomized to receive nintedanib (250 mg twice daily), afatinib (40 mg once daily [q.d.]), or alternating sequential 7-day nintedanib (250 mg twice daily) and afatinib (70 mg q.d. [Combi70]), which was reduced to 40 mg q.d. (Combi40) due to adverse events. The primary end point was progression-free rate at 12 weeks. Of the 85 patients treated 46, 20, 16 and three received nintedanib, afatinib, Combi40 and Combi70, respectively. At 12 weeks, the progression-free rate was 26% (seven out of 27 patients) for nintedanib, and 0% for afatinib and Combi40 groups. Two patients had a ≥50% decline in PSA (nintedanib and the Combi40 groups). The most common drug-related adverse events were diarrhea, nausea, vomiting and lethargy. Nintedanib and/or afatinib demonstrated limited anti-tumor activity in unselected advanced castration-resistant prostate cancer patients.

  1. NOGA-guided analysis of regional myocardial perfusion abnormalities treated with intramyocardial injections of plasmid encoding vascular endothelial growth factor A-165 in patients with chronic myocardial ischemia: subanalysis of the EUROINJECT-ONE multicenter double-blind randomized study.

    Science.gov (United States)

    Gyöngyösi, Mariann; Khorsand, Aliasghar; Zamini, Sholeh; Sperker, Wolfgang; Strehblow, Christoph; Kastrup, Jens; Jorgensen, Eric; Hesse, Birger; Tägil, Kristina; Bøtker, Hans Erik; Ruzyllo, Witold; Teresiñska, Anna; Dudek, Dariusz; Hubalewska, Alicja; Rück, Andreas; Nielsen, Søren Steen; Graf, Senta; Mundigler, Gerald; Novak, Jacek; Sochor, Heinz; Maurer, Gerald; Glogar, Dietmar; Sylven, Christer

    2005-08-30

    The aim of this substudy of the EUROINJECT-ONE double-blind randomized trial was to analyze changes in myocardial perfusion in NOGA-defined regions with intramyocardial injections of plasmid encoding plasmid human (ph)VEGF-A(165) using an elaborated transformation algorithm. After randomization, 80 no-option patients received either active, phVEGF-A165 (n=40), or placebo plasmid (n=40) percutaneously via NOGA-Myostar injections. The injected area (region of interest, ROI) was delineated as a best polygon by connecting of the injection points marked on NOGA polar maps. The ROI was projected onto the baseline and follow-up rest and stress polar maps of the 99m-Tc-sestamibi/tetrofosmin single-photon emission computed tomography scintigraphy calculating the extent and severity (expressed as the mean normalized tracer uptake) of the ROI automatically. The extents of the ROI were similar in the VEGF and placebo groups (19.4+/-4.2% versus 21.5+/-5.4% of entire myocardium). No differences were found between VEGF and placebo groups at baseline with regard to the perfusion defect severity (rest: 69+/-11.7% versus 68.7+/-13.3%; stress: 63+/-13.3% versus 62.6+/-13.6%; and reversibility: 6.0+/-7.7% versus 6.7+/-9.0%). At follow-up, a trend toward improvement in perfusion defect severity at stress was observed in VEGF group as compared with placebo (68.5+/-11.9% versus 62.5+/-13.5%, P=0.072) without reaching normal values. The reversibility of the ROI decreased significantly at follow-up in VEGF group as compared with the placebo group (1.2+/-9.0% versus 7.1+/-9.0%, P=0.016). Twenty-one patients in VEGF and 8 patients in placebo group (Por =5% increase in the normalized tracer uptake of the ROI. Projection of the NOGA-guided injection area onto the single-photon emission computed tomography polar maps permits quantitative evaluation of myocardial perfusion in regions treated with angiogenic substances. Injections of phVEGF A165 plasmid improve, but do not normalize, the stress

  2. Spin {ital M}1 excitations in deformed nuclei from self-consistent Hartree-Fock plus random-phase approximation

    Energy Technology Data Exchange (ETDEWEB)

    Sarriguren, P.; Moya de Guerra, E.; Nojarov, R. [Instituto de Estructura de la Materia, Consejo Superior de Investigaciones Cientificas, Serrano 119, E-28006 Madrid (Spain)

    1996-08-01

    We present a method to study spin magnetic dipole excitations in deformed nuclei within the quasiparticle random phase approximation based on self-consistent Hartree-Fock mean fields and residual interactions derived from the same effective two-body force. We perform a comprehensive study covering different Skyrme forces and various mass regions, and discussing the role of the mean field and of the residual interaction. An overall agreement with experimental data is obtained with the SG2 force. We study the systematics and the deformation dependence of the spin {ital M}1 strength distributions of {ital K}{sup {pi}}=1{sup +} excitations. It is found for the first time that the summed spin {ital M}1 strength obeys a quadratic dependence on deformation in the two isotope chains studied, {sup 142,146,148,150}Nd and {sup 144,148,150,152,154}Sm. {copyright} {ital 1996 The American Physical Society.}

  3. Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial

    DEFF Research Database (Denmark)

    Ravaud, Alain; Hawkins, Robert; Gardner, Jason P

    2008-01-01

    of metastatic sites--were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses. RESULTS: Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks......PURPOSE: Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib...... was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2. PATIENTS AND METHODS: Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy--stratified by Karnofsky performance status and number...

  4. Factors associated with publication of randomized phase iii cancer trials in journals with a high impact factor.

    Science.gov (United States)

    Tang, P A; Pond, G R; Welch, S; Chen, E X

    2014-08-01

    Impact factor (if) is often used as a measure of journal quality. The purpose of the present study was to determine whether trials with positive outcomes are more likely to be published in journals with higher ifs. We reviewed 476 randomized phase iii cancer trials published in 13 journals between 1995 and 2005. Multivariate logistic regression models were used to investigate predictors of publication in journals with high ifs (compared with low and medium ifs). A positive outcome had the strongest association with publication in high-if journals [odds ratio (or): 4.13; 95% confidence interval (ci): 2.67 to 6.37; p impact factor bias," and investigators should be encouraged to submit reports of trials of high methodologic quality to journals with high ifs regardless of study outcomes.

  5. Application of an extended random-phase approximation to giant resonances in light-, medium-, and heavy-mass nuclei

    Science.gov (United States)

    Tselyaev, V.; Lyutorovich, N.; Speth, J.; Krewald, S.; Reinhard, P.-G.

    2016-09-01

    We present results of the time blocking approximation (TBA) for giant resonances in light-, medium-, and heavy-mass nuclei. The TBA is an extension of the widely used random-phase approximation (RPA) adding complex configurations by coupling to phonon excitations. A new method for handling the single-particle continuum is developed and applied in the present calculations. We investigate in detail the dependence of the numerical results on the size of the single-particle space and the number of phonons as well as on nuclear matter properties. Our approach is self-consistent, based on an energy-density functional of Skyrme type where we used seven different parameter sets. The numerical results are compared with experimental data.

  6. Double, Rydberg and charge transfer excitations from pairing matrix fluctuation and particle-particle random phase approximation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yang [Department of Chemistry, Duke University, Durham, North Carolina 27708 (United States); Aggelen, Helen van [Department of Chemistry, Duke University, Durham, North Carolina 27708 (United States); Department of Inorganic and Physical Chemistry, Ghent University, 9000 Ghent (Belgium); Yang, Weitao, E-mail: weitao.yang@duke.edu [Department of Chemistry and Department of Physics, Duke University, Durham, North Carolina 27708 (United States)

    2013-12-14

    Double, Rydberg, and charge transfer (CT) excitations have been great challenges for time-dependent density functional theory (TDDFT). Starting from an (N ± 2)-electron single-determinant reference, we investigate excitations for the N-electron system through the pairing matrix fluctuation, which contains information on two-electron addition/removal processes. We adopt the particle-particle random phase approximation (pp-RPA) and the particle-particle Tamm-Dancoff approximation (pp-TDA) to approximate the pairing matrix fluctuation and then determine excitation energies by the differences of two-electron addition/removal energies. This approach captures all types of interesting excitations: single and double excitations are described accurately, Rydberg excitations are in good agreement with experimental data and CT excitations display correct 1/R dependence. Furthermore, the pp-RPA and the pp-TDA have a computational cost similar to TDDFT and consequently are promising for practical calculations.

  7. Hubbard-U corrected Hamiltonians for non-self-consistent random-phase approximation total-energy calculations

    DEFF Research Database (Denmark)

    Patrick, Christopher; Thygesen, Kristian Sommer

    2016-01-01

    In non-self-consistent calculations of the total energy within the random-phase approximation (RPA) for electronic correlation, it is necessary to choose a single-particle Hamiltonian whose solutions are used to construct the electronic density and noninteracting response function. Here we...... investigate the effect of including a Hubbard-U term in this single-particle Hamiltonian, to better describe the on-site correlation of 3d electrons in the transitionmetal compounds ZnS, TiO2, and NiO.We find that the RPA lattice constants are essentially independent of U, despite large changes...... and qualitatively different from that found from calculations employingU-corrected (semi)local functionals.However we also find that the+U term cannot be used to correct the RPA’s poor description of the heat of formation of NiO....

  8. A block variational procedure for the iterative diagonalization of non-Hermitian random-phase approximation matrices.

    Science.gov (United States)

    Rocca, Dario; Bai, Zhaojun; Li, Ren-Cang; Galli, Giulia

    2012-01-21

    We present a technique for the iterative diagonalization of random-phase approximation (RPA) matrices, which are encountered in the framework of time-dependent density-functional theory (TDDFT) and the Bethe-Salpeter equation. The non-Hermitian character of these matrices does not permit a straightforward application of standard iterative techniques used, i.e., for the diagonalization of ground state Hamiltonians. We first introduce a new block variational principle for RPA matrices. We then develop an algorithm for the simultaneous calculation of multiple eigenvalues and eigenvectors, with convergence and stability properties similar to techniques used to iteratively diagonalize Hermitian matrices. The algorithm is validated for simple systems (Na(2) and Na(4)) and then used to compute multiple low-lying TDDFT excitation energies of the benzene molecule. © 2012 American Institute of Physics

  9. Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

    Directory of Open Access Journals (Sweden)

    Dietlind L. Wahner-Roedler

    2011-01-01

    Full Text Available Most patients with fibromyalgia use complementary and alternative medicine (CAM. Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ and the Center for Epidemiologic Studies Depression Scale (CES-D at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02 and by 18% in the placebo group (P < .001. The difference in change in scores between the groups was not significant (P = .16. With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004 and in the placebo group by 15% (P = .05. The change in scores was similar in the groups (P = .83. Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated.

  10. Self-consistent random phase approximation - application to systems of strongly correlated fermions; Approximation des phases aleatoires self-consistante - applications a des systemes de fermions fortement correles

    Energy Technology Data Exchange (ETDEWEB)

    Jemai, M

    2004-07-01

    In the present thesis we have applied the self consistent random phase approximation (SCRPA) to the Hubbard model with a small number of sites (a chain of 2, 4, 6,... sites). Earlier SCRPA had produced very good results in other models like the pairing model of Richardson. It was therefore interesting to see what kind of results the method is able to produce in the case of a more complex model like the Hubbard model. To our great satisfaction the case of two sites with two electrons (half-filling) is solved exactly by the SCRPA. This may seem a little trivial but the fact is that other respectable approximations like 'GW' or the approach with the Gutzwiller wave function yield results still far from exact. With this promising starting point, the case of 6 sites at half filling was considered next. For that case, evidently, SCRPA does not any longer give exact results. However, they are still excellent for a wide range of values of the coupling constant U, covering for instance the phase transition region towards a state with non zero magnetisation. We consider this as a good success of the theory. Non the less the case of 4 sites (a plaquette), as indeed all cases with 4n sites at half filling, turned out to have a problem because of degeneracies at the Hartree Fock level. A generalisation of the present method, including in addition to the pairs, quadruples of Fermions operators (called second RPA) is proposed to also include exactly the plaquette case in our approach. This is therefore a very interesting perspective of the present work. (author)

  11. A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia.

    Science.gov (United States)

    Kuriakose, Moni Abraham; Ramdas, Kunnambath; Dey, Bindu; Iyer, Subramanya; Rajan, Gunaseelan; Elango, Kalavathy K; Suresh, Amritha; Ravindran, Divya; Kumar, Rajneesh R; R, Prathiba; Ramachandran, Surya; Kumar, Nisha Asok; Thomas, Gigi; Somanathan, Thara; Ravindran, Hiran K; Ranganathan, Kannan; Katakam, Sudhakar Babu; Parashuram, Shivashankar; Jayaprakash, Vijayvel; Pillai, M Radhakrishna

    2016-08-01

    Oral leukoplakia is a potentially malignant lesion of the oral cavity, for which no effective treatment is available. We investigated the effectiveness of curcumin, a potent inhibitor of NF-κB/COX-2, molecules perturbed in oral carcinogenesis, to treat leukoplakia. Subjects with oral leukoplakia (n = 223) were randomized (1:1 ratio) to receive orally, either 3.6 g/day of curcumin (n = 111) or placebo (n = 112), for 6 months. The primary endpoint was clinical response obtained by bi-dimensional measurement of leukoplakia size at recruitment and 6 months. Histologic response, combined clinical and histologic response, durability and effect of long-term therapy for an additional six months in partial responders, safety and compliance were the secondary endpoints. Clinical response was observed in 75 (67.5%) subjects [95% confidence interval (CI), 58.4-75.6] in the curcumin and 62 (55.3%; 95% CI, 46.1-64.2) in placebo arm (P = 0.03). This response was durable, with 16 of the 18 (88.9%; 95% CI, 67.2-96.9) subjects with complete response in curcumin and 7 of 8 subjects (87.5%) in placebo arm, demonstrating no relapse after 6 months follow-up. Difference in histologic response between curcumin and placebo was not significant (HR, 0.88, 95% CI, 0.45-1.71; P = 0.71). Combined clinical and histologic response assessment indicated a significantly better response with curcumin (HR, 0.50; 95% CI, 0.27-0.92; P = 0.02). Continued therapy, in subjects with partial response at 6 months, did not yield additional benefit. The treatment did not raise any safety concerns. Treatment of oral leukoplakia with curcumin (3.6 g for six months), thus was well tolerated and demonstrated significant and durable clinical response for 6 months. Cancer Prev Res; 9(8); 683-91. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.

    Science.gov (United States)

    Delrieu, Isabelle; Leboulleux, Didier; Ivinson, Karen; Gessner, Bradford D

    2015-03-24

    Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer: A Phase II Open Label Prospective Randomized Controlled Trial.

    Science.gov (United States)

    Kim, Min Jung; Park, Sung Chan; Park, Ji Won; Chang, Hee Jin; Kim, Dae Yong; Nam, Byung-Ho; Sohn, Dae Kyung; Oh, Jae Hwan

    2018-02-01

    The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer. The feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet. Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life. A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03). Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.

  14. Does magnesium sulfate delay the active phase of labor in women with premature rupture of membranes? A randomized controlled trial.

    Science.gov (United States)

    Mirzamoradi, Masoumeh; Behnam, Marzieh; Jahed, Tayebeh; Saleh-Gargari, Soraya; Bakhtiyari, Mahmood

    2014-09-01

    Administration of many drugs including magnesium sulfate (MS) has considerable influences on pregnancy outcomes. The present study investigates the effects of MS administration on reaching the active phase of labor in women with premature rupture of membrane (PROM) and subsequent fetal complications. A double blind, randomized, placebo-controlled trial was performed among primipara women referred to the PROM center in Tehran, Iran between March 2010 and August 2012. Patients were equally allocated into two groups; the intervention group who received MS (n = 46) and the control (placebo) group (n = 46). Both groups received a corticosteroid, 1g oral azithromycin (oral) and 2 g ampicillin (IV) every 6 hours for 48 hours, followed by amoxicillin (500 mg orally 3 times daily) for an additional 5 days. None of the research staff were aware of the treatment allocation of patients in order for blinding purposes. Administration of MS in intervention group increases this period 2.7 times compared to the control group. In women whose gestational age was magnesium sulfate reduced the risk of respiratory distress syndrome significantly (p = 0 .002), without producing any adverse pregnancy outcomes. Magnesium sulfate increases delay in reaching the active phase of labor in mothers with PROM, without producing adverse birth outcomes. (Registration ID in IRCT; IRCT2012091810876N1). Copyright © 2014. Published by Elsevier B.V.

  15. Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive.

    Directory of Open Access Journals (Sweden)

    Marla J Keller

    Full Text Available BACKGROUND: Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. METHODS: Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. RESULTS: The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002. While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra, an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08. CONCLUSIONS: Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than

  16. Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive.

    Science.gov (United States)

    Keller, Marla J; Carpenter, Colleen A; Lo, Yungtai; Einstein, Mark H; Liu, Congzhou; Fredricks, David N; Herold, Betsy C

    2012-01-01

    Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08). Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels of antimicrobial (lactoferrin) and anti

  17. Randomized phase II clinical trial of chemo-immunotherapy in advanced nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Eduardo Lasalvia-Prisco

    2008-09-01

    Full Text Available Eduardo Lasalvia-Prisco1,4, Emilio Garcia-Giralt2, Jesús Vázquez2,4, Marta Aghazarian4, Eduardo Lasalvia-Galante3,4, Joshemaria Larrañaga3,4, Gonzalo Spera31Interdoctors Medical Procedures, North Miami Beach, FL, USA; 2Centre De Cancérologie Hartmann, Neuilly Sur Seine, France; 3Interdoctors Medical Procedures, Montevideo, Uruguay; 4National Institute of Oncology, Montevideo, Uruguay (initial dataAbstract: The purpose of this study was to compare chemotherapy-naive patients with stage IV nonsmall cell lung cancer patients treated with chemotherapy or chemoimmunotherapy. We tested doxetacel plus cisplatinum as chemotherapy protocol. An immunomodulatory adjuvant system was added as chemoimmunotherapy to the previously mentioned protocol. This system contains three well-known and complementary conditioners of protective immune-responses: cyclophosphamide low-dose, granulocyte macrophage-colony stimulant factor and magnesium silicate granuloma. Eighty-eight patients were randomly assigned to receive every 3-weeks one of the treatments under comparison. Patients received four cycles of treatment unless disease progression or unacceptable toxicity was documented. The maximum follow-up was one year. In each arm, tumor response (rate, duration, median survival time, 1-year overall survival, safety, and immunity modifications were assessed. Immunity was evaluated by submitting peripheral blood mononuclear cells to laboratory tests for nonspecific immunity: a phytohemaglutinin-induced lymphocyte proliferation, b prevalence of T-Regulatory (CD4+CD25+ cells and for specific immunity: a lymphocyte proliferation induced by tumor-associated antigens (TAA contained in a previously described autologous thermostable hemoderivative. The difference (chemotherapy vs. chemoimmunotherapy in response rate induced by the two treatments (39.0% and 35.0% was not statistically significant. However, the response duration (22 and 31 weeks, the median survival time (32

  18. Survival Outcomes With Short-Course Radiation Therapy in Elderly Patients With Glioblastoma: Data From a Randomized Phase 3 Trial.

    Science.gov (United States)

    Guedes de Castro, Douglas; Matiello, Juliana; Roa, Wilson; Ghosh, Sunita; Kepka, Lucyna; Kumar, Narendra; Sinaika, Valery; Lomidze, Darejan; Hentati, Dalenda; Rosenblatt, Eduardo; Fidarova, Elena

    2017-07-15

    To perform a subset analysis of survival outcomes in elderly patients with glioblastoma from a randomized phase 3 trial comparing 2 short-course radiation therapy (RT) regimens in elderly and/or frail patients. The original trial population included elderly and/or frail patients with a diagnosis of glioblastoma. Patients joined the phase 3, randomized, multicenter, prospective, noninferiority trial; were assigned to 1 of 2 groups in a 1:1 ratio, either short-course RT (25 Gy in 5 fractions, arm 1) or commonly used RT (40 Gy in 15 fractions, arm 2); and were stratified by age (elderly and frail patients were defined as patients aged ≥65 years with KPS of 50%-70%; elderly and non-frail patients were defined as patients aged ≥65 years with KPS of 80%-100%); 61 of the 98 initial patients comprised the patient population, with 26 patients randomized to arm 1 and 35 to arm 2. In this unplanned analysis, the short-course RT results were not statistically significantly different from the results of commonly used RT in elderly patients. The median overall survival time was 6.8 months (95% confidence interval [CI], 4.5-9.1 months) in arm 1 and 6.2 months (95% CI, 4.7-7.7 months) in arm 2 (P=.936). The median progression-free survival time was 4.3 months (95% CI, 2.6-5.9 months) in arm 1 and 3.2 months (95% CI, 0.1-6.3 months) in arm 2 (P=.706). A short-course RT regimen of 25 Gy in 5 fractions is an acceptable treatment option for patients aged ≥65 years, mainly those with a poor performance status or contraindication to chemotherapy, which would be indicated in cases of methylated O6 methylguanine-DNA-methyltransferase promoter tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial.

    Directory of Open Access Journals (Sweden)

    Victoria K Snowdon

    2017-02-01

    Full Text Available Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2 is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1 and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension.To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v. infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d or terlipressin (single 2-mg i.v. bolus, and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow. Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the AKT

  20. Effects of acute methamphetamine on emotional memory formation in humans: encoding vs consolidation.

    Science.gov (United States)

    Ballard, Michael E; Weafer, Jessica; Gallo, David A; de Wit, Harriet

    2015-01-01

    Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH), administered either before (encoding phase) or immediately after (consolidation phase) study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60) were randomly assigned to either an encoding group (N = 29) or a consolidation group (N = 31). Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg) either 45 min before (encoding) or immediately after (consolidation) viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29) or adequate sleepers (6 or more hours; n = 31) prior to analyses. For adequate sleepers, METH (20 mg) administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative), compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies.

  1. Effects of acute methamphetamine on emotional memory formation in humans: encoding vs consolidation.

    Directory of Open Access Journals (Sweden)

    Michael E Ballard

    Full Text Available Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH, administered either before (encoding phase or immediately after (consolidation phase study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60 were randomly assigned to either an encoding group (N = 29 or a consolidation group (N = 31. Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg either 45 min before (encoding or immediately after (consolidation viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29 or adequate sleepers (6 or more hours; n = 31 prior to analyses. For adequate sleepers, METH (20 mg administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative, compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies.

  2. Effects of Acute Methamphetamine on Emotional Memory Formation in Humans: Encoding vs Consolidation

    Science.gov (United States)

    Ballard, Michael E.; Weafer, Jessica; Gallo, David A.; de Wit, Harriet

    2015-01-01

    Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH), administered either before (encoding phase) or immediately after (consolidation phase) study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60) were randomly assigned to either an encoding group (N = 29) or a consolidation group (N = 31). Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg) either 45 min before (encoding) or immediately after (consolidation) viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29) or adequate sleepers (6 or more hours; n = 31) prior to analyses. For adequate sleepers, METH (20 mg) administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative), compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies. PMID:25679982

  3. Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    Science.gov (United States)

    2013-09-01

    10-1-0699 TITLE: Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after...apoptosis. WT1 protein is highly expressed in malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a...this project is to conduct a multicenter, double-blinded, randomized trial comparing treatment with the WT-1 peptide vaccine + Montanide/GM-CSF to

  4. An encoding device and a method of encoding

    DEFF Research Database (Denmark)

    2012-01-01

    The present invention relates to an encoding device, such as an optical position encoder, for encoding input from an object, and a method for encoding input from an object, for determining a position of an object that interferes with light of the device. The encoding device comprises a light source...... in the area in the space and may interfere with the light, which interference may be encoded into a position or activation....

  5. Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment

    DEFF Research Database (Denmark)

    Johnsen, H E; Geisler, C; Juvonen, E

    2011-01-01

    SCF has been shown to synergize with G-CSF to mobilize CD34(+) PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with malignant lymphoma randomized to receive recombinant methionyl human SCF (ancestim, r-metHuSCF) in combination with recombinant...... and thrombocytopenia was documented in arm B. Third, 9/14 (64%) patients in arm A reached the target of 5 million CD34(+) cells/kg body weight (bw) compared with 13/15 (87%) in arm B. The results represent the first randomized trial of growth factor plus chemotherapy priming and indicate that a formal phase III trial...

  6. Survival benefit with capecitabine/docetaxel versus docetaxel alone: analysis of therapy in a randomized phase III trial.

    Science.gov (United States)

    Miles, David; Vukelja, Svetislava; Moiseyenko, Vladimir; Cervantes, Guadalupe; Mauriac, Louis; Van Hazel, Guy; Liu, Wing-Yiu; Ayoub, Jean-Pierre; O'Shaughnessy, Joyce A

    2004-10-01

    In a large phase III trial of 511 patients with anthracycline-pretreated advanced/metastatic breast cancer, capecitabine/docetaxel combination therapy was shown to have significantly superior efficacy compared with single-agent docetaxel, including superior progression-free and overall survival and objective response rate. An updated survival analysis with >/= 27 months follow-up shows that patients receiving combination therapy maintained significantly superior survival (hazard ratio [HR], 0.777 [95% CI, 0.645-0.942]; P < 0.01; median survival, 14.5 months vs. 11.5 months) compared with those receiving single-agent docetaxel. Following the failure of docetaxel monotherapy, 35% of patients did not receive additional cytotoxic chemotherapy. Among patients randomized to single-agent docetaxel, only those given poststudy single-agent capecitabine had significantly prolonged survival compared with those given any other poststudy chemotherapy (HR, 0.500; P = 0.0046; median survival, 21.0 months vs. 12.3 months, respectively). By contrast, poststudy vinorelbine-containing chemotherapy did not affect survival following progression on single-agent docetaxel compared with other poststudy chemotherapy regimens (HR, 1.014; P = 0.94; median survival, 13.5 months vs. 12.6 months, respectively). Among patients randomized to combination therapy, discontinuing docetaxel of capecitabine has a similar effect on survival (HR, 0.720; P = 0.20; median survival, 15.8 months vs. 18.3 months, respectively). Median survival was 18.3 months in patients who discontinued docetaxel and continued to receive capecitabine versus 15.8 months in patients who discontinued capecitabine and continued to receive docetaxel, with a trend toward improved survival in patients continuing to receive capecitabine. Although this is a retrospective analysis, these data suggest that the sequential administration of docetaxel followed by capecitabine is associated with prolonged survival in patients who are

  7. Pharmacokinetics of lacosamide and omeprazole coadministration in healthy volunteers: results from a phase I, randomized, crossover trial.

    Science.gov (United States)

    Cawello, Willi; Mueller-Voessing, Christa; Fichtner, Andreas

    2014-05-01

    The antiepileptic drug lacosamide has a low potential for drug-drug interactions, but is a substrate and moderate inhibitor of the cytochrome P450 (CYP) enzyme CYP2C19. This phase I, randomized, open-label, two-way crossover trial evaluated the pharmacokinetic effects of lacosamide and omeprazole coadministration. Healthy, White, male volunteers (n = 36) who were not poor metabolizers of CYP2C19 were randomized to treatment A (single-dose 40 mg omeprazole on days 1 and 8 together with 6 days of multiple-dose lacosamide [200-600 mg/day] on days 3-8) and treatment B (single doses of 300 mg lacosamide on days 1 and 8 with 7 days of 40 mg/day omeprazole on days 3-9) in pseudorandom order, separated by a ≥ 7-day washout period. Area under the concentration-time curve (AUC) and peak concentration (C(max)) were the primary pharmacokinetic parameters measured for lacosamide or omeprazole administered alone (reference) or in combination (test). Bioequivalence was determined if the 90 % confidence interval (CI) of the ratio (test/reference) fell within the acceptance range of 0.8-1.25. The point estimates (90 % CI) of the ratio of omeprazole + lacosamide coadministered versus omeprazole alone for AUC (1.098 [0.996-1.209]) and C(max) (1.105 [0.979-1.247]) fell within the acceptance range for bioequivalence. The point estimates (90 % CI) of the ratio of lacosamide + omeprazole coadministration versus lacosamide alone also fell within the acceptance range for bioequivalence (AUC 1.133 [1.102-1.165]); C(max) 0.996 (0.947-1.047). Steady-state lacosamide did not influence omeprazole single-dose pharmacokinetics, and multiple-dose omeprazole did not influence lacosamide single-dose pharmacokinetics.

  8. Comparison of Iohexol-380 and Iohexol-350 for coronary CT angiography: A multicenter, randomized, double-blind phase 3 trial

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun Ah; Lee, Whal [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Kang, Doo Kyoung [Dept. of Radiology, Ajou University School of Medicine, Suwon (Korea, Republic of); and others

    2016-06-15

    This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects. Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated. A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05). Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine.

  9. Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease.

    Science.gov (United States)

    Field, Joshua J; Majerus, Elaine; Gordeuk, Victor R; Gowhari, Michel; Hoppe, Carolyn; Heeney, Matthew M; Achebe, Maureen; George, Alex; Chu, Hillary; Sheehan, Brian; Puligandla, Maneka; Neuberg, Donna; Lin, Gene; Linden, Joel; Nathan, David G

    2017-09-12

    Adenosine A 2A receptor (A 2A R) agonists have been shown to decrease tissue inflammation induced by hypoxia/reoxygenation in mice with sickle cell disease (SCD). The key mediator of the A 2A R agonist's anti-inflammatory effects is a minor lymphocyte subset, invariant natural killer T (iNKT) cells. We tested the hypothesis that administration of an A 2A R agonist in patients with SCD would decrease iNKT cell activation and dampen the severity of vaso-occlusive (VO) crises. In a phase 2, randomized, placebo-controlled trial, we administered a 48-hour infusion of the A 2A R agonist regadenoson (1.44 μg/kg per hour) to patients with SCD during VO crises to produce a plasma concentration of ∼5 nM, a concentration known from prior studies to suppress iNKT cell activation in SCD. The primary outcome measure was a >30% reduction in the percentage of activated iNKT cells. Ninety-two patients with SCD were randomized to receive a 48-hour infusion of regadenoson or placebo, in addition to standard-of-care treatment, during hospital admission for a VO crisis and had analyzable iNKT cell samples. The proportion of subjects who demonstrated a reduction of >30% in activated iNKT cells was not significantly different between the regadenoson and placebo arms (43% vs 23%; P = .07). There were also no differences between regadenoson and placebo groups in length of hospital stay, mean total opioid use, or pain scores. These data demonstrate that a low-dose infusion of regadenoson intended to reduce the activity of iNKT cells is not sufficient to produce a statistically significant reduction in such activation or in measures of clinical efficacy. This trial was registered at www.clinicaltrials.gov as #NCT01788631.

  10. A Randomized Controlled Trial of Cognitive-Behavior Therapy Plus Bright Light Therapy for Adolescent Delayed Sleep Phase Disorder

    Science.gov (United States)

    Gradisar, Michael; Dohnt, Hayley; Gardner, Greg; Paine, Sarah; Starkey, Karina; Menne, Annemarie; Slater, Amy; Wright, Helen; Hudson, Jennifer L.; Weaver, Edward; Trenowden, Sophie

    2011-01-01

    Objective: To evaluate cognitive-behavior therapy plus bright light therapy (CBT plus BLT) for adolescents diagnosed with delayed sleep phase disorder (DSPD). Design: Randomized controlled trial of CBT plus BLT vs. waitlist (WL) control with comparisons at pre- and post-treatment. There was 6-month follow-up for the CBT plus BLT group only. Setting: Flinders University Child & Adolescent Sleep Clinic, Adelaide, South Australia. Patients: 49 adolescents (mean age 14.6 ± 1.0 y, 53% males) diagnosed with DSPD; mean chronicity 4 y 8 months; 16% not attending school. Eighteen percent of adolescents dropped out of the study (CBT plus BLT: N = 23 vs WL: N = 17). Interventions: CBT plus BLT consisted of 6 individual sessions, including morning bright light therapy to advance adolescents' circadian rhythms, and cognitive restructuring and sleep education to target associated insomnia and sleep hygiene. Measurements and Results: DSPD diagnosis was performed via a clinical interview and 7-day sleep diary. Measurements at each time-point included online sleep diaries and scales measuring sleepiness, fatigue, and depression symptoms. Compared to WL, moderate-to-large improvements (d = 0.65-1.24) were found at post-treatment for CBT plus BLT adolescents, including reduced sleep latency, earlier sleep onset and rise times, total sleep time (school nights), wake after sleep onset, sleepiness, and fatigue. At 6-month follow-up (N = 15), small-to-large improvements (d = 0.24-1.53) continued for CBT plus BLT adolescents, with effects found for all measures. Significantly fewer adolescents receiving CBT plus BLT met DPSD criteria at post-treatment (WL = 82% vs. CBT plus BLT = 13%, P sleep and daytime impairments in the immediate and long-term. Studies evaluating the treatment effectiveness of each treatment component are needed. Clinical Trial Information: Australia – New Zealand Trials Registry Number: ACTRN12610001041044. Citation: Gradisar M; Dohnt H; Gardner G; Paine S; Starkey

  11. Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Mahamadou A Thera

    2008-01-01

    Full Text Available The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1 based on apical membrane antigen-1 (AMA-1 from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert. Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

  12. Randomized Phase 2 Trial of S1 and Oxaliplatin-Based Chemoradiotherapy With or Without Induction Chemotherapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Dok Hyun [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jang, Geundoo [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Internal Medicine, Hallym Medical Center, Hallym University College of Medicine, Seoul (Korea, Republic of); Kim, Jong Hoon [Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Yong-Hee [Department of Thoracic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Ji Youn [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Hyeong Ryul [Department of Thoracic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jung, Hwoon-Yong; Lee, Gin-Hyug [Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Song, Ho Young [Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Cho, Kyung-Ja [Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Ryu, Jin-Sook [Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sung-Bae, E-mail: sbkim3@amc.seoul.kr [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2015-03-01

    Purpose: To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. Patients and Methods: Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m{sup 2} on day 1 and S1 at 40 mg/m{sup 2} twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m{sup 2} on days 1 and 21 and S1 30 mg/m{sup 2} twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. Results: A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. Conclusions: Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.

  13. Safety and Activity of UR-1505 in Atopic Dermatitis: A Randomized, Double-blind Phase II Exploratory Trial.

    Science.gov (United States)

    Vives, Roser; Pontes, Caridad; Sarasa, Maria; Millier, Aurelie

    2015-09-01

    UR-1505 is a new small molecule with immune modulator properties intended for the topical treatment of inflammatory skin diseases that has shown anti-inflammatory effects in models of skin inflammation. We compared the activity of UR-1505 ointment against its vehicle in the treatment of atopic dermatitis. Secondary objectives included exploring dose response, safety, and local tolerability of UR-1505. Patients with AD lesions on 2 symmetrical topographic areas (arms, leg, or trunk) were included in this unicenter randomized, double-blind, within-patient, controlled Phase II exploratory trial and received simultaneously 2 different treatments (0.5%, 1%, or 2% UR-1505 and vehicle or 0.1% tacrolimus ointment) once daily during 28 days. The primary efficacy end point was the change from baseline in the Investigator Global Assessment score at Day 28. Secondary end points were percentage of area clearance, local Eczema Area Severity Index (local EASI), and local tolerability. A linear mixed model was used, fitting treatment, body side, and group (treatment at the contralateral side) as fixed factors and the patient as a random effect. Twenty-eight patients were randomized and 25 patients were included in the per protocol analysis, with 50 evaluable lesions (n = 13 for vehicle, n = 8 for UR-1505 0.5%, n = 9 for 1% UR-1505, n=8 for 2% UR-1505, and n=12 for tacrolimus). The mean Investigator Global Assessment score change from baseline at Day 28 was -1.7 for vehicle, -1.0, -1.2, and -1.5 for 0.5%, 1%, and 2% UR-1505, respectively, and -2.6% for tacrolimus (P = 0.002). No serious nor causal adverse reactions were reported in this study, but patients reported numerous local symptoms after product applications, especially itching, tingling, tightness, and heat/burning sensations at frequencies that were similar for vehicle, 1% UR-1505, and 2% UR-1505; more frequent with 0.5% UR-1505; and lowest for tacrolimus. This study found that UR-1505 may not be a suitable option for the

  14. Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis.

    Science.gov (United States)

    Constantinescu, Cris S; Asher, Aliya; Fryze, Waldemar; Kozubski, Wojciech; Wagner, Frank; Aram, Jehan; Tanasescu, Radu; Korolkiewicz, Roman P; Dirnberger-Hertweck, Maren; Steidl, Stefan; Libretto, Susan E; Sprenger, Till; Radue, Ernst W

    2015-08-01

    To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time. MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found. This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS.

  15. Amino acid supplementation is anabolic during the acute phase of endotoxin-induced inflammation: A human randomized crossover trial.

    Science.gov (United States)

    Rittig, N; Bach, E; Thomsen, H H; Johannsen, M; Jørgensen, J O; Richelsen, B; Jessen, N; Møller, N

    2016-04-01

    Inflammation is catabolic and causes muscle loss. It is unknown if amino acid supplementation reverses these effects during the acute phase of inflammation. The aim was to test whether amino acid supplementation counteracts endotoxin-induced catabolism. Eight young, healthy, lean males were investigated three times in randomized order: (i) normal conditions (Placebo), (ii) endotoxemia (LPS), and (iii) endotoxemia with amino acid supplementation (LPS + A). Protein kinetics were determined using phenylalanine, tyrosine, and urea tracers. Each study day consisted of a four-hour non-insulin stimulated period and a two-hour hyperinsulinemic euglycemic clamp period. Muscle biopsies were collected once each period. Endotoxin administration created a significant inflammatory response (cytokines, hormones, and vital parameters) without significant differences between LPS and LPS + A. Whole body protein breakdown was elevated during LPS compared with Placebo and LPS + A (p translation factor 4E-binding protein 1 (4EBP1) phosphorylation (p = 0.007) without activating AMPK or affecting insulin signaling through Akt. During insulin stimulation net muscle phenylalanine release and protein degradation were further reduced. Amino acid supplementation in the acute phase of inflammation reduces whole body and muscle protein loss, and this effect is associated with activation of mTOR and downstream signaling to protein synthesis through mTORC1, suggesting a therapeutic role for intravenous amino acids in inflammatory states. The Central Denmark Region Ethics Commitee (1-10-71-410-12) www.clinicaltrials.gov (identification number NCT01705782). Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  16. Ixekizumab treatment improves fingernail psoriasis in patients with moderate-to-severe psoriasis: results from the randomized, controlled and open-label phases of UNCOVER-3

    NARCIS (Netherlands)

    Kerkhof, P. van de; Guenther, L.; Gottlieb, A.B.; Sebastian, M.; Wu, J.J.; Foley, P.; Morita, A.; Goldblum, O.; Zhang, L.; Erickson, J.; Ball, S.; Rich, P.

    2017-01-01

    BACKGROUND: Fingernail psoriasis is difficult to treat. OBJECTIVE: The objective was to evaluate the effect of ixekizumab, a monoclonal antibody selectively targeting IL-17A, on fingernail psoriasis. METHODS: This Phase 3, double-blind trial (UNCOVER-3) randomized patients to placebo, etanercept

  17. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    Escudier, Bernard; Sharma, Padmanee; McDermott, David F

    2017-01-01

    BACKGROUND: The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). OBJECTIV...

  18. ACUTE TOXICITY PROFILE AND COMPLIANCE TO ACCELERATED RADIOTHERAPY PLUS CARBOGEN AND NICOTINAMIDE FOR CLINICAL STAGE T2-4 LARYNGEAL CANCER : RESULTS OF A PHASE III RANDOMIZED TRIAL

    NARCIS (Netherlands)

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; van den Ende, Piet; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-01-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with

  19. Acute toxicity profile and compliance to accelerated radiotherapy plus carbogen and nicotinamide for clinical stage T2-4 laryngeal cancer: results of a phase III randomized trial.

    NARCIS (Netherlands)

    Janssens, G.O.R.J.; Terhaard, C.H.J.; Doornaert, P.A.; Bijl, H.P.; Ende, P. van den; Chin, A.; Pop, L.A.M.; Kaanders, J.H.A.M.

    2012-01-01

    PURPOSE: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. METHODS AND MATERIALS: From April 2001 to February 2008, 345 patients with

  20. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma.

    NARCIS (Netherlands)

    Lokhorst, H.M.; Holt, B. van der; Zweegman, S.; Vellenga, E.; Croockewit, S.; Oers, M.H. van; Borne, P. von dem; Wijermans, P.; Schaafsma, R.; Weerdt, O. de; Wittebol, S.; Delforge, M.; Berenschot, H.; Bos, G.M.; Jie, K.S.; Sinnige, H.; Marwijk-Kooy, M. van; Joosten, P.; Minnema, M.C.; Ammerlaan, R. van; Sonneveld, P.

    2010-01-01

    The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and

  1. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma

    NARCIS (Netherlands)

    Lokhorst, Henk M.; van der Holt, Bronno; Zweegman, Sonja; Vellenga, Edo; Croockewit, Sandra; van Oers, Marinus H.; von dem Borne, Peter; Wijermans, Pierre; Schaafsma, Ron; de Weerdt, Okke; Wittebol, Shulamiet; Delforge, Michel; Berenschot, Henriëtte; Bos, Gerard M.; Jie, Kon-Siong G.; Sinnige, Harm; van Marwijk-Kooy, Marinus; Joosten, Peter; Minnema, Monique C.; van Ammerlaan, Rianne; Sonneveld, Pieter

    2010-01-01

    The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and

  2. Randomized double-blind controlled Phase I/IIa trial to assess the efficacy of malaria vaccine PfCS102 to protect against challenge with P. falciparum.

    NARCIS (Netherlands)

    Genton, B.; D'Acremont, V.; Lurati-Ruiz, F.; Verhage, D.F.; Audran, R.; Hermsen, C.C.; Wolters, L.; Reymond, C.; Spertini, F.; Sauerwein, R.W.

    2010-01-01

    The aim of this Phase I/IIa double-blind controlled trial was to test the efficacy of the sporozoite-based malaria vaccine PfCS 282-383 (PfCS102) to protect against Plasmodium falciparum parasitaemia. 16 volunteers were randomized to receive twice 30 mug of PfCS102 formulated in Montanide ISA 720 or

  3. The FINISH-3 Trial : A Phase 3, International, Randomized, Single-Blind, Controlled Trial of Topical Fibrocaps in Intraoperative Surgical Hemostasis

    NARCIS (Netherlands)

    Bochicchio, Grant V.; Gupta, Navyash; Porte, Robert J.; Renkens, Kenneth L.; Pattyn, Piet; Topal, Baki; Troisi, Roberto Ivan; Muir, William; Chetter, Ian; Gillen, Daniel L.; Zuckerman, Linda A.; Frohna, Paul A.

    BACKGROUND: This Phase 3, international, randomized, single-blind, controlled trial (FINISH-3) compared the efficacy and safety of Fibrocaps, a ready-to-use, dry-powder fibrin sealant containing human plasma-derived thrombin and fibrinogen, vs gelatin sponge alone for use as a hemostat for surgical

  4. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma

    NARCIS (Netherlands)

    H.M. Lokhorst (Henk); B. van der Holt (Bronno); S. Zweegman (Sonja); E. Vellenga (Edo); S. Croockewit (Sandra); M.H.J. van Oers (Marinus); P.A. von dem Borne (P. A.); P.W. Wijermans (Pierre); R. Schaafsma (Ron); O. de Weerdt (Okke); S. Wittebol (Shulamit); M. Delforge (Michel); H. Berenschot (Henriëtte); G.M. Bos (Gerard); K.S-G. Jie; H. Sinnige (Harm); M. van Marwijk Kooy (Marinus); P. Joosten (Peter); M.C. Minnema (Monique); R.A.H.M. Ammerlaan (Rianne); P. Sonneveld (Pieter)

    2010-01-01

    textabstractThe phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and

  5. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial

    NARCIS (Netherlands)

    Breugom, A.J.; Gijn, W. van; Muller, E.W.; Berglund, A; Broek, C.B. van den; Fokstuen, T.; Gelderblom, H.; Kapiteijn, E.; Leer, J.W.H.; Marijnen, C.A.; Martijn, H.; Meershoek-Klein Kranenbarg, E.; Nagtegaal, I.D.; Pahlman, L.; Punt, C.J.A.; Putter, H.; Roodvoets, A.G.; Rutten, H.J.; Steup, W.H.; Glimelius, B.; Velde, C.J. van de

    2015-01-01

    BACKGROUND: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients

  6. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial

    NARCIS (Netherlands)

    Breugom, A. J.; van Gijn, W.; Muller, E. W.; Berglund, Å; van den Broek, C. B. M.; Fokstuen, T.; Gelderblom, H.; Kapiteijn, E.; Leer, J. W. H.; Marijnen, C. A. M.; Martijn, H.; Meershoek-Klein Kranenbarg, E.; Nagtegaal, I. D.; Påhlman, L.; Punt, C. J. A.; Putter, H.; Roodvoets, A. G. H.; Rutten, H. J. T.; Steup, W. H.; Glimelius, B.; van de Velde, C. J. H.

    2015-01-01

    The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with

  7. A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer

    Directory of Open Access Journals (Sweden)

    Charafeddine Maya

    2010-09-01

    Full Text Available Abstract Purpose/Objective This is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma. Materials/Methods Between May 2000 and May 2004, 31 women with FIGO stage IB2-IVA cervical cancer or with postsurgical pelvic recurrence were enrolled into this phase II study and randomized to receive on a weekly basis either 40 mg/m2 Cisplatin (group I; 16 patients or 50 mg/m2 paclitaxel (group II; 15 patients concurrently with radiotherapy. Median total dose to point A was 74 Gy (range: 66-92 Gy for group I and 66 Gy (range: 40-98 Gy for group II. Median follow-up time was 46 months. Results Patient and tumor characteristics were similar in both groups. The mean number of chemotherapy cycles was also comparable with 87% and 80% of patients receiving at least 4 doses in groups I and II, respectively. Seven patients (44% of group I and 8 patients (53% of group II developed tumor recurrence. The Median Survival time was not reached for Group I and 53 months for group II. The proportion of patients surviving at 2 and 5 years was 78% and 54% for group I and 73% and 43% for group II respectively. Conclusions This small prospective study shows that weekly paclitaxel does not provide any clinical advantage over weekly cisplatin for concurrent chemoradiation for advanced carcinoma of the cervix.

  8. A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma.

    Science.gov (United States)

    Szefler, Stanley J; Murphy, Kevin; Harper, Thomas; Boner, Attilio; Laki, István; Engel, Michael; El Azzi, Georges; Moroni-Zentgraf, Petra; Finnigan, Helen; Hamelmann, Eckard

    2017-11-01

    Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma. We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma. In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, add-on therapy improved the primary end point, peak FEV 1 within 3 hours after dosing (5 μg, 139 mL [95% CI, 75-203; P add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Effect of dance labor on the management of active phase labor pain & clients' satisfaction: a randomized controlled trial study.

    Science.gov (United States)

    Abdolahian, Somayeh; Ghavi, Fatemeh; Abdollahifard, Sareh; Sheikhan, Fatemeh

    2014-03-30

    There are a wide variety of non- pharmacologic pain relief techniques for labor which include pelvic movement, upright position, back massage and partner support during the first stage of labor. The effectiveness of dance labor- which is a combination of these techniques- has not been evaluated. This study aimed to evaluate the effectiveness of dance labor in pain reduction and woman's satisfaction during the first stage of labor. 60 primiparous women aged 18-35 years old were randomly assigned to dance labor and control groups. In the dance labor group, women were instructed to do standing upright with pelvic tilt and rock their hips back and forth or around in a circle while their partner massaged their back and sacrum for a minimum of 30 minutes. In the control group, the participants received usual care during physiologic labor. Pain and satisfaction scores were measured by Visual Analogue Scale. Data were analyzed by using the t. test and Chi-square. Mean pain score in the dance labor group was significantly lower than the control group (P dance labor group was significantly higher than in the control group (P Dance labor which is a complementary treatment with low risk can reduce the intensity of pain and increase mothers, satisfaction with care during the active phase of labor.

  10. Detection and measurement of fetal abdominal contour in ultrasound images via local phase information and iterative randomized Hough transform.

    Science.gov (United States)

    Wang, Weiming; Qin, Jing; Zhu, Lei; Ni, Dong; Chui, Yim-Pan; Heng, Pheng-Ann

    2014-01-01

    Due to the characteristic artifacts of ultrasound images, e.g., speckle noise, shadows and intensity inhomogeneity, traditional intensity-based methods usually have limited success on the segmentation of fetal abdominal contour. This paper presents a novel approach to detect and measure the abdominal contour from fetal ultrasound images in two steps. First, a local phase-based measure called multiscale feature asymmetry (MSFA) is de ned from the monogenic signal to detect the boundaries of fetal abdomen. The MSFA measure is intensity invariant and provides an absolute measurement for the signi cance of features in the image. Second, in order to detect the ellipse that ts to the abdominal contour, the iterative randomized Hough transform is employed to exclude the interferences of the inner boundaries, after which the detected ellipse gradually converges to the outer boundaries of the abdomen. Experimental results in clinical ultrasound images demonstrate the high agreement between our approach and manual approach on the measurement of abdominal circumference (mean sign difference is 0.42% and correlation coef cient is 0.9973), which indicates that the proposed approach can be used as a reliable and accurate tool for obstetrical care and diagnosis.

  11. Effect of sacrum-perineum heat therapy on active phase labor pain and client satisfaction: a randomized, controlled trial study.

    Science.gov (United States)

    Taavoni, Simin; Abdolahian, Somayeh; Haghani, Hamid

    2013-09-01

    Reduction of labor pain is one of the most important aspects of obstetric care. Heat therapy, typically applied to the woman's back, lower abdomen, groin, and/or perineum during last stage of labor, is an easy pain relief method that does not require highly skilled care. The effectiveness of heat therapy applied to the perineum during the first stage of labor has not been evaluated. This study aimed to evaluate the effectiveness of heat therapy for pain and woman's satisfaction during physiological labor. Sixty primiparous women aged 18-35 years old were randomly assigned to heat therapy and control groups. Pain and satisfaction scores were measured by visual analog scale. The measurements of satisfaction were accomplished after birth. Data were analyzed by using the t-test and chi-square Mean pain scores in the heat therapy group were significantly lower than the control group (P < 0.05). The mean satisfaction score in the heat therapy group was significantly higher than in the control group (P < 0.05). Heat therapy, an inexpensive complementary treatment with low risk, can reduce the intensity of pain and increase mothers' satisfaction with care during the active phase of labor. Wiley Periodicals, Inc.

  12. Critical points of quadratic renormalizations of random variables and phase transitions of disordered polymer models on diamond lattices.

    Science.gov (United States)

    Monthus, Cécile; Garel, Thomas

    2008-02-01

    We study the wetting transition and the directed polymer delocalization transition on diamond hierarchical lattices. These two phase transitions with frozen disorder correspond to the critical points of quadratic renormalizations of the partition function. (These exact renormalizations on diamond lattices can also be considered as approximate Migdal-Kadanoff renormalizations for hypercubic lattices.) In terms of the rescaled partition function z=Z/Z(typ) , we find that the critical point corresponds to a fixed point distribution with a power-law tail P(c)(z) ~ Phi(ln z)/z(1+mu) as z-->+infinity [up to some subleading logarithmic correction Phi(ln z)], so that all moments z(n) with n>mu diverge. For the wetting transition, the first moment diverges z=+infinity (case 0infinity (case 1fixed point distribution coincides with the transfer matrix describing a directed polymer on the Cayley tree, but the random weights determined by the fixed point distribution P(c)(z) are broadly distributed. This induces some changes in the traveling wave solutions with respect to the usual case of more narrow distributions.

  13. Spin-unrestricted random-phase approximation with range separation: Benchmark on atomization energies and reaction barrier heights

    CERN Document Server

    Mussard, Bastien; Angyan, Janos; Toulouse, Julien

    2015-01-01

    We consider several spin-unrestricted random-phase approximation (RPA) variants for calculating correlation energies, with and without range separation, and test them on datasets of atomization energies and reaction barrier heights. We show that range separation greatly improves the accuracy of all RPA variants for these properties. Moreover, we show that a RPA variant with exchange, hereafter referred to as RPAx-SO2, first proposed by Sz-abo and Ostlund [A. Szabo and N. S. Ostlund, J. Chem. Phys. 67, 4351 (1977)] in a spin-restricted closed-shell formalism, and extended here to a spin-unrestricted formalism, provides on average the most accurate range-separated RPA variant for atomization energies and reaction barrier heights. Since this range-separated RPAx-SO2 method had already been shown to be among the most accurate range-separated RPA variants for weak intermolecular interactions [J. Toulouse, W. Zhu, A. Savin, G. Jansen, and J. G. {\\'A}ngy{\\'a}n, J. Chem. Phys. 135, 084119 (2011)], this works confirms...

  14. Video time encoding machines.

    Science.gov (United States)

    Lazar, Aurel A; Pnevmatikakis, Eftychios A

    2011-03-01

    We investigate architectures for time encoding and time decoding of visual stimuli such as natural and synthetic video streams (movies, animation). The architecture for time encoding is akin to models of the early visual system. It consists of a bank of filters in cascade with single-input multi-output neural circuits. Neuron firing is based on either a threshold-and-fire or an integrate-and-fire spiking mechanism with feedback. We show that analog information is represented by the neural circuits as projections on a set of band-limited functions determined by the spike sequence. Under Nyquist-type and frame conditions, the encoded signal can be recovered from these projections with arbitrary precision. For the video time encoding machine architecture, we demonstrate that band-limited video streams of finite energy can be faithfully recovered from the spike trains and provide a stable algorithm for perfect recovery. The key condition for recovery calls for the number of neurons in the population to be above a threshold value.

  15. IDENTIFICATION OF ENCODED BEADS

    DEFF Research Database (Denmark)

    2005-01-01

    The present invention is relates to methods for the identification of spatially encoded beaded or granulated matrices comprising a plurality of immobilised particles. The identification is based on a distance matrix determination or based on a set of geometrical figures, such a triangles...

  16. Fearful contextual expression impairs the encoding and recognition of target faces: an ERP study

    Directory of Open Access Journals (Sweden)

    Huiyan eLin

    2015-09-01

    Full Text Available Previous event-related potential (ERP studies have shown that the N170 to faces is modulated by the emotion of the face and its context. However, it is unclear how the encoding of emotional target faces as reflected in the N170 is modulated by the preceding contextual facial expression when temporal onset and identity of target faces are unpredictable. In addition, no study as yet has investigated whether contextual facial expression modulates later recognition of target faces. To address these issues, participants in the present study were asked to identify target faces (fearful or neutral that were presented after a sequence of fearful or neutral contextual faces. The number of sequential contextual faces was random and contextual and target faces were of different identities so that temporal onset and identity of target faces were unpredictable. Electroencephalography (EEG data was recorded during the encoding phase. Subsequently, participants had to perform an unexpected old/new recognition task in which target face identities were presented in either the encoded or the non-encoded expression. ERP data showed a reduced N170 to target faces in fearful as compared to neutral context regardless of target facial expression. In the later recognition phase, recognition rates were reduced for target faces in the encoded expression when they had been encountered in fearful as compared to neutral context. The present findings suggest that fearful compared to neutral contextual faces reduce the allocation of attentional resources towards target faces, which results in limited encoding and recognition of target faces.

  17. A simplification of the fractional Hartley transform applied to image security system in phase

    Science.gov (United States)

    Jimenez, Carlos J.; Vilardy, Juan M.; Perez, Ronal

    2017-01-01

    In this work we develop a new encryption system for encoded image in phase using the fractional Hartley transform (FrHT), truncation operations and random phase masks (RPMs). We introduce a simplification of the FrHT with the purpose of computing this transform in an efficient and fast way. The security of the encryption system is increased by using nonlinear operations, such as the phase encoding and the truncation operations. The image to encrypt (original image) is encoded in phase and the truncation operations applied in the encryption-decryption system are the amplitude and phase truncations. The encrypted image is protected by six keys, which are the two fractional orders of the FrHTs, the two RPMs and the two pseudorandom code images generated by the amplitude and phase truncation operations. All these keys have to be correct for a proper recovery of the original image in the decryption system. We present digital results that confirm our approach.

  18. Encoding negative events under stress: high subjective arousal is related to accurate emotional memory despite misinformation exposure.

    Science.gov (United States)

    Hoscheidt, Siobhan M; LaBar, Kevin S; Ryan, Lee; Jacobs, W Jake; Nadel, Lynn

    2014-07-01

    Stress at encoding affects memory processes, typically enhancing, or preserving, memory for emotional information. These effects have interesting implications for eyewitness accounts, which in real-world contexts typically involve encoding an aversive event under stressful conditions followed by potential exposure to misinformation. The present study investigated memory for a negative event encoded under stress and subsequent misinformation endorsement. Healthy young adults participated in a between-groups design with three experimental sessions conducted 48 h apart. Session one consisted of a psychosocial stress induction (or control task) followed by incidental encoding of a negative slideshow. During session two, participants were asked questions about the slideshow, during which a random subgroup was exposed to misinformation. Memory for the slideshow was tested during the third session. Assessment of memory accuracy across stress and no-stress groups revealed that stress induced just prior to encoding led to significantly better memory for the slideshow overall. The classic misinformation effect was also observed - participants exposed to misinformation were significantly more likely to endorse false information during memory testing. In the stress group, however, memory accuracy and misinformation effects were moderated by arousal experienced during encoding of the negative event. Misinformed-stress group participants who reported that the negative slideshow elicited high arousal during encoding were less likely to endorse misinformation for the most aversive phase of the story. Furthermore, these individuals showed better memory for components of the aversive slideshow phase that had been directly misinformed. Results from the current study provide evidence that stress and high subjective arousal elicited by a negative event act concomitantly during encoding to enhance emotional memory such that the most aversive aspects of the event are well remembered and

  19. High-speed quantum-random number generation by continuous measurement of arrival time of photons.

    Science.gov (United States)

    Yan, Qiurong; Zhao, Baosheng; Hua, Zhang; Liao, Qinghong; Yang, Hao

    2015-07-01

    We demonstrate a novel high speed and multi-bit optical quantum random number generator by continuously measuring arrival time of photons with a common starting point. To obtain the unbiased and post-processing free random bits, the measured photon arrival time is converted into the sum of integral multiple of a fixed period and a phase time. Theoretical and experimental results show that the phase time is an independent and uniform random variable. A random bit extraction method by encoding the phase time is proposed. An experimental setup has been built and the unbiased random bit generation rate could reach 128 Mb/s, with random bit generation efficiency of 8 bits per detected photon. The random numbers passed all tests in the statistical test suite.

  20. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2016-09-01

    statistical  design  was  reviewed  and  approved  from  the DSMB  and  IRB. Please find approved justification listed below: “The  study  is  a  randomized ... Randomization  will be performed by using  a  series of  randomized   blocks  of  6 within  each participating  site/primary  therapy  stratum  (with  a...reported during the conduct of the study. 13. STATISTICAL CONSIDERATIONS 13.1 Study Design /Endpoints The study is a randomized phase 2

  1. Phase 3 Randomized Low-Dose Paclitaxel Chemoradiotherapy Study for Locally Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Lin, Hongmei; Chen, Yuhchyau; Shi, Anhui; Pandya, Kishan J; Yu, Rong; Yuan, Yannan; Li, Jiancheng; Li, Hang; Wang, Yingjie; Xia, Tingyi; Feng, Linchun; Ma, Huimin; Geng, Jianhao; Zhu, Guangying

    2016-01-01

    Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with poor chest tumor control. Here, we report results of a randomized phase 3 study comparing two CCRT regimens in improving chest tumor control by low-dose paclitaxel chemoradiation for LA-NSCLC. Due to the logistics of local referral pattern, the study was designed to enroll patients with stage III LA-NSCLC who had completed 2-4 cycles of full-dose chemotherapy. One hundred thirty four were randomized to either Arm 1 [paclitaxel at 15 mg/m2, three times per week (Monday, Wednesday, and Friday) for 6 weeks, n = 74] or Arm 2 (weekly paclitaxel at 45 mg/m2 for 6 weeks, n = 60). Chest radiotherapy was 60-70 Gy in standard fractionation. Response rate was the primary endpoint, with recurrence-free survival (RFS) as the secondary endpoint. From March 2006 to February 2013, 71 patients completed Arm 1 treatment and 59 completed Arm 2 treatment. The response rate for Arm 1 was significantly higher (83.1%) than Arm 2 (54.2%) (p=0.001). RFS was superior in Arm 1: median 14.6 vs. 9.4 months, p = 0.005, Hazard ratio (HR) 1.87 [95% confidence interval (CI) 1.20, 2.90]. Overall survival was not significantly different: median 32.6 months in Arm 1 vs. 31.3 months in Arm 2, p = 0.91, HR 0.97 (95% CI 0.55, 1.70). Toxicity was significantly lower in Arm 1 for Grade 3 and 4 leukopenia/neutropenia (p < 0.001). Pulsed low-dose paclitaxel CCRT resulted in significantly better RFS and tumor response rate, and less hematologic toxicities than weekly CCRT for LA-NSCLC.

  2. Testing two different doses of tiotropium Respimat® in cystic fibrosis: phase 2 randomized trial results.

    Directory of Open Access Journals (Sweden)

    Judy M Bradley

    Full Text Available Tiotropium is a once-daily, long-acting anticholinergic bronchodilator with the potential to alleviate airway obstruction in cystic fibrosis. Our objective was to evaluate the efficacy and safety of 2.5 and 5 µg once-daily tiotropium delivered via the Respimat Soft Mist Inhaler vs. placebo in people with cystic fibrosis.This phase 2, 12-week, randomized, double-blind, placebo-controlled parallel-group study of tiotropium Respimat as add-on to usual cystic fibrosis maintenance therapy included people with cystic fibrosis with pre-bronchodilator forced expiratory volume in 1 second (FEV1 ≥ 25% predicted. Co-primary efficacy end points were change from baseline in percent-predicted FEV1 area under the curve from 0 to 4 hours (FEV1 AUC0-4h, and trough FEV1 at the end of week 12.A total of 510 subjects with cystic fibrosis aged 5-69 years were randomized. Both doses of tiotropium resulted in significant improvement compared with placebo in the co-primary efficacy end points at the end of week 12 (change from baseline in percent-predicted FEV1 AUC0-4h: 2.5 µg: 2.94%, 95% confidence interval 1.19-4.70, p = 0.001; 5 µg: 3.39%, 95% confidence interval 1.67-5.12, p = 0.0001; in percent-predicted trough FEV1 ∶ 2.5 µg: 2.24%, p = 0.2; 5 µg: 2.22%, p = 0.02. There was a greater benefit with tiotropium 5 vs. 2.5 µg. No treatment-related adverse events or unexpected safety findings were observed in patients taking tiotropium.Tiotropium significantly improved lung function in people with cystic fibrosis. The improvement was greater with the higher dose than the lower dose, with no difference in adverse events.ClinicalTrials.gov NCT00737100 EudraCT 2008-001156-43.

  3. Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol.

    Science.gov (United States)

    Martinez, Jessica A; Chalasani, Pavani; Thomson, Cynthia A; Roe, Denise; Altbach, Maria; Galons, Jean-Philippe; Stopeck, Alison; Thompson, Patricia A; Villa-Guillen, Diana Evelyn; Chow, H-H Sherry

    2016-07-19

    Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n = 75) or placebo (n = 75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin

  4. Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: Phase I single group and phase II randomized placebo-controlled studies.

    Science.gov (United States)

    Lovera, Jesus; Ramos, Alexander; Devier, Deidre; Garrison, Virginia; Kovner, Blake; Reza, Tara; Koop, Dennis; Rooney, William; Foundas, Anne; Bourdette, Dennis

    2015-11-15

    Phase I (PhI): assess the safety of Polyphenon E in people with multiple sclerosis (MS) and determine the futility of Polyphenon E as a neuroprotective agent. Correlate plasma levels of EGCG with neuroprotective effects. Phase II (PhII): Further assess safety and confirm the neuroprotective effects of Polyphenon E. PhI: single group futility study. PhII: parallel group randomized double-blind placebo-controlled study. Recruitment area (both studies): LSU MS Center, New Orleans, LA and general public from surrounding areas. Inclusion criteria (both studies): 1) MS per 2005 McDonald criteria; 2) relapsing remitting or secondary progressive MS; 3) stable for six months prior to enrollment on either no therapy or glatiramer acetate (GA) for the PhI study and on either on GA or Interferon β for the PhII study. Exclusion criteria (both studies): 1) complete bone marrow ablation or alentuzumab use at any time; 2) mitoxantrone, cyclophosphamide, natalizumab or fingolimod use in the prior nine months; 3) liver problems or significant medical problems. PhI: Polyphenon E, a green tea extract containing 50% of the antioxidant Epigallocatechin-gallate (EGCG), two capsules twice daily (200mg of EGCG per capsule; total daily dose 800mg) for six months. PhII: Polyphenon E or matching placebo capsules, same dose for one year. Only the research pharmacist knew treatment assignment and she randomized participants (one-to-one, stratified by GA or Interferon β, blocks of 4 or 6). Outcome evaluators did not discuss side effects with participants. PhI: 1) adverse events (AE); 2) futility: decrease in N-acetyl aspartate (NAA) from baseline to six months of 10% or more; 3) association between EGCG plasma levels and change in NAA. PhII: 1) AEs; 2) difference in the rate of change of NAA-levels over twelve months.We measured NAA using a point resolved magnetic resonance spectroscopic imaging sequence (TE30/TR2000) on a 10cm×10cm×1cm volume of interest (VOI) located just superior to the

  5. Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials.

    Science.gov (United States)

    Jacobson, Ira M; Lawitz, Eric; Gane, Edward J; Willems, Bernard E; Ruane, Peter J; Nahass, Ronald G; Borgia, Sergio M; Shafran, Stephen D; Workowski, Kimberly A; Pearlman, Brian; Hyland, Robert H; Stamm, Luisa M; Svarovskaia, Evguenia; Dvory-Sobol, Hadas; Zhu, Yanni; Subramanian, G Mani; Brainard, Diana M; McHutchison, John G; Bräu, Norbert; Berg, Thomas; Agarwal, Kosh; Bhandari, Bal Raj; Davis, Mitchell; Feld, Jordan J; Dore, Gregory J; Stedman, Catherine A M; Thompson, Alexander J; Asselah, Tarik; Roberts, Stuart K; Foster, Graham R

    2017-07-01

    Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic response (SVR) after 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. We assessed the efficacy of 8 weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpatasvir-voxilaprevir). In 2 phase 3, open-label trials, patients with HCV infection who had not been treated previously with a direct-acting antiviral agent were assigned randomly to groups given sofosbuvir-velpatasvir-voxilaprevir for 8 weeks or sofosbuvir-velpatasvir for 12 weeks. POLARIS-2, which enrolled patients infected with all HCV genotypes with or without cirrhosis, except patients with genotype 3 and cirrhosis, was designed to test the noninferiority of 8 weeks of sofosbuvir-velpatasvir-voxilaprevir to 12 weeks of sofosbuvir-velpatasvir using a noninferiority margin of 5%. POLARIS-3, which enrolled patients infected with HCV genotype 3 who had cirrhosis, compared rates of SVR in both groups with a performance goal of 83%. In POLARIS-2, 95% (95% confidence interval [CI], 93%-97%) of patients had an SVR to 8 weeks of sofosbuvir-velpatasvir-voxilaprevir; this did not meet the criterion to establish noninferiority to 12 weeks of sofosbuvir-velpatasvir, which produced an SVR in 98% of patients (95% CI, 96%-99%; difference in the stratum-adjusted Mantel-Haenszel proportions of -3.2%; 95% CI, -6.0% to -0.4%). The difference in the efficacy was owing primarily to a lower rate of SVR (92%) among patients with HCV genotype 1a infection receiving 8 weeks of sofosbuvir-velpatasvir-voxilaprevir. In POLARIS-3, 96% of patients (95% CI, 91%-99%) achieved an SVR in both treatment groups, which was significantly superior to the performance goal. Overall, the most common adverse events were headache, fatigue, diarrhea, and nausea; diarrhea and nausea were reported more frequently by

  6. Assessment of the therapeutic benefit of dexamethasone cyclophosphamide pulse versus only oral cyclophosphamide in phase II of the dexamethasone cyclophosphamide pulse therapy: A preliminary prospective randomized controlled study

    Directory of Open Access Journals (Sweden)

    Nisha V Parmar

    2013-01-01

    Full Text Available Background: Dexamethasone cyclophosphamide pulse (DCP therapy is an established mode of treatment for pemphigus in India. Aims: To assess the therapeutic benefit of additional DCPs (phase II, consolidation phase versus immediate oral cyclophosphamide, usually used in phase III (maintenance phase, after initial DCP therapy (phase I and to assess which laboratory test (DIF or ELISA will reflect the clinical relapse best. Methods: Nineteen newly recruited patients of pemphigus vulgaris (PV received monthly DCPs in phase I and were then randomized into two groups. Group A (10 patients received monthly DCPs for nine months and Group B (nine patients received only oral cyclophosphamide for nine months. Direct immunofluorescence (DIF and enzyme-linked immunosorbent assay (ELISA were tested before starting DCP regimen, and at 0,3,6,9 months after randomization. Results: Clinical relapse by the end of follow-up period occurred in only one patient in each group. In these cases, DIF became (again positive before the relapse. No statistically significant difference between the two groups was found at three, six and nine months by ELISA indices and DIF grading. Conclusion: Although the DCP regimen is the standard therapy for pemphigus in India, we found no difference in the clinical outcome between patients receiving nine DCPs in phase II and patients shifted directly from phase I to III. Periodic testing using DIF and Dsg ELISA were found to be useful to monitor disease activity and predict a relapse. Further large scale studies are required to assess if patients can be shifted directly from phase I to III and maintained only on oral cyclophosphamide.

  7. Dynamical encoding of cursive handwriting.

    Science.gov (United States)

    Singer, Y; Tishby, N

    1994-01-01

    A model-based approach to on-line cursive handwriting analysis and recognition is presented and evaluated. In this model, on-line handwriting is considered as a modulation of a simple cycloidal pen motion, described by two coupled oscillations with a constant linear drift along the line of the writing. By slow modulations of the amplitudes and phase lags of the two oscillators, a general pen trajectory can be efficiently encoded. These parameters are then quantized into a small number of values without altering the writing intelligibility. A general procedure for the estimation and quantization of these cycloidal motion parameters for arbitrary handwriting is presented. The result is a discrete motor control representation of the continuous pen motion, via the quantized levels of the model parameters. This motor control representation enables successful word spotting and matching of cursive scripts. Our experiments clearly indicate the potential of this dynamic representation for complete cursive handwriting recognition.

  8. Three-dimensional MRI with independent slab excitation and encoding.

    Science.gov (United States)

    Eissa, Amir; Wilman, Alan H

    2012-02-01

    Three-dimensional MRI is typically performed with the same orientation for radiofrequency slab excitation and slab select phase encoding. We introduce independent slab excitation and encoding to create a new degree of freedom in three-dimensional MRI, which is the angular relationship between the prescribed excitation volume and the voxel encoding grid. By separating the directions of slab excitation and slab phase encoding, the independent slab excitation and encoding method allows choice of optimal voxel orientation, while maintaining volume excitation based on anatomic landmarks. The method requires simple pulse sequence modifications and uses standard image reconstruction followed by removal of aliasing and image reformatting. The independent slab excitation and encoding method enables arbitrary oblique angle imaging using fixed voxel encoding gradients to maintain similar eddy current, concomitant field, or magnetic dipole effects independent of the oblique angle of excitation. We apply independent slab excitation and encoding to phase and susceptibility-weighted imaging using fixed voxel encoding aligned with the main magnetic field to demonstrate its value in both standardizing and improving image contrast, when using arbitrary oblique imaging volumes. Copyright © 2011 Wiley Periodicals, Inc.

  9. Abuse liability assessment of eslicarbazepine acetate in healthy male and female recreational sedative users: A Phase I randomized controlled trial.

    Science.gov (United States)

    Levy-Cooperman, Naama; Schoedel, Kerri A; Chakraborty, Bijan; Blum, David; Cheng, Hailong

    2016-08-01

    Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug for the treatment of partial-onset seizures. Adverse events such as dizziness and somnolence reported in clinical studies suggest that ESL has detectable central nervous system (CNS) effects in addition to its antiepileptic effects. This Phase I study evaluated the abuse liability of ESL compared with that of alprazolam (ALP) and placebo (PBO) in recreational CNS depressant users. In this single-dose, randomized, double-blind, PBO- and active-controlled crossover study, healthy recreational CNS depressant users who could discern between ALP 2mg and PBO received single oral doses of each of the following treatments with a washout interval of ≥7days between each treatment: ESL (800mg, 1600mg, 2000mg, and 2400mg); ALP (1.5mg and 3.0mg); and PBO. Subjective measures, including visual analog scales (VASs) e.g., Drug-Liking (primary endpoint), and Addiction Research Center Inventory (ARCI) Morphine-Benzedrine Group (MBG), Pentobarbital Chlorpromazine Alcohol Group (PCAG), and Lysergic Acid Diethylamide Group scales were evaluated at multiple time points up to 24h postdose. Cognitive effects were evaluated using the Choice Reaction Time (CRT), Divided Attention (DAT) and Hopkins Verbal Learning Task-Revised tests. Peak scores for Drug-Liking VAS (maximum effect [Emax]) were significantly higher for both ALP doses than for PBO (peslicarbazepine, increased with increasing ESL dose. Pharmacokinetic parameters estimated for eslicarbazepine were generally comparable with results from previous studies in healthy volunteers. This study demonstrated that single doses of ESL may have less abuse liability than ALP in recreational sedative users. Although ESL had detectable subjective effects and showed some drug-'liking' at higher doses, the magnitude of these effects was small. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. A randomized controlled trial of cognitive-behavior therapy plus bright light therapy for adolescent delayed sleep phase disorder.

    Science.gov (United States)

    Gradisar, Michael; Dohnt, Hayley; Gardner, Greg; Paine, Sarah; Starkey, Karina; Menne, Annemarie; Slater, Amy; Wright, Helen; Hudson, Jennifer L; Weaver, Edward; Trenowden, Sophie

    2011-12-01

    To evaluate cognitive-behavior therapy plus bright light therapy (CBT plus BLT) for adolescents diagnosed with delayed sleep phase disorder (DSPD). Randomized controlled trial of CBT plus BLT vs. waitlist (WL) control with comparisons at pre- and post-treatment. There was 6-month follow-up for the CBT plus BLT group only. Flinders University Child & Adolescent Sleep Clinic, Adelaide, South Australia. 49 adolescents (mean age 14.6 ± 1.0 y, 53% males) diagnosed with DSPD; mean chronicity 4 y 8 months; 16% not attending school. Eighteen percent of adolescents dropped out of the study (CBT plus BLT: N = 23 vs. WL: N = 17). CBT plus BLT consisted of 6 individual sessions, including morning bright light therapy to advance adolescents' circadian rhythms, and cognitive restructuring and sleep education to target associated insomnia and sleep hygiene. DSPD diagnosis was performed via a clinical interview and 7-day sleep diary. Measurements at each time-point included online sleep diaries and scales measuring sleepiness, fatigue, and depression symptoms. Compared to WL, moderate-to-large improvements (d = 0.65-1.24) were found at post-treatment for CBT plus BLT adolescents, including reduced sleep latency, earlier sleep onset and rise times, total sleep time (school nights), wake after sleep onset, sleepiness, and fatigue. At 6-month follow-up (N = 15), small-to-large improvements (d = 0.24-1.53) continued for CBT plus BLT adolescents, with effects found for all measures. Significantly fewer adolescents receiving CBT plus BLT met DPSD criteria at post-treatment (WL = 82% vs. CBT plus BLT = 13%, P adolescent DSPD is effective for improving multiple sleep and daytime impairments in the immediate and long-term. Studies evaluating the treatment effectiveness of each treatment component are needed. Australia-New Zealand Trials Registry Number: ACTRN12610001041044.

  11. Design and initial results of a multi-phase randomized trial of ceftriaxone in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    James D Berry

    Full Text Available Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. A trial using a novel three stage nonstop design, incorporating Phases I-III, tested ceftriaxone in ALS. Stage 1 determined the cerebrospinal fluid pharmacokinetics of ceftriaxone in subjects with ALS. Stage 2 evaluated safety and tolerability for 20-weeks. Analysis of the pharmacokinetics, tolerability, and safety was used to determine the ceftriaxone dosage for Stage 3 efficacy testing.In Stage 1, 66 subjects at ten clinical sites were enrolled and randomized equally into three study groups receiving intravenous placebo, ceftriaxone 2 grams daily or ceftriaxone 4 grams daily divided BID. Participants provided serum and cerebrospinal fluid for pharmacokinetic analysis on study day 7. Participants continued their assigned treatment in Stage 2. The Data and Safety Monitoring Board (DSMB reviewed the data after the last participants completed 20 weeks on study drug.Stage 1 analysis revealed linear pharmacokinetics, and CSF trough levels for both dosage levels exceeding the pre-specified target trough level of 1 µM (0.55 µg/mL. Tolerability (Stages 1 and 2 results showed that ceftriaxone at dosages up to 4 grams/day was well tolerated at 20 weeks. Biliary adverse events were more common with ceftriaxone but not dose-dependent and improved with ursodeoxycholic (ursodiol therapy.The goals of Stages 1 and 2 of the ceftriaxone trial were successfully achieved. Based on the pre-specified decision rules, the DSMB recommended the use of ceftriaxone 4 g/d (divided BID for Stage 3, which recently closed.ClinicalTrials.gov NCT00349622.

  12. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma.

    Science.gov (United States)

    Corren, Jonathan; Busse, William; Meltzer, Eli O; Mansfield, Lyndon; Bensch, George; Fahrenholz, John; Wenzel, Sally E; Chon, Yun; Dunn, Meleana; Weng, Haoling H; Lin, Shao-Lee

    2010-04-15

    IL-4 and IL-13 share many biological functions important in the development of allergic airway inflammation and are implicated in the pathogenesis of asthma. AMG 317 is a fully human monoclonal antibody to IL-4Ralpha that blocks both IL-4 and IL-13 pathways. To evaluate efficacy and safety of AMG 317 in patients with moderate to severe asthma. In this phase 2, randomized, double-blind, placebo-controlled study, patients received weekly subcutaneous injections of placebo or AMG 317 (75-300 mg) for 12 weeks, followed by a 4-week follow-up period. The primary endpoint was change from baseline at Week 12 in Asthma Control Questionnaire (ACQ) symptom score. Mean ACQ change (SE) was -0.49 (0.09) in placebo (n = 74), and -0.43 (0.11), -0.58 (0.12), and -0.70 (0.09) in the AMG 317 75 mg (n = 73), 150 mg (n = 73), and 300 mg (n = 74) groups, respectively (treatment effect P = 0.25). No statistically significant differences were observed in the secondary endpoints. Numerical decreases in number of and time to exacerbations were noted in patients receiving AMG 317 150 mg and 300 mg. Preplanned analyses by tertile of baseline ACQ revealed that patients with higher baseline ACQ scores (>or=2.86) were more likely to respond to AMG 317. Serious adverse events were reported in three patients, each noted as not related to study drug. AMG 317 did not demonstrate clinical efficacy across the overall group of patients. Clinically significant improvements were observed in several outcome measures in patients with higher baseline ACQ scores. AMG 317 was safe and well tolerated in this study population. Clinical trial registered with www.clinicaltrials.gov (NCT 00436670).

  13. An interesterified palm olein test meal decreases early-phase postprandial lipemia compared to palm olein: a randomized controlled trial.

    Science.gov (United States)

    Hall, Wendy L; Brito, Marcela Fiuza; Huang, Junlan; Wood, Lucy V; Filippou, Androulla; Sanders, Thomas A B; Berry, Sarah E E

    2014-09-01

    Palm oil that has been interesterified to produce a higher proportion of palmitic acid (16:0) in the sn-2 position reduces postprandial lipemia in young, normolipidemic men and women, but effects in older subjects with higher fasting triacylglycerol (TAG) concentrations are unknown. We tested the hypothesis that high-fat meals rich in interesterified palm olein (IPO) decrease lipemia and alter plasma lipoprotein fraction composition compared to native palm olein (NPO) in men aged 40-70 years with fasting TAG concentrations ≥1.2 mmol/L. Postprandial changes in plasma lipids following meals containing 75 g fat (NPO and IPO) were compared using a randomized, double-blind crossover design (n = 11). Although there were no significant differences in plasma TAG concentrations between meals over the total 6-h postprandial measurement period, IPO resulted in a decreased plasma TAG response during the first 4 h of the postprandial period (iAUC 1.65 mmol/L h, 95% CI 1.01-2.29) compared to NPO (iAUC 2.33 mmol/L h, 95% CI 1.58-3.07); meal effect P = 0.024. Chylomicron fraction TAG concentrations at 4-6 h were slightly reduced following IPO compared to NPO [NPO-IPO mean difference 0.29 mmol/L (95% CI -0.01-0.59), P = 0.055]. There were no differences in IDL fraction TAG, cholesterol or apolipoprotein B48 concentrations following IPO compared with NPO. In conclusion, consuming a meal containing palm olein with a higher proportion of 16:0 in the sn-2 position decreases postprandial lipemia compared to native palm olein during the early phase of the postprandial period in men with higher than optimal fasting triacylglycerol concentrations.

  14. A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007.

    Directory of Open Access Journals (Sweden)

    Ian McGowan

    Full Text Available Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal, adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel.Participants were randomized 1:1:1:1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein, microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively.Sixty-five participants (45 men and 20 women were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability was 87% (reduced glycerin formulation of tenofovir 1% gel, 93% (hydroxyethyl cellulose placebo gel, and 63% (nonoxynol-9 gel. Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms.The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development.ClinicalTrials.gov NCT01232803.

  15. Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033.

    Science.gov (United States)

    Tran, Jonathan Q; Rana, Jitesh; Barkhof, Frederik; Melamed, Isaac; Gevorkyan, Hakop; Wattjes, Mike P; de Jong, Remko; Brosofsky, Kristin; Ray, Soma; Xu, Lei; Zhao, Jim; Parr, Edward; Cadavid, Diego

    2014-08-01

    To evaluate the safety, tolerability, and pharmacokinetics (PK) of BIIB033 (anti-LINGO-1 monoclonal antibody) in healthy volunteers and participants with multiple sclerosis (MS). In 2 separate randomized, placebo-controlled studies, single ascending doses (SAD; 0.1-100 mg/kg) of BIIB033 or placebo were administered via IV infusion or subcutaneous injection to 72 healthy volunteers, and multiple ascending doses (MAD; 0.3-100 mg/kg; 2 doses separated by 14 days) of BIIB033 or placebo were administered via IV infusion to 47 participants with relapsing-remitting or secondary progressive MS. Safety assessments included adverse event (AE) monitoring, neurologic examinations, conventional and nonconventional MRI, EEG, optical coherence tomography, retinal examinations, and evoked potentials. Serum and CSF PK as well as the immunogenicity of BIIB033 were also evaluated. All 72 healthy volunteers and 47 participants with MS were included in the safety analyses. BIIB033 infusions were well tolerated. The frequency of AEs was similar between BIIB033 and placebo. There were no serious AEs or deaths. No clinically significant changes in any of the safety measures were observed. BIIB033 PK was similar between healthy volunteers and participants with MS. Doses of ≥10 mg/kg resulted in BIIB033 concentrations similar to or higher than the concentration associated with 90% of the maximum remyelination effect in rat remyelination studies. The incidence of anti-drug antibody production was low. The emerging safety, tolerability, and PK of BIIB033 support advancing BIIB033 into phase II clinical development as a potential treatment for CNS demyelination disorders. This study provides Class I evidence that BIIB033 is well tolerated and safe (serious adverse event rate 0%, 95% confidence interval 0-7.6%).

  16. Phase III, randomized controlled trial to evaluate lot consistency of a trivalent subunit egg-based influenza vaccine in adults.

    Science.gov (United States)

    Rivera, Luis; Mazara, Sonia; Vargas, Maria; Fragapane, Elena; Casula, Daniela; Groth, Nicola

    2012-07-27

    Vaccination is the most effective preventive strategy to control influenza. The demonstration of lot-to-lot consistency to confirm the reliability of the manufacturing process has become a mandatory step in vaccine development. This phase III, observer-blind, controlled trial assessed lot-to-lot consistency, immunogenicity, and safety of a subunit trivalent influenza vaccine (Agrippal®, Novartis Vaccines and Diagnostics) in healthy adults aged 18-49 years. The immunogenicity and safety profile of Agrippal was compared with a control vaccine (Fluvirin®, Novartis Vaccines and Diagnostics). A total of 1507 subjects were randomized 2:2:2:1 to receive one vaccination of one of the three lots of influenza vaccine or control vaccine. Antibody levels were measured by hemagglutination inhibition assay on days 1 and 22. Adverse reactions were solicited via diary cards for 7 days after vaccination, and unsolicited adverse events were collected throughout the study period. Equivalence of day 22 immune responses to the three lots was shown for each of the three strains. Robust immunogenic responses after one dose were observed for all vaccine groups, and both Center for Biologics Evaluation and Research criteria for licensure of influenza vaccines were met for all three virus strains. Both vaccines exhibited a robust safety profile and were well tolerated, with no differences in local and systemic solicited reactions or in unsolicited adverse events. The demonstration of consistency between manufacturing lots confirms for purposes of clinical development the reliability of the production process. The robust immunogenic responses and favorable safety profiles further support the use of trivalent subunit influenza vaccines Agrippal and Fluvirin for active immunization against influenza. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Optical image encoding based on digital holographic recording on polarization state of vector wave.

    Science.gov (United States)

    Lin, Chao; Shen, Xueju; Xu, Qinzu

    2013-10-01

    We propose and analyze a compact optical image encoder based on the principle of digital holographic recording on the polarization state of a vector wave. The optical architecture is a Mach-Zehnder interferometer with in-line digital holographic recording mechanism. The original image is represented by distinct polarization states of elliptically polarized light. This state of polarization distribution is scrambled and then recorded by a two-step digital polarization holography method with random phase distributed reference wave. Introduction of a rotation key in the object arm and phase keys in the reference arm can achieve the randomization of plaintext. Statistical property of cyphertext is analyzed from confusion and diffusion point of view. Fault tolerance and key sensitivity of the proposed approach are also investigated. A chosen plaintext attack on the proposed algorithm exhibits its high security level. Simulation results that support the theoretical analysis are presented.

  18. Neural Semantic Encoders.

    Science.gov (United States)

    Munkhdalai, Tsendsuren; Yu, Hong

    2017-04-01

    We present a memory augmented neural network for natural language understanding: Neural Semantic Encoders. NSE is equipped with a novel memory update rule and has a variable sized encoding memory that evolves over time and maintains the understanding of input sequences through read, compose and write operations. NSE can also access multiple and shared memories. In this paper, we demonstrated the effectiveness and the flexibility of NSE on five different natural language tasks: natural language inference, question answering, sentence classification, document sentiment analysis and machine translation where NSE achieved state-of-the-art performance when evaluated on publically available benchmarks. For example, our shared-memory model showed an encouraging result on neural machine translation, improving an attention-based baseline by approximately 1.0 BLEU.

  19. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy

    DEFF Research Database (Denmark)

    De Santis, Maria; Bellmunt, Joaquim; Mead, Graham

    2012-01-01

    This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy.......This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy....

  20. Phase transition and random-field induced domain wall response in quantum ferroelectrics SrTi18O3: review and perspective

    Directory of Open Access Journals (Sweden)

    Mitsuru Itoh, Toshirou Yagi, Yoshiaki Uesu, Wolfgang Kleemann and Robert Blinc

    2004-01-01

    Full Text Available The oxygen isotope exchange of 16O by 18O in SrTiO3 causes a drastic change from paraelectric to ferroelectric, due to the suppression of quantum fluctuation. The phase transition and origin of the huge domain wall response were evaluated by dielectric, magnetic (NMR, and optical measurements (SHG, light scattering. The results obtained corroborate (1 smeared ferroelectric transition at Tc due to quenched random field, (2 a quite large dielectric contribution from domain walls, (3 incomplete softening of the transverse optic mode, and (4 a large contribution from the relaxational mode to the phase transition. Quantitative explanations, given to individual results, may give hints to grasp the mechanism for the evolution of ferroelectricity, in which quantum fluctuation and random fields are dominant perturbations. Finally, some of the news studies on the SrTiO3 were also introduced.

  1. Effect of Mo on the phase stability and elastic mechanical properties of Ti-Mo random alloys from ab initio calculations

    Science.gov (United States)

    Cao, Peiyu; Tian, Fuyang; Wang, Yandong

    2017-11-01

    Ti-Mo alloys are promising materials for shape memory alloys and biomedical materials. Whereas, the appearance of metastable ω phase can cause embrittlement and destroy the shape memory effect. In order to avoid the ω phase, the effect of Mo on the temperature dependent lattice parameters, phase stability and elastic mechanical properties of β, α, and ω Ti1-x Mo x (x  =  0-2.0) random alloys was systematically investigated by using the exact muffin-tin orbitals method in combination with the coherent potential approximation. The theoretical predictions for the lattice parameters are in good agreement with the available experiments. Results show that β Ti0.96Mo0.04 can almost transform to ω phase without lattice deformation and volume change, which suggests that the athermal ω phase is easier to precipitate and grow near 4 at.% Mo content in the β Ti1-x Mo x alloys. The critical content of Mo for the competed stabilization of β phase at T  =  300 K is ~11.2 at.%. Its valence electron concentration of 4.224 is viewed as a necessary criterion for the competed phase stability. The calculations of formation energy are used to explain successfully why the partitioning of Mo can be found in Ti0.91Mo0.09 alloy after annealing. Through the analysis of formation energy, both Mo addition and increasing temperature can stabilize the β phase. The calculated Cauchy pressure, Pugh’s ratio, Poisson ratio, and Young’s modulus suggests that ω phase is intrinsically brittle and has large Young’s modulus compared with β and α phases.

  2. Efficacy of an Ayurvedic Formulation for Mild-to-moderate Osteoarthritis: A Phase 3, Randomized Controlled Study.

    Science.gov (United States)

    Modak, Milind Dattatraya; Barde, Mohini Prajak

    2017-01-01

    Context • Current treatment options offer only symptomatic pain relief for patients with osteoarthritis (OA). Thus, a need exists for effective treatment of the disability-causing disease. The proprietary polyherbal formulation, Nartana, has been used for several years for OA. Objective • The study intended to compare the benefits of the herbal formulation with those of routinely used nonsteroidal anti-inflammatory drugs (NSAIDs) for patients with mild-to-moderate OA. Design • The research team designed a phase 3, double-blind, double-dummy, randomized controlled study. Setting • The study was conducted at 2 hospital sites in Pune, India. Participants • The participants were 80 outpatients with OA at the hospitals. Intervention • The participants were randomly assigned to receive either the intervention (herbal formulation) or the active control (diclofenac) for 12 wk. The herbal formulation group received 450 mg of Nartana capsule and diclofenac-matching placebo. Treatment was given 2 ×/d for first 15 d and then 1 ×/d until the end of the study. The control group received 50 mg of diclofenac tablet 2 ×/d for first 15 d and then 100 mg of diclofenac tablet 1 ×/d and a Nartana-matching placebo until end of the study. Outcome Measures • To measure efficacy, the study used the modified Center for Rheumatic Diseases Pune version of the Western Ontario and McMaster Universities OA index (WOMAC) and the Health Assessment Questionnaire (HAQ). The study also measured overall perceived pain relief. The primary outcome measure was the change in the combined WOMAC score from baseline to postintervention (12 wk). Safety and other efficacy measures were the secondary end points. Results • The herbal formulation and diclofenac groups matched well at baseline for demographic profile, disease status, and WOMAC scores. The combined WOMAC scores were significantly reduced from baseline to postintervention for both groups (P < .01). The earliest significant

  3. Efficacy and safety of bilastine in Japanese patients with perennial allergic rhinitis: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study

    OpenAIRE

    Okubo, Kimihiro; Gotoh, Minoru; Asako, Mikiya; Nomura, Yasuyuki; Togawa, Michinori; Saito, Akihiro; Honda, Takayuki; Ohashi, Yoshihiro

    2016-01-01

    Background: Bilastine, a novel non-sedating second-generation H1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). Methods: This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexo...

  4. M1 (e, e') excitations in {sup 30}Si and {sup 31}S from the quasiparticle random-phase approximation

    Energy Technology Data Exchange (ETDEWEB)

    Udias, J.M.; Faessler, Amand [Institut fuer Theoretische Physik, Universitaet Tuebingen, Auf der Morgenstelle 14, D-72076, Tuebingen (Germany); Nojarov, R. [Institute of Nuclear Research and Nuclear Energy, Bulgarian Academy of Sciences, BG-1784, Sofia (Bulgaria)

    1997-11-01

    We apply the QRPA formalism developed in previous works to study the excitation of the M1 mode through (e, e') scattering on {sup 30}Si and {sup 32}S. The agreement with experiment is comparable with that of the shell model for sd-shell nuclei. Having in view previous works for heavy and medium nuclei, one could conclude that the quasiparticle random-phase approximation (QRPA) is applicable to nuclei from a wide range of masses. (author)

  5. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.

    Science.gov (United States)

    Burri, Christian; Yeramian, Patrick D; Allen, James L; Merolle, Ada; Serge, Kazadi Kyanza; Mpanya, Alain; Lutumba, Pascal; Mesu, Victor Kande Betu Ku; Bilenge, Constantin Miaka Mia; Lubaki, Jean-Pierre Fina; Mpoto, Alfred Mpoo; Thompson, Mark; Munungu, Blaise Fungula; Manuel, Francisco; Josenando, Théophilo; Bernhard, Sonja C; Olson, Carol A; Blum, Johannes; Tidwell, Richard R; Pohlig, Gabriele

    2016-02-01

    Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT. The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent. Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.

  6. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.

    Directory of Open Access Journals (Sweden)

    Christian Burri

    2016-02-01

    Full Text Available Sleeping sickness (human African trypanosomiasis [HAT] is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC] between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2, where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a or 3 months (Phase 2b after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93% than pafuramidine treatment for 5 days (25% and 10 days (57%. These results support continuation of the development program for pafuramidine into Phase 3.

  7. Spin-adapted open-shell random phase approximation and time-dependent density functional theory. I. Theory.

    Science.gov (United States)

    Li, Zhendong; Liu, Wenjian

    2010-08-14

    The spin-adaptation of single-reference quantum chemical methods for excited states of open-shell systems has been nontrivial. The primary reason is that the configuration space, generated by a truncated rank of excitations from only one component of a reference multiplet, is spin-incomplete. Those "missing" configurations are of higher ranks and can, in principle, be recaptured by a particular class of excitation operators. However, the resulting formalisms are then quite involved and there are situations [e.g., time-dependent density functional theory (TD-DFT) under the adiabatic approximation] that prevent one from doing so. To solve this issue, we propose here a tensor-coupling scheme that invokes all the components of a reference multiplet (i.e., a tensor reference) rather than increases the excitation ranks. A minimal spin-adapted n-tuply excited configuration space can readily be constructed by tensor products between the n-tuple tensor excitation operators and the chosen tensor reference. Further combined with the tensor equation-of-motion formalism, very compact expressions for excitation energies can be obtained. As a first application of this general idea, a spin-adapted open-shell random phase approximation is first developed. The so-called "translation rule" is then adopted to formulate a spin-adapted, restricted open-shell Kohn-Sham (ROKS)-based TD-DFT (ROKS-TD-DFT). Here, a particular symmetry structure has to be imposed on the exchange-correlation kernel. While the standard ROKS-TD-DFT can access only excited states due to singlet-coupled single excitations, i.e., only some of the singly excited states of the same spin (S(i)) as the reference, the new scheme can capture all the excited states of spin S(i)-1, S(i), or S(i)+1 due to both singlet- and triplet-coupled single excitations. The actual implementation and computation are very much like the (spin-contaminated) unrestricted Kohn-Sham-based TD-DFT. It is also shown that spin-contaminated spin

  8. Critical analysis of an oncolytic herpesvirus encoding granulocyte-macrophage colony stimulating factor for the treatment of malignant melanoma.

    Science.gov (United States)

    Hughes, Tasha; Coffin, Robert S; Lilley, Caroline E; Ponce, Rafael; Kaufman, Howard L

    2014-01-01

    Oncolytic viruses that selectively lyse tumor cells with minimal damage to normal cells are a new area of therapeutic development in oncology. An attenuated herpesvirus encoding the granulocyte-macrophage colony stimulating factor (GM-CSF), known as talimogene laherparepvec (T-VEC), has been identified as an attractive oncolytic virus for cancer therapy based on preclinical tumor studies and results from early-phase clinical trials and a large randomized Phase III study in melanoma. In this review, we discuss the basic biology of T-VEC, describe the role of GM-CSF as an immune adjuvant, summarize the preclinical data, and report the outcomes of published clinical trials using T-VEC. The emerging data suggest that T-VEC is a safe and potentially effective antitumor therapy in malignant melanoma and represents the first oncolytic virus to demonstrate therapeutic activity against human cancer in a randomized, controlled Phase III study.

  9. Designing the selenium and bladder cancer trial (SELEBLAT, a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

    Directory of Open Access Journals (Sweden)

    Goossens Maria E

    2012-03-01

    Full Text Available Abstract Background In Belgium, bladder cancer is the fifth most common cancer in males (5.2% and the sixth most frequent cause of death from cancer in males (3.8%. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence. Method The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 μg/day supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study. Design The SELEnium and BLAdder cancer Trial (SELEBLAT is a phase III randomized, placebo-controlled, academic, double-blind superior trial. Discussion This is the first report on a selenium randomized trial in bladder cancer patients. Trial registration ClinicalTrials.gov identifier: NCT00729287

  10. Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma : A Randomized, Multicenter, Open-Label Phase 3 Trial

    NARCIS (Netherlands)

    Geissler, Edward K.; Schnitzbauer, Andreas A.; Zuelke, Carl; Lamby, Philipp E.; Proneth, Andrea; Duvoux, Christophe; Burra, Patrizia; Jauch, Karl-Walter; Rentsch, Markus; Ganten, Tom M.; Schmidt, Jan; Settmacher, Utz; Heise, Michael; Rossi, Giorgio; Cillo, Umberto; Kneteman, Norman; Adam, Rene; van Hoek, Bart; Bachellier, Philippe; Wolf, Philippe; Rostaing, Lionel; Bechstein, Wolf O.; Rizell, Magnus; Powell, James; Hidalgo, Ernest; Gugenheim, Jean; Wolters, Heiner; Brockmann, Jens; Roy, Andre; Mutzbauer, Ingrid; Schlitt, Angela; Beckebaum, Susanne; Graeb, Christian; Nadalin, Silvio; Valente, Umberto; Sanchez Turrion, Victor; Jamieson, Neville; Scholz, Tim; Colledan, Michele; Faendrich, Fred; Becker, Thomas; Soderdahl, Gunnar; Chazouilleres, Olivier; Makisalo, Heikki; Pageaux, Georges-Philippe; Steininger, Rudolf; Soliman, Thomas; de Jong, Koert P.; Pirenne, Jacques; Margreiter, Raimund; Pratschke, Johann; Pinna, Antonio D.; Hauss, Johann; Schreiber, Stefan; Strasser, Simone; Klempnauer, Juergen; Troisi, Roberto I.; Bhoori, Sherrie; Lerut, Jan; Bilbao, Itxarone; Klein, Christian G.; Koenigsrainer, Alfred; Mirza, Darius F.; Otto, Gerd; Mazzaferro, Vincenzo; Neuhaus, Peter; Schlitt, Hans J.

    Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target

  11. GnRH agonist during luteal phase in women undergoing assisted reproductive techniques: systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Martins, W P; Ferriani, R A; Navarro, P A; Nastri, C O

    2016-02-01

    To identify, evaluate and summarize the available evidence regarding the effectiveness and safety of administering a gonadotropin releasing hormone (GnRH) agonist during the luteal phase in women undergoing assisted reproductive techniques. In this systematic review and meta-analysis, we searched for randomized controlled trials (RCTs) comparing the addition of a GnRH agonist during the luteal phase, compared with standard luteal-phase support. We searched seven electronic databases and hand-searched the reference lists of included studies and related reviews. Our primary outcome was live birth or ongoing pregnancy per randomized woman. Our secondary outcomes were clinical pregnancy per randomized woman, miscarriage per clinical pregnancy, adverse perinatal outcome and congenital malformations. The evidence from eight studies examining 2776 women showed a relative risk (RR) for live birth or ongoing pregnancy of 1.26 (95% CI, 1.04-1.53; I(2) = 58%). Sensitivity analysis when excluding the studies that did not report live birth and those at high risk of bias resulted in one study examining 181 women with an RR of 1.07 (95% CI, 0.73-1.58). Subgroup analysis separating the studies by single/multiple doses of GnRH agonists or by ovarian stimulation with GnRH agonist/antagonist was unable to explain the observed heterogeneity. The quality of the evidence was deemed to be very low: it was downgraded because of the limitation of the included studies, imprecision, inconsistency across the studies' results, and suspicion of publication bias. None of the included studies reported adverse perinatal outcomes or congenital malformations. There is evidence that adding GnRH agonist during the luteal phase improves the likelihood of ongoing pregnancy. However, this evidence is of very low quality and there is no evidence for adverse perinatal outcome and congenital malformations. We therefore believe that including this intervention in clinical practice would be premature

  12. Encoding the Factorisation Calculus

    Directory of Open Access Journals (Sweden)

    Reuben N. S. Rowe

    2015-08-01

    Full Text Available Jay and Given-Wilson have recently introduced the Factorisation (or SF- calculus as a minimal fundamental model of intensional computation. It is a combinatory calculus containing a special combinator, F, which is able to examine the internal structure of its first argument. The calculus is significant in that as well as being combinatorially complete it also exhibits the property of structural completeness, i.e. it is able to represent any function on terms definable using pattern matching on arbitrary normal forms. In particular, it admits a term that can decide the structural equality of any two arbitrary normal forms. Since SF-calculus is combinatorially complete, it is clearly at least as powerful as the more familiar and paradigmatic Turing-powerful computational models of Lambda Calculus and Combinatory Logic. Its relationship to these models in the converse direction is less obvious, however. Jay and Given-Wilson have suggested that SF-calculus is strictly more powerful than the aforementioned models, but a detailed study of the connections between these models is yet to be undertaken. This paper begins to bridge that gap by presenting a faithful encoding of the Factorisation Calculus into the Lambda Calculus preserving both reduction and strong normalisation. The existence of such an encoding is a new result. It also suggests that there is, in some sense, an equivalence between the former model and the latter. We discuss to what extent our result constitutes an equivalence by considering it in the context of some previously defined frameworks for comparing computational power and expressiveness.

  13. Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

    Directory of Open Access Journals (Sweden)

    Nativ Ofer

    2012-11-01

    Full Text Available Abstract Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10, and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC-controlled Phase I/II study (N = 7 in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10: All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7: Hemostatic success at 10 min (primary endpoint was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial

  14. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial

    Science.gov (United States)

    Gimsing, Peter; Hjertner, Oyvind; Lenhoff, Stig; Laane, Edward; Remes, Kari; Steingrimsdottir, Hlif; Abildgaard, Niels; Ahlberg, Lucia; Blimark, Cecilie; Dahl, Inger Marie; Forsberg, Karin; Gedde-Dahl, Tobias; Gregersen, Henrik; Gruber, Astrid; Guldbrandsen, Nina; Haukås, Einar; Carlson, Kristina; Kvam, Ann Kristin; Nahi, Hareth; Lindås, Roald; Andersen, Niels Frost; Turesson, Ingemar; Waage, Anders; Westin, Jan; Gregersen, Henrik; Frost Andersen, Niels; Gimsing, Peter; Toffner-Clausen, Nilsaage; Abildgaard, Niels; Laane, Edward; Silvennoinen, Raija; Remes, Kari; Steingrimsdottir, Hlif; Lindås, Roald; Gedde-Dahl, Tobias; Guldbrandsen, Nina; Kristin Kvam, Ann; Haukås, Einar; Marie Dahl, Inger; Hjertner, Oyvind; Waage, Anders; Blimark, Cecilie; Mellqvist, Ulf-Henrik; Westin, Jan; Ahlberg, Lucia; Lenhoff, Stig; Turesson, Ingemar; Linder, Olle; Gruber, Astrid; Nahi, Hareth; Forsberg, Karin; Carlson, Kristina

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370 patients were centrally randomly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation. The hypothesis was that consolidation therapy would prolong progression-free survival (PFS). The PFS after randomization was 27 months for the bortezomib group compared with 20 months for the control group (P = .05). Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after randomization (P = .007). No difference in overall survival was seen. Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality-of-life (QOL) questionnaires, whereas no other major differences in QOL were recorded between the groups. Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response (VGPR) but not for patients in the ≥ VGPR category at randomization. Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL. This trial was registered at www.clinicaltrials.gov as #NCT00417911. PMID:23616624

  15. The phase diagrams of the mixed-spin ternary-alloy consisting of half-integer spins: Standard-random approach

    Science.gov (United States)

    Albayrak, Erhan

    2018-02-01

    The ternary-alloy in the form ABpC1-p is investigated on the Bethe lattice with the odd numbered shells containing only A atoms (spin-1/2), while the even shells randomly containing either B (spin-3/2) or C (spin-5/2) atoms with different concentrations p and 1 - p, respectively. The phase diagrams are calculated on the (p ,kTc /JAB) and (R = |JAC | /JAB ,kTc /JAB) planes for given values of R and p, respectively, with the coordination numbers z = 3 , 4 , 5 and 6 by studying the thermal variations of the order-parameters. It is found that there exist a critical value of R, i.e. Rc ≅ 0.653, which is independent of z. In addition, the critical temperatures increase as z increases. The present work is an extension of the previous work [1] and it only differs from it by the implementation technique of randomness into the model. The obtained phase diagrams are in agreement with the site-dependent random case [1] except at low temperatures. On the other hand, there is an overall agreement with the literature.

  16. Bit error rate analysis of Gaussian, annular Gaussian, cos Gaussian, and cosh Gaussian beams with the help of random phase screens.

    Science.gov (United States)

    Eyyuboğlu, Halil T

    2014-06-10

    Using the random phase screen approach, we carry out a simulation analysis of the probability of error performance of Gaussian, annular Gaussian, cos Gaussian, and cosh Gaussian beams. In our scenario, these beams are intensity-modulated by the randomly generated binary symbols of an electrical message signal and then launched from the transmitter plane in equal powers. They propagate through a turbulent atmosphere modeled by a series of random phase screens. Upon arriving at the receiver plane, detection is performed in a circuitry consisting of a pin photodiode and a matched filter. The symbols detected are compared with the transmitted ones, errors are counted, and from there the probability of error is evaluated numerically. Within the range of source and propagation parameters tested, the lowest probability of error is obtained for the annular Gaussian beam. Our investigation reveals that there is hardly any difference between the aperture-averaged scintillations of the beams used, and the distinctive advantage of the annular Gaussian beam lies in the fact that the receiver aperture captures the maximum amount of power when this particular beam is launched from the transmitter plane.

  17. A shoe sole-based apparatus and method for randomly perturbing the stance phase of gait: test-retest reliability in young adults.

    Science.gov (United States)

    Kim, Hogene; Ashton-Miller, James A

    2012-06-26

    Walking on an irregular surface is associated with an elevated risk for a fall at any age. Yet, relatively little is known about how a human responds to an unexpected underfoot perturbation during gait. This is partly due to the difficulty of generating an intermittent but repeatable, unexpected, underfoot perturbation whose size and location are precisely known. So we developed a shoe sole-embedded apparatus for randomly perturbing the stance phase of gait. Medial and lateral flaps were concealed in the soles of pairs of sandals, along with their actuators. Either flap could be deployed within 400ms in the parasagittal plane under a swing foot; this altered the resulting sagittal and frontal plane orientations of the foot during the next stance phase, whereafter the flap was retracted following toe-off for the rest of that gait trial. We tested six healthy young subjects by randomly presenting a single medial or lateral perturbation in 12 of 30 gait trials. Traditional step kinematic measures were used to evaluate the test-retest reliability of the response to the stimulus at two different walking speeds in 60 randomized trials conducted 1 week apart. The method was effective in systematically inducing an alteration in gait, reproducible across visits, as evidenced by acceptable intraclass correlation coefficients for step width, time and length. We conclude that the apparatus and method has potential for measuring the ability of humans to reject one or more unexpected underfoot perturbations during gait. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Add-on mirtazapine improves depressive symptoms in schizophrenia: a double-blind randomized placebo-controlled study with an open-label extension phase.

    Science.gov (United States)

    Terevnikov, Viacheslav; Stenberg, Jan-Henry; Tiihonen, Jari; Joffe, Marina; Burkin, Mark; Tchoukhine, Evgueni; Joffe, Grigori

    2011-04-01

    Depression is common in schizophrenia and worsens its course. The role of antidepressants for schizophrenic depression remains unclear. In this study, the efficacy of add-on mirtazapine on depression in schizophrenia was explored in a subsidiary arm of a recent randomized controlled trial. Patients (n = 41) with chronic but stable schizophrenia and inadequate response to stable doses of different first-generation antipsychotics were treated with add-on mirtazapine 30 mg or placebo during a 6-week double-blind phase and with open-label add-on mirtazapine during a 6-week extension phase. Efficacy measures were the Calgary Depression Scale for Schizophrenia (CDSS) and the Positive and Negative Syndrome Scale depression item. During the double-blind phase, both measures' scores decreased significantly in the mirtazapine group but not in the placebo group (for the CDSS, 52.0% vs 19.6%, respectively). During the open‐label phase, both groups demonstrated significant improvements. In between‐group comparison, a trend favoring mirtazapine did not reach statistical significance. The changes in the CDSS correlated positively with those in the Positive and Negative Syndrome Scale negative, positive and total (sub)scales for mirtazapine‐treated patients during the double‐blind phase. Depressed patients with schizophrenia may benefit from mirtazapine–first‐generation antipsychotics combination, with no increased risk for psychosis. However, more studies are needed.

  19. Biological 18[F]-FDG-PET image-guided dose painting by numbers for painful uncomplicated bone metastases: A 3-arm randomized phase II trial.

    Science.gov (United States)

    Berwouts, Dieter; De Wolf, Katrien; Lambert, Bieke; Bultijnck, Renée; De Neve, Wilfried; De Lobel, Lizzy; Jans, Lennart; Goetghebeur, Els; Speleers, Bruno; Olteanu, Luiza A M; Madani, Indira; Goethals, Ingeborg; Ost, Piet

    2015-05-01

    Antalgic radiotherapy for bone metastases might be improved by implementing biological information in the radiotherapy planning using (18)F-FDG-PET-CT based dose painting by numbers (DPBN). Patients with uncomplicated painful bone metastases were randomized (1:1:1) and blinded to receive either 8Gy in a single fraction with conventionally planned radiotherapy (arm A) or 8Gy in a single fraction with DPBN (dose range between 610Gy and 10Gy) (arm B) or 16Gy in a single fraction with DPBN (dose range between 1410Gy and 18Gy) (arm C). The primary endpoint was overall pain response at 1month. The phase II trial was designed to select the experimental arm with sufficient promise of efficacy to continue to a phase III trial. Forty-five patients were randomized. Eight (53%), 12 (80%) and 9 patients (60%) had an overall response to treatment in arm A, B and C, respectively. The estimated odds ratio of overall response for arm B vs. A is 3.5 (95% CI: 0.44-17.71, p=0.12). The estimated odds ratio of arm C vs. A is 1.31 (95% CI: 0.31-5.58, p=0.71). A single fraction of 8Gy with DPBN will be further evaluated in a phase III-trial. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Effects of motive-oriented therapeutic relationship in early-phase treatment of borderline personality disorder: a pilot study of a randomized trial.

    Science.gov (United States)

    Kramer, Ueli; Berger, Thomas; Kolly, Stéphane; Marquet, Pierre; Preisig, Martin; de Roten, Yves; Despland, Jean-Nicolas; Caspar, Franz

    2011-04-01

    Motive-oriented therapeutic relationship (MOTR, also called complementary therapeutic relationship) was postulated to be a particularly helpful therapeutic ingredient in the early-phase treatment of patients with personality disorders, in particular borderline personality disorder (BPD). The present pilot study of randomized controlled trial using an add-on design aims to investigate the effects of MOTR in early-phase treatment (up to session 10), with BPD patients on therapeutic alliance, session impact, and outcome. In total, N = 25 patients participated in the study. BPD patients were randomly allocated to a manual-based investigation process in 10 sessions or to the same investigation process infused with MOTR. Adherence ratings were performed and yielded satisfactory results. The results suggested a specific effectiveness of MOTR on the interpersonal problem area, on the quality of the therapeutic alliance and the quality of the therapeutic relationship, as rated by the patient. These results may have important clinical implications for the early-phase treatment of patients presenting with BPD.

  1. Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factor-bearing microparticles: a randomized-controlled phase II trial (the Microtec study).

    Science.gov (United States)

    Zwicker, Jeffrey I; Liebman, Howard A; Bauer, Kenneth A; Caughey, Thomas; Campigotto, Federico; Rosovsky, Rachel; Mantha, Simon; Kessler, Craig M; Eneman, Jonathan; Raghavan, Vidya; Lenz, Heinz-Joseph; Bullock, Andrea; Buchbinder, Elizabeth; Neuberg, Donna; Furie, Bruce

    2013-02-01

    Elevated levels of circulating tissue factor-bearing microparticles (TFMP) have been associated with an increased risk of developing venous thromboembolism (VTE) in cancer patients. We performed a randomized phase II study to evaluate the cumulative incidence of VTE in advanced cancer patients with lower levels of TFMP not receiving thromboprophylaxis and those with higher levels of circulating TFMP randomized to enoxaparin or observation. The cumulative incidence of VTE at 2 months in the higher TFMP group randomized to enoxaparin (N = 23) was 5·6% while the higher TFMP group observation arm (N = 11) was 27·3% (Gray test P = 0·06). The cumulative incidence of VTE in the low TFMP was 7·2% (N = 32). No major haemorrhages were observed in the enoxaparin arm. The median survival for patients with higher levels of TFMP followed by observation was 11·8 months compared with 17·8 months on enoxaparin (P = 0·58). In a prospective randomized trial, increased numbers of circulating TFMP detected by impedance flow cytometry identified cancer patients with a high incidence of VTE. Enoxaparin demonstrated a clear trend towards reducing the rate of VTE in patients with elevated levels of TFMP, with an overall rate of VTE similar in magnitude to the lower TFMP group. © 2012 Blackwell Publishing Ltd.

  2. Motor Recovery and Cortical Reorganization After Mirror Therapy in Chronic Stroke Patients : A Phase II Randomized Controlled Trial

    NARCIS (Netherlands)

    Michielsen, Marian E.; Selles, Ruud W.; van der Geest, Jos N.; Eckhardt, Martine; Yavuzer, Gunes; Stam, Henk J.; Smits, Marion; Ribbers, Gerard M.; Bussmann, Johannes B. J.

    2011-01-01

    Objective. To evaluate for any clinical effects of home-based mirror therapy and subsequent cortical reorganization in patients with chronic stroke with moderate upper extremity paresis. Methods. A total of 40 chronic stroke patients (mean time post. onset, 3.9 years) were randomly assigned to the

  3. Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma : Randomized phase III EORTC study

    NARCIS (Netherlands)

    Kluin-Nelemans, HC; Zagonel, [No Value; Anastasopoulou, A; Bron, D; Roozendaal, KJ; Noordijk, EM; Musson, H; Teodorovic, [No Value; Maes, B; Carbone, A; Carde, P

    2001-01-01

    Background: The long-term outcome for patients with aggressive non-Hodgkin's lymphoma (NHL) is poor. Consequently; the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone

  4. A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia

    DEFF Research Database (Denmark)

    Birgens, Henrik; Frederiksen, Henrik; Hasselbalch, Hans Carl

    2013-01-01

    The impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and ritu...

  5. Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study.

    NARCIS (Netherlands)

    Richards, D.A.; Boehm, K.A.; Waterhouse, D.M.; Wagener, D.J.T.; Krishnamurthi, S.S.; Rosemurgy, A.; Grove, W.; Macdonald, K.; Gulyas, S.; Clark, M.; Dasse, K.D.

    2006-01-01

    BACKGROUND: CI-994, an oral histone deacetylase inhibitor, has antineoplastic activity and synergism with gemcitabine preclinically. This randomized phase II trial explored whether CI-994 plus gemcitabine improves overall survival, objective response, duration of response, time to treatment failure

  6. Up-front fludarabine impairs stem cell harvest in multiple myeloma: report from an interim analysis of the NMSG 13/03 randomized placebo controlled phase II trial

    DEFF Research Database (Denmark)

    Johnsen, Hans Erik; Knudsen, Lene Meldgaard; Mylin, Anne Kærsgaard

    2009-01-01

    toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p lower than 0.05). In conclusion, the scheduled fludarabine dosage in 2 cycles......The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conclusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim...

  7. Up-front fludarabine impairs stem cell harvest in multiple myeloma: report of the NMSG 13/03 randomized placebo controlled phase II trial

    DEFF Research Database (Denmark)

    Johnsen, Hans E.; Meldgaard Knudsen, Lene; Mylin, Anne K.

    2009-01-01

    toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p...The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conlusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim...

  8. An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin

    2013-01-01

    This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer.......This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

  9. Phase Vocoder

    Directory of Open Access Journals (Sweden)

    J.L. Flanagan

    2013-08-01

    Full Text Available A vocoder technique is described in which speech signals are represented by their short-time phase and amplitude spectra. A complete transmission system utilizing this approach is simulated on a digital computer. The encoding method leads to an economy in transmission bandwidth and to a means for time compression and expansion of speech signals.

  10. Optical cryptosystem based on phase-truncated Fresnel diffraction and transport of intensity equation.

    Science.gov (United States)

    Zhang, Chenggong; He, Wenqi; Wu, Jiachen; Peng, Xiang

    2015-04-06

    A novel optical cryptosystem based on phase-truncated Fresnel diffraction (PTFD) and transport of intensity equation (TIE) is proposed. By using the phase truncation technique, a phase-encoded plaintext could be encrypted into a real-valued noise-like intensity distribution by employing a random amplitude mask (RAM) and a random phase mask (RPM), which are regarded as two secret keys. For decryption, a generalized amplitude-phase retrieval (GAPR) algorithm combined with the TIE method are proposed to recover the plaintext with the help of two keys. Different from the current phase-truncated-based optical cryptosystems which need record the truncated phase as decryption keys, our scheme do not need the truncated phase because of the introducing of the TIE method. Moreover, the proposed scheme is expected to against existing attacks. A set of numerical simulation results show the feasibility and security of the proposed method.

  11. Ocular comfort assessment of lifitegrast ophthalmic solution 5.0% in OPUS-3, a Phase III randomized controlled trial.

    Science.gov (United States)

    Nichols, Kelly K; Holland, Edward; Toyos, Melissa M; Peace, James H; Majmudar, Parag; Raychaudhuri, Aparna; Hamdani, Mohamed; Roy, Monica; Shojaei, Amir

    2018-01-01

    To evaluate ocular comfort of lifitegrast ophthalmic solution 5.0% among patients with dry eye disease (DED) in the OPUS-3 trial. OPUS-3 was a multicenter, randomized, double-masked, placebo-controlled study. Adults with DED and recent artificial tear use were randomized 1:1 (lifitegrast:placebo) to ophthalmic drops twice daily for 84 days. On days 0 (baseline), 14, 42, and 84, drop comfort score (scale, 0-10; 0 = very comfortable, 10 = very uncomfortable) was measured at 0, 1, 2, and 3 minutes postinstillation. If the score was >3 at 3 minutes, assessment was repeated at 5, 10, and 15 minutes until score ≤3. Ocular treatment-emergent adverse events (TEAEs) were assessed. Overall, 711 participants were randomized (n=357 received lifitegrast; n=354 received placebo). Drop comfort scores for lifitegrast-treated participants improved within 3 minutes of instillation (mean scores on day 84 for both study and fellow eyes: instillation: lifitegrast, 3.4, placebo, 1.0; 3 minutes: lifitegrast, 1.5, placebo, 0.7). The majority (64%-66%) of participants had scores 3 at 3 minutes, the mean score in the lifitegrast group was similar to or better than that in the placebo group at 5, 10, or 15 minutes postinstillation. Lifitegrast appeared to be well tolerated, with ocular TEAEs rarely leading to discontinuation. In OPUS-3, lifitegrast appeared to be well tolerated and drop comfort scores approached placebo levels by 3 minutes postinstillation.

  12. Self-perpetuating development of encoding biases in person perception.

    Science.gov (United States)

    Hill, T; Lewicki, P; Czyzewska, M; Boss, A

    1989-09-01

    It was hypothesized that encoding (interpretive) biases may develop in a self-perpetuating manner through biased, self-supportive encoding (even in the absence of any objectively supportive evidence). This process was investigated in 3 experiments with different stimulus materials (matrices of digits, silhouettes of persons, descriptions of personal problems). In the learning phase of each study, Ss nonconsciously acquired some encoding bias. In the testing phase, Ss' encoding of new material was predictably biased, and, consistent with the self-perpetuation hypothesis, the strength of the bias gradually increased over the segments of the material, even though the material did not contain any evidence supportive of the bias. Given the ambiguity of many (particularly social) stimuli, the self-perpetuation process may play a ubiquitous role in the development of interpretive categories and other individually differentiated cognitive dispositions.

  13. Detecting Faults from Encoded Information

    NARCIS (Netherlands)

    Persis, Claudio De

    2003-01-01

    The problem of fault detection for linear continuous-time systems via encoded information is considered. The encoded information is received at a remote location by the monitoring deiice and assessed to infer the occurrence of the fault. A class of faults is considered which allows to use a simple

  14. Bioengineered Temporomandibular Joint Disk Implants: Study Protocol for a Two-Phase Exploratory Randomized Preclinical Pilot Trial in 18 Black Merino Sheep (TEMPOJIMS)

    Science.gov (United States)

    Monje, Florencio Gil; González-García, Raúl; Little, Christopher B; Mónico, Lisete; Pinho, Mário; Santos, Fábio Abade; Carrapiço, Belmira; Gonçalves, Sandra Cavaco; Morouço, Pedro; Alves, Nuno; Moura, Carla; Wang, Yadong; Jeffries, Eric; Gao, Jin; Sousa, Rita; Neto, Lia Lucas; Caldeira, Daniel; Salvado, Francisco

    2017-01-01

    Background Preclinical trials are essential to test efficacious options to substitute the temporomandibular joint (TMJ) disk. The contemporary absence of an ideal treatment for patients with severe TMJ disorders can be related to difficulties concerning the appropriate study design to conduct preclinical trials in the TMJ field. These difficulties can be associated with the use of heterogeneous animal models, the use of the contralateral TMJ as control, the absence of rigorous randomized controlled preclinical trials with blinded outcomes assessors, and difficulties involving multidisciplinary teams. Objective This study aims to develop a new, reproducible, and effective study design for preclinical research in the TMJ domain, obtaining rigorous data related to (1) identify the impact of bilateral discectomy in black Merino sheep, (2) identify the impact of bilateral discopexy in black Merino sheep, and (3) identify the impact of three different bioengineering TMJ discs in black Merino sheep. Methods A two-phase exploratory randomized controlled preclinical trial with blinded outcomes is proposed. In the first phase, nine sheep are randomized into three different surgical bilateral procedures: bilateral discectomy, bilateral discopexy, and sham surgery. In the second phase, nine sheep are randomized to bilaterally test three different TMJ bioengineering disk implants. The primary outcome is the histological gradation of TMJ. Secondary outcomes are imaging changes, absolute masticatory time, ruminant time per cycle, ruminant kinetics, ruminant area, and sheep weight. Results Previous preclinical studies in this field have used the contralateral unoperated side as a control, different animal models ranging from mice to a canine model, with nonrandomized, nonblinded and uncontrolled study designs and limited outcomes measures. The main goal of this exploratory preclinical protocol is to set a new standard for future preclinical trials in oromaxillofacial surgery

  15. Parenteral nutrition at the palliative phase of advanced cancer: the ALIM-K study protocol for a randomized controlled trial

    OpenAIRE

    Pazart, Lionel; Cretin, Elodie; Grodard, Ghislain; Cornet, Cecile; Mathieu-Nicot, Florence; Bonnetain, Franck; Mercier, Mariette; Cuynet, Patrice; Bouleuc, Carole; Aubry, Regis

    2014-01-01

    Background Malnutrition is a common complication in patients at the palliative stage of cancer. During the curative phase of cancer, optimal enteral or parenteral nutrition intake can reduce morbidity and mortality, and improve quality of life. When the main goal of treatment becomes palliative, introduction of artificial nutrition is controversial. Although scientific societies do not recommend the introduction of artificial nutrition in all cases of malnutrition, especially in hypophagic pa...

  16. Secure Optical Storage that Uses Fully Phase Encryption

    Science.gov (United States)

    Tan, Xiaodi; Matoba, Osamu; Shimura, Tsutomu; Kuroda, Kazuo; Javidi, Bahram

    2000-12-01

    A secure holographic memory system that uses fully phase encryption is presented. Two-dimensional arrays of data are phase encoded. Each array is then transformed into a stationary white-noise-like pattern by use of a random-phase mask located at the input plane and another at the Fourier plane. This encrypted information is then stored holographically in a photorefractive LiNbO 3 :Fe crystal. The original phase-encoded data can be recovered, by use of the two random-phase masks, with a phase-conjugate readout beam. This phase information can then be converted back to intensity information with an interferometer. Recording multiple images by use of angular multiplexing is demonstrated. The influence of a limited system bandwidth on the quality of reconstructed data is evaluated numerically. These computer simulation results show that a fully phase-based encryption system generally performs better than an amplitude-based encryption system when the system bandwidth is limited by a moderate amount.

  17. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study.

    Science.gov (United States)

    Guttman-Yassky, Emma; Silverberg, Jonathan I; Nemoto, Osamu; Forman, Seth B; Wilke, August; Prescilla, Randy; de la Peña, Amparo; Nunes, Fabio P; Janes, Jonathan; Gamalo, Margaret; Donley, David; Paik, Jim; DeLozier, Amy M; Nickoloff, Brian J; Simpson, Eric L

    2018-02-01

    Baricitinib, an oral selective inhibitor of Janus kinase (JAK)1 and JAK2, modulates pro-inflammatory cytokine signaling. The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD). In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCS) for 4 weeks before randomization to once daily placebo, baricitinib 2 mg, or baricitinib 4 mg for 16 weeks. Use of TCS was permitted during the study. Primary outcome was the proportion of patients achieving ≥50% reduction in the Eczema Area and Severity Index (EASI-50) compared to placebo. Significantly more baricitinib 4-mg patients achieved EASI-50 compared to placebo (61% vs 37%; P=0.027) at 16 weeks. The proportion of baricitinib 2- and 4-mg patients achieving EASI-50 compared to placebo was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 (49%) placebo, 17 (46%) baricitinib 2-mg, and 27 (71%) baricitinib 4-mg patients. A TCS standardization period prior to randomization reduced disease severity, limiting the ability to compare results to baricitinib monotherapy. Longer studies are required to confirm baricitinib efficacy and safety in AD patients. Baricitinib used with TCS reduced inflammation and pruritus in patients with moderate-to-severe atopic dermatitis (AD). Copyright © 2018. Published by Elsevier Inc.

  18. Cubic anisotropy created by defects of "random local anisotropy" type, and phase diagram of the O( n) Model

    Science.gov (United States)

    Berzin, A. A.; Morosov, A. I.; Sigov, A. S.

    2017-12-01

    The expression for the cubic-type-anisotropy constant created by defects of "random local anisotropy" type is derived. It is shown that the Imry-Ma theorem stating that in space dimensions d equilibrium one. At the defect concentration lower than the critical one the long-range order takes place in the system. For a strongly anisotropic distribution of the easy axes, the Imry-Ma state is suppressed completely and the long-range order state takes place at any defect concentration.

  19. A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults.

    Directory of Open Access Journals (Sweden)

    Pablo Tebas

    Full Text Available BACKGROUND: Neurokinin-1 receptor (NK1R antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic. METHODS: We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm(3 and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml and randomized within each stratum to receive aprepitant at 125 mg QD(Low, or 250 mg QD(High, or placebo(PL for 14 days, and followed for 42 days. RESULTS: Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low, 250 (High, and PL groups. 63% were male; 37% white; mean (SD age 43 (9.3 years. Geometric mean baseline viral load (copies/ml for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI change in log10 viral load at day 14 for Low, High, and PL was -0.02(-0.24,+0.20, -0.05(-0.21,+0.10, and +0.04(-0.08,+0.16, respectively. The number of subjects with AEs was 4(44.4%, 5(62.5%, and 1(10% for Low, High, and PL. No Grade 4 AEs occurred. CONCLUSIONS: Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00428519.

  20. A Phase 2 Randomized, Double-Blind, Multicenter Trial of Imexon Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy-naïve Pancreatic Adenocarcinoma.

    Science.gov (United States)

    Cohen, Steven J; Zalupski, Mark M; Conkling, Paul; Nugent, Francis; Ma, Wen Wee; Modiano, Manuel; Pascual, Rolan; Lee, Fa Chyi; Wong, Lucas; Hersh, Evan

    2015-12-24

    Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study. Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m days 1, 8, and 15 with either imexon, 875 mg/m or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate. A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7%), whereas 9 did in the placebo arm (17%). In the imexon arm, 23 patients had ≥50% reduction in CA 19-9 from baseline (33%), whereas 22 did in the placebo arm (31.4%). The median progression-free survival was 2.8 months in the imexon arm (95% confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95% CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95% CI, 4.2-6.7 m) as compared with 6.8 m (95% CI, 4.9-8.5 m) in the placebo arm, P=0.6822. The combination of imexon and gemcitabine does not result in improved outcome as initial therapy of metastatic pancreatic adenocarcinoma.

  1. A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Wun Ted

    2013-02-01

    Full Text Available Abstract Background Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study. Methods The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41 or placebo (n = 21 for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients. Results There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events. Conclusions Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain.

  2. A Phase II Randomized, Double-Blind, Placebo-Controlled Safety and Efficacy Study of Lenalidomide in Lumbar Radicular Pain with a Long-Term Open-Label Extension Phase.

    Science.gov (United States)

    Manning, Donald C; Gimbel, Joseph; Wertz, Robert; Rauck, Richard; Cooper, Alyse; Zeldis, Jerome B; Levinsky, Dale M

    2017-03-01

    This phase II study assessed lenalidomide efficacy and safety. Three-phase core study: 14-day prerandomization, 12-week treatment, and 52-week open-label extension. Fourteen US centers from July 2005 to July 2007. Chronic lumbar radicular pain patients without history of nerve injury or deficit. Subjects were randomized (1:1) to double-blind treatment with lenalidomide 10 mg or placebo once daily for 12 weeks, followed by a 52-week open-label extension. A 12-week, single-center, randomized-withdrawal (1:2, lenalidomide:placebo), exploratory study with open-label extension was undertaken in 12 subjects from the core extension who were naïve to neuropathic medications and with at least a two-point decrease from baseline average daily Pain Intensity-Numerical Rating Scale score. Of 180 subjects enrolled, 176 had at least one postbaseline measure; 132 completed the 12-week treatment phase. In the core study, no statistically significant difference in Pain Intensity-Numerical Rating Scale mean change (-0.02, P  =   0.958) was observed at week 12 between lenalidomide and placebo; proportions achieving pain reduction at week 12 and other secondary measures were comparable between lenalidomide and placebo. In the exploratory study, week 12 mean changes in Pain Intensity-Numerical Rating Scale scores were -0.05 (lenalidomide: N = 3) and 2.11 (placebo: N = 8). Mean changes in Brief Pain Inventory-short form interference scores were -3.33 and 8.38, respectively; scores at six months were maintained or decreased in 10 of 12 subjects. While this study does not support lenalidomide use in an unselected lumbar radicular pain population, an immunomodulating agent may relieve pain in select subjects naïve to neuropathic pain medications. ClinicalTrials.gov identifier: NCT00120120.

  3. Treatment efficacy of sacral nerve stimulation in slow transit constipation: a two-phase, double-blind randomized controlled crossover study.

    Science.gov (United States)

    Dinning, Phil G; Hunt, Linda; Patton, Vicki; Zhang, Teng; Szczesniak, Michal; Gebski, Val; Jones, Mike; Stewart, Peter; Lubowski, David Z; Cook, Ian J

    2015-05-01

    Sacral nerve stimulation (SNS) is a potential treatment for constipation refractory to standard therapies. However, there have been no randomized controlled studies examining its efficacy. In patients with slow transit constipation, we evaluated the efficacy of suprasensory and subsensory SNS compared with sham, in a prospective, 18-week randomized, double-blind, placebo-controlled, two-phase crossover study. The primary outcome measure was the proportion of patients who, on more than 2 days/week for at least 2 of 3 weeks, reported a bowel movement associated with a feeling of complete evacuation. After 3 weeks of temporary peripheral nerve evaluation (PNE), all patients had permanent implantation and were randomized to subsensory/sham (3 weeks each) and then re-randomized to suprasensory/sham (3 weeks each) with a 2-week washout period between each arm. Daily stool dairies were kept, and quality of life (QoL; SF36) was measured at the end of each arm. Between November 2006 and March 2012, 234 constipated patients were assessed, of whom 59 were willing and deemed eligible to participate (4 male; median age 42 years). Of the 59 patients, 16 (28%) responded to PNE. Fifty-five patients went on to permanent SNS implantation. The proportion of patients satisfying the primary outcome measure did not differ between suprasensory (30%) and sham (21%) stimulations, nor between subsensory (25%) and sham (25%) stimulations. There were no significant changes in QoL scores. In patients with refractory slow transit constipation, SNS did not improve the frequency of complete bowel movements over the 3-week active period.

  4. Comparison of antiplatelet effect and safety of clopidogrel napadisilate with clopidogrel bisulfate in stroke patients: multicenter, randomized, open-label, phase 4, non-inferiority clinical trial.

    Science.gov (United States)

    Kang, Kyusik; Lee, Se-Jin; Kim, Hee-Jin; Koh, Seong-Ho; Kim, Byung Kun

    2016-01-01

    Clopidogrel napadisilate has better chemical stability than clopidogrel bisulfate. Our trial's objective was to compare the efficacy and safety of clopidogrel napadisilate with clopidogrel bisulfate in participants with ischemic stroke. The study was a phase 4, 4 week, randomized, parallel-group, non-inferiority trial. Patients with ischemic stroke were randomized to receive either clopidogrel napadisilate 75 mg or clopidogrel bisulfate 75 mg. The primary study endpoint was change from baseline in P2Y12 percentage inhibition at week 4. The primary analysis was conducted in the per-protocol population. Non-inferiority was confirmed if the lower limit of the 95% confidence interval (CI) of the treatment difference was greater than or equal to -9.0% points. Sixty-one participants were randomly assigned clopidogrel napadisilate and 60 were randomly assigned clopidogrel bisulfate. Thirty-nine participants in the clopidogrel napadisilate group and 39 in the clopidogrel bisulfate group were analyzed for the primary endpoint. At 4 weeks, mean P2Y12 percentage inhibition had increased in both treatment groups. The estimated mean change from baseline was 22.3% with clopidogrel napadisilate and 21.4% with clopidogrel bisulfate; the estimated treatment difference of 0.9% (95% CI, -8.6 to 10.4) confirmed the non-inferiority of clopidogrel napadisilate to clopidogrel bisulfate. Clopidogrel napadisilate was non-inferior to clopidogrel bisulfate as assessed by change in P2Y12 percentage inhibition. Rates of adverse events were similar between the two groups. Therefore, clopidogrel napadisilate is a useful alternative option for the dosing of ischemic stroke patient populations.

  5. Hepatic and vascular enhancement at dual-phase helical CT: comparison of Iobitridol 300 and Iohexol 300 in a prospective randomized study

    Energy Technology Data Exchange (ETDEWEB)

    Legmann, P.; Vignaux, O.; Bahurel, H.; Oudjit, A. [Dept. of Radiology, Universite Rene Descartes, Paris (France); Coste, J. [Dept. of Biostatistics and Epidemiology, Universite Rene Descartes, Paris (France)

    2001-11-01

    The purpose of this study was to determine hepatic and vascular enhancement, clinical tolerance, and iconographic quality of Iobitridol (300 mg/ml) at dual-phase helical CT and to compare it with Iohexol (300 mg/ml). One hundred forty-six patients were randomly divided into two groups. Each group received 120 ml of Iohexol (group A) or Iobitridol (group B). Mean enhancement of liver, aorta and portal vein was obtained at the arterial phase and at the portal-venous phase. Overall image quality was assessed by two independent blinded investigators. Adverse reactions were recorded. There were no significant differences in demographic characteristics and distribution of patient intrinsic parameters between the two groups, except for blood pressure but without statistical correlation between the difference in blood pressure and the impact on enhancement measurements. There was no significant difference in clinical tolerance and image quality. Mean liver as well as aortic and portal vein enhancement measurements did not show any significant difference. Iobitridol compares favorably with Iohexol. Both products have similar safety, tolerance, and efficacy. Both contrast media have equivalent blood pool concentration and interstitial compartment diffusion. (orig.)

  6. Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel.

    Science.gov (United States)

    Hoskins, P; Vergote, I; Cervantes, A; Tu, D; Stuart, G; Zola, P; Poveda, A; Provencher, D; Katsaros, D; Ojeda, B; Ghatage, P; Grimshaw, R; Casado, A; Elit, L; Mendiola, C; Sugimoto, A; D'Hondt, V; Oza, A; Germa, J R; Roy, M; Brotto, L; Chen, D; Eisenhauer, E A

    2010-10-20

    Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and

  7. Ocular comfort assessment of lifitegrast ophthalmic solution 5.0% in OPUS-3, a Phase III randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Nichols KK

    2018-01-01

    Full Text Available Kelly K Nichols,1 Edward Holland,2 Melissa M Toyos,3 James H Peace,4 Parag Majmudar,5 Aparna Raychaudhuri,6 Mohamed Hamdani,6 Monica Roy,6 Amir Shojaei6 1School of Optometry, University of Alabama at Birmingham, Birmingham, AL, 2Cincinnati Eye Institute, Edgewood, KY, 3Toyos Clinic, Nashville, TN, 4United Medical Research Institute, Inglewood, CA, 5Chicago Cornea Consultants, Ltd., Hoffman Estates, IL, 6Shire, Lexington, MA, USA Purpose: To evaluate ocular comfort of lifitegrast ophthalmic solution 5.0% among patients with dry eye disease (DED in the OPUS-3 trial. Methods: OPUS-3 was a multicenter, randomized, double-masked, placebo-controlled study. Adults with DED and recent artificial tear use were randomized 1:1 (lifitegrast:placebo to ophthalmic drops twice daily for 84 days. On days 0 (baseline, 14, 42, and 84, drop comfort score (scale, 0–10; 0 = very comfortable, 10 = very uncomfortable was measured at 0, 1, 2, and 3 minutes postinstillation. If the score was >3 at 3 minutes, assessment was repeated at 5, 10, and 15 minutes until score ≤3. Ocular treatment-emergent adverse events (TEAEs were assessed. Results: Overall, 711 participants were randomized (n=357 received lifitegrast; n=354 received placebo. Drop comfort scores for lifitegrast-treated participants improved within 3 minutes of instillation (mean scores on day 84 for both study and fellow eyes: instillation: lifitegrast, 3.4, placebo, 1.0; 3 minutes: lifitegrast, 1.5, placebo, 0.7. The majority (64%–66% of participants had scores <3 within 3 minutes postinstillation on days 14, 42, and 84. In participants with scores >3 at 3 minutes, the mean score in the lifitegrast group was similar to or better than that in the placebo group at 5, 10, or 15 minutes postinstillation. Lifitegrast appeared to be well tolerated, with ocular TEAEs rarely leading to discontinuation. Conclusion: In OPUS-3, lifitegrast appeared to be well tolerated and drop comfort scores approached placebo

  8. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial†

    Science.gov (United States)

    Skorupski, K. A.; Uhl, J. M.; Szivek, A; Allstadt Frazier, S. D.; Rebhun, R. B.; Rodriguez, C. O.

    2016-01-01

    Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. PMID:24118677

  9. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial.

    Science.gov (United States)

    Skorupski, K A; Uhl, J M; Szivek, A; Allstadt Frazier, S D; Rebhun, R B; Rodriguez, C O

    2016-03-01

    Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. © 2013 John Wiley & Sons Ltd.

  10. A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children

    DEFF Research Database (Denmark)

    Sirima, Sodiomon B; Mordmüller, Benjamin; Milligan, Paul

    2016-01-01

    randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. RESULTS: A cohort of 1849...... in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). CONCLUSIONS: GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially...

  11. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

    DEFF Research Database (Denmark)

    Bernsdorf, M.; Ingvar, C.; Jorgensen, L.

    2011-01-01

    a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups...... was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI -7....... A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE....

  12. Evaluation of spatial-encoding-related geometric distortion in magnetic resonance imaging

    Science.gov (United States)

    Hong, Cheol Pyo; Lee, Dong Hoon; Lee, Man Woo; Woo, Youngkeun

    2012-12-01

    This study demonstrated the characteristics of spatial encoding-related geometric distortion in magnetic resonance imaging (MRI) by using a phantom with known physical dimensions to detect geometric distortion in MR scans. The amount of distortion was calculated as the difference between the physical coordinates of control points in the phantom and those of the corresponding points in the distorted MR image of the phantom. The phase and the frequency encoding directions were swapped to acquire a phantom image for movement of a patient table 120 mm to the right and left, allowing comprehensive distortion mapping over the isocentric plane and the entire field of view (FOV) along the spatial encoding. The geometric distortion of phase encoding directions over the entire FOV was small compared to the distortion of frequency encoding directions. The maximum absolute deviations were 28.00 mm and 20.00 mm along the frequency and the phase encoding directions over the entire FOV, respectively. The mean absolute deviations along the frequency and the phase encoding directions were 2.85 mm and 1.97 mm, respectively. Although geometric distortion along the phase encoding axis near the isocenter was small, the distortion increased slightly toward the peripheral regions. The distortion of the phase encoding direction in the peripheral region can be severely affected by the imaging gradient's nonlinearity.

  13. Topical Minocycline Foam for the Treatment of Impetigo in Children: Results of a Randomized, Double-Blind, Phase 2 Study.

    Science.gov (United States)

    Chamny, Shlomo; Miron, Dan; Lumelsky, Nadia; Shalev, Hana; Gazal, Elana; Keynan, Rita; Shemer, Avner; Tamarkin, Dov

    2016-10-01

    Currently available treatment options for impetigo are limited by either systemic side effects (for oral therapy) or lack of ease of use (for topical ointment). A novel foam formulation of minocycline for topical use may improve convenience and treatment utilization for pediatric patients with impetigo. To evaluate the safety and efficacy of topically applied minocycline foam (FMX-102 1% and 4%) in the treatment of impetigo and to determine the optimal therapeutic active ingredient concentration. In this randomized, parallel-group, double-blind, comparative clinical trial, 32 subjects aged ≥2 years with a clinical diagnosis of pure impetigo, impetigo contagiosa, or uncomplicated blistering impetigo were randomized to treatment with FMX-102 1% or 4%, twice daily for 7 days. Subjects were followed for up to 7 days post-treatment. Clinical cure, defined as ≥80% cured lesions (fully recovered lesions, visually determined by investigators), was achieved by 57.1% and 50.0% of FMX-102 1% and 4% subjects, respectively, at the end of treatment (visit 3). Clinical success, defined as the absence of lesions, or the drying or improvement of treated lesions (decrease in size of affected area, lesion number, or both), was demonstrated in 81.3% and 78.6% of FMX-102 1% and 4% subjects, respectively, following 3 days of treatment (visit 2), in 92.3% and 100% of the respective subjects at the end of treatment, and in 100% in both groups at follow-up (visit 4). Bacteriologic success rates at the end of treatment, defined as complete pathogen eradication, were 85% and 74% in the FMX-102 1% and 4% groups, respectively. The bacteriologic success rate for MRSA infections was 100% (11/11), with no recurrences. Both FMX-102 1% and 4% were considered well tolerated and safe. Topical minocycline foam may be a safe and effective new treatment option for impetigo in children, including those with MRSA. J Drugs Dermatol. 2016;15(10):1238-1243.

  14. A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children.

    Science.gov (United States)

    Sirima, Sodiomon B; Mordmüller, Benjamin; Milligan, Paul; Ngoa, Ulysse Ateba; Kironde, Fred; Atuguba, Frank; Tiono, Alfred B; Issifou, Saadou; Kaddumukasa, Mark; Bangre, Oscar; Flach, Clare; Christiansen, Michael; Bang, Peter; Chilengi, Roma; Jepsen, Søren; Kremsner, Peter G; Theisen, Michael

    2016-08-31

    GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Randomized phase III trial of postoperative radiochemotherapy {+-} amifostine in head and neck cancer. Is there evidence for radioprotection?

    Energy Technology Data Exchange (ETDEWEB)

    Vacha, P.; Fehlauer, F.; Mahlmann, B.; Marx, M.; Richter, E. [Dept. of Radiation Oncology and Nuclear Medicine, Univ. of Luebeck (Germany); Hinke, A. [WiSP Research Inst., Langenfeld (Germany); Sommer, K. [Dept. of Head and Neck Surgery, Univ. of Luebeck (Germany); Feyerabend, T. [Practice for Radiation Therapy Bonn-Rhein-Sieg, Bonn (Germany)

    2003-06-01

    Purpose: Experimental and clincial data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer. Patients and Methods: 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to received RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m{sup 2} carboplatin, day 1-5 week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the common toxicity criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation. Results: 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis. Conclusions: According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary. (orig.)

  16. Driven interfaces in random media at finite temperature: existence of an anomalous zero-velocity phase at small external force.

    Science.gov (United States)

    Monthus, Cécile; Garel, Thomas

    2008-10-01

    The motion of driven interfaces in random media at finite temperature T and small external force F is usually described by a linear displacement h{G}(t) approximately V(F,T)t at large times, where the velocity vanishes according to the creep formula as V(F,T) approximately e;{-K(T)F;{mu}} for F-->0 . In this paper, we question this picture on the specific example of the directed polymer in a two-dimensional random medium. We have recently shown [C. Monthus and T. Garel, J. Phys. A 41, 255002 (2008)] that its dynamics for F=0 can be analyzed in terms of a strong disorder renormalization procedure, where the distribution of renormalized barriers flows towards some "infinite disorder fixed point." In the present paper, we obtain that for small F , this "infinite disorder fixed point" becomes a "strong disorder fixed point" with an exponential distribution of renormalized barriers. The corresponding distribution of trapping times then only decays as a power law P(tau) approximately 1tau;{1+alpha} , where the exponent alpha(F,T) vanishes as alpha(F,T) proportional, variant F micro as F-->0 . Our conclusion is that in the small force region alpha(F,T)infinity induces strong non-self-averaging effects that invalidate the usual creep formula obtained by replacing all trapping times by the typical value. We find instead that the motion is only sublinearly in time h{G}(t) approximately t;{alpha(F,T)} , i.e., the asymptotic velocity vanishes V=0 . This analysis is confirmed by numerical simulations of a directed polymer with a metric constraint driven in a traps landscape. We moreover obtain that the roughness exponent, which is governed by the equilibrium value zeta{eq}=23 up to some large scale, becomes equal to zeta=1 at the largest scales.

  17. Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial.

    Science.gov (United States)

    Grosso, Federica; Steele, Nicola; Novello, Silvia; Nowak, Anna K; Popat, Sanjay; Greillier, Laurent; John, Thomas; Leighl, Natasha B; Reck, Martin; Taylor, Paul; Planchard, David; Sørensen, Jens Benn; Socinski, Mark A; von Wangenheim, Ute; Loembé, Arsène Bienvenu; Barrueco, José; Morsli, Nassim; Scagliotti, Giorgio

    2017-11-01

    Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression. The primary end point was progression-free survival (PFS). Results Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017), which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319). Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR, 0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade ≥ 3 adverse event (AE; nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those receiving nintedanib versus 17.1% of those in the placebo group. Conclusion Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were manageable. The clinical benefit was evident in patients with

  18. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study

    Directory of Open Access Journals (Sweden)

    Moehler Markus

    2011-08-01

    Full Text Available Abstract Background Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neoadjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC has been designed to explore the efficacy of neoadjuvant chemotherapy. Methods/Design This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m2 for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2 followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked

  19. Enhancing evidence-based diabetes and chronic disease control among local health departments: a multi-phase dissemination study with a stepped-wedge cluster randomized trial component.

    Science.gov (United States)

    Parks, Renee G; Tabak, Rachel G; Allen, Peg; Baker, Elizabeth A; Stamatakis, Katherine A; Poehler, Allison R; Yan, Yan; Chin, Marshall H; Harris, Jenine K; Dobbins, Maureen; Brownson, Ross C

    2017-10-18

    The rates of diabetes and prediabetes in the USA are growing, significantly impacting the quality and length of life of those diagnosed and financially burdening society. Premature death and disability can be prevented through implementation of evidence-based programs and policies (EBPPs). Local health departments (LHDs) are uniquely positioned to implement diabetes control EBPPs because of their knowledge of, and focus on, community-level needs, contexts, and resources. There is a significant gap, however, between known diabetes control EBPPs and actual diabetes control activities conducted by LHDs. The purpose of this study is to determine how best to support the use of evidence-based public health for diabetes (and related chronic diseases) control among local-level public health practitioners. This paper describes the methods for a two-phase study with a stepped-wedge cluster randomized trial that will evaluate dissemination strategies to increase the uptake of public health knowledge and EBPPs for diabetes control among LHDs. Phase 1 includes development of measures to assess practitioner views on and organizational supports for evidence-based public health, data collection using a national online survey of LHD chronic disease practitioners, and a needs assessment of factors influencing the uptake of diabetes control EBPPs among LHDs within one state in the USA. Phase 2 involves conducting a stepped-wedge cluster randomized trial to assess effectiveness of dissemination strategies with local-level practitioners at LHDs to enhance capacity and organizational support for evidence-based diabetes prevention and control. Twelve LHDs will be selected and randomly assigned to one of the three groups that cross over from usual practice to receive the intervention (dissemination) strategies at 8-month intervals; the intervention duration for groups ranges from 8 to 24 months. Intervention (dissemination) strategies may include multi-day in-person workshops, electronic

  20. Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials.

    Science.gov (United States)

    O'Neil, Patrick M; Aroda, Vanita R; Astrup, Arne; Kushner, Robert; Lau, David C W; Wadden, Thomas A; Brett, Jason; Cancino, Ana-Paula; Wilding, John P H

    2017-11-01

    Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Because of concerns regarding the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc. Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 or ≥27 kg/m 2 with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3.0 mg (n = 3384) or placebo (n = 1941), both with a 500 kcal/d deficit diet, plus exercise. Adverse events related to neuropsychiatric safety were collected in all trials. Additionally, in the phase 3a trials, validated mental-health questionnaires were prospectively and systematically administered. In the pooled analysis of 5325 randomized and exposed individuals, rates of depression (2.1 vs 2.1 events/100 person-years) and anxiety (1.9 vs 1.7 events/100 person-years) through adverse event reporting were similarly low in liraglutide and placebo groups. Nine (0.3%) individuals receiving liraglutide and 2 (0.1%) receiving placebo reported adverse events of suicidal ideation or behaviour. In phase 3a trials, mean baseline Patient Health Questionnaire-9 scores of 2.8 ± 3.0 vs 2.9 ± 3.1 for liraglutide vs placebo improved to 1.8 ± 2.7 vs 1.9 ± 2.7, respectively, at treatment end; 34/3291 individuals (1.0%) receiving liraglutide 3.0 mg vs 19/1843 (1.0%) receiving placebo reported suicidal ideation on the Columbia-Suicide Severity Rating Scale. Results of this exploratory pooled analysis provide no cause for concern regarding the neuropsychiatric safety of treatment with liraglutide 3.0 mg in patients similar to those included in the examined trials. Although there was a small numerical imbalance in suicidal ideation with liraglutide through adverse event reporting, no

  1. New concepts in PCM encoding

    Science.gov (United States)

    Yun, Paul M.

    The Pulse Coded Modulation (PCM) Encoder Systems used in telemetry have gained enormous flexibility for various applications because the input data channels and frame sync codes are programmable via the EEPROMs or UVEPROMs. The firmware in the current PCM Encoder Systems can be readily tailored for a specific application to monitor numerous types of analog channels, as well as digital channels. However, the current PCM Encoder Systems require several types of strap options which dictate not only a limited choice of gains and offsets, but also a fixed choice of the premodulation filter characteristics. The brain of the 1000 PCM Encoder is the Digital Signal Processor (DSP) which eliminates the fixed premodulation filter characteristics via digital filter functions, and also eliminates strap options via general purpose microprocessor functions.

  2. Improving access to preparatory information for children undergoing general anaesthesia for tooth extraction and their families: study protocol for a Phase III randomized controlled trial.

    Science.gov (United States)

    Hosey, Marie Therese; Donaldson, Ana Nora; Huntington, Corinne; Liossi, Christina; Reynolds, Patricia A; Alharatani, Reham; Newton, J Timothy

    2014-06-11

    Children can find anaesthesia induction especially distressing and postoperative psychological and physical morbidity are common. Preparation programmes for general anaesthesia (GA) are highly effective in reducing this distress. A Phase II study has already verified the effectiveness of a prototype preoperative GA-coping computer game to help children cope with induction in a dental GA setting. The biggest patient users of pediatric GA services in the UK are children who need to have teeth removed (estimated to be 100,000 yearly). Tooth decay is the most common disease in children worldwide. This study is a Phase III randomized controlled trial (RCT) and will evaluate the effectiveness of the new internet version of this game. The Phase III RCT will use a double-blind three-armed design. The clinical trial will recruit up to 210 children and will compare the web-based game against standard care and another non-medical game. At least 53 patients in each group will be required for 90% statistical power. Distress will be assessed through an evaluation of the child's behaviour during the visit and later parental reports of physical and psychological morbidity. The satisfaction of parents and children will be measured; the mode of usage of the web-based game will be automatically recorded and the impact on the service (for example, recovery time and throughput) will be reported.The Phase III study primary outcome will measure: (1) patient experience: acceptance of anaesthetic induction, child cooperation and distress, reduction of peri- and postoperative morbidity, child and family satisfaction, and (2) service improvement: anaesthetic time and improvement in throughput. Measures will be administered at baseline, at the time of the GA treatment visit, and at 48 hours and one week postoperatively. This study aims to determine the effectiveness of an online GA-coping game for children and families undergoing tooth extraction under GA. ISRCTN18265148 (registered 24

  3. A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study.

    Directory of Open Access Journals (Sweden)

    Ian Mcgowan

    Full Text Available The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK, and pharmacodynamics (PD of three tenofovir (TFV gels for rectal application. The vaginal formulation (VF gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF gel was also evaluated in the CHARM-01 study.Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial.All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/106 cells respectively. Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection.All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection.ClinicalTrials.gov NCT01575405.

  4. Accelerated radial Fourier-velocity encoding using compressed sensing.

    Science.gov (United States)

    Hilbert, Fabian; Wech, Tobias; Hahn, Dietbert; Köstler, Herbert

    2014-09-01

    Phase Contrast Magnetic Resonance Imaging (MRI) is a tool for non-invasive determination of flow velocities inside blood vessels. Because Phase Contrast MRI only measures a single mean velocity per voxel, it is only applicable to vessels significantly larger than the voxel size. In contrast, Fourier Velocity Encoding measures the entire velocity distribution inside a voxel, but requires a much longer acquisition time. For accurate diagnosis of stenosis in vessels on the scale of spatial resolution, it is important to know the velocity distribution of a voxel. Our aim was to determine velocity distributions with accelerated Fourier Velocity Encoding in an acquisition time required for a conventional Phase Contrast image. We imaged the femoral artery of healthy volunteers with ECG-triggered, radial CINE acquisition. Data acquisition was accelerated by undersampling, while missing data were reconstructed by Compressed Sensing. Velocity spectra of the vessel were evaluated by high resolution Phase Contrast images and compared to spectra from fully sampled and undersampled Fourier Velocity Encoding. By means of undersampling, it was possible to reduce the scan time for Fourier Velocity Encoding to the duration required for a conventional Phase Contrast image. Acquisition time for a fully sampled data set with 12 different Velocity Encodings was 40 min. By applying a 12.6-fold retrospective undersampling, a data set was generated equal to 3:10 min acquisition time, which is similar to a conventional Phase Contrast measurement. Velocity spectra from fully sampled and undersampled Fourier Velocity Encoded images are in good agreement and show the same maximum velocities as compared to velocity maps from Phase Contrast measurements. Compressed Sensing proved to reliably reconstruct Fourier Velocity Encoded data. Our results indicate that Fourier Velocity Encoding allows an accurate determination of the velocity distribution in vessels in the order of the voxel size. Thus

  5. Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

    Directory of Open Access Journals (Sweden)

    Maneeton Narong

    2012-09-01

    Full Text Available Abstract Background Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect. Objectives This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD. Only the randomized controlled trials (RCTs comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012. Data sources MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression. Study eligible criteria, participants and interventions Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i depression severity, ii response rate, iii overall discontinuation rate, or iv discontinuation rate due to adverse events. No language restriction was applied. Study appraisal and synthesis methods All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs and weighted mean differences (WMDs with 95% confidence intervals (CIs were computed by using a random effect model. Results A total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR. The pooled mean change scores of the Montgomery-Asberg Depression

  6. Assessment of quality of life in advanced, metastatic prostate cancer: an overview of randomized phase III trials.

    Science.gov (United States)

    Adamowicz, Krzysztof

    2017-04-01

    The chief therapeutic goal in metastatic prostate cancer is prolongation of survival with good quality of life . Quality of life (health-related) is often used as an endpoint parameter in phase III trials in metastatic prostate cancer, but the value of using HRQOL in this context has not been assessed to date. In order to evaluate the role of HRQOL assessment in contemporary phase III trials in prostate cancer, we searched the PubMed database to identify publications presenting the results of these trials on systemic therapies for prostate cancer published between January 2000 and December 2015. The analysis was separately presented in ten leading journals. We searched for companion papers reporting on QOL separately. We identified 84 studies which included a total of 57,193 patients in ten leading journals and 27 studies (7270 patients) in other journals. HRQOL parameters were described or mentioned in the main publication in 25 publications and four companions in total. There was no obvious trend in quality of life reported over two 8-year periods . The explicit statistical comparisons were reported in 22/25 cases (88 %), with significant difference in only 10/25 (40 %) studies and in eight cases (80 %) was conducive to the examined arm. There was no significant association between improvements in HRQOL and improvements in overall survival (OS) or any other primary endpoint in the analyzed studies. Only one study was found which presented the difference in quality of life with no difference in the primary endpoint. HRQOL is an indicator of benefit during treatment of patients with metastatic prostate cancer, but it is unlikely that HRQOL results can help clinicians choose between treatments given that they are not correlated with changes in OS or at other primary endpoints.

  7. Response to duloxetine in chronic low back pain: exploratory post hoc analysis of a Japanese Phase III randomized study

    Directory of Open Access Journals (Sweden)

    Tsuji T

    2017-09-01

    Full Text Available Toshinaga Tsuji,1 Naohiro Itoh,1 Mitsuhiro Ishida,2 Toshimitsu Ochiai,3 Shinichi Konno4 1Medical Affairs Department, 2Clinical Research Development, 3Biostatistics Department, Shionogi & Co. Ltd, Osaka, 4Department of Orthopedic Surgery, Fukushima Medical University, Fukushima, Japan Purpose: Duloxetine is efficacious for chronic low back pain (CLBP. This post hoc analysis of a Japanese randomized, placebo-controlled trial (ClinicalTrials.gov, NCT01855919 assessed whether patients with CLBP with early pain reduction or treatment-related adverse events of special interest (TR-AESIs; nausea, somnolence, constipation have enhanced responses to duloxetine. Patients and methods: Patients (N = 456 with CLBP for ≥6 months and Brief Pain Inventory (BPI average pain severity score of ≥4 were randomized (1:1 to duloxetine 60 mg/day or placebo for 14 weeks. Primary outcome was change from baseline in BPI average pain severity score (pain reduction. Subgroup analyses included early pain reduction (≥30%, 10%–30%, or <10% at Week 4 and early TR-AESIs (with or without TR-AESIs by Week 2. Measures included changes from baseline in BPI average pain severity score and BPI Interference scores (quality of life; QOL, and response rate (≥30% or ≥50% pain reduction at Week 14. Results: Patients with ≥30% early pain reduction (n = 108 or early TR-AESIs (n = 50 had significantly greater improvements in pain and QOL than placebo-treated patients (n = 226, whereas patients with 10%–30% (n = 63 or <10% (n = 48 pain reduction did not; patients without early TR-AESIs (n = 180 had significant improvements in pain at Week 14. Response rates (≥30%/≥50% pain reduction were 94.4%/82.4%, 66.7%/49.2%, and 25.0%/18.8% for patients with ≥30%, 10%–30%, and <10% early pain reduction, respectively, 74.0%/64.0% for patients with early TR-AESIs, 67.2%/54.4% for patients without early TR-AESIs, and 52.2%/39.4% for placebo.Conclusion: Early pain reduction or TR

  8. A large-area ultra-precision 2D geometrical measurement technique based on statistical random phase detection

    Science.gov (United States)

    Ekberg, Peter; Stiblert, Lars; Mattsson, Lars

    2012-03-01

    The manufacturing of high-quality chrome masks used in the display industry for the manufacturing of liquid crystals, organic light emission diodes and other display devices would not be possible without high-precision large-area metrology. In contrast to the semiconductor industry where 6‧ masks are most common, the quartz glass masks for the manufacturing of large area TVs can have sizes of up to 1.6 × 1.8 m2. Besides the large area, there are demands of sub-micrometer accuracy in ‘registration’, i.e. absolute dimensional measurements and nanometer requirements for ‘overlay’, i.e. repeatability. The technique for making such precise measurements on large masks is one of the most challenging tasks in dimensional metrology today. This paper presents a new approach to two-dimensional (2D) ultra-precision measurements based on random sampling. The technique was recently presented for ultra-precise one-dimensional (1D) measurement. The 1D method relies on timing the scanning of a focused laser beam 200 µm in the Y-direction from an interferometrically determined reference position. This microsweep is controlled by an acousto-optical deflector. By letting the microsweep scan from random X-positions, we can build XY-recordings through a time-to-space conversion that gives very precise maps of the feature edges of the masks. The method differs a lot from ordinary image processing methods using CCD or CMOS sensors for capturing images in the spatial domain. We use events grabbed by a single detector in the time domain in both the X- and Y-directions. After a simple scaling, we get precise and repeatable spatial information. Thanks to the extremely linear microsweep and its precise power control, spatial and intensity distortions, common in ordinary image processing systems using 2D optics and 2D sensors, can be practically eliminated. Our 2D method has proved to give a standard deviation in repeatability of less than 4 nm (1σ) in both the X- and Y

  9. Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial.

    Science.gov (United States)

    Stark, Dan P; Cook, Adrian; Brown, Julia M; Brundage, Michael D; Embleton, Andrew C; Kaplan, Richard S; Raja, Fharat A; Swart, Ann Marie W; Velikova, Galina; Qian, Wendi; Ledermann, Jonathan A

    2017-07-15

    The ICON6 trial showed that cediranib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, improved clinical outcomes for patients with platinum-sensitive relapsed ovarian cancer when it was used with chemotherapy and was continued as maintenance therapy. This study describes health-related quality of life (QOL) during the first year of treatment. Four hundred fifty-six women were randomly allocated to receive standard chemotherapy only, chemotherapy with concurrent cediranib, or chemotherapy with cediranib administered concurrently and continued as maintenance. Patients completed QOL questionnaires until disease progression every 3 weeks during chemotherapy and then every 6 weeks to 1 year. Patients alive with disease progression completed a QOL form 1 year after randomization. The primary QOL endpoint was the global score from the Quality of Life Questionnaire Core 30 (of the European Organization for Research and Treatment of Cancer) at 1 year, with the standard chemotherapy group compared with the concurrent-maintenance cediranib group. The rate of questionnaire compliance was 90% at the baseline and 76% at 1 year and was similar across the 3 groups. The mean global QOL score at 1 year was 62.6 points for the standard chemotherapy group and 68.7 points for the concurrent-maintenance group (+4.5; 95% confidence interval, -2.0 to 11.0; P = .18). Sensitivity analyses suggested that this finding was robust to the effect of missing data, and the improvement became statistically significant after adjustments for self-reported diarrhea. The 6th study by the International Collaboration in Ovarian Neoplasm (ICON6) showed a significant improvement in progression-free survival with cediranib as concurrent and maintenance therapy. No QOL detriment with cediranib was found 1 year after treatment was commenced. The maintenance of QOL along with prolonged cancer control suggests that cediranib has a valuable role in the treatment of relapsed ovarian

  10. A randomized double-blinded controlled trial of hCG as luteal phase support in natural cycle frozen embryo transfer.

    Science.gov (United States)

    Lee, Vivian Chi Yan; Li, Raymond Hang Wun; Yeung, William Shu Biu; Pak Chung, H O; Ng, Ernest Hung Yu

    2017-05-01

    Does the use of hCG as luteal phase support in natural cycle frozen embryo transfer (FET) increase the ongoing pregnancy rate? The use of hCG in natural cycle FET did not improve the ongoing pregnancy rate. The use of luteal phase support in stimulated cycles has been associated with higher live-birth rates and the results are similar when using hCG or progesterone. This is a randomized double-blinded controlled trial of 450 women recruited between August 2013 and October 2015. Women with regular cycles undergoing natural cycle FET were recruited. Serial serum hormonal concentrations were used to time natural ovulation and at least Day 2 cleavage embryos were replaced. Patients were randomized into either: (i) the treatment group, receiving 1500 IU hCG on the day of FET and 6 days after FET, or (ii) the control group, receiving normal saline on these 2 days. The ongoing pregnancy rate [60/225 (26.7%) in the treatment group vs 70/225 (31.3%) in the control group, odds ratio 1.242 (95% CI 0.825-1.869)], implantation rate and miscarriage rate were comparable between the two groups. In the treatment group, there were significantly more cycles with top quality embryos transferred and a significantly higher serum oestradiol level, but a comparable serum progesterone level, 6 days after FET. However, no significant differences were observed in serum oestradiol and progesterone levels 6 days after FET between the pregnant and non-pregnant women. In the multivariate logistic regression, the number of embryos transferred was the only significant factor predictive of the ongoing pregnancy rate after natural cycle FET. This study only included FET with cleavage stage embryos and only hCG, not vaginal progesterone, was used as luteal phase support. The findings in this study do not support the use of hCG for luteal phase support in natural cycle FET. No external funding was used and there were no competing interests. clinicaltrial.gov identifier: NCT01931384. 23/8/2013. 30/8/2013.

  11. Role of sleep for encoding of emotional memory.

    Science.gov (United States)

    Kaida, Kosuke; Niki, Kazuhisa; Born, Jan

    2015-05-01

    Total sleep deprivation (TSD) has been consistently found to impair encoding of information during ensuing wakefulness, probably through suppressing NonREM (non-rapid eye movement) sleep. However, a possible contribution of missing REM sleep to this encoding impairment after TSD has so far not been systematically examined in humans, although such contribution might be suspected in particular for emotional information. Here, in two separate experiments in young healthy men, we compared effects of TSD and of selective REM sleep deprivation (REMD), relative to respective control conditions of undisturbed sleep, on the subsequent encoding of neutral and emotional pictures. The pictures were presented in conjunction with colored frames to also assess related source memory. REMD was achieved by tones presented contingently upon initial signs of REM sleep. Encoding capabilities were examined in the evening (18:00h) after the experimental nights, by a picture recognition test right after encoding. TSD significantly decreased both the rate of correctly recognized pictures and of recalled frames associated with the pictures. The TSD effect was robust and translated into an impaired long term memory formation, as it was likewise observed on a second recognition testing one week after the encoding phase. Contrary to our expectation, REMD did not affect encoding in general, or particularly of emotional pictures. Also, REMD did not affect valence ratings of the encoded pictures. However, like TSD, REMD distinctly impaired vigilance at the time of encoding. Altogether, these findings indicate an importance of NonREM rather than REM sleep for the encoding of information that is independent of the emotionality of the materials. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

    DEFF Research Database (Denmark)

    Bernsdorf, Mogens; Ingvar, Christian; Jörgensen, Leif

    2011-01-01

    between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR...... (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI -7.19 to 6.33; P = 0.44). CR...... was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI -9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI -9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR...

  13. Intravenous Hydroxypropyl β-Cyclodextrin Formulation of Letermovir: A Phase I, Randomized, Single-Ascending, and Multiple-Dose Trial.

    Science.gov (United States)

    Erb-Zohar, K; Kropeit, D; Scheuenpflug, J; Stobernack, H-P; Hulskotte, Egj; van Schanke, A; Zimmermann, H; Rübsamen-Schaeff, H

    2017-07-04

    Letermovir is a novel antiviral in clinical development for prophylaxis against human cytomegalovirus in immunocompromised transplant recipients. This two-part, single-center, randomized, double-blind, placebo-controlled trial evaluated the safety and pharmacokinetics of a hydroxypropyl β-cyclodextrin (HPβCD)-based intravenous formulation of letermovir in healthy women. Subjects received single, escalating doses (120, 240, 480, 720, and 960 mg; 6 letermovir, 2 placebo per cohort) or multiple, once-daily doses (240 mg; 8 letermovir, 4 placebo) of HPβCD-formulated letermovir and the associated pharmacokinetic profiles and adverse events were investigated. Single-dose and multiple-dose regimens were generally well tolerated. Single-dose escalation resulted in a slightly more-than-dose-proportional increase in the area under the letermovir plasma concentration-time curve (AUC), whereas increase in the maximal observed letermovir plasma concentration (Cmax ) was dose proportional. After once-daily dosing, accumulation ratios in AUC and Cmax were 1.22 and 1.03, respectively. The terminal half-life was 28.3 h, supporting once-daily dosing (EudraCT Number: 2012-001603-20). © 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  14. Randomized phase II exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis

    Directory of Open Access Journals (Sweden)

    Karavasilis Vasileios

    2010-06-01

    Full Text Available Abstract Background This study aimed to investigate the efficacy of prophylactic amifostine in reducing the risk of severe radiation colitis in cancer patients receiving radical radiotherapy to the pelvis. Methods Patients with pelvic tumours referred for radical radiotherapy who consented participation in this trial, were randomly assigned to receive daily amifostine (A (subcutaneously, 500 mg flat dose before radiotherapy or radiotherapy alone (R. Sigmoidoscopy and blinded biopsies were scheduled to conduct prior to initiation and following completion of radiotherapy and again 6 to 9 months later. Radiation colitis was assessed by clinical, endoscopic and histolopathological criteria. Results A total 44 patients were enrolled in this trial, the majority with rectal (20 patients and cervical cancer (12 patients and were assigned 23 in R arm and 21 in the A arm. In total 119 sigmoidoscopies were performed and 18 patients (18/44, 40.9% were diagnosed with radiation colitis (15 grade 1 and 2, and 3 grade 3 and 4. Of them, 6 patients belonged to the A group (6/21, 28.6% and 12 to the R group (12/23, 52.2%. Acute and grade IV radiation colitis was only developed in four patients (17.4% in the R group. Amifostine side effects were mild. Amifostine treated patients were less likely to develop histologically detectable mucosal lesions, which indicate protection from acute mucosal injury. Conclusions Amifostine given subcutaneously can lower the risk of acute severe radiation colitis in patients who receive radical radiotherapy to pelvic tumors.

  15. Randomized phase II exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis.

    Science.gov (United States)

    Katsanos, Konstantinos H; Briasoulis, Evangelos; Tsekeris, Pericles; Batistatou, Anna; Bai, Maria; Tolis, Christos; Capizzello, Antonio; Panelos, Ioannis; Karavasilis, Vasileios; Christodoulou, Dimitrios; Tsianos, Epameinondas V

    2010-06-10

    This study aimed to investigate the efficacy of prophylactic amifostine in reducing the risk of severe radiation colitis in cancer patients receiving radical radiotherapy to the pelvis. Patients with pelvic tumours referred for radical radiotherapy who consented participation in this trial, were randomly assigned to receive daily amifostine (A) (subcutaneously, 500 mg flat dose) before radiotherapy or radiotherapy alone (R). Sigmoidoscopy and blinded biopsies were scheduled to conduct prior to initiation and following completion of radiotherapy and again 6 to 9 months later. Radiation colitis was assessed by clinical, endoscopic and histolopathological criteria. A total 44 patients were enrolled in this trial, the majority with rectal (20 patients) and cervical cancer (12 patients) and were assigned 23 in R arm and 21 in the A arm. In total 119 sigmoidoscopies were performed and 18 patients (18/44, 40.9%) were diagnosed with radiation colitis (15 grade 1 and 2, and 3 grade 3 and 4). Of them, 6 patients belonged to the A group (6/21, 28.6%) and 12 to the R group (12/23, 52.2%). Acute and grade IV radiation colitis was only developed in four patients (17.4%) in the R group. Amifostine side effects were mild. Amifostine treated patients were less likely to develop histologically detectable mucosal lesions, which indicate protection from acute mucosal injury. Amifostine given subcutaneously can lower the risk of acute severe radiation colitis in patients who receive radical radiotherapy to pelvic tumors.

  16. Chaotic eigenfunctions in phase space

    CERN Document Server

    Nonnenmacher, S

    1997-01-01

    We study individual eigenstates of quantized area-preserving maps on the 2-torus which are classically chaotic. In order to analyze their semiclassical behavior, we use the Bargmann-Husimi representations for quantum states, as well as their stellar parametrization, which encodes states through a minimal set of points in phase space (the constellation of zeros of the Husimi density). We rigorously prove that a semiclassical uniform distribution of Husimi densities on the torus entails a similar equidistribution for the corresponding constellations. We deduce from this property a universal behavior for the phase patterns of chaotic Bargmann eigenfunctions, which reminds of the WKB approximation for eigenstates of integrable systems (though in a weaker sense). In order to obtain more precise information on ``chaotic eigenconstellations", we then model their properties by ensembles of random states, generalizing former results on the 2-sphere to the torus geometry. This approach yields statistical predictions fo...

  17. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters

    Directory of Open Access Journals (Sweden)

    Carolina L. Haass-Koffler

    2017-12-01

    Full Text Available The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled “Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers” (Haass-Koffler et al., 2017 [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73. Keywords: Glutamate receptor subtype 5 (mGlu5, Allosteric modulator, GET 73, Safety, Tolerability

  18. HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial.

    Science.gov (United States)

    Ensoli, Fabrizio; Cafaro, Aurelio; Casabianca, Anna; Tripiciano, Antonella; Bellino, Stefania; Longo, Olimpia; Francavilla, Vittorio; Picconi, Orietta; Sgadari, Cecilia; Moretti, Sonia; Cossut, Maria R Pavone; Arancio, Angela; Orlandi, Chiara; Sernicola, Leonardo; Maggiorella, Maria T; Paniccia, Giovanni; Mussini, Cristina; Lazzarin, Adriano; Sighinolfi, Laura; Palamara, Guido; Gori, Andrea; Angarano, Gioacchino; Di Pietro, Massimo; Galli, Massimo; Mercurio, Vito S; Castelli, Francesco; Di Perri, Giovanni; Monini, Paolo; Magnani, Mauro; Garaci, Enrico; Ensoli, Barbara

    2015-04-29

    The phase II multicenter, randomized, open label, therapeutic trial (ISS T-002, Clinicaltrials.gov NCT00751595) was aimed at evaluating the immunogenicity and the safety of the biologically active HIV-1 Tat protein administered at 7.5 or 30 μg, given 3 or 5 times monthly, and at exploring immunological and virological disease biomarkers. The study duration was 48 weeks, however, vaccinees were followed until the last enrolled subject reached the 48 weeks. Reported are final data up to 144 weeks of follow-up. The ISS T-002 trial was conducted in 11 clinical centers in Italy on 168 HIV positive subjects under Highly Active Antiretroviral Therapy (HAART), anti-Tat Antibody (Ab) negative at baseline, with plasma viremia immune homeostasis and effective anti-viral responses capable of attacking the virus reservoir. Thus, Tat immunization represents a promising pathogenesis-driven intervention to intensify HAART efficacy.

  19. A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico.

    Science.gov (United States)

    Bauer, Kristen; Esquilin, Ines O; Cornier, Alberto Santiago; Thomas, Stephen J; Quintero Del Rio, Ana I; Bertran-Pasarell, Jorge; Morales Ramirez, Javier O; Diaz, Clemente; Carlo, Simon; Eckels, Kenneth H; Tournay, Elodie; Toussaint, Jean-Francois; De La Barrera, Rafael; Fernandez, Stefan; Lyons, Arthur; Sun, Wellington; Innis, Bruce L

    2015-09-01

    This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1-50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. ClinicalTrials.gov: NCT00468858. © The American Society of Tropical Medicine and Hygiene.

  20. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients

    DEFF Research Database (Denmark)

    Russell, James A; Vincent, Jean-Louis; Kjølbye, Anne Louise

    2017-01-01

    BACKGROUND: Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V1A-selective vasopressin analogue......, was examined in a phase IIa trial in septic shock patients. METHODS: This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support) who received selepressin 1.25 ng/kg/minute (n = 10), 2.5 ng...... for selepressin 2.5 ng/kg/minute and placebo. Two patients were infused at 3.75 ng/kg/minute, one of whom had the study drug infusion discontinued for possible safety reasons, with subsequent discontinuation of this dose group. CONCLUSIONS: In septic shock patients, selepressin 2.5 ng/kg/minute was able...

  1. Cognitive Behavioral Therapy as an Adjunct Treatment to Light Therapy for Delayed Sleep Phase Disorder in Young Adults: A Randomized Controlled Feasibility Study.

    Science.gov (United States)

    Danielsson, Katarina; Jansson-Fröjmark, Markus; Broman, Jan-Erik; Markström, Agneta

    2016-01-01

    Delayed sleep phase disorder (DSPD) is common among young people, but there is still no evidence-based treatment available. In the present study, the feasibility of cognitive behavioral therapy (CBT) was evaluated as an additive treatment to light therapy (LT) in DSPD. A randomized controlled trial with participants aged 16 to 26 years received LT for two weeks followed by either four weeks of CBT or no treatment (NT). LT advanced sleep-wake rhythm in both groups. Comparing LT+CBT with LT+NT, no significant group differences were observed in the primary endpoints. Although anxiety and depression scores were low at pretreatment, they decreased significantly more in LT+CBT compared to LT+NT. The results are discussed and some suggestions are given for further studies.

  2. Tolerability during double-blind randomized phase I trials with the house dust mite allergy immunotherapy tablet in adults and children.

    Science.gov (United States)

    Corzo, J L; Carrillo, T; Pedemonte, C; Plaza Martin, A M; Martín Hurtado, S; Dige, E; Calderon, M A

    2014-01-01

    The orodispersible house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) is being developed for the treatment of HDM respiratory allergic disease. The objective of the 2 phase I trials was to investigate tolerability and the acceptable dose range of HDM SLIT-tablet treatment in adults and children with HDM respiratory allergic disease. The trials were randomized, multiple-dose, dose-escalation, double-blind, placebo-controlled phase I trials including patients with HDM-induced asthma, with or without rhinoconjunctivitis. Both trials were registered in EudraCT (Trial 1: 2005-002151-41; Trial 2: 2007-000402-67). Trial 1 included 71 adults (18-63 years) and trial 2 included 72 children (5-14 years). Both trials included 6 dose groups that were randomized 3:1 to active treatment or placebo once daily for 28 days. Adverse events (AEs) were coded in MedDRA (version 8.1 or later). Immunological variables included specific IgE and IgE-blocking factor. No serious AEs were reported. In trial 1 (maximum dose, 32 development units [DU]), 1 patient in the 16 DU group discontinued due to AEs. The entire 32 DU group was discontinued as 1 patient had a severe adverse reaction. In trial 2 (maximum dose, 12 DU), no patients discontinued prematurely. The most frequently reported AEs were mild application-site related events. The total number of events was dose-related within each trial. HDM SLIT-tablet treatment induced changes in immunological parameters in a dose-dependent manner. These trials demonstrate that doses up to 12 DU of HDM SLIT-tablet were tolerated in the selected populations, and thus are suitable for further clinical investigations in adults and children with HDM respiratory allergic disease.

  3. Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants.

    Science.gov (United States)

    Thase, Michael E; Youakim, James M; Skuban, Aleksandar; Hobart, Mary; Augustine, Carole; Zhang, Peter; McQuade, Robert D; Carson, William H; Nyilas, Margaretta; Sanchez, Raymond; Eriksson, Hans

    2015-09-01

    To assess the efficacy, tolerability, and safety of brexpiprazole as adjunctive therapy to antidepressant treatments (ADTs) in adults with major depressive disorder (as defined by DSM-IV-TR criteria) and inadequate response to ADTs. Patients with historical inadequate response to 1-3 ADTs were enrolled. All patients entered a prospective 8-week phase on physician-determined, open-label ADT. Those with inadequate response were randomized to ADT + brexpiprazole 2 mg/d or ADT + placebo for 6 weeks. The study was conducted between July 2011 and May 2013. The primary efficacy end point was change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The key secondary end point was change from baseline to week 6 in Sheehan Disability Scale (SDS) mean score. The efficacy population comprised all patients who had ≥ 1 dose of study drug in the double-blind phase and both baseline and ≥ 1 postrandomization MADRS scores. The efficacy population per final protocol included patients from the efficacy population who met amended randomization criteria of inadequate response throughout prospective treatment. Brexpiprazole (n = 175) reduced mean MADRS total score versus placebo (n = 178) at week 6 in the efficacy population per final protocol (-8.36 vs -5.15, P = .0002). Brexpiprazole improved SDS mean score versus placebo (-1.35 vs -0.89, P = .0349). The most common treatment-related adverse events were weight gain (brexpiprazole, 8.0%; placebo, 3.1%) and akathisia (7.4% vs 1.0%). Adjunctive brexpiprazole therapy demonstrated efficacy and was well tolerated in patients with major depressive disorder and inadequate response to ADTs. ClinicalTrials.gov identifier: NCT01360645. © Copyright 2015 Physicians Postgraduate Press, Inc.

  4. EFFECT OF SUPERVISED MODERATE INTENSITY EXERCISE PROGRAM IN PHASE ONE CARDIAC REHABILITATION OF POST OPERATIVE CABG PATIENTS - A RANDOMIZED CONTROLLED TRAIL

    Directory of Open Access Journals (Sweden)

    Rajan Modi

    2014-10-01

    Full Text Available Background: With the increasing number of cases for CABG, the cardiac rehabilitation has gained importance. The trends in rehabilitation of a coronary artery disease patient are changing by incorporating a variety of aerobic exercises and resisted training in to their rehabilitation program. The outcome of any exercise chiefly depends on the training parameters like intensity, frequency and duration. Hence the present study focused to know the effects of supervised moderate intensity exercises on patients during hospital discharge following CABG. The objective of is to study the effectiveness of supervised moderate intensity exercise on distance walked and Quality of Life at hospital discharge following CABG. Methods: Study recruited randomly 46 patients between age group 40-65 years who were posted for non-emergency CABG for the first time. Pre-operative assessment was done thoroughly and was divided in to two groups, Group A conventional treatment and Group B Moderate intensity exercise group. The patients were treated using different protocols in terms of intensity for 8-10 days immediate post CABG. Then the outcome parameters of 6MWT and sf-36 were compared for analysis. Results: Both groups individually showed extremely significant results for two outcome measures. 6 MWD difference between two treatment groups showed significant results with unpaired t test (t = 8.5720,p<0.001. Quality of life score difference within group showed very significant results but there is no difference found between both groups. Conclusion: Moderate intensity exercises can also be included in the immediate post-operative phase of CABG, as they reduce the length of hospital stay and quicken the cardiac rehabilitation process. But there need to be a lot of randomized control trails to confirm the benefits of moderate intensity exercises in phase one rehabilitation program after CABG.

  5. Efficacy profile of a bivalent Staphylococcus aureus glycoconjugated vaccine in adults on hemodialysis: Phase III randomized study.

    Science.gov (United States)

    Fattom, Ali; Matalon, Albert; Buerkert, John; Taylor, Kimberly; Damaso, Silvia; Boutriau, Dominique

    2015-01-01

    In a previous study in end-stage renal disease (ESRD) hemodialysis patients, a single dose of Staphylococcus aureus type 5 and 8 capsular polysaccharides (T5/T8) conjugated to nontoxic recombinant Pseudomonas aeruginosa exotoxin A investigational vaccine showed no efficacy against S. aureus bacteremia 1 year post-vaccination, but a trend for efficacy was observed over the first 40 weeks post-vaccination. Vaccine efficacy (VE) of 2 vaccine doses was therefore evaluated. In a double-blind trial 3359 ESRD patients were randomized (1:1) to receive vaccine or placebo at week 0 and 35. VE in preventing S. aureus bacteremia was assessed between 3-35 weeks and 3-60 weeks post-dose-1. Anti-T5 and anti-T8 antibodies were measured. Serious adverse events (SAEs) were recorded for 42 days post-vaccination and deaths until study end. No significant difference in the incidence of S. aureus bacteremia was observed between vaccine and placebo groups between weeks 3-35 weeks post-dose 1 (VE -23%, 95%CI: -98;23, p = 0.39) or at 3-60 weeks post-dose-1 (VE -8%, 95%CI: -57;26, p = 0.70). Day 42 geometric mean antibody concentrations were 272.4 μg/ml and 242.0 μg/ml (T5 and T8, respectively) in vaccinees. SAEs were reported by 24%/25.3% of vaccinees/placebo recipients. These data do not show a protective effect of either 1 or 2 vaccine doses against S. aureus bacteremia in ESRD patients. The vaccine induced a robust immune response and had an acceptable safety profile. Further investigation suggested possible suboptimal vaccine quality (manufacturing) and a need to expand the antigen composition of the vaccine. This study is registered at www.clinicaltrials.gov NCT00071214.

  6. RECAST (Remote Ischemic Conditioning After Stroke Trial): A Pilot Randomized Placebo Controlled Phase II Trial in Acute Ischemic Stroke.

    Science.gov (United States)

    England, Timothy J; Hedstrom, Amanda; O'Sullivan, Saoirse; Donnelly, Richard; Barrett, David A; Sarmad, Sarir; Sprigg, Nikola; Bath, Philip M

    2017-05-01

    Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75-9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group ( P =0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5-5) versus 3 (interquartile range, 2-9.5; P =0.04); RIC augmented plasma HSP27 (heat shock protein 27; P stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. URL: http://www.isrctn.com. Unique identifier: ISRCTN86672015. © 2017 American Heart Association, Inc.

  7. A Randomized, Phase I Pharmacokinetic Study Comparing SB2 and Infliximab Reference Product (Remicade(®)) in Healthy Subjects.

    Science.gov (United States)

    Shin, Donghoon; Kim, Youngdoe; Kim, Yoo Seok; Körnicke, Thomas; Fuhr, Rainard

    2015-12-01

    SB2, a biosimilar to infliximab reference product (INF), has an identical amino acid sequence and similar physicochemical functional properties to its reference product. The primary objective of this study is to demonstrate pharmacokinetic (PK) bioequivalence between SB2 and EU-sourced INF (EU-INF), between SB2 and US-sourced INF (US-INF), and between EU-INF and US-INF. This study was a randomized, single-blind, three-arm, parallel group study in 159 healthy subjects. All subjects received a single 5 mg/kg intravenous infusion of study drug and then were observed for 10 weeks to study PK, safety and immunogenicity. The primary PK parameters were area under the concentration-time curve (AUC) from time zero to infinity (AUCinf), AUC from time zero to the last quantifiable concentration (AUClast) and maximum concentration (C max). Bioequivalence for the primary PK parameters was to be concluded using an analysis of variance (ANOVA) if the 90 % confidence intervals (CIs) for the ratio of geometric least squares means (LSMeans) of the treatments compared were completely contained within the pre-defined equivalence margin, 0.8-1.25. All of the 90 % CIs for the geometric LSMean ratios of primary PK parameters for each comparison were within the pre-defined equivalence margin. The proportion of subjects who experienced treatment-emergent adverse events was comparable between treatments. The incidences of anti-drug antibodies between the three treatments were comparable. This study demonstrated biosimilarity of SB2 to its marketed reference products of infliximab in terms of PK equivalence in healthy subjects. SB2 was generally well tolerated and showed comparable safety and immunogenicity profiles to the reference products (ClinicalTrials.gov Identifier: NCT01922336).

  8. A prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer.

    Science.gov (United States)

    Arcangeli, Giorgio; Saracino, Biancamaria; Gomellini, Sara; Petrongari, Maria Grazia; Arcangeli, Stefano; Sentinelli, Steno; Marzi, Simona; Landoni, Valeria; Fowler, Jack; Strigari, Lidia

    2010-09-01

    To compare the toxicity and efficacy of hypofractionated (62 Gy/20 fractions/5 weeks, 4 fractions per week) vs. conventional fractionation radiotherapy (80 Gy/40 fractions/8 weeks) in patients with high-risk prostate cancer. From January 2003 to December 2007, 168 patients were randomized to receive either hypofractionated or conventional fractionated schedules of three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients received a 9-month course of total androgen deprivation (TAD), and radiotherapy started 2 months thereafter. The median (range) follow-up was 32 (8-66) and 35 (7-64) months in the hypofractionation and conventional fractionation arms, respectively. No difference was found for late toxicity between the two treatment groups, with 3-year Grade 2 rates of 17% and 16% for gastrointestinal and 14% and 11% for genitourinary in the hypofractionation and conventional fractionation groups, respectively. The 3-year freedom from biochemical failure (FFBF) rates were 87% and 79% in the hypofractionation and conventional fractionation groups, respectively (p = 0.035). The 3-year FFBF rates in patients at a very high risk (i.e., pretreatment prostate-specific antigen (iPSA) >20 ng/mL, Gleason score >or=8, or T >or=2c), were 88% and 76% (p = 0.014) in the former and latter arm, respectively. The multivariate Cox analysis confirmed fractionation, iPSA, and Gleason score as significant prognostic factors. Our findings suggest that late toxicity is equivalent between the two treatment groups and that the hypofractionated schedule used in this trial is superior to the conventional fractionation in terms of FFBF. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  9. Omeprazole-Domperidone Fixed Dose Combination vs Omeprazole Monotherapy: A Phase 4, Open-Label, Comparative, Parallel Randomized Controlled Study in Mild to Moderate Gastroesophageal Reflux Disease

    Directory of Open Access Journals (Sweden)

    KY Marakhouski

    2017-05-01

    Full Text Available Aim: To compare the efficacy and safety of omeprazole-domperidone combination vs omeprazole monotherapy in gastroesophageal reflux disease (GERD. Methods: In a comparative, randomized controlled, phase 4 study, outpatients with GERD were randomly allocated to either group 1 (omeprazole 20 mg + domperidone 30 mg or group 2 (omeprazole 20 mg in an equal ratio; 2 capsules daily in the morning were administered for 8 weeks. Results: Sixty patients were enrolled. Esophagitis reversal was observed in 92% patients in group 1 vs 65.2% in group 2. Approximately, 83.3% patients in group 1 vs 43.3% patients in group 2 demonstrated full cupping of reflux symptoms at 8 weeks. Combined therapy resulted in significantly longer period of heartburn-free days (23 vs 12 days on omeprazole. There were no safety concerns. Conclusions: Omeprazole-domperidone combination was more effective than omeprazole alone in providing complete cupping of reflux symptoms and healing of esophagitis in patients with GERD. Both the treatments were well tolerated with few reports of adverse events. Trial registration: This trial is registered with http://clinicaltrials.gov , number NCT02140073.

  10. Safety and acceptability of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 in Bangladeshi infants: a phase I randomized clinical trial.

    Science.gov (United States)

    Hoy-Schulz, Yana Emmy; Jannat, Kaniz; Roberts, Thomas; Zaidi, Saira Husain; Unicomb, Leanne; Luby, Stephen; Parsonnet, Julie

    2016-02-02

    Probiotics have rarely been studied in young healthy infants from low-income countries. This phase I study investigated the safety and acceptability of two probiotics in Bangladesh. Healthy infants aged four to twelve weeks from urban slums in Bangladesh were randomized to one of three different intervention dosing arms (daily, weekly, biweekly - once every two weeks) of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 over one month or to a fourth arm that received no probiotics. All subjects were followed for two additional months. Reported gastrointestinal and respiratory symptoms as well as breastfeeding rates, hospitalizations, differential withdrawals, and caretakers' perception of probiotic use were compared among arms. In total, 160 infants were randomized (40 to each arm) with 137 (Daily n = 35, Weekly n = 35, Biweekly n = 35, Control n = 32) followed up for a median of twelve weeks; 113 completed the study. Illness and breastfeeding rates were similar across all arms. Ten hospitalizations unrelated to probiotic use occurred. Forty eight percent of the caretakers of infants in intervention arms believed that probiotics improved their baby's health. These two commonly used probiotics appeared safe and well-accepted by Bangladeshi families. ClinicalTrials.gov NCT01899378 . Registered July 10, 2013.

  11. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results.

    Science.gov (United States)

    Coronel, Jaime; Cetina, Lucely; Pacheco, Irlanda; Trejo-Becerril, Catalina; González-Fierro, Aurora; de la Cruz-Hernandez, Erick; Perez-Cardenas, Enrique; Taja-Chayeb, Lucia; Arias-Bofill, Daymi; Candelaria, Myrna; Vidal, Silvia; Dueñas-González, Alfonso

    2011-12-01

    The reversing of epigenetic aberrations using the inhibitors of DNA methylation and histone deacetylases may have therapeutic value in cervical cancer. This is a randomized phase III, placebo-controlled study of hydralazine and valproate (HV) added to cisplatin topotecan in advanced cervical cancer. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow acetylators, and valproate at 30 mg/kg, beginning a week before chemotherapy and continued until disease progression. Response, toxicity, and PFS were evaluated, and 36 patients (17 CT + HV and 19 CT + PLA) were included. The median number of cycles was 6. There were four PRs to CT + HV and one in CT + PLA. Stable disease in five (29%) and six (32%) patients, respectively, whereas eight (47%) and 12 (63%) showed progression (P = 0.27). At a median follow-up time of 7 months (1-22), the median PFS is 6 months for CT + PLA and 10 months for CT + HV (P = 0.0384, two tailed). Although preliminary, this study represents the first randomized clinical trial to demonstrate a significant advantage in progression-free survival for epigenetic therapy over one of the current standard combination chemotherapy in cervical cancer. Molecular correlates with response and survival from this trial are pending to analyze.

  12. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

    Science.gov (United States)

    Hegg, Roberto; Mattar, André; de Matos, João Nunes; Pedrini, José Luiz; Aleixo, Sabina Bandeira; Rocha, Roberto Odebrecht; Cramer, Renato Peixoto; van-Eyll-Rocha, Sylvie

    2016-01-01

    OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®). PMID:27759847

  13. Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial.

    Science.gov (United States)

    Elewski, Boni E; Okun, Martin M; Papp, Kim; Baker, Christopher S; Crowley, Jeffrey J; Guillet, Gérard; Sundaram, Murali; Poulin, Yves; Gu, Yihua; Geng, Ziqian; Williams, David A; Rich, Phoebe A

    2018-01-01

    Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P psoriasis versus with placebo and no new safety risks were identified. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  14. Efficacy of tofacitinib for the treatment of nail psoriasis: Two 52-week, randomized, controlled phase 3 studies in patients with moderate-to-severe plaque psoriasis.

    Science.gov (United States)

    Merola, Joseph F; Elewski, Boni; Tatulych, Svitlana; Lan, Shuping; Tallman, Anna; Kaur, Mandeep

    2017-07-01

    Tofacitinib is an oral Janus kinase inhibitor. Efficacy and safety of tofacitinib in patients with moderate-to-severe plaque psoriasis have been demonstrated. We sought to assess the efficacy of tofacitinib for the treatment of nail psoriasis over a period of 52 weeks. In 2 identical phase 3 studies (OPT Pivotal 1 and 2), patients were randomized 2:2:1 to receive tofacitinib 5 mg, tofacitinib 10 mg, or placebo, twice daily. At week 16, placebo-treated patients were re-randomized to tofacitinib. This post hoc analysis of patients with existing nail psoriasis assessed the Nail Psoriasis Severity Index (NAPSI) score and proportions of patients achieving ≥50% reduction in NAPSI from baseline (NAPSI50), NAPSI75, or NAPSI100. Baseline mean NAPSI scores for patients treated with tofacitinib 5 mg (N = 487), tofacitinib 10 mg (N = 476), and placebo (N = 233) twice daily were 27.0, 27.3, and 26.9, respectively. At week 16, significantly (all P psoriasis versus placebo at week 16; improvements were maintained over 52 weeks [NCT01276639; NCT01309737]. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. Effect of Eischens Yoga During Radiation Therapy on Prostate Cancer Patient Symptoms and Quality of Life: A Randomized Phase II Trial.

    Science.gov (United States)

    Ben-Josef, Avital Mazar; Chen, Jerry; Wileyto, Paul; Doucette, Abigail; Bekelman, Justin; Christodouleas, John; Deville, Curtiland; Vapiwala, Neha

    2017-08-01

    A randomized phase II study was performed to measure the potential therapeutic effects of yoga on fatigue, erectile dysfunction, urinary incontinence, and overall quality of life (QOL) in prostate cancer (PCa) patients undergoing external beam radiation therapy (RT). The participants were randomized to yoga and no-yoga cohorts (1:1). Twice-weekly yoga interventions were offered throughout the 6- to 9-week courses of RT. Comparisons of standardized assessments were performed between the 2 cohorts for the primary endpoint of fatigue and the secondary endpoints of erectile dysfunction, urinary incontinence, and QOL before, during, and after RT. From October 2014 to January 2016, 68 eligible PCa patients underwent informed consent and agreed to participate in the study. Of the 68 patients, 18 withdrew early, mostly because of treatment schedule-related time constraints, resulting in 22 and 28 patients in the yoga and no-yoga groups, respectively. Throughout treatment, those in the yoga arm reported less fatigue than those in the control arm, with global fatigue, effect of fatigue, and severity of fatigue subscales showing statistically significant interactions (Pyoga having a significant time by treatment effect on the emotional, physical, and social scores but not on functional scores. A structured yoga intervention of twice-weekly classes during a course of RT was associated with a significant reduction in pre-existing and RT-related fatigue and urinary and sexual dysfunction in PCa patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Non-Hermitian random matrix theory: summation of planar diagrams, the 'single-ring' theorem and the disc-annulus phase transition

    Energy Technology Data Exchange (ETDEWEB)

    Feinberg, Joshua [Physics Department, University of Haifa at Oranim, Tivon 36006 (Israel); Physics Department, Technion, Israel Institute of Technology, Haifa 32000 (Israel)

    2006-08-11

    I review aspects of work done in collaboration with A Zee and R Scalettar (1997 Nucl. Phys. B 504 579; 1997 Nucl. Phys. B 501 643; 2001 J. Math. Phys. 42 5718) on complex non-Hermitian random matrices. I open by explaining why the bag of tools used regularly in analysing Hermitian random matrices cannot be applied directly to analyse non-Hermitian matrices, and then introduce the method of Hermitization, which solves this problem. Then, for rotationally invariant ensembles, I derive a master equation for the average density of eigenvalues in the complex plane, in the limit of infinitely large matrices. This is achieved by resumming all the planar diagrams which appear in the perturbative expansion of the Hermitized Green function. Remarkably, this resummation can be carried out explicitly for any rotationally invariant ensemble. I prove that in the limit of infinitely large matrices, the shape of the eigenvalue distribution is either a disc or an annulus. This is the celebrated 'single-ring' theorem. Which of these shapes is realized is determined by the parameters (coupling constants) which determine the ensemble. By varying these parameters a phase transition may occur between the two possible shapes. I briefly discuss the universal features of this transition. As the analysis of this problem relies heavily on summation of planar Feynman diagrams, I make a special effort at presenting a pedagogical exposition of the diagrammatic method, which some readers may find useful.

  17. Diacerein Orphan Drug Development for Epidermolysis Bullosa Simplex: A Phase 2/3 Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

    Science.gov (United States)

    Wally, Verena; Hovnanian, Alain; Ly, Juliette; Buckova, Hana; Brunner, Victoria; Lettner, Thomas; Ablinger, Michael; Felder, Thomas K; Hofbauer, Peter; Wolkersdorfer, Martin; Lagler, Florian B; Hitzl, Wolfgang; Laimer, Martin; Kitzmüller, Sophie; Diem, Anja; Bauer, Johann W

    2018-02-01

    EBS is a rare genetic, blistering skin disease for which there is no cure. Treatments that address the pathophysiology of EBS are needed. Compare the impact of 1% diacerein cream vs placebo in reducing blister number in EBS. In a randomized, placebo-controlled, phase 2/3 trial we used a 1% diacerein topical formulation to treat defined skin areas in 17 patients. In a 2-period cross-over trial, patients were randomized to either placebo or diacerein for 4-week treatment and a 3-month follow-up in period 1. After a wash-out, patients were crossed-over during period 2. The pre-specified primary endpoint was the proportion of patients with a reduction of blister numbers by >40% from baseline in selected areas over the treatment episode. For patients on diacerein, 86% in episode 1 and 37.5% in episode 2 met the primary endpoint (placebo, 14% and 17%, respectively). This effect was still significant after the follow-up. Changes in absolute blister numbers were significant for the diacerein group only. No adverse effects were observed. Low patient numbers, no invasive data acquisition due to clinical burden in children. This trial provides evidence of the impact of 1% diacerein cream in the treatment of EBS. Copyright © 2018. Published by Elsevier Inc.

  18. Safety and tolerability of topically administered autologous, apoptotic PBMC secretome (APOSEC) in dermal wounds: a randomized Phase 1 trial (MARSYAS I).

    Science.gov (United States)

    Simader, Elisabeth; Traxler, Denise; Kasiri, Mohammad Mahdi; Hofbauer, Helmut; Wolzt, Michael; Glogner, Christoph; Storka, Angela; Mildner, Michael; Gouya, Ghazaleh; Geusau, Alexandra; Fuchs, Carola; Eder, Claudia; Graf, Alexandra; Schaden, Michaela; Golabi, Bahar; Aretin, Marie-Bernadette; Suessner, Susanne; Gabriel, Christian; Klepetko, Walter; Tschachler, Erwin; Ankersmit, Hendrik Jan

    2017-07-24

    Developing effective therapies against chronic wound healing deficiencies is a global priority. Thus we evaluated the safety of two different doses of topically administered autologous APOSEC, the secretome of apoptotic peripheral blood mononuclear cells (PBMCs), in healthy male volunteers with artificial dermal wounds. Ten healthy men were enrolled in a single-center, randomized, double-blinded, placebo-controlled phase 1 trial. Two artificial wounds at the upper arm were generated using a 4-mm punch biopsy. Each participant was treated with both topically applied APOSEC and placebo in NuGel for 7 consecutive days. The volunteers were randomized into two groups: a low-dose group (A) receiving the supernatant of 12.5 × 10 6 PBMCs and a high-dose group (B) receiving an equivalent of 25 × 10 6 PBMCs resuspended in NuGel Hydrogel. Irradiated medium served as placebo. The primary outcome was the tolerability of the topical application of APOSEC. All adverse events were recorded until 17 days after the biopsy. Local tolerability assessment was measured on a 4-point scale. Secondary outcomes were wound closure and epithelization at day 7. No therapy-related serious adverse events occurred in any of the participants, and both low- and high-dose treatments were well tolerated. Wound closure was not affected by APOSEC therapy.

  19. Three-Arm Randomized Phase III Trial: Quality Aloe and Placebo Cream Versus Powder as Skin Treatment During Breast Cancer Radiation Therapy.

    Science.gov (United States)

    Hoopfer, Donna; Holloway, Caroline; Gabos, Zsolt; Alidrisi, Maha; Chafe, Susan; Krause, Barbara; Lees, Alan; Mehta, Nirmal; Tankel, Keith; Strickland, Faith; Hanson, John; King, Charlotte; Ghosh, Sunita; Severin, Diane

    2015-06-01

    The efficacy of aloe extract in reducing radiation-induced skin injury is controversial. The purpose of the present 3-arm randomized trial was to test the efficacy of quality-tested aloe extract in reducing the severity of radiation-induced skin injury and, secondarily, to examine the effect of a moist cream versus a dry powder skin care regimen. A total of 248 patients with breast cancer were randomized to powder, aloe cream, or placebo cream. Acute skin toxicity was scored weekly and after treatment at weeks 1, 2, and 4 using a modified 10-point Catterall scale. The patients scored their symptom severity using a 6-point Likert scale and kept an acute phase diary. The aloe formulation did not reduce acute skin toxicity or symptom severity. Patients with a greater body mass index were more likely to develop acute skin toxicity. A similar pattern of increased skin reaction toxicity occurred with both study creams compared with the dry powder regimen. No evidence was found to support prophylactic application of quality aloe extract or cream to improve the symptoms or reduce the skin reaction severity. Our results support a dry skin care regimen of powder during radiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114).

    Science.gov (United States)

    Schwartz, Gary K; Winter, Kathryn; Minsky, Bruce D; Crane, Christopher; Thomson, P John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

    2009-04-20

    The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials.

  1. Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin Administered via an Inhaled Route in Healthy Females: Randomized, Single-blind, Phase 1 Study.

    Science.gov (United States)

    Fernando, Disala; Siederer, Sarah; Singh, Sunita; Schneider, Ian; Gupta, Ashutosh; Powell, Marcy; Richards, Duncan; McIntosh, Michelle P; Lambert, Peter; Fowles, Susan

    2017-08-01

    The utility of intramuscular (IM) oxytocin for the prevention of postpartum hemorrhage in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. We evaluated the safety, tolerability and pharmacokinetics (PK) of a heat-stable, inhaled (IH) oxytocin formulation. This phase 1, randomized, single-center, single-blind, dose-escalation, fixed-sequence study (NCT02542813) was conducted in healthy, premenopausal, non-pregnant, non-lactating women aged 18-45years. Subjects initially received IM oxytocin 10 international units (IU) on day 1, IH placebo on day 2, and IH oxytocin 50μg on day 3. Subjects were then randomized 4:1 using validated GSK internal software to IH placebo or ascending doses of IH oxytocin (200, 400, 600μg). PK was assessed by comparing systemic exposure (maximum observed plasma concentration, area under the concentration-time curve, and plasma concentrations at 10 and 30min post dose) for IH versus IM oxytocin. Adverse events (AEs), spirometry, laboratory tests, vital signs, electrocardiograms, physical examinations, and cardiac telemetry were assessed. Subjects were recruited between September 14, 2015 and October 12, 2015. Of the 16 subjects randomized following initial dosing, 15 (IH placebo n=3; IH oxytocin n=12) completed the study. IH (all doses) and IM oxytocin PK profiles were comparable in shape. However, systemic exposure with IH oxytocin 400μg most closely matched IM oxytocin 10IU. Systemic exposure was approximately dose proportional for IH oxytocin. No serious AEs were reported. No clinically significant findings were observed for any safety parameters. These data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings. Copyright

  2. Clarithromycin Plus Intravenous Immunoglobulin Therapy Can Reduce the Relapse Rate of Kawasaki Disease: A Phase 2, Open-Label, Randomized Control Study.

    Science.gov (United States)

    Nanishi, Etsuro; Nishio, Hisanori; Takada, Hidetoshi; Yamamura, Kenichiro; Fukazawa, Mitsuharu; Furuno, Kenji; Mizuno, Yumi; Saigo, Kenjiro; Kadoya, Ryo; Ohbuchi, Noriko; Onoe, Yasuhiro; Yamashita, Hironori; Nakayama, Hideki; Hara, Takuya; Ohno, Takuro; Takahashi, Yasuhiko; Hatae, Ken; Harada, Tatsuo; Shimose, Takayuki; Kishimoto, Junji; Ohga, Shouichi; Hara, Toshiro

    2017-07-06

    We previously reported that biofilms and innate immunity contribute to the pathogenesis of Kawasaki disease. Therefore, we aimed to assess the efficacy of clarithromycin, an antibiofilm agent, in patients with Kawasaki disease. We conducted an open-label, multicenter, randomized, phase 2 trial at 8 hospitals in Japan. Eligible patients included children aged between 4 months and 5 years who were enrolled between days 4 and 8 of illness. Participants were randomly allocated to receive either intravenous immunoglobulin (IVIG) or IVIG plus clarithromycin. The primary end point was the duration of fever after the initiation of IVIG treatment. Eighty-one eligible patients were randomized. The duration of the fever did not differ between the 2 groups (mean±SD, 34.3±32.4 and 31.1±31.1 hours in the IVIG plus clarithromycin group and the IVIG group, respectively [ P =0.66]). The relapse rate of patients in the IVIG plus clarithromycin group was significantly lower than that in the IVIG group (12.5% versus 30.8%, P =0.046). No serious adverse events occurred during the study period. In a post hoc analysis, the patients in the IVIG plus clarithromycin group required significantly shorter mean lengths of hospital stays than those in the IVIG group (8.9 days versus 10.3 days, P =0.049). Although IVIG plus clarithromycin therapy failed to shorten the duration of fever, it reduced the relapse rate and shortened the duration of hospitalization in patients with Kawasaki disease. URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000015437. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  3. The RESPIRE trials: Two phase III, randomized, multicentre, placebo-controlled trials of Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) in non-cystic fibrosis bronchiectasis.

    Science.gov (United States)

    Aksamit, Timothy; Bandel, Tiemo-Joerg; Criollo, Margarita; De Soyza, Anthony; Elborn, J Stuart; Operschall, Elisabeth; Polverino, Eva; Roth, Katrin; Winthrop, Kevin L; Wilson, Robert

    2017-07-01

    The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve quality of life. However, currently no therapies are licensed for this. Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients. The RESPIRE programme consists of two international phase III prospective, parallel-group, randomized, double-blinded, multicentre, placebo-controlled trials of the same design. Adult patients with idiopathic or post-infectious NCFB, a history of ≥2 exacerbations in the previous 12months, and positive sputum culture for one of seven pre-specified pathogens, undergo stratified randomization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5mg or placebo using a pocket-sized inhaler in one of two regimens: 28days on/off treatment or 14days on/off treatment. The treatment period is 48weeks plus an 8-week follow-up after the last dose. The primary efficacy endpoints are time to first exacerbation after treatment initiation and frequency of exacerbations using a stringent definition of exacerbation. Secondary endpoints, including frequency of events using different exacerbation definitions, microbiology, quality of life and lung function will also be evaluated. The RESPIRE trials will determine the efficacy and safety of Ciprofloxacin DPI. The strict entry criteria and stratified randomization, the inclusion of two treatment regimens and a stringent definition of exacerbation should clarify the patient population best positioned to benefit from long-term inhaled antibiotic therapy. Additionally RESPIRE will increase understanding of NCFB treatment and could lead to an important new therapy for sufferers. The RESPIRE trials are registered in ClinicalTrials.gov, ID number NCT01764841 (RESPIRE 1; date of registration January 8, 2013) and NCT02106832 (RESPIRE 2; date of registration

  4. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS).

    Science.gov (United States)

    Hájek, R; Masszi, T; Petrucci, M T; Palumbo, A; Rosiñol, L; Nagler, A; Yong, K L; Oriol, A; Minarik, J; Pour, L; Dimopoulos, M A; Maisnar, V; Rossi, D; Kasparu, H; Van Droogenbroeck, J; Yehuda, D B; Hardan, I; Jenner, M; Calbecka, M; Dávid, M; de la Rubia, J; Drach, J; Gasztonyi, Z; Górnik, S; Leleu, X; Munder, M; Offidani, M; Zojer, N; Rajangam, K; Chang, Y-L; San-Miguel, J F; Ludwig, H

    2017-01-01

    This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m2 on days 1 and 2 of cycle 1; 27 mg/m2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients.

  5. Health-related quality of life outcomes from CABARET: a randomized phase 2 trial of carboplatin and bevacizumab in recurrent glioblastoma.

    Science.gov (United States)

    Field, Kathryn M; King, Madeleine T; Simes, John; Espinoza, David; Barnes, Elizabeth H; Sawkins, Kate; Rosenthal, Mark A; Cher, Lawrence; Hovey, Elizabeth; Wheeler, Helen; Nowak, Anna K

    2017-07-01

    In recurrent glioblastoma, health-related quality of life (HRQL) is a crucial trial endpoint. We examined HRQL outcomes as a secondary endpoint for patients in the CABARET randomized phase 2 trial. 122 patients were randomly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin. We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Brain Cancer Module (QLQ-BN20), together with time to deterioration in HRQL, and the proportion of participants with clinically meaningful improvements in specific disease-related symptoms. At baseline, 117 of 122 randomized patients (96%) attempted questionnaires. Questionnaire participation rates were >90% for patients continuing on treatment, however at the end-of-treatment visit only 72 (64% of eligible participants) returned a form. There were no differences between arms in change scores over the treatment period. Time to ≥10 point deterioration in scores from baseline was also similar between arms. HRQL deterioration occurred largely before progression for the domains tested, but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50% of patients with symptoms at baseline. Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab, with a proportion of patients on both arms experiencing symptomatic benefit. Given the reduced questionnaire completion at end of treatment, time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population. Clinical trials registration number: ACTRN12610000915055.

  6. PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer.

    Science.gov (United States)

    Naumann, R Wendel; Coleman, Robert L; Burger, Robert A; Sausville, Edward A; Kutarska, Elzbieta; Ghamande, Sharad A; Gabrail, Nashat Y; Depasquale, Stephen E; Nowara, Elzbieta; Gilbert, Lucy; Gersh, Robert H; Teneriello, Michael G; Harb, Wael A; Konstantinopoulos, Panagiotis A; Penson, Richard T; Symanowski, James T; Lovejoy, Chandra D; Leamon, Christopher P; Morgenstern, David E; Messmann, Richard A

    2013-12-10

    Vintafolide (EC145) is a folic acid-desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, (99m)Tc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m(2) intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P = .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P = .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.

  7. Axitinib dose titration: analyses of exposure, blood pressure and clinical response from a randomized phase II study in metastatic renal cell carcinoma.

    Science.gov (United States)

    Rini, B I; Melichar, B; Fishman, M N; Oya, M; Pithavala, Y K; Chen, Y; Bair, A H; Grünwald, V

    2015-07-01

    In a randomized, double-blind phase II trial in patients with metastatic renal cell carcinoma (mRCC), axitinib versus placebo titration yielded a significantly higher objective response rate. We evaluated pharmacokinetic and blood pressure (BP) data from this study to elucidate relationships among axitinib exposure, BP change, and efficacy. Patients received axitinib 5 mg twice daily during a lead-in period. Patients who met dose-titration criteria were randomized 1:1 to stepwise dose increases with axitinib or placebo. Patients ineligible for randomization continued without dose increases. Serial 6-h and sparse pharmacokinetic sampling were carried out; BP was measured at clinic visits and at home in all patients, and by 24-h ambulatory BP monitoring (ABPM) in a subset of patients. Area under the plasma concentration-time curve from 0 to 24 h throughout the course of treatment (AUCstudy) was higher in patients with complete or partial responses than those with stable or progressive disease in the axitinib-titration arm, but comparable between these groups in the placebo-titration and nonrandomized arms. In the overall population, AUCstudy and efficacy outcomes were not strongly correlated. Mean BP across the population was similar when measured in clinic, at home, or by 24-h ABPM. Weak correlations were observed between axitinib steady-state exposure and diastolic BP. When grouped by change in diastolic BP from baseline, patients in the ≥10 and ≥15 mmHg groups had longer progression-free survival. Optimal axitinib exposure may differ among patients with mRCC. Pharmacokinetic or BP measurements cannot be used exclusively to guide axitinib dosing. Individualization of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors, including axitinib, is thus more complex than anticipated and cannot be limited to a single clinical factor. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical

  8. Which luteal phase support is better for each IVF stimulation protocol to achieve the highest pregnancy rate? A superiority randomized clinical trial.

    Science.gov (United States)

    Gizzo, Salvatore; Andrisani, Alessandra; Esposito, Federica; Noventa, Marco; Di Gangi, Stefania; Angioni, Stefano; Litta, Pietro; Gangemi, Michele; Nardelli, Giovanni Battista

    2014-01-01

    In vitro fertilization (IVF) cycles generate abnormalities in luteal-phase sex steroid concentrations and this represent an important limiting factor to achieve a good pregnancy rate. Although there are evidences about the usefulness of luteal phase support (LPS) after IVF cycles, no consensus exist about the best dose and way of progesterone (PG) administration, the advantages of estradiol (E2) supplementation and which IVF protocol could benefit from one more than other LPS scheme. Aim of the study was to assess the best LPS (low-dose PG, high-dose PG, high-dose PG and E2 supplementation) to achieve the highest clinical/ongoing pregnancy rate according to stimulation protocol, E2 at ovulation induction, endometrial thickness at pick-up and women's age. We conducted a randomized trial on 360 women undergoing IVF (180 treated by long-GnRH agonist, 90 by short-GnRH agonist and 90 by short-GnRH antagonist protocol) and stimulated by recombinant follicle-stimulating hormone alone. Our data demonstrated that high-dose PG is better than low-dose to increase both clinical and ongoing pregnancy rate. E2 supplementation are mandatory in case of short-GnRH antagonist protocol and strongly suggested in all protocols when E2max 35 years, the real advantages of E2 supplementation remain debatable and require further confirmation.

  9. Lifitegrast for the Treatment of Dry Eye Disease: Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3).

    Science.gov (United States)

    Holland, Edward J; Luchs, Jodi; Karpecki, Paul M; Nichols, Kelly K; Jackson, Mitchell A; Sall, Kenneth; Tauber, Joseph; Roy, Monica; Raychaudhuri, Aparna; Shojaei, Amir

    2017-01-01

    Lifitegrast is a lymphocyte function-associated antigen-1 antagonist developed to reduce inflammation in dry eye disease (DED). We report the results of OPUS-3 (NCT02284516), a phase III study evaluating the efficacy and safety of lifitegrast versus placebo in participants with DED. Twelve-week, phase III, randomized, double-masked, multicenter, placebo-controlled study. Adults aged ≥18 years with Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, corneal fluorescein staining score ≥2.0 (0-4 scale), eye dryness score (EDS) ≥40 (0-100 visual analogue scale [VAS]), and history of artificial tear use within 30 days of study entry. After a 14-day placebo run-in, participants were randomized 1:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. The primary efficacy end point was change from baseline to day 84 in EDS. Key secondary efficacy end points were change from baseline to days 42 and 14 in EDS. Other secondary efficacy end points included additional VAS items (burning/stinging, itching, foreign body sensation, eye discomfort, photophobia, pain), ocular discomfort score (ODS), and safety/tolerability of lifitegrast versus placebo. In the study, 711 participants were randomized: placebo, 356; lifitegrast, 355 (intention-to-treat [ITT] population). At day 84, lifitegrast-treated participants experienced significantly greater improvement from baseline in EDS versus those receiving placebo (treatment effect [TE], 7.16; 95% confidence interval [CI], 3.04-11.28; P = 0.0007). Mean changes from baseline in EDS also significantly favored lifitegrast on days 42 (TE, 9.32; 95% CI, 5.44-13.20; P lifitegrast-treated participants at day 42 in itching (nominal P = 0.0318), foreign body sensation (nominal P = 0.0418), and eye discomfort (P = 0.0048) versus participants receiving placebo. Most treatment-emergent adverse events were mild to moderate in severity; no serious ocular adverse events were reported. Lifitegrast significantly

  10. Randomized phase II trial of hypofractionated proton versus carbon ion radiation therapy in patients with sacrococcygeal chordoma-the ISAC trial protocol.

    Science.gov (United States)

    Uhl, Matthias; Edler, Lutz; Jensen, Alexandra D; Habl, Gregor; Oelmann, Jan; Röder, Falk; Jäckel, Oliver; Debus, Jürgen; Herfarth, Klaus

    2014-04-29

    Chordomas are relatively rare lesions of the bones. About 30% occur in the sacrococcygeal region. Surgical resection is still the standard treatment. Due to the size, proximity to neurovascular structures and the complex anatomy of the pelvis, a complete resection with adequate safety margin is difficult to perform. A radical resection with safety margins often leads to the loss of bladder and rectal function as well as motoric/sensoric dysfunction. The recurrence rate after surgery alone is comparatively high, such that adjuvant radiation therapy is very important for improving local control rates. Proton therapy is still the international standard in the treatment of chordomas. High-LET beams such as carbon ions theoretically offer biologic advantages in slow-growing tumors. Data of a Japanese study of patients with unresectable sacral chordoma showed comparable high control rates after hypofractionated carbon ion therapy only. This clinical study is a prospective randomized, monocentric phase II trial. Patients with histologically confirmed sacrococcygeal chordoma will be randomized to either proton or carbon ion radiation therapy stratified regarding the clinical target volume. Target volume delineation will be carried out based on CT and MRI data. In each arm the PTV will receive 64 GyE in 16 fractions. The primary objective of this trial is safety and feasibility of hypofractionated irradiation in patients with sacrococygeal chordoma using protons or carbon ions in raster scan technique for primary or additive treatment after R2 resection. The evaluation is therefore based on the proportion of treatments without Grade 3-5 toxicity (CTCAE, version 4.0) up to 12 months after treatment and/or discontinuation of the treatment for any reason as primary endpoint. Local-progression free survival, overall survival and quality of life will be analyzed as secondary end points. The aim of this study is to confirm the toxicity results of the Japanese data in raster scan

  11. A randomized, double-blind, phase 2 study evaluating the safety and efficacy of AMG 416 for the treatment of secondary hyperparathyroidism in hemodialysis patients.

    Science.gov (United States)

    Bell, Gregory; Huang, Saling; Martin, Kevin J; Block, Geoffrey A

    2015-05-01

    Secondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease. We evaluated AMG 416, a long-acting peptide agonist of the calcium-sensing receptor, to assess its safety, tolerability, and efficacy and to determine a safe and effective starting dose for subsequent phase 2 studies. The study was not designed to titrate AMG 416 dosing to achieve a specific PTH treatment goal. This is a multicenter, double-blind, randomized, placebo-controlled, dose-escalation study designed to evaluate the safety and efficacy of AMG 416 administered thrice weekly by IV bolus at the end of hemodialysis for up to 4 weeks. Eligible subjects were enrolled in one of three cohorts and treated with 5 mg of AMG 416 or placebo for 2 weeks (Cohort 1) or 5 or 10 mg of AMG 416 or placebo for 4 weeks (Cohorts 2 and 3). The primary endpoint was mean percentage change from baseline in PTH during the efficacy assessment phase (EAP) in Cohorts 2 and 3. Analysis of the primary endpoint showed that treatment with AMG 416 at 10 mg (Cohort 2) and 5 mg (Cohort 3) for up to 4 weeks resulted in mean 49.4% and 33.0% reductions from baseline in PTH during the efficacy assessment phase, respectively (p AMG 416 achieved PTH ≤300 pg/mL and ≥30% reduction in PTH from baseline in both cohorts. The observed decreases in serum-corrected calcium were well tolerated and serum phosphate levels also tended to decrease. The present clinical findings support the continued development of AMG 416 as a treatment for SHPT in hemodialysis patients.

  12. Multidimensionally encoded magnetic resonance imaging.

    Science.gov (United States)

    Lin, Fa-Hsuan

    2013-07-01

    Magnetic resonance imaging (MRI) typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here, we propose the multidimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel radiofrequency coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled. Copyright © 2012 Wiley Periodicals, Inc.

  13. Therapeutic vaccination with TNF-Kinoid in TNF antagonist-resistant rheumatoid arthritis: a phase II randomized, controlled clinical trial.

    Directory of Open Access Journals (Sweden)

    Patrick Durez

    Full Text Available OBJECTIVES: Active immunization, or vaccination, with tumor necrosis factor (TNF-Kinoid (TNF-K is a novel approach to induce polyclonal anti-TNF antibodies in immune-mediated inflammatory diseases. This study was performed to transfer the proof of concept obtained in mice model of rheumatoid arthritis (RA into human. We designed a pilot study to demonstrate the feasibility of therapeutic vaccination in RA. METHODS: This was a phase IIa, placebo-controlled, multicenter study in adults with RA who previously experienced secondary failure of TNF antagonists. Patients were immunized intramuscularly with 2 or 3 doses of placebo (n = 10 or 90 (n = 6, 180 (n = 12, or 360 µg TNF-K (n = 12. The primary objective was to identify the best dose and schedule based on anti-TNF antibody titers. Clinical symptoms and safety were assessed during 12 months and solicited reactions for 7 days after each injection. RESULTS: The highest anti-TNF antibody response was detected in patients immunized with 360 µg TNF-K and with 3 injections, although this difference was not significant with all other groups. Similar proportions of patients receiving TNF-K and placebo reported adverse events up to month 12. Serious adverse events were reported by 4 patients treated with TNF-K (13.3% and 3 treated with placebo (30.0%, all unrelated to treatment. At month 12, DAS28-CRP, tender and swollen joint counts, and HAQ scores decreased significantly more in patients who exhibited anti-TNF antibody response than in patients who did not. CONCLUSIONS: TNF-K therapeutic vaccination induced dose- and schedule-dependent anti-TNF antibodies in RA patients and was well tolerated. Patients who developed anti-TNF antibodies showed a trend toward clinical improvement. Although the most aggressive dose and schedule, i.e. 360 mg dose administered 3 times, did show a strong trend of higher antibody response, further studies are warranted to examine even higher and more frequent

  14. A randomized phase 2 study of combination cediranib and olaparib versus olaparib alone as recurrence therapy in platinum-sensitive ovarian cancer

    Science.gov (United States)

    Liu, Joyce F.; Barry, William T.; Birrer, Michael; Lee, Jung-Min; Buckanovich, Ronald J.; Fleming, Gini F.; Rimel, BJ; Buss, Mary K.; Nattam, Sreenivasa; Hurteau, Jean; Luo, Weixiu; Quy, Philippa; Whalen, Christin; Obermayer, Lisa; Lee, Hang; Winer, Eric P.; Kohn, Elise C.; Ivy, S. Percy; Matulonis, Ursula A.

    2015-01-01

    Background Olaparib is an oral poly(ADP-ribose) polymerase inhibitor and cediranib is an oral anti-angiogenic with activity against VEGFR-1, 2, and 3. Both agents have antitumor activity in women with recurrent ovarian cancer, and the combination of these agents was active and had manageable toxicities in a Phase 1 trial. We asked whether the combination of cediranib and olaparib could improve progression-free survival compared to olaparib monotherapy in women with recurrent platinum-sensitive ovarian cancer. Methods We conducted a randomized, open-label, phase 2 study to evaluate the activity of olaparib monotherapy compared with combination cediranib and olaparib in women with ovarian cancer with measurable platinum-sensitive, relapsed, high-grade serous or endometrioid disease or those with deleterious germline BRCA1/2 mutations (gBRCAm). Patients were randomized using permuted blocks within stratum defined by gBRCA status and prior anti-angiogenic therapy to receive olaparib capsules 400mg twice daily or the combination at the recommended phase 2 dose of cediranib 30mg daily and olaparib capsules 200mg twice daily. The primary endpoint was progression-free survival (PFS) analyzed under intention to treat. The trial is registered with ClinicalTrials.gov, NCT01116648. The Phase 2 portion of the trial reported here is no longer accruing patients. Findings Forty-six of 90 randomized patients received olaparib alone, and 44 received cediranib/olaparib. Median PFS was significantly longer with cediranib/olaparib (17.7 vs. 9.0 mos, HR 0.42; p = 0.005). Grade 3 and 4 adverse events were more common with cediranib/olaparib, including fatigue (12 vs. 5), diarrhea (10 vs. 0), and hypertension (18 vs. 0). Subset analysis within stratum defined by BRCA1/2 status demonstrated activity of cediranib/olaparib in both gBRCAm and gBRCAwt/u (wild-type/unknown) patients. Significant improvement in PFS occurred in gBRCAwt/u women receiving cediranib/olaparib (16.5 vs. 5.7 mos, p = 0

  15. Safety, reactogenicity and immunogenicity of the human rotavirus vaccine in preterm European Infants: a randomized phase IIIb study.

    Science.gov (United States)

    Omenaca, Felix; Sarlangue, Jean; Szenborn, Leszek; Nogueira, Marta; Suryakiran, Pemmaraju V; Smolenov, Igor V; Han, Htay H

    2012-05-01

    Rotavirus disease is more severe in preterm infants than in full-term infants. This study assessed the safety, reactogenicity and immunogenicity of a human rotavirus vaccine, RIX4414, in European preterm infants. A total of 1009 preterm infants were randomized (2:1, vaccine:placebo) and stratified into 2 groups: 20% of early (27-30 weeks, group 1) and 80% of late (31-36 weeks, group 2) gestational age preterm infants in each group. Two doses of RIX4414/placebo were administered to these preterm infants according to the recommended chronologic age for full-term infants with an interval of 30-83 days between doses. Serious adverse events were recorded throughout the study period. Solicited and unsolicited adverse events were recorded for 15 and 31 days post-each dose. Antirotavirus IgA concentrations (enzyme-linked immunosorbent assay cutoff = 20 U/mL) and geometric mean concentration were determined pre-dose 1 and 30-83 days post-dose 2 in a subset of 300 infants. This study is registered with ClinicalTrials.gov, number NCT00420745 (eTrack106481). Serious adverse events were reported at a similar frequency in both groups (P = 0.266). Fifty-seven infants reported at least 1 serious adverse event (5.1% [3.5-7.0] in the RIX4414 group and 6.8% [4.3-10.0] in the placebo group). During the 15-day postvaccination follow-up period, diarrhea, vomiting and fever occurred at a similar frequency in both groups; fever could have been due to concomitant vaccines. Five cases (RIX4414 = 3, Placebo = 2) of rotavirus gastroenteritis were reported. The onset of rotavirus gastroenteritis in the RIX4414 group was 1-5 days after vaccination (vaccine strain identified in all cases) and in the placebo group it was 3-4 days after receiving placebo (wild-type rotavirus identified from both cases). Antirotavirus IgA seroconversion rates at 30-83 days post-dose 2 were 85.7% (79.0-90.9) in the RIX4414 group and 16.0% (8.8-25.9) in the placebo group. Geometric mean concentrations were 202.2 U

  16. Tapentadol immediate-release for acute postbunionectomy pain: a phase 3, randomized, double-blind, placebo-controlled, parallel-group study in Taiwan.

    Science.gov (United States)

    Chen, Yeung-Jen; Chiang, Chao-Ching; Huang, Peng-Ju; Huang, Jason; Karcher, Keith; Li, Honglan

    2015-11-01

    To evaluate the efficacy and safety of tapentadol immediate-release (IR) for treating acute pain following orthopedic bunionectomy surgery in a Taiwanese population. This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group bridging study in which Taiwanese patients (N = 60) with moderate-to-severe pain following bunionectomy were randomized (1:1:1) to receive tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours over a 72 hour period. The primary endpoint was the sum of pain intensity difference over 48 hours (SPID48), analyzed using analysis of variance. Out of 60 patients randomized (mainly women [96.7%]; median age 44 years), 41 (68.3%) completed the treatment. Mean SPID48 values were significantly higher for tapentadol IR (p ≤ 0.006: 50 mg, p ≤ 0.004: 75 mg) compared with placebo. Between-group differences in LS means of SPID48 (vs. placebo) were tapentadol IR 50 mg: 105.6 (95% CI: 32.0; 179.2); tapentadol IR 75 mg: 126.6 (95% CI: 49.5; 203.7). Secondary endpoints including SPID at 12, 24, and 72 hours, time to first use of rescue medication, cumulative distribution of responder rates, total pain relief and sum of total pain relief and sum of pain intensity difference at 12, 24, 48, and 72 hours, and patient global impression of change showed numerically better results supporting that tapentadol IR (50 and 75 mg) was more efficacious than placebo in relieving acute pain. The most frequent treatment emergent adverse events reported in ≥ 10% patients in either group were dizziness, nausea, and vomiting. A limitation of this study may possibly include more controlled patient monitoring through 4-6 hour dosing intervals, which reflects optimal conditions and thus may not approximate real-world clinical practice. However, all treatment groups would be equally affected by such bias of frequent monitoring, if any, since it was a randomized and double-blind study. Tapentadol IR treatment significantly relieved acute postoperative

  17. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial.

    Science.gov (United States)

    Breugom, A J; van Gijn, W; Muller, E W; Berglund, Å; van den Broek, C B M; Fokstuen, T; Gelderblom, H; Kapiteijn, E; Leer, J W H; Marijnen, C A M; Martijn, H; Meershoek-Klein Kranenbarg, E; Nagtegaal, I D; Påhlman, L; Punt, C J A; Putter, H; Roodvoets, A G H; Rutten, H J T; Steup, W H; Glimelius, B; van de Velde, C J H

    2015-04-01

    The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete

  18. Optical image encryption in phase space

    Science.gov (United States)

    Liu, Jun; Xu, Xiaobin; Situ, Guohai; Wu, Quanying

    2014-11-01

    In the field of optical information security, the research of double random phase encoding is becoming deeper with each passing day, however the encryption system is linear, and the dependencies between plaintext and ciphertext is not complicated, with leaving a great hidden danger to the security of the encryption system. In this paper, we encrypted the higher dimensional Wigner distribution function of low dimensional plaintext by using the bilinear property of Wigner distribution function. Computer simulation results show that this method can not only enlarge the key space, but also break through the linear characteristic of the traditional optical encryption technology. So it can significantly improve the safety of the encryption system.

  19. Genetically Encoded Fluorescent Redox Probes

    Directory of Open Access Journals (Sweden)

    Hui-Wang Ai

    2013-11-01

    Full Text Available Redox processes are involved in almost every cell of the body as a consequence of aerobic life. In the past decades, redox biology has been increasingly recognized as one of the key themes in cell signaling. The progress has been accelerated by development of fluorescent probes that can monitor redox conditions and dynamics in cells and cell compartments. This short paper focuses on fluorescent redox probes that are genetically encoded, and discusses their properties, molecular mechanism, advantages and pitfalls. Our recent work on reaction-based encoded probes that are responsive to particular redox signaling molecules is also reviewed. Future challenges and directions are also commented.

  20. Genetically encoded fluorescent redox probes.

    Science.gov (United States)

    Ren, Wei; Ai, Hui-Wang

    2013-11-11

    Redox processes are involved in almost every cell of the body as a consequence of aerobic life. In the past decades, redox biology has been increasingly recognized as one of the key themes in cell signaling. The progress has been accelerated by development of fluorescent probes that can monitor redox conditions and dynamics in cells and cell compartments. This short paper focuses on fluorescent redox probes that are genetically encoded, and discusses their properties, molecular mechanism, advantages and pitfalls. Our recent work on reaction-based encoded probes that are responsive to particular redox signaling molecules is also reviewed. Future challenges and directions are also commented.

  1. Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study

    Directory of Open Access Journals (Sweden)

    Babu KG

    2014-06-01

    Full Text Available K Govind Babu,1 Kumar Prabhash,2 Ashok K Vaid,3 Bhawna Sirohi,3 Ravi B Diwakar,4 Raghunadha Rao,5 Madhuchanda Kar,6 Hemant Malhotra,7 Shona Nag,8 Chanchal Goswami,9 Vinod Raina,10 Ravi Mohan111Kidwai Memorial Institute of Oncology, Bangalore, 2Tata Memorial Hospital, Mumbai, 3Artemis Health Institute, Delhi, 4Bangalore Institute of Oncology, Bangalore, 5Nizam Institute of Medical Sciences, Hyderabad, 6B R Singh Hospital, Kolkata, 7Birla Cancer Centre, Jaipur, 8Jehangir Hospital, Pune, 9B P Poddar Hospital and Medical Research Ltd, Kolkata, 10Institute Rotary Cancer Hospital, New Delhi, 11King George Hospital, Visakhapatnam, IndiaBackground: The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.Methods: This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group or chemotherapy alone (control group, and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response. Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.Results: The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04. A complete response and partial response were achieved in 3

  2. Spatio-Temporal Encoding in Medical Ultrasound Imaging

    DEFF Research Database (Denmark)

    Gran, Fredrik

    2005-01-01

    In this dissertation two methods for spatio-temporal encoding in medical ultrasound imaging are investigated. The first technique is based on a frequency division approach. Here, the available spectrum of the transducer is divided into a set of narrow bands. A waveform is designed for each band...... are also included in the dissertation. The second method is based on encoding the transmitters with pseudo-random sequences. The signals can be separated after only one transmission using an estimation based technique. Broadband decoding can, therefore, be performed at the receiver after a single...

  3. VLSI Architecture Design for H.264/AVC Intra-frame Video Encoding

    National Research Council Canada - National Science Library

    Kuo, Huang-Chih; Lin, Youn-Long

    2013-01-01

    Intra-frame encoding is useful for many video applications such as security surveillance, digital cinema, and video conferencing because it supports random access to every video frame for easy editing...

  4. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

    Energy Technology Data Exchange (ETDEWEB)

    Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Brunner, Thomas B. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); University Hospital Freiburg, Department of Radiation Oncology, Freiburg (Germany); Witzigmann, Helmut [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Marti, Lukas [Hospital of Kanton St. Gallen, General Surgery, St. Gallen (Switzerland); Bechstein, Wolf-Otto [University Hospital Frankfurt, Department of Surgery, Frankfurt/Main (Germany); Bruns, Christiane [University Hospital Munich, Department of Surgery - Hospital Campus Grosshadern, Munich (Germany); University Hospital Magdeburg, Department of Surgery, Magdeburg (Germany); Jungnickel, Henry [Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Schreiber, Stefan [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Grabenbauer, Gerhard G. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Hospital Coburg, Department of Radiation Oncology, Coburg (Germany); Meyer, Thomas [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Hospital Ansbach, General Surgery, Ansbach (Germany); Fietkau, Rainer [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany)

    2014-09-25

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [German] Mehrere nichtrandomisierte Studien zeigten, dass eine neoadjuvante Therapie das Ueberleben bei Patienten mit Pankreaskarzinom verlaengert. Beim lokal fortgeschrittenen Rektumkarzinom gehoert die

  5. Two schedules of chemotherapy for patients with non-small cell lung cancer in poor performance status: a phase II randomized trial.

    Science.gov (United States)

    Zwitter, Matjaz; Kovac, Viljem; Rajer, Mirjana; Vrankar, Martina; Smrdel, Uros

    2010-07-01

    We present experience from a phase II randomized clinical trial, comparing standard gemcitabine as monotherapy with low-dose gemcitabine in long infusion in a doublet with cisplatin at reduced dose for patients with non-small cell lung cancer (NSCLC) and who are unfit for standard platin-based chemotherapy. Eligible patients had microscopically confirmed NSCLC in stage IIIB (wet) or IV, were chemo-naive, and were in poor performance status or presented with significant comorbidity. Standard treatment with gemcitabine, 1250 mg/m in 20-30 min on days 1 and 8 as monotherapy (arm A) was compared with low-dose gemcitabine in long infusion (200 mg/m in 6 h on day 1) and cisplatin at 60 mg/m on day 2 (arm B). Both treatment schedules were repeated every 3 weeks until disease progression, unacceptable toxicity, or to a maximum of six cycles. A total of 112 patients (83 male, 29 female, median age 66 years) were randomized between arm A (57 patients) and B (55 patients). The two groups were balanced for prognostic factors. Fifty-three patients in arm A and 52 in arm B received at least one application of chemotherapy and were evaluable for toxicity and response. The median number of cycles was four and five for arms A and B, respectively. Except for grade 3 anemia (one patient in arm A and two in arm B), no other major toxicity was seen. Regarding response to treatment, arm B was superior: 1 complete response and 13 partial remissions (response rate 26.9%) as compared with five partial remissions (response rate 9.4%) in arm A (Psuperior to monotherapy with gemcitabine in standard doses, and is suitable for patients with NSCLC who cannot tolerate a standard platin-based doublet.

  6. A Phase IIIb, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of dexmedetomidine for sedation during awake fiberoptic intubation.

    Science.gov (United States)

    Bergese, Sergio D; Candiotti, Keith A; Bokesch, Paula M; Zura, Andrew; Wisemandle, Wayne; Bekker, Alex Y

    2010-01-01

    GABA-mediated sedatives have respiratory depressant properties that may be detrimental in patients with difficult airways. In this randomized, double-blind, multicenter, Phase IIIb Food and Drug Administration study, safety and efficacy of dexmedetomidine compared with placebo were evaluated as the primary sedative for awake fiberoptic intubation (AFOI). Patients were randomized to receive dexmedetomidine or saline. Patients were sedated with dexmedetomidine or rescue midazolam to achieve targeted sedation (Ramsay Sedation Scale ≥ 2) before topicalization and throughout AFOI. Primary efficacy endpoint was percentage of patients requiring rescue midazolam; secondary efficacy endpoints were total dose of rescue midazolam, percentage requiring additional rescue nonmidazolam medications, anesthesiologist's assessment of ease of subject care, and patient recall and satisfaction 24 hours postoperatively. Less rescue midazolam was required to maintain Ramsay Sedation Scale ≥2 (47.3% vs. 86.0%, P < 0.001), and supplemental midazolam dose was lower (1.07 ± 1.5 mg vs. 2.85 ± 3.0 mg, P < 0.001) with dexmedetomidine compared with placebo. More Mallampati Class IV patients treated with dexmedetomidine were successfully intubated without midazolam than with placebo (66.7% vs. 8.3%, P = 0.009). Dexmedetomidine decreased blood pressure and heart rate compared with placebo patients sedated with midazolam. Patients and anesthesiologists showed favorable satisfaction responses in both groups. Adverse events and patient recall were similar in both groups. Dexmedetomidine is effective as the primary sedative in patients undergoing AFOI. Some patients may require small supplemental doses of midazolam, in addition to dexmedetomidine, to achieve sufficient sedation for AFOI. Dexmedetomidine provides another AFOI option for sedation of patients with difficult airways.

  7. Efficacy and safety of bilastine in Japanese patients with perennial allergic rhinitis: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study.

    Science.gov (United States)

    Okubo, Kimihiro; Gotoh, Minoru; Asako, Mikiya; Nomura, Yasuyuki; Togawa, Michinori; Saito, Akihiro; Honda, Takayuki; Ohashi, Yoshihiro

    2017-01-01

    Bilastine, a novel non-sedating second-generation H 1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexofenadine (60 mg twice daily), or a matched placebo (double dummy) in patients with PAR. All patients were instructed to record individual nasal and ocular symptoms in diaries daily. The primary endpoint was the mean change in total nasal symptom scores (TNSS) from baseline to Week 2 (Days 10-13). A total of 765 patients were randomly allocated to receive bilastine, fexofenadine, or placebo (256, 254, and 255 patients, respectively). The mean change in TNSS from baseline at Week 2 was significantly decreased by bilastine (-0.98) compared to placebo (-0.63, P = 0.023). Bilastine and fexofenadine showed no significant difference in the primary endpoint. However, the mean change in TNSS from baseline on Day 1 was more significantly decreased by bilastine (-0.99) than by placebo (-0.28, P bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  8. Tretinoin Nanogel 0.025% Versus Conventional Gel 0.025% in Patients with Acne Vulgaris: A Randomized, Active Controlled, Multicentre, Parallel Group, Phase IV Clinical Trial.

    Science.gov (United States)

    Chandrashekhar, B S; Anitha, M; Ruparelia, Mukesh; Vaidya, Pradyumna; Aamir, Riyaz; Shah, Sunil; Thilak, S; Aurangabadkar, Sanjeev; Pal, Sandeep; Saraswat, Abir; Sanmukhani, Jayesh J

    2015-01-01

    Conventional topical tretinoin formulation is often associated with local adverse events. Nanogel formulation of tretinoin has good physical stability and enables good penetration of tretinoin into the pilo-sebaceous glands. The present study was conducted to assess the efficacy and safety of a nanogel formulation of tretinoin as compared to its conventional gel formulation in the treatment of acne vulgaris of the face. This randomized, active controlled, multicentric, phase IV clinical trial evaluated the treatment of patients with acne vulgaris of the face by the two gel formulations locally applied once daily at night for 12 wk. Acne lesion counts (inflammatory, non-inflammatory & total) and severity grading were carried out on the monthly scheduled visits along with the tolerability assessments. A total of 207 patients were randomized in the study. Reductions in the total (72.9% vs. 65.0%; p = 0.03) and inflammatory (78.1% vs. 66.9%; p = 0.02) acne lesions were reported to be significantly greater with the nanogel formulation as compared to the conventional gel formulation. Local adverse events were significantly less (p = 0.04) in the nanogel group (13.3%) as compared to the conventional gel group (24.7%). Dryness was the most common adverse event reported in both the treatment groups while peeling of skin, burning sensation and photosensitivity were reported in patients using the conventional gel only. In the treatment of acne vulgaris of the face, tretinoin nanogel formulation appears to be more effective and better tolerated than the conventional gel formulation.

  9. Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study.

    Science.gov (United States)

    Borg, C; André, T; Mantion, G; Boudghène, F; Mornex, F; Maingon, P; Adenis, A; Azria, D; Piutti, M; Morsli, O; Bosset, J F

    2014-11-01

    In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes. This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5-FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU-RT before TME. Primary end point was pathological complete response (pCR) rate. Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B). Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab-Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. ClinicalTrials.gov Identifier: NCT 00865189. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Clinical feasibility of the Nintendo Wii™ for balance training post-stroke: a phase II randomized controlled trial in an inpatient setting.

    Science.gov (United States)

    Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

    2014-09-01

    To investigate the feasibility and potential efficacy of the Nintendo Wii™ for balance rehabilitation after stroke. Phase II, single-blind, randomized controlled trial. Inpatient rehabilitation facility. Thirty adults (mean age 63.6 (14.7) years) undergoing inpatient rehabilitation who were less than three months post-stroke and able to stand unsupported. Participants were allocated to a Balance Group, using the 'Wii Fit Plus' in standing, or Upper Limb Group, using the 'Wii Sports/Sports Resort' in sitting. Both groups undertook three 45 minute sessions per week over two to four weeks in addition to standard care. The primary focus was feasibility, addressed by recruitment, retention, adherence, acceptability and safety. Efficacy was evaluated by balance, mobility and upper limb outcomes. Twenty-one percent of individuals screened were recruited and 86% (n = 30) of eligible people agreed to participate. Study retention and session adherence was 90% and > 99%, respectively, at two weeks; dropping to 70% and 87% at four weeks due to early discharge. All participants reported enjoying the sessions and most felt they were beneficial. No major adverse events occurred. Wii use by the Balance Group was associated with trends for improved balance, with significantly greater improvement in outcomes including the Step Test and Wii Balance Board-derived centre of pressure scores. The Upper Limb Group had larger, non-significant changes in arm function. A Wii-based approach appears feasible and promising for post-stroke balance rehabilitation. A larger randomized controlled trial is recommended to further investigate efficacy. © The Author(s) 2014.

  11. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial.

    Science.gov (United States)

    Demetri, George D; von Mehren, Margaret; Jones, Robin L; Hensley, Martee L; Schuetze, Scott M; Staddon, Arthur; Milhem, Mohammed; Elias, Anthony; Ganjoo, Kristen; Tawbi, Hussein; Van Tine, Brian A; Spira, Alexander; Dean, Andrew; Khokhar, Nushmia Z; Park, Youn Choi; Knoblauch, Roland E; Parekh, Trilok V; Maki, Robert G; Patel, Shreyaskumar R

    2016-03-10

    This multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen. Patients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control-progression-free survival (PFS), time to progression, objective response rate, and duration of response-as well as safety and patient-reported symptom scoring. A total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); benefits were observed across all preplanned subgroup analyses. The interim analysis of OS (64% censored) demonstrated a 13% reduction in risk of death in the trabectedin arm compared with dacarbazine (median OS for trabectedin v dacarbazine, 12.4 v 12.9 months; hazard ratio, 0.87; P = .37). The safety profiles were consistent with the well-characterized toxicities of both agents, and the most common grade 3 to 4 adverse effects were myelosuppression and transient elevation of transaminases in the trabectedin arm. Trabectedin demonstrates superior disease control versus conventional dacarbazine in patients who have advanced liposarcoma and leiomyosarcoma after they experience failure of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies. © 2015 by American Society of Clinical Oncology.

  12. Effects of high-intensity aerobic interval training on cardiovascular disease risk in testicular cancer survivors: A phase 2 randomized controlled trial.

    Science.gov (United States)

    Adams, Scott C; DeLorey, Darren S; Davenport, Margie H; Stickland, Michael K; Fairey, Adrian S; North, Scott; Szczotka, Alexander; Courneya, Kerry S

    2017-10-15

    Testicular cancer survivors (TCS) have an increased risk of treatment-related cardiovascular disease (CVD), which may limit their overall survival. We evaluated the effects of high-intensity aerobic interval training (HIIT) on traditional and novel CVD risk factors and surrogate markers of mortality in a population-based sample of TCS. This phase 2 trial (ClinicalTrials.gov identifier NCT02459132) randomly assigned 63 TCS to usual care (UC) or 12 weeks of supervised HIIT (ie, alternating periods of vigorous-intensity and light-intensity aerobic exercise). The primary outcome was peak aerobic fitness (VO2peak ) assessed via a treadmill-based maximal cardiorespiratory exercise test. Secondary endpoints included CVD risk (eg, Framingham Risk Score), arterial health, parasympathetic nervous system function, and blood-based biomarkers. Postintervention VO2peak data were obtained for 61 participants (97%). HIIT participants attended 99% of the exercise sessions and achieved 98% of the target exercise intensity. Analysis of covariance demonstrated that HIIT was superior to UC for improving VO2peak (adjusted between-group mean difference, 3.7 mL O2 /kg/min; 95% confidence interval, 2.4-5.1 [P<.001]) and multiple secondary outcomes including CVD risk (P = .011), arterial thickness (P<.001), arterial stiffness (P<.001), postexercise parasympathetic reactivation (P = .001), inflammation (P = .045), and low-density lipoprotein (P = .014). Overall, HIIT reduced the prevalence of modifiable CVD risk factors by 20% compared with UC. This randomized trial provides the first evidence that HIIT improves cardiorespiratory fitness, multiple pathways of CVD risk, and surrogate markers of mortality in TCS. These findings have important implications for the management of TCS. Further research concerning the long-term effects of HIIT on CVD morbidity and mortality in TCS is warranted. Cancer 2017;123:4057-65. © 2017 American Cancer Society. © 2017 American Cancer

  13. STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer.

    Science.gov (United States)

    Chibaudel, Benoist; Bonnetain, Franck; Tournigand, Christophe; de Larauze, Marine Hug; de Gramont, Armand; Laurent-Puig, Pierre; Paget, Jérôme; Hadengue, Alexandra; Notelet, Dominique; Benetkiewicz, Magdalena; André, Thierry; de Gramont, Aimery

    2015-07-04

    The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013

  14. Safety and Immunogenicity of Cell Culture-Derived A/H3N2 Variant Influenza Vaccines: A Phase I Randomized, Observer-Blind, Dose-Ranging Study.

    Science.gov (United States)

    Johnson, Casey; Hohenboken, Matthew; Poling, Terry; Jaehnig, Peter; Kanesa-Thasan, Niranjan

    2015-07-01

    A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important. In this phase I, randomized, observer-blind, dose-ranging study, 627 healthy subjects ≥ 3 years of age were randomized to receive 2 vaccinations with H3N2c cell-culture-derived vaccine doses containing 3.75 µg, 7.5 µg, or 15 µg hemagglutinin antigen of H3N2v with or without MF59 (registered trademark of Novartis AG) adjuvant (an oil-in-water emulsion). This paper reports Day 43 planned interim data. Single MF59-adjuvanted H3N2c doses elicited immune responses in almost all subjects regardless of antigen and adjuvant dose; the Center for Biologics Evaluation Research and Review (CBER) licensure criteria were met for all groups. Subjects with prevaccination hemagglutination inhibition titers vaccine. Highest antibody titers were observed in the 7.5 µg + 0.25 mL MF59 groups in all age cohorts. MF59-adjuvanted H3N2c vaccines showed the highest rates of solicited local and systemic events, predominately mild or moderate. A single dose of H3N2c vaccine may be immunogenic and supports further development of MF59-adjuvanted H3N2c vaccines, especially for pediatric populations. ClinicalTrials.gov identifier NCT01855945 (http://clinicaltrials.gov/ct2/show/NCT01855945). © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Acute toxicity profile and compliance to accelerated radiotherapy plus carbogen and nicotinamide for clinical stage T2-4 laryngeal cancer: results of a phase III randomized trial.

    Science.gov (United States)

    Janssens, Geert O; Terhaard, Chris H; Doornaert, Patricia A; Bijl, Hendrik P; van den Ende, Piet; Chin, Alim; Pop, Lucas A; Kaanders, Johannes H

    2012-02-01

    To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Terhaard, Chris H. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Doornaert, Patricia A. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Bijl, Hendrik P. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands); Ende, Piet van den [Department of Radiation Oncology, Maastricht University Medical Centre, Maastricht (Netherlands); Chin, Alim [Department of Clinical Oncology, Leiden University Medical Centre, Leiden (Netherlands); Pop, Lucas A.; Kaanders, Johannes H. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  17. A double-blind, randomized, and active-controlled phase III study of Herbiron drink in the treatment of iron-deficiency anemia in premenopausal females in Taiwan

    Directory of Open Access Journals (Sweden)

    Ching-Tzu Lee

    2016-06-01

    Full Text Available Background: About 468 million non-pregnant women are estimated to suffer from iron-deficiency anemia (IDA worldwide. The highest prevalence of IDA occurs in the Taiwanese population. Objective: To evaluate the effectiveness of Herbiron to increase iron absorption in women with IDA. Design: Phase III double-blind, randomized, active-controlled, and parallel comparative study enrolled 124 patients with IDA and consisted of a 2-week run-in period, randomization, 12 weeks of supplementation, and 4 weeks of follow-up. The treatment group received Herbiron drink 50 mL p.o., b.i.d., before meals (daily iron intake: 21 mg/day plus placebo tablets. The control group received a ferrous sulfate tablet, t.i.d., plus placebo 50-mL drink before meals (daily iron intake: 195 mg/day. Results: Both treatments significantly improved hemoglobin and all secondary efficacy endpoints. Most IDA patients treated with Herbiron or ferrous sulfate finished the study in the normal range. Ferrous sulfate treatment induced a rapid rate of hemoglobin synthesis, which plateaued by week 8, whereas Herbiron treatment increased the rate of hemoglobin synthesis more slowly, likely due to its nine-fold lower iron content. Gastrointestinal adverse events (diarrhea, abdominal pain, dyspepsia, and nausea but not infectious adverse events were significantly more common in the ferrous sulfate group (n=11, 18.3% than those in the Herbiron group (n=1, 1.6% (p=0.004. Conclusion: Twelve weeks of Herbiron treatment delivering 21mg of iron or ferrous sulfate treatment delivering 195 mg of iron induced normal hemoglobin levels in 62 or 91% of non-pregnant women with IDA in Taiwan, respectively, suggesting dose-dependent and bioavailability effects.

  18. A randomized, phase 2, dose-ranging study in the treatment of moderate to severe inflammatory facial acne vulgaris with doxycycline calcium.

    Science.gov (United States)

    Leyden, James J; Bruce, Suzanne; Lee, Chai Sue; Ling, Mark; Sheth, Pranav B; Stewart, Daniel M; Werschler, William P; Gilbert, Richard D; Kircik, Leon

    2013-06-01

    Doxycycline calcium (WC2055) is a drug substance with a possible role in the treatment of acne. The objective of this study was to evaluate the safety and efficacy of three doses of doxycycline calcium tablets compared with placebo in the treatment of moderate to severe inflammatory facial acne vulgaris. This was a randomized, double-blind, phase 2 dose-ranging study in subjects with moderate to severe inflammatory acne aged 12 years to 45 years. Subjects were randomized to receive doxycycline calcium tablets 0.6, 1.2, or 2.4 mg/kg/day or placebo, and instructed to take their tablets once daily for 12 weeks, in the evening at least 1 hour before or 2 hours after mealtime. The primary efficacy variables were the dichotomized Investigator's Global Assessment score (success or failure) at week 12 (success defined as ≥ 2 score decrease from baseline) and the absolute change from baseline to week 12 in inflammatory lesion count. A dose-response effect was seen with doxycycline calcium formulation in subjects with moderate to severe inflammatory acne. The highest dose-group (corresponding to approximately 2.4 mg/kg/day) showed a statistically significant difference from placebo. The dose-response effect was confirmed by logistic regression analysis for both treatment success and incidence of gastrointestinal adverse events. A limitation of this study is that safety and efficacy were only studied on moderate to severe inflammatory acne. Also, the study was not prospectively powered to show efficacy differences. Doxycycline calcium shows a dose-response effect in reducing inflammatory lesions in subjects with moderate to severe inflammatory acne.

  19. The FINISH-3 trial: a phase 3, international, randomized, single-blind, controlled trial of topical fibrocaps in intraoperative surgical hemostasis.

    Science.gov (United States)

    Bochicchio, Grant V; Gupta, Navyash; Porte, Robert J; Renkens, Kenneth L; Pattyn, Piet; Topal, Baki; Troisi, Roberto Ivan; Muir, William; Chetter, Ian; Gillen, Daniel L; Zuckerman, Linda A; Frohna, Paul A

    2015-01-01

    This Phase 3, international, randomized, single-blind, controlled trial (FINISH-3) compared the efficacy and safety of Fibrocaps, a ready-to-use, dry-powder fibrin sealant containing human plasma-derived thrombin and fibrinogen, vs gelatin sponge alone for use as a hemostat for surgical bleeding in 4 indications (ie, spinal, hepatic, vascular, soft tissue dissection). Adults with mild to moderate surgical bleeding (randomized 2:1; Fibrocaps vs gelatin sponge) were treated at a single bleeding site (day 1). Time to hemostasis (TTH) during 5 minutes was compared (log-rank statistic) within each indication. Safety follow-up continued to day 29. Patients were treated (Fibrocaps, n = 480; gelatin sponge, n = 239) when undergoing spinal (n = 183), vascular (n = 175), hepatic (n = 180), or soft-tissue (n = 181) procedures. Fibrocaps was applied by spray device in 53% of all procedures (94% of hepatic and soft-tissue procedures). Fibrocaps significantly reduced TTH compared with gelatin sponge; estimated hazard ratios were 3.3, 2.1, 2.3, and 3.4 for the 4 surgical indications, respectively (each p < 0.001; primary end point). Fibrocaps significantly reduced median TTH for each indication (p < 0.001) and was superior for secondary efficacy end points of restricted mean TTH (p < 0.001) and probability of hemostasis at 3 (p < 0.001) and 5 (p ≤ 0.002) minutes. Adverse event incidences were generally similar between treatment arms. Non-neutralizing, anti-thrombin antibodies developed in 2% of Fibrocaps-treated and 3% of gelatin sponge-treated patients. Fibrocaps was well tolerated and significantly reduced TTH relative to gelatin sponge alone in all 4 surgical indications. These findings demonstrate the broad utility of Fibrocaps as a hemostatic agent for mild to moderate surgical bleeding. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  20. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab.

    Science.gov (United States)

    Stroes, Erik; Colquhoun, David; Sullivan, David; Civeira, Fernando; Rosenson, Robert S; Watts, Gerald F; Bruckert, Eric; Cho, Leslie; Dent, Ricardo; Knusel, Beat; Xue, Allen; Scott, Rob; Wasserman, Scott M; Rocco, Michael

    2014-06-17

    This study sought to evaluate the efficacy and safety of subcutaneous evolocumab compared with oral ezetimibe in hypercholesterolemic patients who are unable to tolerate effective statin doses. Statin intolerance, which is predominantly due to muscle-related side effects, is reported in up to 10% to 20% of patients. Evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), demonstrated marked reductions in plasma low-density lipoprotein cholesterol (LDL-C) in a phase 2 study in statin-intolerant patients. The GAUSS-2 (Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects) trial was a 12-week, double-blind study of randomized patients (2:2:1:1) to evolocumab 140 mg every two weeks (Q2W) or evolocumab 420 mg once monthly (QM) both with daily oral placebo or subcutaneous placebo Q2W or QM both with daily oral ezetimibe 10 mg. Co-primary endpoints were percent change from baseline in LDL-C at the mean of weeks 10 and 12, and at week 12. Three hundred seven patients (age 62 ± 10 years; LDL-C 193 ± 59 mg/dl) were randomized. Evolocumab reduced LDL-C from baseline by 53% to 56%, corresponding to treatment differences versus ezetimibe of 37% to 39% (p <0.001). Muscle adverse events occurred in 12% of evolocumab-treated patients and 23% of ezetimibe-treated patients. Treatment-emergent adverse events and laboratory abnormalities were comparable across treatment groups. Robust efficacy combined with favorable tolerability makes evolocumab a promising therapy for addressing the largely unmet clinical need in high-risk patients with elevated cholesterol who are statin intolerant. (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2; NCT01763905). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study.

    Science.gov (United States)

    Richardson, Paul G; Siegel, David S; Vij, Ravi; Hofmeister, Craig C; Baz, Rachid; Jagannath, Sundar; Chen, Christine; Lonial, Sagar; Jakubowiak, Andrzej; Bahlis, Nizar; Song, Kevin; Belch, Andrew; Raje, Noopur; Shustik, Chaim; Lentzsch, Suzanne; Lacy, Martha; Mikhael, Joseph; Matous, Jeffrey; Vesole, David; Chen, Min; Zaki, Mohamed H; Jacques, Christian; Yu, Zhinuan; Anderson, Kenneth C

    2014-03-20

    This multicenter, open-label, randomized phase 2 study assessed the efficacy and safety of pomalidomide (POM) with/without low-dose dexamethasone (LoDEX) in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior therapies (including lenalidomide [LEN] and bortezomib [BORT]) and had progressed within 60 days of their last therapy were randomized to POM (4 mg/day on days 1-21 of each 28-day cycle) with/without LoDEX (40 mg/week). The primary end point was progression-free survival (PFS). In total, 221 patients (median 5 prior therapies, range 1-13) received POM+LoDEX (n = 113) or POM (n = 108). With a median follow-up of 14.2 months, median PFS was 4.2 and 2.7 months (hazard ratio = 0.68, P = .003), overall response rates (ORRs) were 33% and 18% (P = .013), median response duration was 8.3 and 10.7 months, and median overall survival (OS) was 16.5 and 13.6 months, respectively. Refractoriness to LEN, or resistance to both LEN and BORT, did not affect outcomes with POM+LoDEX (median PFS 3.8 months for both; ORRs 30% and 31%; and median OS 16 and 13.4 months). Grade 3-4 neutropenia occurred in 41% (POM+LoDEX) and 48% (POM); no grade 3-4 peripheral neuropathy was reported. POM+LoDEX was effective and generally well tolerated and provides an important new treatment option for RRMM patients who have received multiple prior therapies. This trial was registered at www.clinicaltrials.gov as #NCT00833833.

  2. Effectiveness of prophylactic non-invasive ventilation on respiratory function in the postoperative phase of pediatric cardiac surgery: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Camilla R. S. Silva

    Full Text Available ABSTRACT Objective To evaluate the effectiveness of prophylactic, non-invasive ventilation (NIV on respiratory function in seven- to 16-year-old children in the post-operative phase of cardiac surgery. Method A randomized, controlled trial with 50 children who had undergone cardiac surgery with median sternotomy. After extubation, patients were randomly assigned to one of two groups: control group (n=26, which received instructions regarding posture, early ambulation, and cough stimulation, and CPAP group (continuous positive airway pressure; n=24, which received the same instructions as the control group and CPAP=10 cmH20 twice daily for 30 minutes from the 1st to the 5th post-operative day (POD. As a primary outcome, lung function was evaluated before and on the 1st, 3rd, and 5th PODs with measures of respiratory rate (RR, tidal volume (TV, slow vital capacity (SVC, inspiratory capacity (IC, minute volume (MV, peak expiratory flow (PEF, and maximal inspiratory pressure (MIP. As secondary outcomes, the time of hospitalization and intensive care were recorded. A mixed, linear regression model and z-test were used to analyze respiratory function, considering p<0.05. Results All variables, except RR and MV, showed a significant drop on the 1st POD, with gradual recovery; however, only MIP had returned to pre-operative values on the 5th POD in both groups. The RR showed a significant increase on the 1st POD, with a gradual reduction but without returning to baseline. In the intergroup analysis, significant improvement (p=0.04 was observed only in PEF in the CPAP group on the 1st DPO. The length of hospitalization and intensive care showed no significant differences. Conclusion NIV was safe and well accepted in this group of patients, and the protocol used was effective in improving PEF on the 1st DPO in the CPAP group.

  3. Sequential FOLFIRI.3 + Gemcitabine Improves Health-Related Quality of Life Deterioration-Free Survival of Patients with Metastatic Pancreatic Adenocarcinoma: A Randomized Phase II Trial.

    Directory of Open Access Journals (Sweden)

    Amélie Anota

    Full Text Available A randomized multicenter phase II trial was conducted to assess the sequential treatment strategy using FOLFIRI.3 and gemcitabine alternately (Arm 2 compared to gemcitabine alone (Arm 1 in patients with metastatic non pre-treated pancreatic adenocarcinoma. The primary endpoint was the progression-free survival (PFS rate at 6 months. It concludes that the sequential treatment strategy appears to be feasible and effective with a PFS rate of 43.5% in Arm 2 at 6 months (26.1% in Arm 1. This paper reports the results of the longitudinal analysis of the health-related quality of life (HRQoL as a secondary endpoint of this study.HRQoL was evaluated using the EORTC QLQ-C30 at baseline and every two months until the end of the study or death. HRQoL deterioration-free survival (QFS was defined as the time from randomization to a first significant deterioration as compared to the baseline score with no further significant improvement, or death. A propensity score was estimated comparing characteristics of partial and complete responders. Analyses were repeated with inverse probability weighting method using the propensity score. Multivariate Cox regression analyses were performed to identify independent factors influencing QFS.98 patients were included between 2007 and 2011. Adjusting on the propensity score, patients of Arm 2 presented a longer QFS of Global Health Status (Hazard Ratio: 0.52 [0.31-0.85], emotional functioning (0.35 [0.21-0.59] and pain (0.50 [0.31-0.81] than those of Arm 1.Patients of Arm 2 presented a better HRQoL with a longer QFS than those of Arm 1. Moreover, the propensity score method allows to take into account the missing data depending on patients' characteristics.Eudract N° 2006-005703-34. (Name of the Trial: FIRGEM.

  4. Platelet aggregation unchanged by lipoprotein-associated phospholipase A₂ inhibition: results from an in vitro study and two randomized phase I trials.

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    Bonnie C Shaddinger

    Full Text Available We explored the theorized upregulation of platelet-activating factor (PAF- mediated biologic responses following lipoprotein-associated phospholipase A2 (Lp-PLA2 inhibition using human platelet aggregation studies in an in vitro experiment and in 2 clinical trials.Full platelet aggregation concentration response curves were generated in vitro to several platelet agonists in human plasma samples pretreated with rilapladib (selective Lp-PLA2 inhibitor or vehicle. This was followed by a randomized, double-blind crossover study in healthy adult men (n = 26 employing a single-agonist dose assay of platelet aggregation, after treatment of subjects with 250 mg oral rilapladib or placebo once daily for 14 days. This study was followed by a second randomized, double-blind parallel-group trial in healthy adult men (n = 58 also treated with 250 mg oral rilapladib or placebo once daily for 14 days using a full range of 10 collagen concentrations (0-10 µg/ml for characterizing EC50 values for platelet aggregation for each subject. Both clinical studies were conducted at the GlaxoSmithKline Medicines Research Unit in the Prince of Wales Hospital, Sydney, Australia. EC50 values derived from multiple agonist concentrations were compared and no pro-aggregant signals were observed during exposure to rilapladib in any of these platelet studies, despite Lp-PLA2 inhibition exceeding 90%. An increase in collagen-mediated aggregation was observed 3 weeks post drug termination in the crossover study (15.4% vs baseline; 95% confidence interval [CI], 3.9-27.0, which was not observed during the treatment phase and was not observed in the parallel-group study employing a more robust EC50 examination.Lp-PLA2 inhibition does not enhance platelet aggregation.1 Study 1: ClinicalTrials.gov NCT01745458 2 Study 2: ClinicalTrials.gov NCT00387257.

  5. Randomized Phase II Trial Evaluating Two Paclitaxel and Cisplatin–Containing Chemoradiation Regimens As Adjuvant Therapy in Resected Gastric Cancer (RTOG-0114)

    Science.gov (United States)

    Schwartz, Gary K.; Winter, Kathryn; Minsky, Bruce D.; Crane, Christopher; Thomson, P. John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

    2009-01-01

    Purpose The investigational arm of INT0116, a fluorouracil (FU) and leucovorin–containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. Patients and Methods We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin–containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. Results From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Conclusion Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials. PMID:19273696

  6. Axitinib and/or bevacizumab with modified FOLFOX-6 as first-line therapy for metastatic colorectal cancer: a randomized phase 2 study.

    Science.gov (United States)

    Infante, Jeffrey R; Reid, Tony R; Cohn, Allen L; Edenfield, William J; Cescon, Terrence P; Hamm, John T; Malik, Imtiaz A; Rado, Thomas A; McGee, Philip J; Richards, Donald A; Tarazi, Jamal; Rosbrook, Brad; Kim, Sinil; Cartwright, Thomas H

    2013-07-15

    In this multicenter, open-label, randomized phase 2 trial, the authors evaluated the vascular endothelial growth factor receptor inhibitor axitinib, bevacizumab, or both in combination with chemotherapy as first-line treatment of metastatic colorectal cancer (mCRC). Patients with previously untreated mCRC were randomized 1:1:1 to receive continuous axitinib 5 mg twice daily, bevacizumab 5 mg/kg every 2 weeks, or axitinib 5 mg twice daily plus bevacizumab 2 mg/kg every 2 weeks, each in combination with modified 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX-6). The primary endpoint was the objective response rate (ORR). In all, 126 patients were enrolled from August 2007 to September 2008. The ORR was numerically inferior in the axitinib arm (n = 42) versus the bevacizumab arm (n = 43; 28.6% vs 48.8%; 1-sided P = .97). Progression-free survival (PFS) (11.0 months vs 15.9 months; 1-sided P = .57) and overall survival (OS) (18.1 months vs 21.6 months; 1-sided P = .69) also were numerically inferior in the axitinib arm. Similarly, efficacy endpoints for the axitinib/bevacizumab arm (n = 41) were numerically inferior (ORR, 39%; PFS, 12.5 months; OS, 19.7 months). The patients who received axitinib had fewer treatment cycles compared with other arms. Common all-grade adverse events across all 3 treatment arms were fatigue, diarrhea, and nausea (all ≥49%). Hypertension and headache were more frequent in the patients who received axitinib. Patients in the bevacizumab arm had the longest treatment exposures and the highest rates of peripheral neuropathy. Neither the addition of continuous axitinib nor the axitinib/bevacizumab combination to FOLFOX-6 improved ORR, PFS, or OS compared with bevacizumab as first-line treatment of mCRC. © 2013 American Cancer Society.

  7. RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer.

    Science.gov (United States)

    Baselga, José; Zamagni, Claudio; Gómez, Patricia; Bermejo, Begoña; Nagai, Shigenori E; Melichar, Bohuslav; Chan, Arlene; Mángel, Lászlo; Bergh, Jonas; Costa, Frederico; Gómez, Henry L; Gradishar, William J; Hudis, Clifford A; Rapoport, Bernardo L; Roché, Henri; Maeda, Patricia; Huang, Liping; Meinhardt, Gerold; Zhang, Joshua; Schwartzberg, Lee S

    2017-12-01

    Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. In this randomized, double-blind, placebo-controlled phase III trial, we assessed first- or second-line capecitabine with sorafenib or placebo in patients with locally advanced/metastatic HER2-negative breast cancer resistant to a taxane and anthracycline and with known estrogen/progesterone receptor status. A total of 537 patients were randomized to capecitabine 1000 mg/m2 orally twice per day for days 1 to 14 every 21 days with oral sorafenib 600 mg/d or placebo. The primary end point was progression-free survival (PFS). Patients were stratified according to hormone receptor status, previous chemotherapies for metastatic breast cancer, and geographic region. Treatment with sorafenib with capecitabine, compared with capecitabine with placebo, did not prolong median PFS (5.5 vs. 5.4 months; hazard ratio [HR], 0.973; 95% confidence interval [CI], 0.779-1.217; P = .811) or overall survival (OS; 18.9 vs. 20.3 months; HR, 1.195; 95% CI, 0.943-1.513; P = .140); or enhance overall response rate (ORR; 13.5% vs. 15.5%; P = .515). Any grade toxicities (sorafenib vs. placebo) included palmar-plantar erythrodysesthesia syndrome (PPES; 79.2% vs. 59.6%), diarrhea (47.3% vs. 37.8%), mucosal inflammation (15.4% vs. 6.7%), and hypertension (26.2% vs. 5.6%). Grade 3/4 toxicities included PPES (15.4% vs. 7.1%), diarrhea (4.2% vs. 6.4%), and vomiting (3.5% vs. 0.7%). The combination of sorafenib with capecitabine did not improve PFS, OS, or ORR in patients with HER2-negative advanced breast cancer. Rates of Grade 3 toxicities were higher in the sorafenib arm. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Dolutegravir/abacavir/lamivudine versus current ART in virally suppressed patients (STRIIVING): a 48-week, randomized, non-inferiority, open-label, Phase IIIb study.

    Science.gov (United States)

    Trottier, Benoît; Lake, Jordan E; Logue, Ken; Brinson, Cynthia; Santiago, Lizette; Brennan, Clare; Koteff, Justin A; Wynne, Brian; Hopking, Judy; Granier, Catherine; Aboud, Michael

    2017-01-01

    Simplified dosing regimens are important for patients who face challenges in adhering to HIV-1 therapy. We investigated the safety and virological efficacy of switching to once-daily abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). The STRIIVING study was a randomized, open-label, Phase IIIb study in adults with HIV-1 RNA ART) at enrolment (ClinicalTrials.gov identifier, NCT02105987). Subjects were randomly assigned to switch to ABC/DTG/3TC once daily for 48 weeks (early-switch group) or continue current ART for 24 weeks and then switch to ABC/DTG/3TC (late-switch group). The primary end point was the proportion of subjects with HIV-1 RNA ART. At week 24, 85% and 88% of subjects who switched to ABC/DTG/3TC or remained on current ART, respectively, were virologically suppressed, indicating that ABC/DTG/3TC was non-inferior (difference in proportion, -3.4%; 95% CI -9.1, 2.4). At week 48, 83% and 92% were virologically suppressed in the early- and late-switch groups, respectively. Adverse events were reported more frequently with ABC/DTG/3TC (66%) than with current ART (47%) by week 24, and in the late-switch group, 60% of subjects reported adverse events post-switch. Pharmacokinetic data supported immediate switch. HIV Treatment Satisfaction Questionnaire scores improved in participants switching to ABC/DTG/3TC versus current ART. Data demonstrating non-inferiority of switching to ABC/DTG/3TC versus continuing current ART support ABC/DTG/3TC as an option when considering switch regimens in HIV-1-infected adults with stable viral suppression.

  9. Early Decoding and Encoding Strategies.

    Science.gov (United States)

    Goldwater-Rozensher, Susan; Hebard, Amy J.

    A combination of case study observation and mini-experimentation techniques were used to examine a number of issues of relevance in the study of the acquisition of beginning reading skills. Six children were divided equally among three instructional modes: phonics, whole word, and mixed. They were asked to decode and encode words, and their…

  10. First line chemotherapy with gemcitabine in advanced non-small cell lung cancer elderly patients: a randomized phase II study of 3-week versus 4-week schedule.

    Science.gov (United States)

    Quoix, Elisabeth; Breton, Jean-Luc; Ducoloné, Alain; Mennecier, Bertrand; Depierre, Alain; Lemarié, Etienne; Moro-Sibilot, Denis; Germa, Caroline; Neidhardt, Anne-Catherine

    2005-03-01

    This randomized phase II multicenter trial aimed at evaluating the efficacy and safety of the 4-week versus 3-week schedules of gemcitabine monotherapy in previously untreated elderly patients with advanced non-small cell lung cancer (NSCLC). Chemonaive patients with stage IIIB or IV NSCLC, and age between 70 and 90 years, were randomized to receive gemcitabine dose of either 1000 mg/m2 on days 1, 8, 15, every 28 days (arm Q4W), or 1125 mg/m2 on days 1 and 8, every 21 days (arm Q3W). From June 1999 to January 2001, 81 patients (42 on arm Q4W; 39 on arm Q3W) were included. The median age was 75 on both arms; most patients (82.7%) were male, and had a Karnofsky performance status of 80 or 90 (76.5%). For arms Q4W and Q3W, respectively, the median time to treatment failure was 83 days (95% CI, 69-98 days) versus 92 days (95% CI, 63-113), and the median survival was 154 days (95% CI, 108-227) versus 205 days (95% CI, 125-344). The objective response rate was higher on arm Q3W (28.2%) than on arm Q4W (14.3%). Total number of cycles administered was 132 on arm Q4W (median 3, range 1-10 cycles) and 169 on arm Q3W (median 4, range 1-9 cycles). Patients on arm Q4W and Q3W, respectively, received 100.1 and 99.8% of the planned weekly mean dose. The most common grade, three to four toxicities, was neutropenia (17.1% on arm Q4W versus 18.9% on arm Q3W) and thrombocytopenia (12.2% on arm Q4W versus 2.6% on arm Q3W). Although both 3- and 4-week gemcitabine regimens were safely and effectively administered in chemonaive elderly patients with advanced NSCLC, the 3-week schedule appears to be the more convenient for this population. Moreover, even if this is only a phase II study this 3-week schedule appears to be at least as efficient as the 4-week regimen.

  11. A randomized phase II study of carboplatin plus pegylated liposomal doxorubicin versus carboplatin plus paclitaxel in platinum sensitive ovarian cancer patients: a Hellenic Cooperative Oncology Group study

    Directory of Open Access Journals (Sweden)

    Briasoulis Evangelos

    2010-01-01

    Full Text Available Abstract Background Platinum-based combinations are the standard second-line treatment for platinum-sensitive ovarian cancer (OC. This randomized phase II study was undertaken in order to compare the combination of carboplatin and pegylated liposomal doxorubicin (LD with carboplatin and paclitaxel (CP in this setting. Methods Patients with histologically confirmed recurrent OC, at the time of or more than 6 months after platinum-based chemotherapy, were randomized to six cycles of CP (carboplatin AUC5 + paclitaxel 175 mg/m2, d1q21 or CLD (carboplatin AUC5 + pegylated LD 45 mg/m2, d1q28. Results A total of 189 eligible patients (CP 96, CLD 93, with a median age of 63 years, median Performance Status (PS 0 and a median platinum free interval (PFI of 16.5 months, entered the study. Discontinuation due to toxicity was higher in the CP patients (13.5% versus 3%, P = 0.016. The overall response rate was similar: CP 58% versus CLD 51%, P = 0.309 (Complete Response; CR 34% versus 23% and there was no statistical difference in time-to-progression (TTP or overall survival (OS; TTP 10.8 months CP versus 11.8 CLD, P = 0.904; OS 29.4 months CP versus 24.7 CLD, P = 0.454. No toxic deaths were recorded. Neutropenia was the most commonly seen severe toxicity (CP 30% versus CLD 35%. More frequent in CLD were severe thrombocytopenia (11% versus 2%, P = 0.016, skin toxicity and Palmar-plantar erythrodysesthesia (PPE grade 1-2 (38% versus 9%, PP = 0.029, 20% versus 5%, P = 0.003. PS and PFI were independent prognostic factors for TTP and OS. Conclusions The combination of pegylated LD with carboplatin is effective, showing less neurotoxicity and alopecia than paclitaxel-carboplatin. It thus warrants a further phase III evaluation as an alternative treatment option for platinum-sensitive OC patients. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12609000436279

  12. PLANNING PHASE 2 MULTICENTER RANDOMIZED TRIAL OF NEOADJUVANT CHEMO-RADIOTHERAPY FOLLOWED BY D2 GASTRECTOMY AND ADJUVANT CHEMOTHERAPY FOR LOCALLY ADVANCED GASTRIC CANCER

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    V. Yu. Skoropad

    2016-01-01

    Full Text Available Introduction. The prognosis for surgical treatment of locally advanced gastric cancer remains disappointing. Neoadjuvant chemo-radiation therapy is relatively new and the least researched method of treatment, it is attracting more and more attention, mainly abroad in recent years. The aims of neoadjuvant therapy is the earliest start of systemic therapy, damage of the primary tumor and regional metastases, an increase in the percentage of radical operations, improving treatment outcome. Material and methods. The planning study is a multicenter, randomized clinical phase II trial. Patients of the first (experimental group will be treated as the followes: neoadjuvant chemo-radiotherapy (total tumor dose of 46 Gy in 23 fractions with the concurrent modified CapOX scheme followed by D2 gastrectomy and adjuvant chemotherapy. Patients of the second (control group will be treated with D2 gastrectomy and adjuvant chemotherapy. Adjuvant chemotherapy will be carried out under the following schemes (optional for the researchers: CapOX or FOLFOX. Toxicity evaluation of neoadjuvant chemo-radiotherapy and adjuvant chemotherapy will be conducted with NCI CTC Toxicity Scale Version 3.0. The main objectives of the trial are to assess the safety and immediate effectiveness of neoadjuvant chemo-radiotherapy according to the criteria of the frequency and severity of postoperative complications and mortality, and tumor response. We are planning to include 80 patients with morphologically confirmed gastric cancer сT2–4N1–3, сT3–4N0–3; М0. The proposed trial will be carried out in accordance with the principles of the Helsinki Declaration, it has been approved by local ethic committees of the participated institutions. Results. As a result of this multicenter randomized trial it is planned to show the reproducibility of obtained in MRRC and a number of foreign centers results – that is, the safety and high immediate effectiveness of neoadjuvant chemo

  13. Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

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    Seiwert, Tanguy Y., E-mail: tseiwert@medicine.bsd.uchicago.edu [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Melotek, James M. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Blair, Elizabeth A. [Department of Otolaryngology, University of Chicago, Chicago, Illinois (United States); Stenson, Kerstin M. [Department of Otolaryngology, Rush University, Chicago, Illinois (United States); Salama, Joseph K. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Witt, Mary Ellyn [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Lingen, Mark W. [Department of Pathology, University of Chicago, Chicago, Illinois (United States); Kocherginsky, Masha [Department of Public Health Sciences, University of Chicago, Chicago, Illinois (United States); Villaflor, Victoria M. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Cohen, Ezra E.W. [Moores Cancer Center, University of California, San Diego, San Diego, California (United States); Haraf, Daniel J. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Vokes, Everett E. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States)

    2016-09-01

    Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further

  14. Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease: Results of the Randomized Phase III OPUS-2 Study.

    Science.gov (United States)

    Tauber, Joseph; Karpecki, Paul; Latkany, Robert; Luchs, Jodi; Martel, Joseph; Sall, Kenneth; Raychaudhuri, Aparna; Smith, Valerie; Semba, Charles P

    2015-12-01

    Lifitegrast is an integrin antagonist that decreases T-cell-mediated inflammation associated with dry eye disease (DED). We report the results of OPUS-2, a phase III study evaluating the efficacy and safety of lifitegrast compared with placebo for the treatment of DED. A 12-week, multicenter, randomized, prospective, double-masked, placebo-controlled clinical trial. Adults aged ≥18 years with use of artificial tears within 30 days, inferior corneal staining score ≥0.5 (0-4 scale), Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, and eye dryness score ≥40 (0-100 visual analogue scale [VAS]). Subjects were randomized 1:1 after 14-day placebo run-in to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. Co-primary efficacy end points were change, from baseline to day 84, in eye dryness score (VAS, both eyes) and inferior corneal fluorescein staining score in the designated study eye. Secondary end points were change, from baseline to day 84, in ocular discomfort score (0-4 scale) in study eye, eye discomfort score (VAS), total corneal staining score in the study eye, and nasal conjunctival lissamine green staining score (0-4 scale) in the study eye. Treatment-emergent adverse events (TEAEs) were recorded. A total of 718 subjects were randomized: placebo, n = 360; lifitegrast, n = 358 (intent-to-treat population). Lifitegrast-treated subjects experienced greater improvement in eye dryness than placebo-treated subjects (treatment effect, 12.61; 95% confidence interval [CI], 8.51-16.70; P lifitegrast-treated subjects: ocular discomfort (nominal P = 0.0005) and eye discomfort (nominal, P lifitegrast-treated subjects (33.7%) than placebo-treated subjects (16.4%) experienced ocular TEAEs; no ocular TEAEs were serious. Lifitegrast met the co-primary symptom end point (eye dryness) but not the co-primary sign end point (inferior corneal staining). Secondary end point findings were consistent with this pattern. Most ocular TEAEs were mild

  15. A phase 2 randomized, double-blind study of AMG 108, a fully human monoclonal antibody to IL-1R, in patients with rheumatoid arthritis.

    Science.gov (United States)

    Cardiel, Mario H; Tak, Paul P; Bensen, William; Burch, Francis X; Forejtova, Sarka; Badurski, Janusz E; Kakkar, Tarundeep; Bevirt, Terry; Ni, Liyun; McCroskery, Ellen; Jahreis, Angelika; Zack, Debra J

    2010-01-01

    Preclinical work has suggested that IL-1 plays a critical role in the pathogenesis of rheumatoid arthritis (RA). The objective of the present study was to determine the effect of a long-acting IL-1 receptor inhibitor, AMG 108, in a double-blind, placebo-controlled, parallel-dosing study in patients with active RA who were receiving stable methotrexate (15 to 25 mg/week). Patients were randomized equally to receive placebo or 50, 125, or 250 mg AMG 108 subcutaneously every 4 weeks for 6 months. The primary efficacy endpoint was a 20% improvement in the American College of Rheumatology response (ACR20) at week 24; other efficacy endpoints included the ACR50, the ACR70, and the RA disease activity score (28-joint count Disease Activity Score) responses, patient-reported outcomes, and pharmacokinetic parameters. Safety endpoints included treatment-emergent adverse events (AEs), infectious AEs, serious AEs, serious infections, injection site reactions, laboratory abnormalities, and antibodies to AMG 108. Of 813 patients enrolled in the study, 204 patients were randomized to the 50 mg group, 203 to the 125 mg group, 203 to the 250 mg group, and 203 to placebo. At week 24, 40.4% of the 250 mg group, 36% of the 125 mg group, 30.9% of the 50 mg group, and 29.1% of the placebo group achieved an ACR20 (P = 0.022, 250 mg vs. placebo). Of the individual ACR components, numerical dose-dependent improvements were only seen in tender joint counts, pain (visual analog scale), and the acute phase reactants, erythrocyte sedimentation rate and C-reactive protein. No dose-related increase was observed in the incidence of treatment-emergent AEs. No deaths were reported, and the incidence of AEs and infections, serious AEs and infections, and withdrawals from study for safety were similar in the AMG 108 and placebo groups. This large double-blind randomized trial with a long-acting IL-1 receptor blocker, AMG 108, is consistent with the experience of other IL-1 blockers, represents a

  16. The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study.

    Science.gov (United States)

    Garcia, Esther; Robert, Marta; Peris, Francesc; Nakamura, Hiroshi; Sato, Noriko; Terazawa, Yoshikatsu

    2009-01-01

    Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents. To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia. This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables. All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not seen with any dose of

  17. Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec.

    Science.gov (United States)

    Walker, Dave; Ng Kwet Shing, Richard; Jones, Deborah; Gruss, Hans-Jurgen; Reguła, Jarosław

    2015-01-01

    Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD). Patients with a history of frequent (2 3 days/week) uncomplicated GERD, were randomized to receive Zegerid (20 mg) or Losec (20 mg) with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale). Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes). Of patients randomized to Zegerid (N=122) or Losec (N=117), 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively), sustained partial response (both, 37.5 minutes) and sustained total relief (both, 105 minutes). Significantly more patients treated with Zegerid reached sustained total relief within 0-30 minutes post dose in all analysis sets (p<0.05). Both treatments were well tolerated and did not raise any safety concerns. Superiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in correlating intra-gastric pH change with

  18. Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec.

    Directory of Open Access Journals (Sweden)

    Dave Walker

    Full Text Available Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole, suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD.Patients with a history of frequent (2 3 days/week uncomplicated GERD, were randomized to receive Zegerid (20 mg or Losec (20 mg with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale. Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes.Of patients randomized to Zegerid (N=122 or Losec (N=117, 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively, sustained partial response (both, 37.5 minutes and sustained total relief (both, 105 minutes. Significantly more patients treated with Zegerid reached sustained total relief within 0-30 minutes post dose in all analysis sets (p<0.05. Both treatments were well tolerated and did not raise any safety concerns.Superiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in correlating intra-gastric pH change with

  19. Randomized Phase III Multi-Institutional Study of TNFerade Biologic With Fluorouracil and Radiotherapy for Locally Advanced Pancreatic Cancer: Final Results

    Science.gov (United States)

    Herman, Joseph M.; Wild, Aaron T.; Wang, Hao; Tran, Phuoc T.; Chang, Kenneth J.; Taylor, Gretchen E.; Donehower, Ross C.; Pawlik, Timothy M.; Ziegler, Mark A.; Cai, Hongyan; Savage, Dionne T.; Canto, Marcia I.; Klapman, Jason; Reid, Tony; Shah, Raj J.; Hoffe, Sarah E.; Rosemurgy, Alexander; Wolfgang, Christopher L.; Laheru, Daniel A.

    2013-01-01

    Purpose TNFerade biologic is a novel means of delivering tumor necrosis factor alpha to tumor cells by gene transfer. We herein report final results of the largest randomized phase III trial performed to date among patients with locally advanced pancreatic cancer (LAPC) and the first to test gene transfer against this malignancy. Patients and Methods In all, 304 patients were randomly assigned 2:1 to standard of care plus TNFerade (SOC + TNFerade) versus standard of care alone (SOC). SOC consisted of 50.4 Gy in 28 fractions with concurrent fluorouracil (200 mg/m2 per day continuous infusion). TNFerade was injected intratumorally before the first fraction of radiotherapy each week at a dose of 4 × 1011 particle units by using either a percutaneous transabdominal or an endoscopic ultrasound approach. Four weeks after chemoradiotherapy, patients began gemcitabine (1,000 mg/m2 intravenously) with or without erlotinib (100 to 150 mg per day orally) until progression or toxicity. Results The analysis included 187 patients randomly assigned to SOC + TNFerade and 90 to SOC by using a modified intention-to-treat approach. Median follow-up was 9.1 months (range, 0.1 to 50.5 months). Median survival was 10.0 months for patients in both the SOC + TNFerade and SOC arms (hazard ratio [HR], 0.90; 95% CI, 0.66 to 1.22; P = .26). Median progression-free survival (PFS) was 6.8 months for SOC + TNFerade versus 7.0 months for SOC (HR, 0.96; 95% CI, 0.69 to 1.32; P = .51). Among patients treated on the SOC + TNFerade arm, multivariate analysis showed that TNFerade injection by an endoscopic ultrasound-guided transgastric/transduodenal approach rather than a percutaneous transabdominal approach was a risk factor for inferior PFS (HR, 2.08; 95% CI, 1.06 to 4.06; P = .032). The patients in the SOC + TNFerade arm experienced more grade 1 to 2 fever and chills than those in the SOC arm (P .05). Conclusion SOC + TNFerade is safe but not effective for prolonging survival in patients with

  20. Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

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    Robert S B Clark

    Full Text Available There are no therapies shown to improve outcome after severe traumatic brain injury (TBI in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children.IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8 requiring an externalized ventricular drain for measurement of intracranial pressure (ICP. Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses, or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS score was assessed at 3 months.There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 μg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM. Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups.Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children

  1. Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

    Science.gov (United States)

    Clark, Robert S B; Empey, Philip E; Bayır, Hülya; Rosario, Bedda L; Poloyac, Samuel M; Kochanek, Patrick M; Nolin, Thomas D; Au, Alicia K; Horvat, Christopher M; Wisniewski, Stephen R; Bell, Michael J

    2017-01-01

    There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children. IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months. There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 μg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups. Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children. Clinical

  2. Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma.

    Science.gov (United States)

    Chesney, Jason; Puzanov, Igor; Collichio, Frances; Singh, Parminder; Milhem, Mohammed M; Glaspy, John; Hamid, Omid; Ross, Merrick; Friedlander, Philip; Garbe, Claus; Logan, Theodore F; Hauschild, Axel; Lebbé, Celeste; Chen, Lisa; Kim, Jenny J; Gansert, Jennifer; Andtbacka, Robert H I; Kaufman, Howard L

    2017-10-05

    Purpose We evaluated the combination of talimogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with advanced melanoma in a phase II study. To our knowledge, this was the first randomized trial to evaluate addition of an oncolytic virus to a checkpoint inhibitor. Methods Patients with unresectable stages IIIB to IV melanoma