Sample records for advanced bionics ci

  1. Bionic Nanosystems

    NASA Astrophysics Data System (ADS)

    Sebastian Mannoor, Manu

    Direct multidimensional integration of functional electronics and mechanical elements with viable biological systems could allow for the creation of bionic systems and devices possessing unique and advanced capabilities. For example, the ability to three dimensionally integrate functional electronic and mechanical components with biological cells and tissue could enable the creation of bionic systems that can have tremendous impact in regenerative medicine, prosthetics, and human-machine interfaces. However, as a consequence of the inherent dichotomy in material properties and limitations of conventional fabrication methods, the attainment of truly seamless integration of electronic and/or mechanical components with biological systems has been challenging. Nanomaterials engineering offers a general route for overcoming these dichotomies, primarily due to the existence of a dimensional compatibility between fundamental biological functional units and abiotic nanomaterial building blocks. One area of compelling interest for bionic systems is in the field of biomedical sensing, where the direct interfacing of nanosensors onto biological tissue or the human body could stimulate exciting opportunities such as on-body health quality monitoring and adaptive threat detection. Further, interfacing of antimicrobial peptide based bioselective probes onto the bionic nanosensors could offer abilities to detect pathogenic bacteria with bio-inspired selectivity. Most compellingly, when paired with additive manufacturing techniques such as 3D printing, these characteristics enable three dimensional integration and merging of a variety of functional materials including electronic, structural and biomaterials with viable biological cells, in the precise anatomic geometries of human organs, to form three dimensionally integrated, multi-functional bionic hybrids and cyborg devices with unique capabilities. In this thesis, we illustrate these approaches using three representative

  2. Coming Soon: The Bionic Man

    ERIC Educational Resources Information Center

    Woodard, Colin

    2006-01-01

    This article describes the latest advancement in the development of prosthetic arms. Bionic researchers are making significant advances in creating more agile prosthetics that users can control via their own nervous system. The bionic arm, which is still under development, can not only execute complex, thought-controlled movements, but also can…

  3. Multicentre evaluation of music perception in adult users of Advanced Bionics cochlear implants.

    PubMed

    Adams, Doris; Ajimsha, Khalid Mohamed; Barberá, Manuel Tomás; Gazibegovic, Dzemal; Gisbert, Javier; Gómez, Justo; Raveh, Eyal; Rocca, Christine; Romanet, Philipe; Seebens, Yvonne; Zarowski, Andrzej

    2014-01-01

    To document musical listening and enjoyment in recipients of Advanced Bionics cochlear implants (CIs) and to compare musical perception in those using early coding strategies with subjects using the newer HiRes and HiRes 120 strategies. A questionnaire was completed by 136 adult subjects, including questions on the ability to identify specific musical features. The subjects were in three groups: those using early coding strategies (n = 29), HiRes (n = 59), and HiRes 120 (n = 48), and results were compared with a group of 84 normally hearing (NH) subjects. Of the CI users, 79% reported listening to music. The NH group rated listening frequency and enjoyment higher than the CI users. Thirty-five users reported that they sang and this group had significantly higher overall performance. There were no significant differences in overall perception of specific musical features among the strategy groups, though some individual questions showed significantly higher performance in the HiRes 120 users. Users of current CI technology show a high level of musical appreciation, though still significantly less than NH subjects. Frequency of listening and enjoyment were significantly correlated and active participation in musical activities, specifically singing, resulted in significantly higher overall performance scores.

  4. Recent Progress in Bionic Condensate Microdrop Self-Propelling Surfaces.

    PubMed

    Gong, Xiaojing; Gao, Xuefeng; Jiang, Lei

    2017-12-01

    Bionic condensate microdrop self-propelling (CMDSP) surfaces are attracting increased attention as novel, low-adhesivity superhydrophobic surfaces due to their value in fundamental research and technological innovation, e.g., for enhancing heat transfer, energy-effective antifreezing, and electrostatic energy harvesting. Here, the focus is on recent progress in bionic CMDSP surfaces. Metal-based CMDSP surfaces, which are the most promising in their respective fields, are highlighted for use in future applications. The selected topics are divided into four sections: biological prototypes, mechanism and construction rules, fabrication, and applications of metal-based CMDSP surfaces. Finally, the challenges and future development trends in bionic CMDSP surfaces are envisioned, especially the utilization of potential bionic inspiration in the design of more advanced CMDSP surfaces. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Optimization of programming parameters in children with the advanced bionics cochlear implant.

    PubMed

    Baudhuin, Jacquelyn; Cadieux, Jamie; Firszt, Jill B; Reeder, Ruth M; Maxson, Jerrica L

    2012-05-01

    Cochlear implants provide access to soft intensity sounds and therefore improved audibility for children with severe-to-profound hearing loss. Speech processor programming parameters, such as threshold (or T-level), input dynamic range (IDR), and microphone sensitivity, contribute to the recipient's program and influence audibility. When soundfield thresholds obtained through the speech processor are elevated, programming parameters can be modified to improve soft sound detection. Adult recipients show improved detection for low-level sounds when T-levels are set at raised levels and show better speech understanding in quiet when wider IDRs are used. Little is known about the effects of parameter settings on detection and speech recognition in children using today's cochlear implant technology. The overall study aim was to assess optimal T-level, IDR, and sensitivity settings in pediatric recipients of the Advanced Bionics cochlear implant. Two experiments were conducted. Experiment 1 examined the effects of two T-level settings on soundfield thresholds and detection of the Ling 6 sounds. One program set T-levels at 10% of most comfortable levels (M-levels) and another at 10 current units (CUs) below the level judged as "soft." Experiment 2 examined the effects of IDR and sensitivity settings on speech recognition in quiet and noise. Participants were 11 children 7-17 yr of age (mean 11.3) implanted with the Advanced Bionics High Resolution 90K or CII cochlear implant system who had speech recognition scores of 20% or greater on a monosyllabic word test. Two T-level programs were compared for detection of the Ling sounds and frequency modulated (FM) tones. Differing IDR/sensitivity programs (50/0, 50/10, 70/0, 70/10) were compared using Ling and FM tone detection thresholds, CNC (consonant-vowel nucleus-consonant) words at 50 dB SPL, and Hearing in Noise Test for Children (HINT-C) sentences at 65 dB SPL in the presence of four-talker babble (+8 signal

  6. Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial

    PubMed Central

    El-Khatib, Firas H; Balliro, Courtney; Hillard, Mallory A; Magyar, Kendra L; Ekhlaspour, Laya; Sinha, Manasi; Mondesir, Debbie; Esmaeili, Aryan; Hartigan, Celia; Thompson, Michael J; Malkani, Samir; Lock, J Paul; Harlan, David M; Clinton, Paula; Frank, Eliana; Wilson, Darrell M; DeSalvo, Daniel; Norlander, Lisa; Ly, Trang; Buckingham, Bruce A; Diner, Jamie; Dezube, Milana; Young, Laura A; Goley, April; Kirkman, M Sue; Buse, John B; Zheng, Hui; Selagamsetty, Rajendranath R; Damiano, Edward R; Russell, Steven J

    2017-01-01

    ·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8–1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0–10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21–0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study. Interpretation Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas. Funding National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences. PMID:28007348

  7. Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial.

    PubMed

    El-Khatib, Firas H; Balliro, Courtney; Hillard, Mallory A; Magyar, Kendra L; Ekhlaspour, Laya; Sinha, Manasi; Mondesir, Debbie; Esmaeili, Aryan; Hartigan, Celia; Thompson, Michael J; Malkani, Samir; Lock, J Paul; Harlan, David M; Clinton, Paula; Frank, Eliana; Wilson, Darrell M; DeSalvo, Daniel; Norlander, Lisa; Ly, Trang; Buckingham, Bruce A; Diner, Jamie; Dezube, Milana; Young, Laura A; Goley, April; Kirkman, M Sue; Buse, John B; Zheng, Hui; Selagamsetty, Rajendranath R; Damiano, Edward R; Russell, Steven J

    2017-01-28

    glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8-1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0-10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21-0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study. Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas. National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Holographic cosmology from BIonic solutions

    NASA Astrophysics Data System (ADS)

    Sepehri, Alireza; Faizal, Mir; Setare, Mohammad Reza; Ali, Ahmed Farag

    2017-02-01

    In this paper, we will use a BIonic solution for analyzing the holographic cosmology. A BIonic solution is a configuration of a D3-brane and an anti-D3-brane connected by a wormhole, and holographic cosmology is a recent proposal to explain cosmic expansion by using the holographic principle. In our model, a BIonic configuration will be produced by the transition of fundamental black strings. The formation of a BIonic configuration will cause inflation. As the D3-brane moves away from the anti-D3-brane, the wormhole will get annihilated, and the inflation will end with the annihilation of this wormhole. However, it is possible for a D3-brane to collide with an anti-D3-brane. Such a collision will occur if the distance between the D3-brane and the anti-D3-brane reduces, and this will create tachyonic states. We will demonstrate that these tachyonic states will lead to the formation of a new wormhole, and this will cause acceleration of the universe before such a collision.

  9. Crashworthiness Design for Bionic Bumper Structures Inspired by Cattail and Bamboo.

    PubMed

    Xu, Tao; Liu, Nian; Yu, Zhenglei; Xu, Tianshuang; Zou, Meng

    2017-01-01

    Many materials in nature exhibit excellent mechanical properties. In this study, we evaluated the bionic bumper structure models by using nonlinear finite element (FE) simulations for their crashworthiness under full-size impact loading. The structure contained the structural characteristics of cattail and bamboo. The results indicated that the bionic design enhances the specific energy absorption (SEA) of the bumper. The numerical results showed that the bionic cross-beam and bionic box of the bionic bumper have a significant effect on the crashworthiness of the structure. The crush deformation of bionic cross-beam and box bumper model was reduced by 33.33%, and the total weight was reduced by 44.44%. As the energy absorption capacity under lateral impact, the bionic design can be used in the future bumper body.

  10. Crashworthiness Design for Bionic Bumper Structures Inspired by Cattail and Bamboo

    PubMed Central

    Xu, Tao; Liu, Nian

    2017-01-01

    Many materials in nature exhibit excellent mechanical properties. In this study, we evaluated the bionic bumper structure models by using nonlinear finite element (FE) simulations for their crashworthiness under full-size impact loading. The structure contained the structural characteristics of cattail and bamboo. The results indicated that the bionic design enhances the specific energy absorption (SEA) of the bumper. The numerical results showed that the bionic cross-beam and bionic box of the bionic bumper have a significant effect on the crashworthiness of the structure. The crush deformation of bionic cross-beam and box bumper model was reduced by 33.33%, and the total weight was reduced by 44.44%. As the energy absorption capacity under lateral impact, the bionic design can be used in the future bumper body. PMID:29118571

  11. "Bionic Woman" (2007): Gender, Disability and Cyborgs

    ERIC Educational Resources Information Center

    Quinlan, Margaret M.; Bates, Benjamin R.

    2009-01-01

    This paper explores a representation of overlapping categories of gender, disability and cyborgs in "Bionic Woman" (2007). The television show "Bionic Woman" (2007) is a popular culture representation that uniquely brings together these categories. Three themes emerged from an analysis of blogger discourse surrounding the show. The themes reveal…

  12. Regenerative Engineering and Bionic Limbs.

    PubMed

    James, Roshan; Laurencin, Cato T

    2015-03-01

    Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next

  13. Regenerative Engineering and Bionic Limbs

    PubMed Central

    James, Roshan; Laurencin, Cato T.

    2015-01-01

    Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next

  14. The quest for the bionic arm.

    PubMed

    Hutchinson, Douglas T

    2014-06-01

    The current state of research of upper extremity prosthetic devices is focused on creating a complete prosthesis with full motor and sensory function that will provide amputees with a near-normal human arm. Although advances are being made rapidly, many hurdles remain to be overcome before a functional, so-called bionic arm is a reality. Acquiring signals via nerve or muscle inputs will require either a reliable wireless device or direct wiring through an osseous-integrated implant. The best way to tap into the "knowledge" present in the peripheral nerve is yet to be determined. Copyright 2014 by the American Academy of Orthopaedic Surgeons.

  15. Design of a hydraulically-driven bionic folding wing.

    PubMed

    Zhang, Zhijun; Sun, Xuwei; Du, Pengyu; Sun, Jiyu; Wu, Yongfeng

    2018-06-01

    Membranous hind wings of the beetles can be folded under the elytra when they are at rest, and rotate and lift the elytra up only when they need to fly. This characteristic provides excellent flying capability and good environment adaptability. Inspired by the beetles, the new type of the bionic folding wing for the flapping wing Micro Air Vehicle (MAV) was designed. This flapping wing can be unfolded to get a sufficient lift in flight, and can be folded off flight to reduce the wing area and risk of the wing damage. The relationship between the internal pressures of the hydraulic system for the bionic wing folding varies and temperature was analyzed, the results show that the pressure within the system tends to increase with temperature, which proves the feasibility of the schematic design in theory. Stress analysis of the bionic wing was conducted, it was shown that stress distributions and deformation of the bionic wing under the positive and negative side loading are basically the same, which demonstrates that the strength of the bionic folding wing meets the requirements and further proves the feasibility of the schematic design. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Bionic Design, Materials and Performance of Bone Tissue Scaffolds

    PubMed Central

    Wu, Tong; Yu, Suihuai; Chen, Dengkai; Wang, Yanen

    2017-01-01

    Design, materials, and performance are important factors in the research of bone tissue scaffolds. This work briefly describes the bone scaffolds and their anatomic structure, as well as their biological and mechanical characteristics. Furthermore, we reviewed the characteristics of metal materials, inorganic materials, organic polymer materials, and composite materials. The importance of the bionic design in preoperative diagnosis models and customized bone scaffolds was also discussed, addressing both the bionic structure design (macro and micro structure) and the bionic performance design (mechanical performance and biological performance). Materials and performance are the two main problems in the development of customized bone scaffolds. Bionic design is an effective way to solve these problems, which could improve the clinical application of bone scaffolds, by creating a balance between mechanical performance and biological performance. PMID:29039749

  17. Bionic Design, Materials and Performance of Bone Tissue Scaffolds.

    PubMed

    Wu, Tong; Yu, Suihuai; Chen, Dengkai; Wang, Yanen

    2017-10-17

    Design, materials, and performance are important factors in the research of bone tissue scaffolds. This work briefly describes the bone scaffolds and their anatomic structure, as well as their biological and mechanical characteristics. Furthermore, we reviewed the characteristics of metal materials, inorganic materials, organic polymer materials, and composite materials. The importance of the bionic design in preoperative diagnosis models and customized bone scaffolds was also discussed, addressing both the bionic structure design (macro and micro structure) and the bionic performance design (mechanical performance and biological performance). Materials and performance are the two main problems in the development of customized bone scaffolds. Bionic design is an effective way to solve these problems, which could improve the clinical application of bone scaffolds, by creating a balance between mechanical performance and biological performance.

  18. Investigation of the Effect of Dimple Bionic Nonsmooth Surface on Tire Antihydroplaning.

    PubMed

    Zhou, Haichao; Wang, Guolin; Ding, Yangmin; Yang, Jian; Zhai, Huihui

    2015-01-01

    Inspired by the idea that bionic nonsmooth surfaces (BNSS) reduce fluid adhesion and resistance, the effect of dimple bionic nonsmooth structure arranged in tire circumferential grooves surface on antihydroplaning performance was investigated by using Computational Fluid Dynamics (CFD). The physical model of the object (model of dimple bionic nonsmooth surface distribution, hydroplaning model) and SST k - ω turbulence model are established for numerical analysis of tire hydroplaning. By virtue of the orthogonal table L16(4(5)), the parameters of dimple bionic nonsmooth structure design compared to the smooth structure were analyzed, and the priority level of the experimental factors as well as the best combination within the scope of the experiment was obtained. The simulation results show that dimple bionic nonsmooth structure can reduce water flow resistance by disturbing the eddy movement in boundary layers. Then, optimal type of dimple bionic nonsmooth structure is arranged on the bottom of tire circumferential grooves for hydroplaning performance analysis. The results show that the dimple bionic nonsmooth structure effectively decreases the tread hydrodynamic pressure when driving on water film and increases the tire hydroplaning velocity, thus improving tire antihydroplaning performance.

  19. Investigation of the Effect of Dimple Bionic Nonsmooth Surface on Tire Antihydroplaning

    PubMed Central

    Zhou, Haichao; Wang, Guolin; Ding, Yangmin; Yang, Jian; Zhai, Huihui

    2015-01-01

    Inspired by the idea that bionic nonsmooth surfaces (BNSS) reduce fluid adhesion and resistance, the effect of dimple bionic nonsmooth structure arranged in tire circumferential grooves surface on antihydroplaning performance was investigated by using Computational Fluid Dynamics (CFD). The physical model of the object (model of dimple bionic nonsmooth surface distribution, hydroplaning model) and SST k − ω turbulence model are established for numerical analysis of tire hydroplaning. By virtue of the orthogonal table L16(45), the parameters of dimple bionic nonsmooth structure design compared to the smooth structure were analyzed, and the priority level of the experimental factors as well as the best combination within the scope of the experiment was obtained. The simulation results show that dimple bionic nonsmooth structure can reduce water flow resistance by disturbing the eddy movement in boundary layers. Then, optimal type of dimple bionic nonsmooth structure is arranged on the bottom of tire circumferential grooves for hydroplaning performance analysis. The results show that the dimple bionic nonsmooth structure effectively decreases the tread hydrodynamic pressure when driving on water film and increases the tire hydroplaning velocity, thus improving tire antihydroplaning performance. PMID:27018311

  20. Speech understanding in noise with the Roger Pen, Naida CI Q70 processor, and integrated Roger 17 receiver in a multi-talker network.

    PubMed

    De Ceulaer, Geert; Bestel, Julie; Mülder, Hans E; Goldbeck, Felix; de Varebeke, Sebastien Pierre Janssens; Govaerts, Paul J

    2016-05-01

    Roger is a digital adaptive multi-channel remote microphone technology that wirelessly transmits a speaker's voice directly to a hearing instrument or cochlear implant sound processor. Frequency hopping between channels, in combination with repeated broadcast, avoids interference issues that have limited earlier generation FM systems. This study evaluated the benefit of the Roger Pen transmitter microphone in a multiple talker network (MTN) for cochlear implant users in a simulated noisy conversation setting. Twelve post-lingually deafened adult Advanced Bionics CII/HiRes 90K recipients were recruited. Subjects used a Naida CI Q70 processor with integrated Roger 17 receiver. The test environment simulated four people having a meal in a noisy restaurant, one the CI user (listener), and three companions (talkers) talking non-simultaneously in a diffuse field of multi-talker babble. Speech reception thresholds (SRTs) were determined without the Roger Pen, with one Roger Pen, and with three Roger Pens in an MTN. Using three Roger Pens in an MTN improved the SRT by 14.8 dB over using no Roger Pen, and by 13.1 dB over using a single Roger Pen (p < 0.0001). The Roger Pen in an MTN provided statistically and clinically significant improvement in speech perception in noise for Advanced Bionics cochlear implant recipients. The integrated Roger 17 receiver made it easy for users of the Naida CI Q70 processor to take advantage of the Roger system. The listening advantage and ease of use should encourage more clinicians to recommend and fit Roger in adult cochlear implant patients.

  1. Research on the Integration of Bionic Geometry Modeling and Simulation of Robot Foot Based on Characteristic Curve

    NASA Astrophysics Data System (ADS)

    He, G.; Zhu, H.; Xu, J.; Gao, K.; Zhu, D.

    2017-09-01

    The bionic research of shape is an important aspect of the research on bionic robot, and its implementation cannot be separated from the shape modeling and numerical simulation of the bionic object, which is tedious and time-consuming. In order to improve the efficiency of shape bionic design, the feet of animals living in soft soil and swamp environment are taken as bionic objects, and characteristic skeleton curve, section curve, joint rotation variable, position and other parameters are used to describe the shape and position information of bionic object’s sole, toes and flipper. The geometry modeling of the bionic object is established by using the parameterization of characteristic curves and variables. Based on this, the integration framework of parametric modeling and finite element modeling, dynamic analysis and post-processing of sinking process in soil is proposed in this paper. The examples of bionic ostrich foot and bionic duck foot are also given. The parametric modeling and integration technique can achieve rapid improved design based on bionic object, and it can also greatly improve the efficiency and quality of robot foot bionic design, and has important practical significance to improve the level of bionic design of robot foot’s shape and structure.

  2. EDITORIAL: Special issue on medical bionics Special issue on medical bionics

    NASA Astrophysics Data System (ADS)

    Shepherd, Robert K.; D, Ph

    2009-12-01

    This special section of the Journal of Neural Engineering contains eight invited papers presented as part of the inaugural conference `Medical Bionics: A New Paradigm for Human Health' held in the beautiful seaside village of Lorne, Victoria, Australia from 16-19 November 2008. This meeting formed part of the Sir Mark Oliphant International Conference Series (www.oliphant.org.au) and was generously supported by the Department of Innovation, Industry, Science and Research of the Australian Government, the Australian Academy of Science and the Australian Academy of Technological Sciences and Engineering. This meeting was designed to bring experts from a variety of scientific, engineering and clinical disciplines together in a unique environment to discuss current progress in the field of medical bionics and to develop the concepts and techniques required to build the next generation of devices. The field is rapidly expanding, with new engineering solutions for neurological disorders being developed at an astonishing rate. Successful application of emerging engineering technologies into medical bionics devices requires a multidisciplinary research environment in order to deliver clinical solutions that are both safe and effective. Clinical success stories to date include spinal cord stimulators for the management of chronic neurological pain; auditory prostheses that allow the profoundly deaf to hear; and deep brain stimulation to negate movement disorders in Parkinson's disease. Other research programs currently undergoing clinical trials include devices that allow paraplegics to stand and even walk; brain-machine interfaces that provide quadriplegic patients with rudimentary control of a computer but may ultimately provide control of wheel chairs and artificial limbs; devices that detect and suppress epileptic seizures using brief trains of electrical stimulation; and retinal prostheses that will provide vision to the blind. The future for medical bionics is indeed

  3. [The white coat as a cape: doctors, superheroes and bionics].

    PubMed

    Engelberts, Connie E; Mevius, Lucas

    2013-01-01

    To study the relationship between doctors and comic books, cartoons, superheroes and bionic prosthetic organs. Descriptive survey. For this study, 341 doctors and medical students filled in a digital survey in the autumn of 2013. The questionnaire contained questions about comic books and cartoons, their superheroes, prosthetic organs and about bionic and non-bionic super powers. As a child more than half of the participants read comic books regularly or often, and most watched cartoons regularly or often. Now their childhood interest in this subject has mostly been lost. In their youth, Suske & Wiske were the favourite, and now it is Donald Duck. The number of doctors with a favourite superhero decreased as aged increased from 52% to 37%. The care givers entertain lively fantasies about having bionic superpowers. According to the participants, the idea doctor would have ultrasonic eyes and all sorts of other super senses. Ninety-one per cent thought that 'the development of prosthetic organs is not a waste of money'. If Batman and Superman come to blows, Catwoman wins.

  4. Bionic Design for Mars Sampling Scoop Inspired by Himalayan Marmot Claw

    PubMed Central

    2016-01-01

    Cave animals are often adapted to digging and life underground, with claw toes similar in structure and function to a sampling scoop. In this paper, the clawed toes of the Himalayan marmot were selected as a biological prototype for bionic research. Based on geometric parameter optimization of the clawed toes, a bionic sampling scoop for use on Mars was designed. Using a 3D laser scanner, the point cloud data of the second front claw toe was acquired. Parametric equations and contour curves for the claw were then built with cubic polynomial fitting. We obtained 18 characteristic curve equations for the internal and external contours of the claw. A bionic sampling scoop was designed according to the structural parameters of Curiosity's sampling shovel and the contours of the Himalayan marmot's claw. Verifying test results showed that when the penetration angle was 45° and the sampling speed was 0.33 r/min, the bionic sampling scoops' resistance torque was 49.6% less than that of the prototype sampling scoop. When the penetration angle was 60° and the sampling speed was 0.22 r/min, the resistance torque of the bionic sampling scoop was 28.8% lower than that of the prototype sampling scoop. PMID:28127229

  5. A pneumatic Bionic Voice prosthesis-Pre-clinical trials of controlling the voice onset and offset.

    PubMed

    Ahmadi, Farzaneh; Noorian, Farzad; Novakovic, Daniel; van Schaik, André

    2018-01-01

    Despite emergent progress in many fields of bionics, a functional Bionic Voice prosthesis for laryngectomy patients (larynx amputees) has not yet been achieved, leading to a lifetime of vocal disability for these patients. This study introduces a novel framework of Pneumatic Bionic Voice Prostheses as an electronic adaptation of the Pneumatic Artificial Larynx (PAL) device. The PAL is a non-invasive mechanical voice source, driven exclusively by respiration with an exceptionally high voice quality, comparable to the existing gold standard of Tracheoesophageal (TE) voice prosthesis. Following PAL design closely as the reference, Pneumatic Bionic Voice Prostheses seem to have a strong potential to substitute the existing gold standard by generating a similar voice quality while remaining non-invasive and non-surgical. This paper designs the first Pneumatic Bionic Voice prosthesis and evaluates its onset and offset control against the PAL device through pre-clinical trials on one laryngectomy patient. The evaluation on a database of more than five hours of continuous/isolated speech recordings shows a close match between the onset/offset control of the Pneumatic Bionic Voice and the PAL with an accuracy of 98.45 ±0.54%. When implemented in real-time, the Pneumatic Bionic Voice prosthesis controller has an average onset/offset delay of 10 milliseconds compared to the PAL. Hence it addresses a major disadvantage of previous electronic voice prostheses, including myoelectric Bionic Voice, in meeting the short time-frames of controlling the onset/offset of the voice in continuous speech.

  6. Design and Test Research on Cutting Blade of Corn Harvester Based on Bionic Principle.

    PubMed

    Tian, Kunpeng; Li, Xianwang; Zhang, Bin; Chen, Qiaomin; Shen, Cheng; Huang, Jicheng

    2017-01-01

    Existing corn harvester cutting blades have problems associated with large cutting resistance, high energy consumption, and poor cut quality. Using bionics principles, a bionic blade was designed by extracting the cutting tooth profile curve of the B. horsfieldi palate. Using a double-blade cutting device testing system, a single stalk cutting performance contrast test for corn stalks obtained at harvest time was carried out. Results show that bionic blades have superior performance, demonstrated by strong cutting ability and good cut quality. Using statistical analysis of two groups of cutting test data, the average cutting force and cutting energy of bionic blades and ordinary blades were obtained as 480.24 N and 551.31 N and 3.91 J and 4.38 J, respectively. Average maximum cutting force and cutting energy consumption for the bionic blade were reduced by 12.89% and 10.73%, respectively. Variance analysis showed that both blade types had a significant effect on maximum cutting energy and cutting energy required to cut a corn stalk. This demonstrates that bionic blades have better cutting force and energy consumption reduction performance than ordinary blades.

  7. Presenting Bionic: Broader Impacts and Outreach Network for Institutional Collaboration

    NASA Astrophysics Data System (ADS)

    Storm, K.

    2014-12-01

    Broader Impact plans are required of all NSF proposals. In 2011 the National Science Board, which oversees NSF, reconfirmed NSF's commitment to Broader Impacts in its task force report on the merit review system. At many institutions there are professionals that focus their work on supporting the Broader Impact work of researchers. This session will share the Broader Impacts and Outreach Network for Institutional Collaboration (BIONIC) plan to create a professional network of individuals and offices committed to planning and carrying out effective Broader Impact programming. BIONIC is an NSF Research Coordination Network that is recommended for funding through the Biology Directorate. In this session we will share the goals of BIONIC, and the progress to date in reaching those goals (of which one aspect is the curating of effective Broader Impact initiatives).

  8. Bionic Design of Wind Turbine Blade Based on Long-Eared Owl's Airfoil.

    PubMed

    Tian, Weijun; Yang, Zhen; Zhang, Qi; Wang, Jiyue; Li, Ming; Ma, Yi; Cong, Qian

    2017-01-01

    The main purpose of this paper is to demonstrate a bionic design for the airfoil of wind turbines inspired by the morphology of Long-eared Owl's wings. Glauert Model was adopted to design the standard blade and the bionic blade, respectively. Numerical analysis method was utilized to study the aerodynamic characteristics of the airfoils as well as the blades. Results show that the bionic airfoil inspired by the airfoil at the 50% aspect ratio of the Long-eared Owl's wing gives rise to a superior lift coefficient and stalling performance and thus can be beneficial to improving the performance of the wind turbine blade. Also, the efficiency of the bionic blade in wind turbine blades tests increases by 12% or above (up to 44%) compared to that of the standard blade. The reason lies in the bigger pressure difference between the upper and lower surface which can provide stronger lift.

  9. Multifocal microlens for bionic compound eye

    NASA Astrophysics Data System (ADS)

    Cao, Axiu; Wang, Jiazhou; Pang, Hui; Zhang, Man; Shi, Lifang; Deng, Qiling; Hu, Song

    2017-10-01

    Bionic compound eye optical element composed of multi-dimensional sub-eye microlenses plays an important role in miniaturizing the volume and weight of an imaging system. In this manuscript, we present a novel structure of the bionic compound eye with multiple focal lengths. By the division of the microlens into two concentric radial zones including the inner zone and the outer zone with independent radius, the sub-eye which is a multi-level micro-scale structure can be formed with multiple focal lengths. The imaging capability of the structure has been simulated. The results show that the optical information in different depths can be acquired by the structure. Meanwhile, the parameters including aperture and radius of the two zones, which have an influence on the imaging quality have been analyzed and discussed. With the increasing of the ratio of inner and outer aperture, the imaging quality of the inner zone is becoming better, and instead the outer zone will become worse. In addition, through controlling the radius of the inner and outer zone independently, the design of sub-eye with different focal lengths can be realized. With the difference between the radius of the inner and outer zone becoming larger, the imaging resolution of the sub-eye will decrease. Therefore, the optimization of the multifocal structure should be carried out according to the actual imaging quality demands. Meanwhile, this study can provide references for the further applications of multifocal microlens in bionic compound eye.

  10. A pneumatic Bionic Voice prosthesis—Pre-clinical trials of controlling the voice onset and offset

    PubMed Central

    Noorian, Farzad; Novakovic, Daniel; van Schaik, André

    2018-01-01

    Despite emergent progress in many fields of bionics, a functional Bionic Voice prosthesis for laryngectomy patients (larynx amputees) has not yet been achieved, leading to a lifetime of vocal disability for these patients. This study introduces a novel framework of Pneumatic Bionic Voice Prostheses as an electronic adaptation of the Pneumatic Artificial Larynx (PAL) device. The PAL is a non-invasive mechanical voice source, driven exclusively by respiration with an exceptionally high voice quality, comparable to the existing gold standard of Tracheoesophageal (TE) voice prosthesis. Following PAL design closely as the reference, Pneumatic Bionic Voice Prostheses seem to have a strong potential to substitute the existing gold standard by generating a similar voice quality while remaining non-invasive and non-surgical. This paper designs the first Pneumatic Bionic Voice prosthesis and evaluates its onset and offset control against the PAL device through pre-clinical trials on one laryngectomy patient. The evaluation on a database of more than five hours of continuous/isolated speech recordings shows a close match between the onset/offset control of the Pneumatic Bionic Voice and the PAL with an accuracy of 98.45 ±0.54%. When implemented in real-time, the Pneumatic Bionic Voice prosthesis controller has an average onset/offset delay of 10 milliseconds compared to the PAL. Hence it addresses a major disadvantage of previous electronic voice prostheses, including myoelectric Bionic Voice, in meeting the short time-frames of controlling the onset/offset of the voice in continuous speech. PMID:29466455

  11. Study on the Mechanical Properties of Bionic Coupling Layered B4C/5083Al Composite Materials

    PubMed Central

    Zhao, Qian; Liang, Yunhong; Liu, Qingping; Zhang, Zhihui; Yu, Zhenglei; Ren, Luquan

    2018-01-01

    Based on microstructure characteristics of Meretrix lusoria shell and Rapana venosa shell, bionic coupling layered B4C/5083Al composites with different layered structures and hard/soft combination models were fabricated via hot pressed sintering. The simplified bionic coupling models with hard and soft layers were similar to layered structure and hardness tendency of shells, guiding the bionic design and fabrication. B4C/5083Al composites with various B4C contents and pure 5083Al were treated as hard and soft layers, respectively. Hot pressed sintering maintained the designed bionic structure and enhanced high bonding strength between ceramics and matrix. Compared with B4C/5083Al composites, bionic layered composites exhibited high mechanical properties including flexural strength, fracture toughness, compressive strength and impact toughness. The hard layers absorbed applied loads in the form of intergranular fracture. Besides connection role, soft layers restrained slabbing phenomenon and reset extension direction of cracks among layers. The coupling functions of bionic composites proved the feasibility and practicability of bionic fabrication, providing a new method for improvement of ceramic/Al composite with properties of being lightweight and high mechanical strength. PMID:29701707

  12. Bionic Design of Wind Turbine Blade Based on Long-Eared Owl's Airfoil

    PubMed Central

    Li, Ming

    2017-01-01

    The main purpose of this paper is to demonstrate a bionic design for the airfoil of wind turbines inspired by the morphology of Long-eared Owl's wings. Glauert Model was adopted to design the standard blade and the bionic blade, respectively. Numerical analysis method was utilized to study the aerodynamic characteristics of the airfoils as well as the blades. Results show that the bionic airfoil inspired by the airfoil at the 50% aspect ratio of the Long-eared Owl's wing gives rise to a superior lift coefficient and stalling performance and thus can be beneficial to improving the performance of the wind turbine blade. Also, the efficiency of the bionic blade in wind turbine blades tests increases by 12% or above (up to 44%) compared to that of the standard blade. The reason lies in the bigger pressure difference between the upper and lower surface which can provide stronger lift. PMID:28243053

  13. 3D Printed Bionic Nanodevices.

    PubMed

    Kong, Yong Lin; Gupta, Maneesh K; Johnson, Blake N; McAlpine, Michael C

    2016-06-01

    The ability to three-dimensionally interweave biological and functional materials could enable the creation of bionic devices possessing unique and compelling geometries, properties, and functionalities. Indeed, interfacing high performance active devices with biology could impact a variety of fields, including regenerative bioelectronic medicines, smart prosthetics, medical robotics, and human-machine interfaces. Biology, from the molecular scale of DNA and proteins, to the macroscopic scale of tissues and organs, is three-dimensional, often soft and stretchable, and temperature sensitive. This renders most biological platforms incompatible with the fabrication and materials processing methods that have been developed and optimized for functional electronics, which are typically planar, rigid and brittle. A number of strategies have been developed to overcome these dichotomies. One particularly novel approach is the use of extrusion-based multi-material 3D printing, which is an additive manufacturing technology that offers a freeform fabrication strategy. This approach addresses the dichotomies presented above by (1) using 3D printing and imaging for customized, hierarchical, and interwoven device architectures; (2) employing nanotechnology as an enabling route for introducing high performance materials, with the potential for exhibiting properties not found in the bulk; and (3) 3D printing a range of soft and nanoscale materials to enable the integration of a diverse palette of high quality functional nanomaterials with biology. Further, 3D printing is a multi-scale platform, allowing for the incorporation of functional nanoscale inks, the printing of microscale features, and ultimately the creation of macroscale devices. This blending of 3D printing, novel nanomaterial properties, and 'living' platforms may enable next-generation bionic systems. In this review, we highlight this synergistic integration of the unique properties of nanomaterials with the

  14. 3D Printed Bionic Nanodevices

    PubMed Central

    Kong, Yong Lin; Gupta, Maneesh K.; Johnson, Blake N.; McAlpine, Michael C.

    2016-01-01

    Summary The ability to three-dimensionally interweave biological and functional materials could enable the creation of bionic devices possessing unique and compelling geometries, properties, and functionalities. Indeed, interfacing high performance active devices with biology could impact a variety of fields, including regenerative bioelectronic medicines, smart prosthetics, medical robotics, and human-machine interfaces. Biology, from the molecular scale of DNA and proteins, to the macroscopic scale of tissues and organs, is three-dimensional, often soft and stretchable, and temperature sensitive. This renders most biological platforms incompatible with the fabrication and materials processing methods that have been developed and optimized for functional electronics, which are typically planar, rigid and brittle. A number of strategies have been developed to overcome these dichotomies. One particularly novel approach is the use of extrusion-based multi-material 3D printing, which is an additive manufacturing technology that offers a freeform fabrication strategy. This approach addresses the dichotomies presented above by (1) using 3D printing and imaging for customized, hierarchical, and interwoven device architectures; (2) employing nanotechnology as an enabling route for introducing high performance materials, with the potential for exhibiting properties not found in the bulk; and (3) 3D printing a range of soft and nanoscale materials to enable the integration of a diverse palette of high quality functional nanomaterials with biology. Further, 3D printing is a multi-scale platform, allowing for the incorporation of functional nanoscale inks, the printing of microscale features, and ultimately the creation of macroscale devices. This blending of 3D printing, novel nanomaterial properties, and ‘living’ platforms may enable next-generation bionic systems. In this review, we highlight this synergistic integration of the unique properties of nanomaterials with

  15. 3D Printed Bionic Ears

    PubMed Central

    Mannoor, Manu S.; Jiang, Ziwen; James, Teena; Kong, Yong Lin; Malatesta, Karen A.; Soboyejo, Winston O.; Verma, Naveen; Gracias, David H.; McAlpine, Michael C.

    2013-01-01

    The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the precise anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing. PMID:23635097

  16. 3D printed bionic ears.

    PubMed

    Mannoor, Manu S; Jiang, Ziwen; James, Teena; Kong, Yong Lin; Malatesta, Karen A; Soboyejo, Winston O; Verma, Naveen; Gracias, David H; McAlpine, Michael C

    2013-06-12

    The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing.

  17. Application of Bionic Design to FRP T-Joints

    NASA Astrophysics Data System (ADS)

    Luo, Guang-Min; Kuo, Chia-Hung

    2017-09-01

    We applied the concepts of bionics to enhance the mechanical strength of fiberglass reinforced plastic T-joints. The failure modes of the designed arthrosis-like and gum-like joints were determined using three-point bending tests and numerical simulations and compared with those of normal T-joints bonded using structural adhesives. In the simulation, we used cohesive elements to simulate the adhesive interface of the structural adhesive. The experimental and simulation results show that the arthrosis-like joint can effectively delay the failure progress and enhance the bonding strength of T-joints, thus confirming that an appropriate bionic design can effectively control the bonding properties of structural adhesives.

  18. Drag reduction through self-texturing compliant bionic materials

    PubMed Central

    Liu, Eryong; Li, Longyang; Wang, Gang; Zeng, Zhixiang; Zhao, Wenjie; Xue, Qunji

    2017-01-01

    Compliant fish skin is effectively in reducing drag, thus the design and application of compliant bionic materials may be a good choice for drag reduction. Here we consider the drag reduction of compliant bionic materials. First, ZnO and PDMS mesh modified with n-octadecane were prepared, the drag reduction of self-texturing compliant n-octadecane were studied. The results show that the mesh modified by ZnO and PDMS possess excellent lipophilic and hydrophobic, thus n-octadecane at solid, semisolid and liquid state all have good adhesion with modified mesh. The states of n-octadecane changed with temperature, thus, the surface contact angle and adhesive force all varies obviously at different state. The contact angle decreases with temperature, the adhesive force shows a lower value at semisolid state. Furthermore, the drag testing results show that the compliant n-octadecane film is more effectively in drag reduction than superhydrophobic ZnO/PDMS film, indicating that the drag reduction mechanism of n-octadecane is significantly different with superhydrophobic film. Further research shows that the water flow leads to self-texturing of semisolid state n-octadecane, which is similar with compliant fish skin. Therefore, the compliant bionic materials of semisolid state n-octadecane with regular bulge plays a major role in the drag reduction. PMID:28053309

  19. Drag reduction through self-texturing compliant bionic materials.

    PubMed

    Liu, Eryong; Li, Longyang; Wang, Gang; Zeng, Zhixiang; Zhao, Wenjie; Xue, Qunji

    2017-01-05

    Compliant fish skin is effectively in reducing drag, thus the design and application of compliant bionic materials may be a good choice for drag reduction. Here we consider the drag reduction of compliant bionic materials. First, ZnO and PDMS mesh modified with n-octadecane were prepared, the drag reduction of self-texturing compliant n-octadecane were studied. The results show that the mesh modified by ZnO and PDMS possess excellent lipophilic and hydrophobic, thus n-octadecane at solid, semisolid and liquid state all have good adhesion with modified mesh. The states of n-octadecane changed with temperature, thus, the surface contact angle and adhesive force all varies obviously at different state. The contact angle decreases with temperature, the adhesive force shows a lower value at semisolid state. Furthermore, the drag testing results show that the compliant n-octadecane film is more effectively in drag reduction than superhydrophobic ZnO/PDMS film, indicating that the drag reduction mechanism of n-octadecane is significantly different with superhydrophobic film. Further research shows that the water flow leads to self-texturing of semisolid state n-octadecane, which is similar with compliant fish skin. Therefore, the compliant bionic materials of semisolid state n-octadecane with regular bulge plays a major role in the drag reduction.

  20. Drag reduction through self-texturing compliant bionic materials

    NASA Astrophysics Data System (ADS)

    Liu, Eryong; Li, Longyang; Wang, Gang; Zeng, Zhixiang; Zhao, Wenjie; Xue, Qunji

    2017-01-01

    Compliant fish skin is effectively in reducing drag, thus the design and application of compliant bionic materials may be a good choice for drag reduction. Here we consider the drag reduction of compliant bionic materials. First, ZnO and PDMS mesh modified with n-octadecane were prepared, the drag reduction of self-texturing compliant n-octadecane were studied. The results show that the mesh modified by ZnO and PDMS possess excellent lipophilic and hydrophobic, thus n-octadecane at solid, semisolid and liquid state all have good adhesion with modified mesh. The states of n-octadecane changed with temperature, thus, the surface contact angle and adhesive force all varies obviously at different state. The contact angle decreases with temperature, the adhesive force shows a lower value at semisolid state. Furthermore, the drag testing results show that the compliant n-octadecane film is more effectively in drag reduction than superhydrophobic ZnO/PDMS film, indicating that the drag reduction mechanism of n-octadecane is significantly different with superhydrophobic film. Further research shows that the water flow leads to self-texturing of semisolid state n-octadecane, which is similar with compliant fish skin. Therefore, the compliant bionic materials of semisolid state n-octadecane with regular bulge plays a major role in the drag reduction.

  1. Simulated effect on the compressive and shear mechanical properties of bionic integrated honeycomb plates.

    PubMed

    He, Chenglin; Chen, Jinxiang; Wu, Zhishen; Xie, Juan; Zu, Qiao; Lu, Yun

    2015-05-01

    Honeycomb plates can be applied in many fields, including furniture manufacturing, mechanical engineering, civil engineering, transportation and aerospace. In the present study, we discuss the simulated effect on the mechanical properties of bionic integrated honeycomb plates by investigating the compressive and shear failure modes and the mechanical properties of trabeculae reinforced by long or short fibers. The results indicate that the simulated effect represents approximately 80% and 70% of the compressive and shear strengths, respectively. Compared with existing bionic samples, the mass-specific strength was significantly improved. Therefore, this integrated honeycomb technology remains the most effective method for the trial manufacturing of bionic integrated honeycomb plates. The simulated effect of the compressive rigidity is approximately 85%. The short-fiber trabeculae have an advantage over the long-fiber trabeculae in terms of shear rigidity, which provides new evidence for the application of integrated bionic honeycomb plates. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. [Design and Preparation of Plant Bionic Materials Based on Optical and Infrared Features Simulation].

    PubMed

    Jiang, Xiao-jun; Lu, Xu-liang; Pan, Jia-liang; Zhang, Shuan-qin

    2015-07-01

    Due to the life characteristics such as physiological structure and transpiration, plants have unique optical and infrared features. In the optical band, because of the common effects of chlorophyll and water, plant leafs show spectral reflectance characteristics change in 550, 680, 1400 and 1900 nm significantly. In the infrared wave band, driven by transpiration, plants could regulate temperature on their own initiative, which make the infrared characteristics of plants different from artificial materials. So palnt bionic materials were proposed to simulate optical and infrared characteristics of plants. By analyzing formation mechanism of optical and infrared features about green plants, the component design and heat-transfer process of plants bionic materials were studied, above these the heat-transfer control formulation was established. Based on water adsorption/release compound, optical pigments and other man-made materials, plant bionic materials preparation methods were designed which could simulate the optical and infrared features of green plants. By chemical casting methods plant bionic material films were prepared, which use polyvinyl alcohol as film forming and water adsorption/release compound, and use optical pigments like chrome green and macromolecule yellow as colouring materials. The research conclusions achieved by testings figured out: water adsorption/release testing showed that the plant bionic materials with a certain thickness could absorb 1.3 kg water per square meter, which could satisfy the water usage of transpiration simulation one day; the optical and infrared simulated effect tests indicated that the plant bionic materials could preferably simulate the spectral reflective performance of green plants in optical wave band (380-2500 nm, expecially in 1400 and 1900 nm which were water absorption wave band of plants), and also it had similar daily infrared radiation variations with green plants, daily average radiation temperature

  3. Bio-Tribology Properties of Bionic Carp Scale Morphology on Ti6A14V Surface

    NASA Astrophysics Data System (ADS)

    Wang, W.; Y Wei, X.; Meng, K.; Zhong, L. H.; Wang, Y.; Yu, X. H.

    2017-12-01

    In order to improve the bio-tribology properties of Ti6A14V surface, the bionic carp scale appearance pattern on Ti6A14V surface was prepared by laser surface texturing technology. The ball-disc reciprocating linear tribological experiment under different lubricants with dry friction was carried out by MRTR multifunction friction and wear testing machine using ZrO2/Ti6A14V as friction pair. The wear scar morphology of the sample surface was observed by SEM. The results show that for dry friction, the friction factor of the bionic carp scale morphology Ti6A14V reduces by 0.23 than those without bionic carp scale morphology, a decline of 45%. Under different lubrication conditions, the friction factors of samples with the bionic carp scale are increased in varying degrees with the increase of size of bionic texturing. The friction factor with same specimen under different lubrication conditions according to the ascending order are 0.5g/dl of sodium hyaluronate +0.5g/dl-γglobulin and 0.5g/dl mixed aqueous solution of sodium hyaluronate solution and artificial saliva. The wear volume also showed a similar variation.

  4. [Theory and practice of bionic cultivation of traditional Chinese medicine].

    PubMed

    Liu, Dahui; Huang, Luqi; Guo, Lanping; Shao, Aijuan; Chen, Meilan

    2009-03-01

    The bionic cultivation of medicinal plant is an ecological cultivation pattern, which is adopting ecological engineering and modern agricultural techniques to simulate the natural ecosystem of wild medicinal plant community, and has been given greater attention on the agriculture of traditional Chinese medicine (TCM). It is also the cross subject that combines Chinese traditional medicine, agronomy, horticulture, ecology, agricultural engineering and management. Moreover, it has significant technology advantages of promoting the sustainable utilization of medicinal plant resources, improving the ecological environment and harmonizing man and nature. So it's important to develop the bionic cultivation of TCM.

  5. Experimental Study of Reciprocating Friction between Rape Stalk and Bionic Nonsmooth Surface Units

    PubMed Central

    Ma, Zheng; Li, Yaoming; Xu, Lizhang

    2015-01-01

    Background. China is the largest producer of rape oilseed in the world; however, the mechanization level of rape harvest is relatively low, because rape materials easily adhere to the cleaning screens of combine harvesters, resulting in significant cleaning losses. Previous studies have shown that bionic nonsmooth surface cleaning screens restrain the adhesion of rape materials, but the underlying mechanisms remain unclear. Objective. The reciprocating friction between rape stalk and bionic nonsmooth metal surface was examined. Methods. The short-time Fourier transform method was used to discriminate the stable phase of friction signals and the stick-lag distance was defined to analyze the stable reciprocating friction in a phase diagram. Results. The reciprocating friction between rape stalk and metal surface is a typical stick-slip friction, and the bionic nonsmooth metal surfaces with concave or convex units reduced friction force with increasing reciprocating frequency. The results also showed that the stick-lag distance of convex surface increased with reciprocating frequency, which indicated that convex surface reduces friction force more efficiently. Conclusions. We suggest that bionic nonsmooth surface cleaning screens, especially with convex units, restrain the adhesion of rape materials more efficiently compared to the smooth surface cleaning screens. PMID:27034611

  6. Bionic ankle–foot prosthesis normalizes walking gait for persons with leg amputation

    PubMed Central

    Herr, Hugh M.; Grabowski, Alena M.

    2012-01-01

    Over time, leg prostheses have improved in design, but have been incapable of actively adapting to different walking velocities in a manner comparable to a biological limb. People with a leg amputation using such commercially available passive-elastic prostheses require significantly more metabolic energy to walk at the same velocities, prefer to walk slower and have abnormal biomechanics compared with non-amputees. A bionic prosthesis has been developed that emulates the function of a biological ankle during level-ground walking, specifically providing the net positive work required for a range of walking velocities. We compared metabolic energy costs, preferred velocities and biomechanical patterns of seven people with a unilateral transtibial amputation using the bionic prosthesis and using their own passive-elastic prosthesis to those of seven non-amputees during level-ground walking. Compared with using a passive-elastic prosthesis, using the bionic prosthesis decreased metabolic cost by 8 per cent, increased trailing prosthetic leg mechanical work by 57 per cent and decreased the leading biological leg mechanical work by 10 per cent, on average, across walking velocities of 0.75–1.75 m s−1 and increased preferred walking velocity by 23 per cent. Using the bionic prosthesis resulted in metabolic energy costs, preferred walking velocities and biomechanical patterns that were not significantly different from people without an amputation. PMID:21752817

  7. Effect of bionic coupling units' forms on wear resistance of gray cast iron under dry linear reciprocating sliding condition

    NASA Astrophysics Data System (ADS)

    Pang, Zuobo; Zhou, Hong; Xie, Guofeng; Cong, Dalong; Meng, Chao; Ren, Luquan

    2015-07-01

    In order to get close to the wear form of guide rails, the homemade linear reciprocating wear testing machine was used for the wear test. In order to improve the wear-resistance of gray cast iron guide rail, bionic coupling units of different forms were manufactured by a laser. Wear behavior of gray-cast-iron with bionic-coupling units has been studied under dry sliding condition at room temperature using the wear testing machine. The wear resistance was evaluated by means of weight loss measurement and wear morphology. The results indicated that bionic coupling unit could improve the wear resistance of gray cast iron. The wear resistance of gray cast iron with reticulation bionic coupling unit is the best. When the load and speed changed, reticulation bionic coupling unit still has excellent performance in improving the wear resistance of gray cast iron.

  8. Innovative Design and Performance Evaluation of Bionic Imprinting Toothed Wheel

    PubMed Central

    Wang, Xiaoyang; Tong, Jin; Stephen, Carr

    2018-01-01

    A highly efficient soil-burrowing dung beetle possesses an intricate outer contour curve on its foreleg end-tooth. This study was carried out based on evidence that this special outer contour curve has the potential of reducing soil penetration resistance and could enhance soil-burrowing efficiency. A toothed wheel is a typical agricultural implement for soil imprinting, to increase its working efficiency; the approach of the bionic geometrical structure was utilized to optimize the innovative shape of imprinting toothed wheel. Characteristics in the dung beetle's foreleg end-tooth were extracted and studied by the edge detection technique. Then, this special outer contour curve was modeled by a nine-order polynomial function and used for the innovative design of imprinting the tooth's cutting edge. Both the conventional and bionic teeth were manufactured, and traction tests in a soil bin were conducted. Taking required draft force and volume of imprinted microbasin as the evaluating indexes, operating efficiency and quality of different toothed wheels were compared and investigated. Results indicate that compared with the conventional toothed wheel, a bionic toothed wheel possesses a better forward resistance reduction property against soil and, meanwhile, can enhance the quality of soil imprinting by increasing the volume of the created micro-basin. PMID:29515651

  9. Innovative Design and Performance Evaluation of Bionic Imprinting Toothed Wheel.

    PubMed

    Zhang, Zhihong; Wang, Xiaoyang; Tong, Jin; Stephen, Carr

    2018-01-01

    A highly efficient soil-burrowing dung beetle possesses an intricate outer contour curve on its foreleg end-tooth. This study was carried out based on evidence that this special outer contour curve has the potential of reducing soil penetration resistance and could enhance soil-burrowing efficiency. A toothed wheel is a typical agricultural implement for soil imprinting, to increase its working efficiency; the approach of the bionic geometrical structure was utilized to optimize the innovative shape of imprinting toothed wheel. Characteristics in the dung beetle's foreleg end-tooth were extracted and studied by the edge detection technique. Then, this special outer contour curve was modeled by a nine-order polynomial function and used for the innovative design of imprinting the tooth's cutting edge. Both the conventional and bionic teeth were manufactured, and traction tests in a soil bin were conducted. Taking required draft force and volume of imprinted microbasin as the evaluating indexes, operating efficiency and quality of different toothed wheels were compared and investigated. Results indicate that compared with the conventional toothed wheel, a bionic toothed wheel possesses a better forward resistance reduction property against soil and, meanwhile, can enhance the quality of soil imprinting by increasing the volume of the created micro-basin.

  10. Design and Analysis of Bionic Cutting Blades Using Finite Element Method.

    PubMed

    Li, Mo; Yang, Yuwang; Guo, Li; Chen, Donghui; Sun, Hongliang; Tong, Jin

    2015-01-01

    Praying mantis is one of the most efficient predators in insect world, which has a pair of powerful tools, two sharp and strong forelegs. Its femur and tibia are both armed with a double row of strong spines along their posterior edges which can firmly grasp the prey, when the femur and tibia fold on each other in capturing. These spines are so sharp that they can easily and quickly cut into the prey. The geometrical characteristic of the praying mantis's foreleg, especially its tibia, has important reference value for the design of agricultural soil-cutting tools. Learning from the profile and arrangement of these spines, cutting blades with tooth profile were designed in this work. Two different sizes of tooth structure and arrangement were utilized in the design on the cutting edge. A conventional smooth-edge blade was used to compare with the bionic serrate-edge blades. To compare the working efficiency of conventional blade and bionic blades, 3D finite element simulation analysis and experimental measurement were operated in present work. Both the simulation and experimental results indicated that the bionic serrate-edge blades showed better performance in cutting efficiency.

  11. Design and Analysis of Bionic Cutting Blades Using Finite Element Method

    PubMed Central

    Li, Mo; Yang, Yuwang; Guo, Li; Chen, Donghui; Sun, Hongliang; Tong, Jin

    2015-01-01

    Praying mantis is one of the most efficient predators in insect world, which has a pair of powerful tools, two sharp and strong forelegs. Its femur and tibia are both armed with a double row of strong spines along their posterior edges which can firmly grasp the prey, when the femur and tibia fold on each other in capturing. These spines are so sharp that they can easily and quickly cut into the prey. The geometrical characteristic of the praying mantis's foreleg, especially its tibia, has important reference value for the design of agricultural soil-cutting tools. Learning from the profile and arrangement of these spines, cutting blades with tooth profile were designed in this work. Two different sizes of tooth structure and arrangement were utilized in the design on the cutting edge. A conventional smooth-edge blade was used to compare with the bionic serrate-edge blades. To compare the working efficiency of conventional blade and bionic blades, 3D finite element simulation analysis and experimental measurement were operated in present work. Both the simulation and experimental results indicated that the bionic serrate-edge blades showed better performance in cutting efficiency. PMID:27019583

  12. The Vienna psychosocial assessment procedure for bionic reconstruction in patients with global brachial plexus injuries.

    PubMed

    Hruby, Laura Antonia; Pittermann, Anna; Sturma, Agnes; Aszmann, Oskar Christian

    2018-01-01

    Global brachial plexopathies cause major sensory and motor deficits in the affected arm and hand. Many patients report of psychosocial consequences including chronic pain, decreased self-sufficiency, and poor body image. Bionic reconstruction, which includes the amputation and prosthetic replacement of the functionless limb, has been shown to restore hand function in patients where classic reconstructions have failed. Patient selection and psychological evaluation before such a life-changing procedure are crucial for optimal functional outcomes. In this paper we describe a psychosocial assessment procedure for bionic reconstruction in patients with complete brachial plexopathies and present psychosocial outcome variables associated with bionic reconstruction. Between 2013 and 2017 psychosocial assessments were performed in eight patients with global brachial plexopathies. We conducted semi-structured interviews exploring the psychosocial adjustment related to the accident, the overall psychosocial status, as well as motivational aspects related to an anticipated amputation and expectations of functional prosthetic outcome. During the interview patients were asked to respond freely. Their answers were transcribed verbatim by the interviewer and analyzed afterwards on the basis of a pre-defined item scoring system. The interview was augmented by quantitative evaluation of self-reported mental health and social functioning (SF-36 Health Survey), body image (FKB-20) and deafferentation pain (VAS). Additionally, psychosocial outcome variables were presented for seven patients before and after bionic reconstruction. Qualitative data revealed several psychological stressors with long-term negative effects on patients with complete brachial plexopathies. 88% of patients felt functionally limited to a great extent due to their disability, and all of them reported constant, debilitating pain in the deafferented hand. After bionic reconstruction the physical component summary

  13. Study on the Impact Resistance of Bionic Layered Composite of TiC-TiB2/Al from Al-Ti-B4C System

    PubMed Central

    Zhao, Qian; Liang, Yunhong; Zhang, Zhihui; Li, Xiujuan; Ren, Luquan

    2016-01-01

    Mechanical property and impact resistance mechanism of bionic layered composite was investigated. Due to light weight and high strength property, white clam shell was chosen as bionic model for design of bionic layered composite. The intercoupling model between hard layer and soft layer was identical to the layered microstructure and hardness tendency of the white clam shell, which connected the bionic design and fabrication. TiC-TiB2 reinforced Al matrix composites fabricated from Al-Ti-B4C system with 40 wt. %, 50 wt. % and 30 wt. % Al contents were treated as an outer layer, middle layer and inner layer in hard layers. Pure Al matrix was regarded as a soft layer. Compared with traditional homogenous Al-Ti-B4C composite, bionic layered composite exhibited high mechanical properties including flexural strength, fracture toughness, compressive strength and impact toughness. The intercoupling effect of layered structure and combination model of hard and soft played a key role in high impact resistance of the bionic layered composite, proving the feasibility and practicability of the bionic model of a white clam shell. PMID:28773827

  14. Cardiac tissue engineering: from matrix design to the engineering of bionic hearts.

    PubMed

    Fleischer, Sharon; Feiner, Ron; Dvir, Tal

    2017-04-01

    The field of cardiac tissue engineering aims at replacing the scar tissue created after a patient has suffered from a myocardial infarction. Various technologies have been developed toward fabricating a functional engineered tissue that closely resembles that of the native heart. While the field continues to grow and techniques for better tissue fabrication continue to emerge, several hurdles still remain to be overcome. In this review we will focus on several key advances and recent technologies developed in the field, including biomimicking the natural extracellular matrix structure and enhancing the transfer of the electrical signal. We will also discuss recent developments in the engineering of bionic cardiac tissues which integrate the fields of tissue engineering and electronics to monitor and control tissue performance.

  15. The Vienna psychosocial assessment procedure for bionic reconstruction in patients with global brachial plexus injuries

    PubMed Central

    Sturma, Agnes

    2018-01-01

    Background Global brachial plexopathies cause major sensory and motor deficits in the affected arm and hand. Many patients report of psychosocial consequences including chronic pain, decreased self-sufficiency, and poor body image. Bionic reconstruction, which includes the amputation and prosthetic replacement of the functionless limb, has been shown to restore hand function in patients where classic reconstructions have failed. Patient selection and psychological evaluation before such a life-changing procedure are crucial for optimal functional outcomes. In this paper we describe a psychosocial assessment procedure for bionic reconstruction in patients with complete brachial plexopathies and present psychosocial outcome variables associated with bionic reconstruction. Methods Between 2013 and 2017 psychosocial assessments were performed in eight patients with global brachial plexopathies. We conducted semi-structured interviews exploring the psychosocial adjustment related to the accident, the overall psychosocial status, as well as motivational aspects related to an anticipated amputation and expectations of functional prosthetic outcome. During the interview patients were asked to respond freely. Their answers were transcribed verbatim by the interviewer and analyzed afterwards on the basis of a pre-defined item scoring system. The interview was augmented by quantitative evaluation of self-reported mental health and social functioning (SF-36 Health Survey), body image (FKB-20) and deafferentation pain (VAS). Additionally, psychosocial outcome variables were presented for seven patients before and after bionic reconstruction. Results Qualitative data revealed several psychological stressors with long-term negative effects on patients with complete brachial plexopathies. 88% of patients felt functionally limited to a great extent due to their disability, and all of them reported constant, debilitating pain in the deafferented hand. After bionic reconstruction the

  16. Bionic Manufacturing: Towards Cyborg Cells and Sentient Microbots.

    PubMed

    Srivastava, Sarvesh Kumar; Yadav, Vikramaditya G

    2018-05-01

    Bio-inspired engineering applies biological design principles towards developing engineering solutions but is not practical as a manufacturing paradigm. We advocate 'bionic manufacturing', a synergistic fusion of biotic and abiotic components, to transition away from bio-inspiration toward bio-augmentation to address current limitations in bio-inspired manufacturing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Graphite Oxide to Graphene. Biomaterials to Bionics.

    PubMed

    Thompson, Brianna C; Murray, Eoin; Wallace, Gordon G

    2015-12-09

    The advent of implantable biomaterials has revolutionized medical treatment, allowing the development of the fields of tissue engineering and medical bionic devices (e.g., cochlea implants to restore hearing, vagus nerve stimulators to control Parkinson's disease, and cardiac pace makers). Similarly, future materials developments are likely to continue to drive development in treatment of disease and disability, or even enhancing human potential. The material requirements for implantable devices are stringent. In all cases they must be nontoxic and provide appropriate mechanical integrity for the application at hand. In the case of scaffolds for tissue regeneration, biodegradability in an appropriate time frame may be required, and for medical bionics electronic conductivity is essential. The emergence of graphene and graphene-family composites has resulted in materials and structures highly relevant to the expansion of the biomaterials inventory available for implantable medical devices. The rich chemistries available are able to ensure properties uncovered in the nanodomain are conveyed into the world of macroscopic devices. Here, the inherent properties of graphene, along with how graphene or structures containing it interface with living cells and the effect of electrical stimulation on nerves and cells, are reviewed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Three-dimensional polylactic acid@graphene oxide/chitosan sponge bionic filter: Highly efficient adsorption of crystal violet dye.

    PubMed

    Zhou, G; Wang, K P; Liu, H W; Wang, L; Xiao, X F; Dou, D D; Fan, Y B

    2018-07-01

    Owing to low bearing capacity and efficiency, traditional filters or adsorbents for removal of contaminants like crystal violet (CV) dye required frequent replacement. Besides, the combination of three-dimensional (3D) printing and bionics could break the constraints of traditional configuration. In this study, a novel depth-type hybrid polylactic acid (PLA)@graphene oxide (GO)/chitosan (CS) sponge filter with bionic fish-mouth structure was prepared and fabricated, assisted by 3D printing and double freeze-drying technology, according to the theories of vertical cross-step filtration and swirling flow. And GO/CS sponge and its filtering device were characterized by FITR, SEM, water adsorption and so on. Moreover, it was explained that the impact factors on dye removal mechanism, like GO content (or CS content), contact time, pH, temperature and bionic configuration. As a result, the bionic 3D filtering device demonstrated excellent removal efficiency (97.8±0.5% for CV) and GO/CS sponge exhibited higher strength (74.5±3.5MPa) at the condition of GO content of 9wt%, contact time of 46min, pH of 8 and 35°C, respectively. Therefore, the resulting 3D PLA@GO/CS sponge bionic filter via gravity and vortex driving provided new alternatives for effectively dye-water separation, and it showed great promise for application of biological macromolecules in adsorption. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Effects of setting angle and chord length on performance of four blades bionic wind turbine

    NASA Astrophysics Data System (ADS)

    Yang, Z. X.; Li, G. S.; Song, L.; Bai, Y. F.

    2017-11-01

    With the energy crisis and the increasing environmental pollution, more and more efforts have been made about wind power development. In this paper, a four blades bionic wind turbine was proposed, and the outline of wind turbine was constructed by the fitted curve. This paper attempted to research the effects of setting angle and chord length on performance of four blades bionic wind turbine by computational fluid dynamics (CFD) simulation. The results showed that the setting angle and chord length of the bionic wind turbine has some significant effects on the efficiency of the wind turbine, and within the range of wind speed from 7 m/s to 15 m/s, the wind turbine achieved maximum efficiency when the setting angle is 31 degree and the chord length is 125 mm. The conclusion will work as a guideline for the improvement of wind turbine design

  20. [The bionic hand].

    PubMed

    Surke, Carsten; Ducommun Dit Boudry, Pascal; Vögelin, Esther

    2015-08-01

    The loss of the upper extremity implicates a grave insult in the life of the involved person. To compensate for the loss of function different powered prosthetic devices are available. Ever since their first development 70 years ago numerous improvements in terms of size, weight and wearing comfort have been developed, but issues regarding the control of upper extremity prostheses remain. Slow grasping speed, limited grip positions and especially failure to provide a sensory feedback limit the acceptance in patients. Recent developments are aimed to allow a more intuitive control of the prosthetic device and to provide a sensory feedback to the amputee. Targeted reinnervation reassignes existing muscles to different peripheral nerves thereby enabling them to fulfill alternate functions. Implanting electrodes into muscle bellies of the forearm allows a more accurate control of the prosthesis. Promising results are being achieved by implanting nerve electrodes by establishing bilateral communication between patient and prosthesis. The following review summarizes the current developments of bionic prostheses in the upper extremity.

  1. Engineering derivatives from biological systems for advanced aerospace applications

    NASA Technical Reports Server (NTRS)

    Winfield, Daniel L.; Hering, Dean H.; Cole, David

    1991-01-01

    The present study consisted of a literature survey, a survey of researchers, and a workshop on bionics. These tasks produced an extensive annotated bibliography of bionics research (282 citations), a directory of bionics researchers, and a workshop report on specific bionics research topics applicable to space technology. These deliverables are included as Appendix A, Appendix B, and Section 5.0, respectively. To provide organization to this highly interdisciplinary field and to serve as a guide for interested researchers, we have also prepared a taxonomy or classification of the various subelements of natural engineering systems. Finally, we have synthesized the results of the various components of this study into a discussion of the most promising opportunities for accelerated research, seeking solutions which apply engineering principles from natural systems to advanced aerospace problems. A discussion of opportunities within the areas of materials, structures, sensors, information processing, robotics, autonomous systems, life support systems, and aeronautics is given. Following the conclusions are six discipline summaries that highlight the potential benefits of research in these areas for NASA's space technology programs.

  2. Research on the Bionics Design of Automobile Styling Based on the Form Gene

    NASA Astrophysics Data System (ADS)

    Aili, Zhao; Long, Jiang

    2017-09-01

    From the heritage of form gene point of view, this thesis has analyzed the gene make-up, cultural inheritance and aesthetic features in the evolution and development of forms of brand automobiles and proposed the bionic design concept and methods in the automobile styling design. And this innovative method must be based on the form gene, and the consistency and combination of form element must be maintained during the design. Taking the design of Maserati as an example, the thesis will show you the design method and philosophy in the aspects of form gene expression and bionic design innovation for the future automobile styling.

  3. BIOCONAID System (Bionic Control of Acceleration Induced Dimming). Final Report.

    ERIC Educational Resources Information Center

    Rogers, Dana B.; And Others

    The system described represents a new technique for enhancing the fidelity of flight simulators during high acceleration maneuvers. This technique forces the simulator pilot into active participation and energy expenditure similar to the aircraft pilot undergoing actual accelerations. The Bionic Control of Acceleration Induced Dimming (BIOCONAID)…

  4. Effects of setting angle on performance of fish-bionic wind wheel

    NASA Astrophysics Data System (ADS)

    Li, G. S.; Yang, Z. X.; Song, L.; Chen, Q.; Li, Y. B.; Chen, W.

    2016-08-01

    With the energy crisis and the increasing environmental pollutionmore and more efforts have been made about wind power development. In this paper, a new type of vertical axis named the fish-bionic wind wheel was proposed, and the outline of wind wheel was constructed by curve of Fourier fitting and polynomial equations. This paper attempted to research the relationship between the setting angle and the wind turbine characteristics by computational fluid dynamics (CFD) simulation. The results showed that the setting angle of the fish-bionic wind wheel has some significant effects on the efficiency of the wind turbine, Within the range of wind speed from 13m/s to 15m/s, wind wheel achieves the maximum efficiency when the setting angle is at 37 degree. The conclusion will work as a guideline for the improvement of wind turbine design.

  5. Dynamic bending of bionic flexible body driven by pneumatic artificial muscles(PAMs) for spinning gait of quadruped robot

    NASA Astrophysics Data System (ADS)

    Lei, Jingtao; Yu, Huangying; Wang, Tianmiao

    2016-01-01

    The body of quadruped robot is generally developed with the rigid structure. The mobility of quadruped robot depends on the mechanical properties of the body mechanism. It is difficult for quadruped robot with rigid structure to achieve better mobility walking or running in the unstructured environment. A kind of bionic flexible body mechanism for quadruped robot is proposed, which is composed of one bionic spine and four pneumatic artificial muscles(PAMs). This kind of body imitates the four-legged creatures' kinematical structure and physical properties, which has the characteristic of changeable stiffness, lightweight, flexible and better bionics. The kinematics of body bending is derived, and the coordinated movement between the flexible body and legs is analyzed. The relationship between the body bending angle and the PAM length is obtained. The dynamics of the body bending is derived by the floating coordinate method and Lagrangian method, and the driving force of PAM is determined. The experiment of body bending is conducted, and the dynamic bending characteristic of bionic flexible body is evaluated. Experimental results show that the bending angle of the bionic flexible body can reach 18°. An innovation body mechanism for quadruped robot is proposed, which has the characteristic of flexibility and achieve bending by changing gas pressure of PAMs. The coordinated movement of the body and legs can achieve spinning gait in order to improve the mobility of quadruped robot.

  6. Research on metallic material defect detection based on bionic sensing of human visual properties

    NASA Astrophysics Data System (ADS)

    Zhang, Pei Jiang; Cheng, Tao

    2018-05-01

    Due to the fact that human visual system can quickly lock the areas of interest in complex natural environment and focus on it, this paper proposes an eye-based visual attention mechanism by simulating human visual imaging features based on human visual attention mechanism Bionic Sensing Visual Inspection Model Method to Detect Defects of Metallic Materials in the Mechanical Field. First of all, according to the biologically visually significant low-level features, the mark of defect experience marking is used as the intermediate feature of simulated visual perception. Afterwards, SVM method was used to train the advanced features of visual defects of metal material. According to the weight of each party, the biometrics detection model of metal material defect, which simulates human visual characteristics, is obtained.

  7. [APPLICATION OF THREE DIMENSIONAL PRINTING ON MANUFACTURING BIONIC SCAFFOLDS OF SPINAL CORD IN RATS].

    PubMed

    Chen, Yisheng; Wang, Jingjing; Chen, Xuyi; Chen, Chong; Tu, Yue; Zhang, Sai; Li, Xiaohong

    2015-03-01

    To fabricate the bionic scaffolds of rat spinal cord by combining three dimensional (3D) printer and 3D software, so as to lay the foundation of theory and technology for the manufacture of scaffolds by using biomaterials. Three female Sprague Dawley rats were scanned by 7.0T MRI to obtain the shape and position data of the cross section and gray matter of T8 to T10 spinal cord. Combined with data of position and shape of nerve conduction beam, the relevant data were obtained via Getdata software. Then the 3D graphics were made and converted to stereolithography (STL) format by using SolidWorks software. Photosensitive resin was used as the materials of spinal cord scaffolds. The bionic scaffolds were fabricated by 3D printer. MRI showed that the section shape of T8 to T10 segments of the spinal cord were approximately oval with a relatively long sagittal diameter of (2.20 ± 0.52) mm and short transverse diameter of (2.05 ± 0.24) mm, and the data of nerve conduction bundle were featured in the STL format. The spinal cord bionic scaffolds of the target segments made by 3D printer were similar to the spinal cord of rat in the morphology and size, and the position of pores simulated normal nerve conduction of rat spinal cord. Spinal cord scaffolds produced by 3D printer which have similar shape and size of normal rat spinal cord are more bionic, and the procedure is simple. This technology combined with biomaterials is also promising in spinal cord repairing after spinal cord injury.

  8. Symmetrical optical imaging system with bionic variable-focus lens for off-axis aberration correction

    NASA Astrophysics Data System (ADS)

    Wang, Xuan-Yin; Du, Jia-Wei; Zhu, Shi-Qiang

    2017-09-01

    A bionic variable-focus lens with symmetrical layered structure was designed to mimic the crystalline lens. An optical imaging system based on this lens and with a symmetrical structure that mimics the human eye structure was proposed. The refractive index of the bionic variable-focus lens increases from outside to inside. The two PDMS lenses with a certain thickness were designed to improve the optical performance of the optical imaging system and minimise the gravity effect of liquid. The paper presents the overall structure of the optical imaging system and the detailed description of the bionic variable-focus lens. By pumping liquid in or out of the cavity, the surface curvatures of the rear PDMS lens were varied, resulting in a change in the focal length. The focal length range of the optical imaging system was 20.71-24.87 mm. The optical performance of the optical imaging system was evaluated by imaging experiments and analysed by ray tracing simulations. On the basis of test and simulation results, the optical performance of the system was quite satisfactory. Off-axis aberrations were well corrected, and the image quality was greatly improved.

  9. Bionic models for identification of biological systems

    NASA Astrophysics Data System (ADS)

    Gerget, O. M.

    2017-01-01

    This article proposes a clinical decision support system that processes biomedical data. For this purpose a bionic model has been designed based on neural networks, genetic algorithms and immune systems. The developed system has been tested on data from pregnant women. The paper focuses on the approach to enable selection of control actions that can minimize the risk of adverse outcome. The control actions (hyperparameters of a new type) are further used as an additional input signal. Its values are defined by a hyperparameter optimization method. A software developed with Python is briefly described.

  10. [Design of plant leaf bionic camouflage materials based on spectral analysis].

    PubMed

    Yang, Yu-Jie; Liu, Zhi-Ming; Hu, Bi-Ru; Wu, Wen-Jian

    2011-06-01

    The influence of structure parameters and contents of plant leaves on their reflectance spectra was analyzed using the PROSPECT model. The result showed that the bionic camouflage materials should be provided with coarse surface and spongy inner structure, the refractive index of main content must be close to that of plant leaves, the contents of materials should contain chlorophyll and water, and the content of C-H bond must be strictly controlled. Based on the analysis above, a novel camouflage material, which was constituted by coarse transparent waterproof surface, chlorophyll, water and spongy material, was designed. The result of verifiable experiment showed that the reflectance spectra of camouflage material exhibited the same characteristics as those of plant leaves. The similarity coefficient of reflectance spectrum of the camouflage material and camphor leaves was 0.988 1, and the characteristics of camouflage material did not change after sunlight treatment for three months. The bionic camouflage material, who exhibited a high spectral similarity with plant leaves and a good weather resistance, will be an available method for reconnaissance of hyperspectral imaging hopefully.

  11. A Bionic Neural Link for peripheral nerve repair.

    PubMed

    Xu, Yong Ping; Yen, Shih-Cheng; Ng, Kian Ann; Liu, Xu; Tan, Ter Chyan

    2012-01-01

    Peripheral nerve injuries with large gaps and long nerve regrowth paths are difficult to repair using existing surgical techniques, due to nerve degeneration and muscle atrophy. This paper proposes a Bionic Neural Link (BNL) as an alternative way for peripheral nerve repair. The concept of the BNL is described, along with the hypothetical benefits. A prototype monolithic single channel BNL has been developed, which consists of 16 neural recording channels and one stimulation channel, and is implemented in a 0.35-µm CMOS technology. The BNL has been tested in in-vivo animal experiments. Full function of the BNL chip has been demonstrated.

  12. Effects of bionic units on the fatigue wear of gray cast iron surface with different shapes and distributions

    NASA Astrophysics Data System (ADS)

    Chen, Zhi-kai; Lu, Shu-chao; Song, Xi-bin; Zhang, Haifeng; Yang, Wan-shi; Zhou, Hong

    2015-03-01

    To improve the fatigue wear resistance of gray cast iron (GCI), GCI samples were modified by a laser to imitate the unique structure of some soil animals alternating between soft and hard phases; the hard phase resists the deformation and the soft phase releases the deformation. Using the self-controlled fatigue wear test method, the fatigue wear behaviors of treated and untreated samples were investigated and compared experimentally. The results show that the bionic non-smooth surface obtains a beneficial effect on improving the fatigue wear resistance of a sample, and the fatigue wear resistance of the bionic sample assembled with reticulate units (60°+0°), whose mass loss was reduced by 62%, was superior to the others. Meanwhile, a finite element (FE) was used to simulate the compression and the distributions of strain and stress on the non-smooth surface was inferred. From these results, we understood that the functions of the bionic unit such as reducing strain and stress, and also obstructing the closure and propagation of cracks were the main reasons for improving the fatigue wear property of GCI.

  13. Towards Extending Forward Kinematic Models on Hyper-Redundant Manipulator to Cooperative Bionic Arms

    NASA Astrophysics Data System (ADS)

    Singh, Inderjeet; Lakhal, Othman; Merzouki, Rochdi

    2017-01-01

    Forward Kinematics is a stepping stone towards finding an inverse solution and subsequently a dynamic model of a robot. Hence a study and comparison of various Forward Kinematic Models (FKMs) is necessary for robot design. This paper deals with comparison of three FKMs on the same hyper-redundant Compact Bionic Handling Assistant (CBHA) manipulator under same conditions. The aim of this study is to project on modeling cooperative bionic manipulators. Two of these methods are quantitative methods, Arc Geometry HTM (Homogeneous Transformation Matrix) Method and Dual Quaternion Method, while the other one is Hybrid Method which uses both quantitative as well as qualitative approach. The methods are compared theoretically and experimental results are discussed to add further insight to the comparison. HTM is the widely used and accepted technique, is taken as reference and trajectory deviation in other techniques are compared with respect to HTM. Which method allows obtaining an accurate kinematic behavior of the CBHA, controlled in the real-time.

  14. BIonic system: Extraction of Lovelock gravity from a Born-Infeld-type theory

    NASA Astrophysics Data System (ADS)

    Naimi, Yaghoob; Sepehri, Alireza; Ghaffary, Tooraj; Ghaforyan, Hossein; Ebrahimzadeh, Majid

    It was shown that both Lovelock gravity and Born-Infeld (BI) electrodynamics can be obtained from low effective limit of string theory. Motivated by the mentioned unique origin of the gauge-gravity theories, we are going to find a close relation between them. In this research, we start from the Lagrangian of a BI-type nonlinear electrodynamics with an exponential form to extract the action of Lovelock gravity. We investigate the origin of Lovelock gravity in a system of branes which are connected with each other by different wormholes through a BIonic system. These wormholes are produced as due to the nonlinear electrodynamics which are emerged on the interacting branes. By approaching branes, wormholes dissolve into branes and Lovelock gravity is generated. Also, throats of some wormholes become smaller than their horizons and they transit to black holes. Generalizing calculations to M-theory, it is found that by compacting Mp-branes, Lovelock gravity changes to nonlinear electrodynamics and thus both of them have the same origin. This result is consistent with the prediction of BIonic model in string theory.

  15. Multiadaptive Bionic Wavelet Transform: Application to ECG Denoising and Baseline Wandering Reduction

    NASA Astrophysics Data System (ADS)

    Sayadi, Omid; Shamsollahi, Mohammad B.

    2007-12-01

    We present a new modified wavelet transform, called the multiadaptive bionic wavelet transform (MABWT), that can be applied to ECG signals in order to remove noise from them under a wide range of variations for noise. By using the definition of bionic wavelet transform and adaptively determining both the center frequency of each scale together with the[InlineEquation not available: see fulltext.]-function, the problem of desired signal decomposition is solved. Applying a new proposed thresholding rule works successfully in denoising the ECG. Moreover by using the multiadaptation scheme, lowpass noisy interference effects on the baseline of ECG will be removed as a direct task. The method was extensively clinically tested with real and simulated ECG signals which showed high performance of noise reduction, comparable to those of wavelet transform (WT). Quantitative evaluation of the proposed algorithm shows that the average SNR improvement of MABWT is 1.82 dB more than the WT-based results, for the best case. Also the procedure has largely proved advantageous over wavelet-based methods for baseline wandering cancellation, including both DC components and baseline drifts.

  16. The Bionic Clicker Mark I & II.

    PubMed

    Magee, Elliott G; Ourselin, S; Nikitichev, Daniil; Vercauteren, T; Vanhoestenberghe, Anne

    2017-08-14

    In this manuscript, we present two 'Bionic Clicker' systems, the first designed to demonstrate electromyography (EMG) based control systems for educational purposes and the second for research purposes. EMG based control systems pick up electrical signals generated by muscle activation and use these as inputs for controllers. EMG controllers are widely used in prosthetics to control limbs. The Mark I (MK I) clicker allows the wearer to change the slide of a presentation by raising their index finger. It is built around a microcontroller and a bio-signals shield. It generated a lot of interest from both the public and research community. The Mark II (MK II) device presented here was designed to be a cheaper, sleeker, and more customizable system that can be easily modified and directly transmit EMG data. It is built using a wireless capable microcontroller and a muscle sensor.

  17. SU-E-T-570: Management of Radiation Oncology Patients with Cochlear Implant and Other Bionic Devices in the Brain and Head and Neck Regions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guo, F.Q; Chen, Z; Nath, R

    Purpose: To investigate the current status of clinical usage of cochlear implant (CI) and other bionic devices (BD) in the brain and head and neck regions (BH and N) and their management in patients during radiotherapy to ensure patient health and safety as well as optimum radiation delivery. Methods: Literature review was performed with both CIs and radiotherapy and their variants as keywords in PubMed, INSPEC and other sources. The focus was on CIs during radiotherapy, but it also included other BDs in BHȦN, such as auditory brainstem implant, bionic retinal implant, and hearing aids, among others. Results: Interactions betweenmore » CIs and radiation may cause CIs malfunction. The presence of CIs may also cause suboptimum dose distribution if a treatment plan was not well designed. A few studies were performed for the hearing functions of CIs under irradiations of 4 MV and 6 MV x-rays. However, x-rays with higher energies (10 to 18 MV) broadly used in radiotherapy have not been explored. These higher energetic beams are more damaging to electronics due to strong penetrating power and also due to neutrons generated in the treatment process. Modern CIs are designed with more and more complicated integrated circuits, which may be more susceptible to radiation damage and malfunction. Therefore, careful management is important for safety and treatment outcomes. Conclusion: Although AAPM TG-34, TG-63, and TG-203 (update of TG-34, not published yet) reports may be referenced for management of CIs and other BDs in the brain and H and N regions, a site- and device-specified guideline should be developed for CIs and other BDs. Additional evaluation of CI functions under clinically relevant set-ups should also be performed to provide clinicians with better knowledge in clinical decision making.« less

  18. Construction of bionic tissue engineering cartilage scaffold based on three-dimensional printing and oriented frozen technology.

    PubMed

    Xu, Yuanyuan; Guo, Xiao; Yang, Shuaitao; Li, Long; Zhang, Peng; Sun, Wei; Liu, Changyong; Mi, Shengli

    2018-06-01

    Articular cartilage (AC) has gradient features in both mechanics and histology as well as a poor regeneration ability. The repair of AC poses difficulties in both research and the clinic. In this paper, a gradient scaffold based on poly(lactic-co-glycolic acid) (PLGA)-extracellular matrix was proposed. Cartilage scaffolds with a three-layer gradient structure were fabricated by PLGA through three-dimensional printing, and the microstructure orientation and pore fabrication were made by decellularized extracellular matrix injection and directional freezing. The manufactured scaffold has a mechanical strength close to that of real cartilage. A quantitative optimization of the Young's modulus and shear modulus was achieved by material mechanics formulas, which achieved a more accurate mechanical bionic and a more stable interface performance because of the one-time molding process. At the same time, the scaffolds have a bionic and gradient microstructure orientation and pore size, and the stratification ratio can be quantitatively optimized by design of the freeze box and temperature simulation. In general, this paper provides a method to optimize AC scaffolds by both mechanics and histology as well as a bionic multimaterial scaffold. This paper is of significance for cell culture and clinical transplantation experiments. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1664-1676, 2018. © 2018 Wiley Periodicals, Inc.

  19. The Bionic Clicker Mark I & II

    PubMed Central

    Magee, Elliott G.; Ourselin, S.; Nikitichev, Daniil; Vercauteren, T.; Vanhoestenberghe, Anne

    2017-01-01

    In this manuscript, we present two 'Bionic Clicker' systems, the first designed to demonstrate electromyography (EMG) based control systems for educational purposes and the second for research purposes. EMG based control systems pick up electrical signals generated by muscle activation and use these as inputs for controllers. EMG controllers are widely used in prosthetics to control limbs. The Mark I (MK I) clicker allows the wearer to change the slide of a presentation by raising their index finger. It is built around a microcontroller and a bio-signals shield. It generated a lot of interest from both the public and research community. The Mark II (MK II) device presented here was designed to be a cheaper, sleeker, and more customizable system that can be easily modified and directly transmit EMG data. It is built using a wireless capable microcontroller and a muscle sensor. PMID:28829413

  20. Real-time processing of EMG signals for bionic arm purposes

    NASA Astrophysics Data System (ADS)

    Olid Dominguez, Ferran; Wawrzyniak, Zbigniew M.

    2016-09-01

    This paper is connected with the problem of prostheses, that have always been a necessity for the human being. Bio-physiological signals from muscles, electromyographic signals have been collected, analyzed and processed in order to implement a real-time algorithm which is capable of differentiation of two different states of a bionic hand: open and closed. An algorithm for real-time electromyographic signal processing with almost no false positives is presented and it is explained that in bio-physiological experiments proper signal processing is of great importance.

  1. Investigation into the efficiency of different bionic algorithm combinations for a COBRA meta-heuristic

    NASA Astrophysics Data System (ADS)

    Akhmedova, Sh; Semenkin, E.

    2017-02-01

    Previously, a meta-heuristic approach, called Co-Operation of Biology-Related Algorithms or COBRA, for solving real-parameter optimization problems was introduced and described. COBRA’s basic idea consists of a cooperative work of five well-known bionic algorithms such as Particle Swarm Optimization, the Wolf Pack Search, the Firefly Algorithm, the Cuckoo Search Algorithm and the Bat Algorithm, which were chosen due to the similarity of their schemes. The performance of this meta-heuristic was evaluated on a set of test functions and its workability was demonstrated. Thus it was established that the idea of the algorithms’ cooperative work is useful. However, it is unclear which bionic algorithms should be included in this cooperation and how many of them. Therefore, the five above-listed algorithms and additionally the Fish School Search algorithm were used for the development of five different modifications of COBRA by varying the number of component-algorithms. These modifications were tested on the same set of functions and the best of them was found. Ways of further improving the COBRA algorithm are then discussed.

  2. Mechanism design and optimization of a bionic kangaroo jumping robot

    NASA Astrophysics Data System (ADS)

    Zhang, Y. H.; Zheng, L.; Ge, W. J.; Zou, Z. H.

    2018-03-01

    Hopping robots have broad application prospects in the fields of military reconnaissance, field search or life rescue. However, current hopping robots still face the problems of weak jumping ability and load bearing. Inspired by the jumping of kangaroo, we design a Kangaroo hopping robot “Zbot”, which has two degrees of freedom and three joints. The geared five-bar mechanism is used to decouple the knee and ankle joints of the robot. In order to get a bionic performance, the coupling mechanism parameters are optimized. The simulation and experiments show that the robot has an excellent jumping ability and load capacity.

  3. ECG denoising with adaptive bionic wavelet transform.

    PubMed

    Sayadi, Omid; Shamsollahi, Mohammad Bagher

    2006-01-01

    In this paper a new ECG denoising scheme is proposed using a novel adaptive wavelet transform, named bionic wavelet transform (BWT), which had been first developed based on a model of the active auditory system. There has been some outstanding features with the BWT such as nonlinearity, high sensitivity and frequency selectivity, concentrated energy distribution and its ability to reconstruct signal via inverse transform but the most distinguishing characteristic of BWT is that its resolution in the time-frequency domain can be adaptively adjusted not only by the signal frequency but also by the signal instantaneous amplitude and its first-order differential. Besides by optimizing the BWT parameters parallel to modifying a new threshold value, one can handle ECG denoising with results comparing to those of wavelet transform (WT). Preliminary tests of BWT application to ECG denoising were constructed on the signals of MIT-BIH database which showed high performance of noise reduction.

  4. Recent advances in bioelectric prostheses

    PubMed Central

    Pasquina, Paul F.; Perry, Briana N.; Miller, Matthew E.; Ling, Geoffrey S.F.; Tsao, Jack W.

    2015-01-01

    Summary Worldwide prevalence of amputation has created an increasing demand for improved upper and lower extremity prostheses. Current prosthetics are often uncomfortable and difficult to control and provide limited functional restoration. Moreover, the inability to normalize anthropomorphic biomechanics with a prosthesis increases one's risk of developing long-term health risks such as arthritis, skin breakdown, and pain. Recent advances in bionic prosthetic development hold great promise for rehabilitation and improving quality of life with limb loss. This brief review discusses the current state of advanced prostheses, the integration of robotics in the care of individuals with major limb amputation, and some innovative surgical techniques that are being explored for clinical feasibility. PMID:29443190

  5. Ego-motion based on EM for bionic navigation

    NASA Astrophysics Data System (ADS)

    Yue, Xiaofeng; Wang, L. J.; Liu, J. G.

    2015-12-01

    Researches have proved that flying insects such as bees can achieve efficient and robust flight control, and biologists have explored some biomimetic principles regarding how they control flight. Based on those basic studies and principles acquired from the flying insects, this paper proposes a different solution of recovering ego-motion for low level navigation. Firstly, a new type of entropy flow is provided to calculate the motion parameters. Secondly, EKF, which has been used for navigation for some years to correct accumulated error, and estimation-Maximization, which is always used to estimate parameters, are put together to determine the ego-motion estimation of aerial vehicles. Numerical simulation on MATLAB has proved that this navigation system provides more accurate position and smaller mean absolute error than pure optical flow navigation. This paper has done pioneering work in bionic mechanism to space navigation.

  6. Design and Implementation of a Quadruped Bionic Robot Based on Virtual Prototype Technology

    NASA Astrophysics Data System (ADS)

    Wang, Li

    2017-10-01

    Design out a quadruped bionic robot with nine degrees of freedom. Conduct virtual assembly and trotting gait simulation on the robot by using NX software. Present the angular velocity and angular displacement curves of the diagonal two legs’ hip joints and knee joints, thus to instruct the practical assemble and control of the robot. The fact that the movement effect of the physical model is consistent with the simulation verifies the validity and practicability of virtual assembly and motion simulation. both.

  7. A Bionic Camera-Based Polarization Navigation Sensor

    PubMed Central

    Wang, Daobin; Liang, Huawei; Zhu, Hui; Zhang, Shuai

    2014-01-01

    Navigation and positioning technology is closely related to our routine life activities, from travel to aerospace. Recently it has been found that Cataglyphis (a kind of desert ant) is able to detect the polarization direction of skylight and navigate according to this information. This paper presents a real-time bionic camera-based polarization navigation sensor. This sensor has two work modes: one is a single-point measurement mode and the other is a multi-point measurement mode. An indoor calibration experiment of the sensor has been done under a beam of standard polarized light. The experiment results show that after noise reduction the accuracy of the sensor can reach up to 0.3256°. It is also compared with GPS and INS (Inertial Navigation System) in the single-point measurement mode through an outdoor experiment. Through time compensation and location compensation, the sensor can be a useful alternative to GPS and INS. In addition, the sensor also can measure the polarization distribution pattern when it works in multi-point measurement mode. PMID:25051029

  8. [Effects of Different Planting Direction and Layer Combination on Gastrodia elata f. elata in Bionic Wild Cultivation].

    PubMed

    Liu, Wei; Zhao, Zhi; Wang, Hua-lei; Luo, Fu-lai; Li, Jin-ling; Liu, Hong-chang; Luo, Chun-li

    2015-05-01

    Combination of different planting direction and layer were set to choose the best technology of cultivation of Gastrodia elata f. elata. To improve the yield and quality of Gastrodia elata f. elata, randomized block design experiments were carried out to investigate the yield and quality, and to analyze their economic effectiveness in bionic wild cultivation. Length, width, thickness and weight of southern direction's Gastrodia elata f. elata developed better than the northeast direction. The three planting layer levels on growth effect of Gastrodia elata f. elata was the 3rd layer > the 2nd layer > the 1st layer. In six treatments, combination of southern direction-the 3rd layer was the best technology of cultivation of Gastrodia elata f. elata, which had the best growth condition, the highest yield significantly higher than other treatments, and the best economic benefits. Southern direction associated with the 3rd layer is the best combination to planting Gastrodia elata f. elata in bionic wild cultivation. The planting ways not only improve the yield and quality, but also save land.

  9. Design and preparation of polyurethane-collagen/heparin-conjugated polycaprolactone double-layer bionic small-diameter vascular graft and its preliminary animal tests.

    PubMed

    Lu, Guang; Cui, Shi-Jun; Geng, Xue; Ye, Lin; Chen, Bing; Feng, Zeng-Guo; Zhang, Jian; Li, Zhong-Zhi

    2013-04-01

    People recently realized that it is important for artificial vascular biodegradable graft to bionically mimic the functions of the native vessel. In order to overcome the high risk of thrombosis and keep the patency in the clinical small-diameter vascular graft (SDVG) transplantation, a double-layer bionic scaffold, which can offer anticoagulation and mechanical strength simultaneously, was designed and fabricated via electrospinning technique. Heparin-conjugated polycaprolactone (hPCL) and polyurethane (PU)-collagen type I composite was used as the inner and outer layers, respectively. The porosity and the burst pressure of SDVG were evaluated. Its biocompatibility was demonstrated by the 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide (MTT) test in vitro and subcutaneous implants in vivo respectively. The grafts of diameter 2.5 mm and length 4.0 cm were implanted to replace the femoral artery in Beagle dog model. Then, angiography was performed in the Beagle dogs to investigate the patency and aneurysm of grafts at 2, 4, and 8 weeks post-transplantation. After angiography, the patent grafts were explanted for histological analysis. The double-layer bionic SDVG meet the clinical mechanical demand. Its good biocompatibility was proven by cytotoxicity experiment (the cell's relative growth rates (RGR) of PU-collagen outer layer were 102.8%, 109.2% and 103.5%, while the RGR of hPCL inner layer were 99.0%, 100.0% and 98.0%, on days 1, 3, and 5, respectively) and the subdermal implants experiment in the Beagle dog. Arteriography showed that all the implanted SDVGs were patent without any aneurismal dilatation or obvious anastomotic stenosis at the 2nd, 4th, and 8th week after the operation, except one SDVG that failed at the 2nd week. Histological analysis and SEM showed that the inner layer was covered by new endothelial-like cells. The double-layer bionic SDVG is a promising candidate as a replacement of native small-diameter vascular graft.

  10. Effect of counterface roughness on the friction of bionic wall-shaped microstructures for gecko-like attachments.

    PubMed

    Kasem, Haytam; Cohen, Yossi

    2017-08-04

    Hairy adhesive systems involved in gecko locomotion have drawn the interest of many researchers regarding the development of bionic solutions for fast and reversible adhesive technologies. To date, despite extensive efforts to design gecko-inspired adhesive surfaces, adhesion and friction capacities are often evaluated using smooth and rigid counterfaces, in general glass, whereas most natural and artificial surfaces inevitably have a certain level of roughness. For that reason, in this study experiments tested the effects of the substrate roughness on the friction of bionic wale-shaped microstructures for gecko-like attachments. To this end, 12 substrates with different isotropic roughness were prepared using the same Epoxy material. Friction force was measured under various normal loads. It was concluded that classical roughness parameters, considered separately, are not appropriate to explain roughness-related variations in friction force. This has led us to develop a new integrative roughness parameter that combines characteristics of the surface. The parameter is capable of classifying the obtained experimental results in a readable way. An analytical model based on the experimental results has been developed to predict the variation of the friction force as a function of counterface roughness and applied normal load.

  11. iCI: Iterative CI toward full CI.

    PubMed

    Liu, Wenjian; Hoffmann, Mark R

    2016-03-08

    It is shown both theoretically and numerically that the minimal multireference configuration interaction (CI) approach [Liu, W.; Hoffmann, M. R. Theor. Chem. Acc. 2014, 133, 1481] converges quickly and monotonically from above to full CI by updating the primary, external, and secondary states that describe the respective static, dynamic, and again static components of correlation iteratively, even when starting with a rather poor description of a strongly correlated system. In short, the iterative CI (iCI) is a very effective means toward highly correlated wave functions and, ultimately, full CI.

  12. A novel in situ device based on a bionic piezoelectric actuator to study tensile and fatigue properties of bulk materials.

    PubMed

    Wang, Shupeng; Zhang, Zhihui; Ren, Luquan; Zhao, Hongwei; Liang, Yunhong; Zhu, Bing

    2014-06-01

    In this work, a miniaturized device based on a bionic piezoelectric actuator was developed to investigate the static tensile and dynamic fatigue properties of bulk materials. The device mainly consists of a bionic stepping piezoelectric actuator based on wedge block clamping, a pair of grippers, and a set of precise signal test system. Tensile and fatigue examinations share a set of driving system and a set of signal test system. In situ tensile and fatigue examinations under scanning electron microscope or metallographic microscope could be carried out due to the miniaturized dimensions of the device. The structure and working principle of the device were discussed and the effects of output difference between two piezoelectric stacks on the device were theoretically analyzed. The tensile and fatigue examinations on ordinary copper were carried out using this device and its feasibility was verified through the comparison tests with a commercial tensile examination instrument.

  13. Medicalization: Current Concept and Future Directions in a Bionic Society

    PubMed Central

    Maturo, Antonio

    2012-01-01

    The article illustrates the main features of the concept of medicalization, starting from its theoretical roots. Although it is the process of extending the medical gaze on human conditions, it appears that medicalization cannot be strictly connected to medical imperialism anymore. Other “engines” of medicalization are influential: consumers, biotechnology and managed care. The growth of research and theoretical reflections on medicalization has led to the proposal of other parallel concepts like pharmaceuticalization, genetization and biomedicalization. These new theoretical tools could be useful in the analysis of human enhancement. Human enhancement can be considered as the use of biomedical technology to improve performance on a human being who is not in need of a cure: a practice that is increasingly spreading in what might be defined as a “bionic society”. PMID:22654387

  14. A novel in situ device based on a bionic piezoelectric actuator to study tensile and fatigue properties of bulk materials

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Shupeng; Zhang, Zhihui, E-mail: zhzh@jlu.edu.cn; Ren, Luquan

    2014-06-15

    In this work, a miniaturized device based on a bionic piezoelectric actuator was developed to investigate the static tensile and dynamic fatigue properties of bulk materials. The device mainly consists of a bionic stepping piezoelectric actuator based on wedge block clamping, a pair of grippers, and a set of precise signal test system. Tensile and fatigue examinations share a set of driving system and a set of signal test system. In situ tensile and fatigue examinations under scanning electron microscope or metallographic microscope could be carried out due to the miniaturized dimensions of the device. The structure and working principlemore » of the device were discussed and the effects of output difference between two piezoelectric stacks on the device were theoretically analyzed. The tensile and fatigue examinations on ordinary copper were carried out using this device and its feasibility was verified through the comparison tests with a commercial tensile examination instrument.« less

  15. Clinician-Focused Overview of Bionic Exoskeleton Use After Spinal Cord Injury.

    PubMed

    Palermo, Anne E; Maher, Jennifer L; Baunsgaard, Carsten Bach; Nash, Mark S

    2017-01-01

    Spinal cord injury (SCI) resulting in paralysis of lower limbs and trunk restricts daily upright activity, work capacity, and ambulation ability, putting persons with an injury at greater risk of developing a myriad of secondary medical issues. Time spent in the upright posture has been shown to decrease the risk of these complications in SCI. Unfortunately, the majority of ambulation assistive technologies are limited by inefficiencies such as high energy demand, lengthy donning and doffing time, and poor gait pattern precluding widespread use. These limitations spurred the development of bionic exoskeletons. These devices are currently being used in rehabilitation settings for gait retraining, and some have been approved for home use. This overview will address the current state of available devices and their utility.

  16. Fermentation based carbon nanotube multifunctional bionic composites

    NASA Astrophysics Data System (ADS)

    Valentini, Luca; Bon, Silvia Bittolo; Signetti, Stefano; Tripathi, Manoj; Iacob, Erica; Pugno, Nicola M.

    2016-06-01

    The exploitation of the processes used by microorganisms to digest nutrients for their growth can be a viable method for the formation of a wide range of so called biogenic materials that have unique properties that are not produced by abiotic processes. Here we produced living hybrid materials by giving to unicellular organisms the nutrient to grow. Based on bread fermentation, a bionic composite made of carbon nanotubes (CNTs) and a single-cell fungi, the Saccharomyces cerevisiae yeast extract, was prepared by fermentation of such microorganisms at room temperature. Scanning electron microscopy analysis suggests that the CNTs were internalized by the cell after fermentation bridging the cells. Tensile tests on dried composite films have been rationalized in terms of a CNT cell bridging mechanism where the strongly enhanced strength of the composite is governed by the adhesion energy between the bridging carbon nanotubes and the matrix. The addition of CNTs also significantly improved the electrical conductivity along with a higher photoconductive activity. The proposed process could lead to the development of more complex and interactive structures programmed to self-assemble into specific patterns, such as those on strain or light sensors that could sense damage or convert light stimulus in an electrical signal.

  17. Fermentation based carbon nanotube multifunctional bionic composites

    PubMed Central

    Valentini, Luca; Bon, Silvia Bittolo; Signetti, Stefano; Tripathi, Manoj; Iacob, Erica; Pugno, Nicola M.

    2016-01-01

    The exploitation of the processes used by microorganisms to digest nutrients for their growth can be a viable method for the formation of a wide range of so called biogenic materials that have unique properties that are not produced by abiotic processes. Here we produced living hybrid materials by giving to unicellular organisms the nutrient to grow. Based on bread fermentation, a bionic composite made of carbon nanotubes (CNTs) and a single-cell fungi, the Saccharomyces cerevisiae yeast extract, was prepared by fermentation of such microorganisms at room temperature. Scanning electron microscopy analysis suggests that the CNTs were internalized by the cell after fermentation bridging the cells. Tensile tests on dried composite films have been rationalized in terms of a CNT cell bridging mechanism where the strongly enhanced strength of the composite is governed by the adhesion energy between the bridging carbon nanotubes and the matrix. The addition of CNTs also significantly improved the electrical conductivity along with a higher photoconductive activity. The proposed process could lead to the development of more complex and interactive structures programmed to self-assemble into specific patterns, such as those on strain or light sensors that could sense damage or convert light stimulus in an electrical signal. PMID:27279425

  18. ["Bionic" arm prostheses. State of the art in research and development].

    PubMed

    Pylatiuk, C; Döderlein, L

    2006-11-01

    A new generation of arm prostheses is being developed worldwide. These so-called bionic prostheses are intended to offer additional functions, such as sensory feedback, extended range of possible movement, intuitive movement control as far as possible, and a more natural cosmetic appearance. In recent years, prosthetic components with much enhanced performance have been developed for use at various levels of the upper limb. Artificial hands that allow for additional grips are are being tested in clinical settings. Innovative methods of signal acquisition and communication with the patient are being intensively researched. Several patients have been provided with prototypes of new arm prostheses. At the moment, the results are limited by the restricted communication between patient and prosthesis. However, we can expect the options for prosthesis control to be extended in the near future.

  19. Nanocarbon-Coated Porous Anodic Alumina for Bionic Devices

    PubMed Central

    Aramesh, Morteza; Tong, Wei; Fox, Kate; Turnley, Ann; Seo, Dong Han; Prawer, Steven; Ostrikov, Kostya (Ken)

    2015-01-01

    A highly-stable and biocompatible nanoporous electrode is demonstrated herein. The electrode is based on a porous anodic alumina which is conformally coated with an ultra-thin layer of diamond-like carbon. The nanocarbon coating plays an essential role for the chemical stability and biocompatibility of the electrodes; thus, the coated electrodes are ideally suited for biomedical applications. The corrosion resistance of the proposed electrodes was tested under extreme chemical conditions, such as in boiling acidic/alkali environments. The nanostructured morphology and the surface chemistry of the electrodes were maintained after wet/dry chemical corrosion tests. The non-cytotoxicity of the electrodes was tested by standard toxicity tests using mouse fibroblasts and cortical neurons. Furthermore, the cell–electrode interaction of cortical neurons with nanocarbon coated nanoporous anodic alumina was studied in vitro. Cortical neurons were found to attach and spread to the nanocarbon coated electrodes without using additional biomolecules, whilst no cell attachment was observed on the surface of the bare anodic alumina. Neurite growth appeared to be sensitive to nanotopographical features of the electrodes. The proposed electrodes show a great promise for practical applications such as retinal prostheses and bionic implants in general. PMID:28793486

  20. Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear.

    PubMed

    Pinyon, Jeremy L; Tadros, Sherif F; Froud, Kristina E; Y Wong, Ann C; Tompson, Isabella T; Crawford, Edward N; Ko, Myungseo; Morris, Renée; Klugmann, Matthias; Housley, Gary D

    2014-04-23

    The cochlear implant is the most successful bionic prosthesis and has transformed the lives of people with profound hearing loss. However, the performance of the "bionic ear" is still largely constrained by the neural interface itself. Current spread inherent to broad monopolar stimulation of the spiral ganglion neuron somata obviates the intrinsic tonotopic mapping of the cochlear nerve. We show in the guinea pig that neurotrophin gene therapy integrated into the cochlear implant improves its performance by stimulating spiral ganglion neurite regeneration. We used the cochlear implant electrode array for novel "close-field" electroporation to transduce mesenchymal cells lining the cochlear perilymphatic canals with a naked complementary DNA gene construct driving expression of brain-derived neurotrophic factor (BDNF) and a green fluorescent protein (GFP) reporter. The focusing of electric fields by particular cochlear implant electrode configurations led to surprisingly efficient gene delivery to adjacent mesenchymal cells. The resulting BDNF expression stimulated regeneration of spiral ganglion neurites, which had atrophied 2 weeks after ototoxic treatment, in a bilateral sensorineural deafness model. In this model, delivery of a control GFP-only vector failed to restore neuron structure, with atrophied neurons indistinguishable from unimplanted cochleae. With BDNF therapy, the regenerated spiral ganglion neurites extended close to the cochlear implant electrodes, with localized ectopic branching. This neural remodeling enabled bipolar stimulation via the cochlear implant array, with low stimulus thresholds and expanded dynamic range of the cochlear nerve, determined via electrically evoked auditory brainstem responses. This development may broadly improve neural interfaces and extend molecular medicine applications.

  1. Bionic multisilicon copolymers used as novel cross-linking agents for preparing anion exchange hybrid membranes.

    PubMed

    Wu, Yonghui; Luo, Jingyi; Wu, Cuiming; Xu, Tongwen; Fu, Yanxun

    2011-05-26

    Bionic multisilicon copolymers have long-main chains and many branched chains, and contain multifunctional groups of -N(+)(CH(3))(3)Cl(-) and -Si(OCH(3))(3), which are similar to the stem, branch, fruit, and acetabula of a vine from bionic aspect, respectively. They have high flexibility, charge density, and cross-linking ability and thus can be used as novel cross-linking agents for preparing anion-exchange hybrid membranes. High content of -Si(OCH(3))(3) groups (68-78%) is suitable to enhance membrane stabilities. The membranes are stable in 65 °C water up to 120 h and can keep integrity in 2 mol/L NaOH for 192 h. High content of -N(+)(CH(3))(3)Cl(-) groups (42-55%) is suitable to enhance membrane electrical properties. The membranes have low membrane resistance (R(m), 0.59-0.94 Ω cm(2)) and high diffusion dialysis performance. The acid (H(+)) dialysis coefficients (U(H)) are in the range of 0.007-0.075 m h(-1) at room temperature and 0.015-0.115 m h(-1) at 40 °C. The separation factor (S(H/Fe)) can reach up to 43 at room temerature and 49 at 40 °C. All of the membranes are highly homogeneous, mechanically stable (21-31 MPa, 25-147%), and thermally stable (227-275 °C for halide form membranes, and 157-172 °C for OH(-) form membranes). Hence, the investigation of multisilicon copolymers will give rise to a new developing field in material and membrane sciences.

  2. A new time-adaptive discrete bionic wavelet transform for enhancing speech from adverse noise environment

    NASA Astrophysics Data System (ADS)

    Palaniswamy, Sumithra; Duraisamy, Prakash; Alam, Mohammad Showkat; Yuan, Xiaohui

    2012-04-01

    Automatic speech processing systems are widely used in everyday life such as mobile communication, speech and speaker recognition, and for assisting the hearing impaired. In speech communication systems, the quality and intelligibility of speech is of utmost importance for ease and accuracy of information exchange. To obtain an intelligible speech signal and one that is more pleasant to listen, noise reduction is essential. In this paper a new Time Adaptive Discrete Bionic Wavelet Thresholding (TADBWT) scheme is proposed. The proposed technique uses Daubechies mother wavelet to achieve better enhancement of speech from additive non- stationary noises which occur in real life such as street noise and factory noise. Due to the integration of human auditory system model into the wavelet transform, bionic wavelet transform (BWT) has great potential for speech enhancement which may lead to a new path in speech processing. In the proposed technique, at first, discrete BWT is applied to noisy speech to derive TADBWT coefficients. Then the adaptive nature of the BWT is captured by introducing a time varying linear factor which updates the coefficients at each scale over time. This approach has shown better performance than the existing algorithms at lower input SNR due to modified soft level dependent thresholding on time adaptive coefficients. The objective and subjective test results confirmed the competency of the TADBWT technique. The effectiveness of the proposed technique is also evaluated for speaker recognition task under noisy environment. The recognition results show that the TADWT technique yields better performance when compared to alternate methods specifically at lower input SNR.

  3. CI-WATER HPC Model: Cyberinfrastructure to Advance High Performance Water Resources Modeling in the Intermountain Western U.S

    NASA Astrophysics Data System (ADS)

    Ogden, F. L.; Lai, W.; Douglas, C. C.; Miller, S. N.; Zhang, Y.

    2012-12-01

    -processing, visualization, and communication of massive amounts of output. The open-source CI-WATER model represents a significant advance in water resources modeling, and will be useful to water managers, planners, resource economists, and the hydrologic research community in general.

  4. Case-study of a user-driven prosthetic arm design: bionic hand versus customized body-powered technology in a highly demanding work environment.

    PubMed

    Schweitzer, Wolf; Thali, Michael J; Egger, David

    2018-01-03

    Prosthetic arm research predominantly focuses on "bionic" but not body-powered arms. However, any research orientation along user needs requires sufficiently precise workplace specifications and sufficiently hard testing. Forensic medicine is a demanding environment, also physically, also for non-disabled people, on several dimensions (e.g., distances, weights, size, temperature, time). As unilateral below elbow amputee user, the first author is in a unique position to provide direct comparison of a "bionic" myoelectric iLimb Revolution (Touch Bionics) and a customized body-powered arm which contains a number of new developments initiated or developed by the user: (1) quick lock steel wrist unit; (2) cable mount modification; (3) cast shape modeled shoulder anchor; (4) suspension with a soft double layer liner (Ohio Willowwood) and tube gauze (Molnlycke) combination. The iLimb is mounted on an epoxy socket; a lanyard fixed liner (Ohio Willowwood) contains magnetic electrodes (Liberating Technologies). An on the job usage of five years was supplemented with dedicated and focused intensive two-week use tests at work for both systems. The side-by-side comparison showed that the customized body-powered arm provides reliable, comfortable, effective, powerful as well as subtle service with minimal maintenance; most notably, grip reliability, grip force regulation, grip performance, center of balance, component wear down, sweat/temperature independence and skin state are good whereas the iLimb system exhibited a number of relevant serious constraints. Research and development of functional prostheses may want to focus on body-powered technology as it already performs on manually demanding and heavy jobs whereas eliminating myoelectric technology's constraints seems out of reach. Relevant testing could be developed to help expediting this. This is relevant as Swiss disability insurance specifically supports prostheses that enable actual work integration. Myoelectric and

  5. Estimation of the Age and Amount of Brown Rice Plant Hoppers Based on Bionic Electronic Nose Use

    PubMed Central

    Xu, Sai; Zhou, Zhiyan; Lu, Huazhong; Luo, Xiwen; Lan, Yubin; Zhang, Yang; Li, Yanfang

    2014-01-01

    The brown rice plant hopper (BRPH), Nilaparvata lugens (Stal), is one of the most important insect pests affecting rice and causes serious damage to the yield and quality of rice plants in Asia. This study used bionic electronic nose technology to sample BRPH volatiles, which vary in age and amount. Principal component analysis (PCA), linear discrimination analysis (LDA), probabilistic neural network (PNN), BP neural network (BPNN) and loading analysis (Loadings) techniques were used to analyze the sampling data. The results indicate that the PCA and LDA classification ability is poor, but the LDA classification displays superior performance relative to PCA. When a PNN was used to evaluate the BRPH age and amount, the classification rates of the training set were 100% and 96.67%, respectively, and the classification rates of the test set were 90.67% and 64.67%, respectively. When BPNN was used for the evaluation of the BRPH age and amount, the classification accuracies of the training set were 100% and 48.93%, respectively, and the classification accuracies of the test set were 96.67% and 47.33%, respectively. Loadings for BRPH volatiles indicate that the main elements of BRPHs' volatiles are sulfur-containing organics, aromatics, sulfur- and chlorine-containing organics and nitrogen oxides, which provide a reference for sensors chosen when exploited in specialized BRPH identification devices. This research proves the feasibility and broad application prospects of bionic electronic noses for BRPH recognition. PMID:25268913

  6. Research on anti crack mechanism of bionic coupling brake disc

    NASA Astrophysics Data System (ADS)

    Shi, Lifeng; Yang, Xiao; Zheng, Lingnan; Wu, Can; Ni, Jing

    2017-09-01

    According to the biological function of fatigue resistance possessed by biology, this study designed a Bionic Coupling Brake Disc (BCBD) which can inhibit crack propagation as the result of improving fatigue property. Thermal stress field of brake disc was calculated under emergency working condition, and circumferential and radial stress field which lead to fatigue failure of brake disc were investigated simultaneously. Results showed that the maximum temperature of surface reached 890°C and the maximum residual tensile stress was 207 Mpa when the initial velocity of vehicle was 200 km/h. Based on the theory of elastic plastic fracture mechanics, the crack opening displacement and the crack front J integrals of the BCBD and traditional brake disc (TBD) with pre-cracking were calculated, and the strength of crack front was compared. Results revealed the growth behavior of fatigue crack located on surface of brake disc, and proved the anti fatigue resistance of BCBD was better, and the strength of crack resistance of BCBD was much stronger than that of TBD. This simulation research provided significant references for optimization and manufacturing of BCBD.

  7. The potential of the second sight system bionic eye implant for partial sight restoration.

    PubMed

    Luo, Yvonne Hsu-Lin; Fukushige, Eka; Da Cruz, Lyndon

    2016-07-01

    Second Sight System bionic eye implant, a commercially available visual prosthesis developed by Second Sight Medical Products, has been implanted in over 125 patients with outer retinal dystrophies such as retinitis pigmentosa. The system has gained regulatory approval in both the USA and Europe, and aims to restore vision by electrical stimulation of the nerve cells of the inner retina. In this review, we present the safety profile of this implant from the international clinical trial and discuss the nature and levels of improvement in visual function achieved by patients implanted with the system. Expert commentary: Future developments for the system will be explored following the discussion of the current usefulness of the device, its limitation as and the areas in which further development is necessary.

  8. Advanced interdisciplinary technologies

    NASA Technical Reports Server (NTRS)

    Anderson, John L.

    1990-01-01

    The following topics are presented in view graph form: (1) breakthrough trust (space research and technology assessment); (2) bionics (technology derivatives from biological systems); (3) biodynamics (modeling of human biomechanical performance based on anatomical data); and (4) tethered atmospheric research probes.

  9. A TPMS-based method for modeling porous scaffolds for bionic bone tissue engineering.

    PubMed

    Shi, Jianping; Zhu, Liya; Li, Lan; Li, Zongan; Yang, Jiquan; Wang, Xingsong

    2018-05-09

    In the field of bone defect repair, gradient porous scaffolds have received increased attention because they provide a better environment for promoting tissue regeneration. In this study, we propose an effective method to generate bionic porous scaffolds based on the TPMS (triply periodic minimal surface) and SF (sigmoid function) methods. First, cortical bone morphological features (e.g., pore size and distribution) were determined for several regions of a rabbit femoral bone by analyzing CT-scans. A finite element method was used to evaluate the mechanical properties of the bone at these respective areas. These results were used to place different TPMS substructures into one scaffold domain with smooth transitions. The geometrical parameters of the scaffolds were optimized to match the elastic properties of a human bone. With this proposed method, a functional gradient porous scaffold could be designed and produced by an additive manufacturing method.

  10. The fabrication and property of hydrophilic and hydrophobic double functional bionic chitosan film.

    PubMed

    Wang, Xiaohong; Xi, Zhen; Liu, Zhongxin; Yang, Liang; Cao, Yang

    2011-11-01

    A new kind of hydrophobic bionic chitosan film was fabricated by simulating the surface structure of lotus leaf. The titanium oxide nanotube array was used as templates. Scanning electron microscopy (SEM) images show that one side of this films have nano-scale rough surface with spherical protrusions alike the surface of lotus leaf. The diameter of the protrusions is about 100 nm, which is equal to diameter of the titanium oxide nanotube. The water contact angle of chitosan films is up to 120 degrees and it is hydrophobic. The other side of the film is flat and the contact angle is 70 degrees. That indicated that the hydrophilism of natural materials is connected with the surface structures. The double functional chitosan films, one side is hydrophilic, the other is hydrophobic, can be made by an easy method. This method is non-toxic and clean. The double functional chitosan film will improve the application of chitosan films in medicine.

  11. Healthons: errorless healthcare with bionic hugs and no need for quality control.

    PubMed

    Bushko, Renata G

    2005-01-01

    Errorless, invisible, continuous and infrastructure-free healthcare should become our goal. In order to achieve that goal, we need to rapidly move from current episodic and emergency-driven "healthcare delivery system" to an intelligent and extelligent health environment. That requires introduction of distributed affective Intelligent Caring Creatures (ICCs) consisting of healthons. Healthons are tools combining prevention with diagnosis and treatment based on continuous monitoring and analyzing of vital signs and biochemistry. Unlike humans, who posses only two or three dimensions of thinking, healthons can assure errorless health because of their adaptability, flexibility, and multidimensional reasoning capability. ICCs can do "the right thing" based on (1) state-of-art medical knowledge, (2) data about emotional, physiological, and genetic state of a consumer and (3) moral values of a consumer. The transition to the intelligent health environment based on ICCs requires the solutions to many currently unsolved healthcare problems. This paper lists the unsolved problems (by analogy to mathematical unsolved problems list) and explains why errorless healthcare with bionic hugs and no need for quality control is possible.

  12. Cities of the future-bionic systems of new urban environment.

    PubMed

    Krzemińska, Alicja Edyta; Zaręba, Anna Danuta; Dzikowska, Anna; Jarosz, Katarzyna Rozalia

    2017-12-07

    The concepts of the cities we know nowadays, and which we are accustomed to, change at a very rapid pace. The philosophy of their design is also changing. It will base on new standards, entering a completely different, futuristic dimension. This stage is related to changes in the perception of space, location and lack of belonging to definite, national or cultural structures. Cities of the future are cities primarily intelligent, zero-energetic, zero-waste, environmentally sustainable, self-sufficient in terms of both organic food production and symbiosis between the environment and industry. New cities will be able to have new organisational structures-either city states, or, apolitical, jigsaw-like structures that can change their position-like in the case of the city of Artisanopolis, designed as a floating city, close to the land, reminiscent of the legendary Atlantis. This paper is focused on the main issues connected with problems of the contemporary city planning. The purpose of the research was to identify existing technological solutions, whose aim is to use solar energy and urban greenery. The studies were based on literature related to future city development issues and futuristic projects of the architects and city planners. In the paper, the following issues have been verified: futuristic cities and districts, and original bionic buildings, both residential and industrial. The results of the analysis have been presented in a tabular form.

  13. [Application of in vitro bionic digestion and biomembrane extraction for metal speciation analysis, bioavailability and risk assessment in lianhua qingwen capsule].

    PubMed

    Lin, Lu-Xiu; Li, Shun-Xing; Zheng, Feng-Ying

    2014-06-01

    One of the causes of the high cost of pharmaceuticals and the major obstacles to rapidly assessing the bioavailability and risk of a chemical is the lack of experimental model systems. A new pre-treatment technology, in vitro bionic digestion was designed for metal analysis in Lianhua Qingwen capsule. The capsule was digested on 37 degrees C under the acidity of the stomach or intestine, and with the inorganic and organic compounds (including digestive enzymes) found in the stomach or intestine, and then the chyme was obtained. Being similar to the biomembrane between the gastrointestinal tract and blood vessels, monolayer liposome was used as biomembrane model Affinity-monolayer liposome metals (AMLMs) and water-soluble metals were used for metal speciation analysis in the capsule. Based on the concentration of AMLMs, the main absorption site of trace metals was proposed. The metal total contents or the concentration of AMLMs in the capsule were compared to the nutritional requirements, daily permissible dose and heavy metal total contents from the "import and export of medicinal plants and preparation of green industry state standards". The metal concentrations in the capsule were within the safety baseline levels for human consumption. After in vitro bionic digestion, most of trace metals were absorbed mainly in intestine. The concentration of As, Cd, Pb was 0.38, 0.07, 1.60 mg x kg(-1), respectively, far less than the permissible dose from the "import and export of medicinal plants and preparation of green industry state standards".

  14. A tricalcium phosphate/polyether ether ketone anchor bionic fixation device for anterior cruciate ligament reconstruction: Safety and efficacy in a beagle model.

    PubMed

    Mao, Genwen; Qin, Zili; Li, Zheng; Li, Xiang; Qiu, Yusheng; Bian, Weiguo

    2018-05-02

    The goal of this study was to develop a bionic fixation device based on the use of a tricalcium phosphate/polyether ether ketone anchor and harvesting of the ulnar carpal flexor muscle tendon for application as a ligament graft in a beagle anterior cruciate ligament (ACL) reconstruction model, with the goal of accelerating the ligament graft-to-bone tunnel healing and providing a robust stability through exploration of this new kind of autologous ligament graft. The safety and efficacy of this fixation device were explored 3 and 6 months after surgery in a beagle ACL reconstruction model using biomechanical tests and comprehensive histological observation. The data were compared using a two-tailed Student's t test and a paired t test. A p value <0.05 was defined as statistically significant. All the models were successfully established. This fixation device possessed the excellent mechanical properties for ACL reconstruction. A comprehensive histological observation revealed that a cartilage layer was visible in the transition zone between the tendon and bone interface at both 3 and 6 months postoperation. The trabecular of the new bone was observed six months after surgery and was found to be similar to a direct connection. This fixation technique provided not only a robust primary mechanical fixation but also a bionic fixation for long-term knee joint stability by accelerating the healing of the tendon to the bone tunnel, showing a high potential for use in clinical practice. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

  15. A Randomized Controlled Trial Comparing the Letter Project Advance Directive to Traditional Advance Directive.

    PubMed

    Periyakoil, Vyjeyanthi S; Neri, Eric; Kraemer, Helena

    2017-09-01

    Simpler alternatives to traditional advance directives that are easy to understand and available in multiple formats and can be initiated by patients and families will help facilitate advance care planning. The goal of this study was to compare the acceptability of the letter advance directive (LAD) to the traditional advance directive (TAD) of the state of California. A web-based, randomized controlled trial was conducted, in which the participants were randomized to one of two types of advance directives (ADs): the LAD (intervention) or the TAD (control). Primary outcomes were participant ratings of the ease, value, and their level of comfort in the AD document they completed. A total of 400 participants completed the study, with 216 randomized to the LAD and 184 to the TAD by a computerized algorithm. Overall, participants preferred the LAD to the TAD (success rate difference [SRD] = 0.46, 95th percentile confidence interval [CI]: 0.36-0.56, p < 0.001). The participants felt that, compared to the TAD, the LAD was easier to read and understand (SRD = 0.56, CI: 0.47-0.65, p < 0.001); better reflected what matters most to them (SRD = 0.39, CI: 0.29-0.48, p < 0.001); helped stimulate their thinking about the types of treatments they wanted at the end of life (SRD = 0.32, CI: 0.23-0.42, p < 0.001); allowed them to describe how they made medical decisions in their family (SRD = 0.31, CI: 0.21-0.40, p < 0.001); and could help their doctor(s) (SRD = 0.24, CI: 0.13-0.34, p < 0.001) and their families (SRD = 0.19, CI: 0.08-0.28, p < 0.001) understand their end-of-life treatment preferences. Patients reported the letter advance directive to be a better alternative to the traditional advance directive form.

  16. Speech Perception for Adult Cochlear Implant Recipients in a Realistic Background Noise: Effectiveness of Preprocessing Strategies and External Options for Improving Speech Recognition in Noise

    PubMed Central

    Gifford, René H.; Revit, Lawrence J.

    2014-01-01

    Background Although cochlear implant patients are achieving increasingly higher levels of performance, speech perception in noise continues to be problematic. The newest generations of implant speech processors are equipped with preprocessing and/or external accessories that are purported to improve listening in noise. Most speech perception measures in the clinical setting, however, do not provide a close approximation to real-world listening environments. Purpose To assess speech perception for adult cochlear implant recipients in the presence of a realistic restaurant simulation generated by an eight-loudspeaker (R-SPACE™) array in order to determine whether commercially available preprocessing strategies and/or external accessories yield improved sentence recognition in noise. Research Design Single-subject, repeated-measures design with two groups of participants: Advanced Bionics and Cochlear Corporation recipients. Study Sample Thirty-four subjects, ranging in age from 18 to 90 yr (mean 54.5 yr), participated in this prospective study. Fourteen subjects were Advanced Bionics recipients, and 20 subjects were Cochlear Corporation recipients. Intervention Speech reception thresholds (SRTs) in semidiffuse restaurant noise originating from an eight-loudspeaker array were assessed with the subjects’ preferred listening programs as well as with the addition of either Beam™ preprocessing (Cochlear Corporation) or the T-Mic® accessory option (Advanced Bionics). Data Collection and Analysis In Experiment 1, adaptive SRTs with the Hearing in Noise Test sentences were obtained for all 34 subjects. For Cochlear Corporation recipients, SRTs were obtained with their preferred everyday listening program as well as with the addition of Focus preprocessing. For Advanced Bionics recipients, SRTs were obtained with the integrated behind-the-ear (BTE) mic as well as with the T-Mic. Statistical analysis using a repeated-measures analysis of variance (ANOVA) evaluated the

  17. Speech perception for adult cochlear implant recipients in a realistic background noise: effectiveness of preprocessing strategies and external options for improving speech recognition in noise.

    PubMed

    Gifford, René H; Revit, Lawrence J

    2010-01-01

    Although cochlear implant patients are achieving increasingly higher levels of performance, speech perception in noise continues to be problematic. The newest generations of implant speech processors are equipped with preprocessing and/or external accessories that are purported to improve listening in noise. Most speech perception measures in the clinical setting, however, do not provide a close approximation to real-world listening environments. To assess speech perception for adult cochlear implant recipients in the presence of a realistic restaurant simulation generated by an eight-loudspeaker (R-SPACE) array in order to determine whether commercially available preprocessing strategies and/or external accessories yield improved sentence recognition in noise. Single-subject, repeated-measures design with two groups of participants: Advanced Bionics and Cochlear Corporation recipients. Thirty-four subjects, ranging in age from 18 to 90 yr (mean 54.5 yr), participated in this prospective study. Fourteen subjects were Advanced Bionics recipients, and 20 subjects were Cochlear Corporation recipients. Speech reception thresholds (SRTs) in semidiffuse restaurant noise originating from an eight-loudspeaker array were assessed with the subjects' preferred listening programs as well as with the addition of either Beam preprocessing (Cochlear Corporation) or the T-Mic accessory option (Advanced Bionics). In Experiment 1, adaptive SRTs with the Hearing in Noise Test sentences were obtained for all 34 subjects. For Cochlear Corporation recipients, SRTs were obtained with their preferred everyday listening program as well as with the addition of Focus preprocessing. For Advanced Bionics recipients, SRTs were obtained with the integrated behind-the-ear (BTE) mic as well as with the T-Mic. Statistical analysis using a repeated-measures analysis of variance (ANOVA) evaluated the effects of the preprocessing strategy or external accessory in reducing the SRT in noise. In addition

  18. Drag Reduction and Performance Improvement of Hydraulic Torque Converters with Multiple Biological Characteristics.

    PubMed

    Chunbao, Liu; Li, Li; Yulong, Lei; Changsuo, Liu; Yubo, Zhang

    2016-01-01

    Fish-like, dolphin-like, and bionic nonsmooth surfaces were employed in a hydraulic torque converter to achieve drag reduction and performance improvement, which were aimed at reducing profile loss, impacting loss and friction loss, respectively. YJSW335, a twin turbine torque converter, was bionically designed delicately. The biological characteristics consisted of fish-like blades in all four wheels, dolphin-like structure in the first turbine and the stator, and nonsmooth surfaces in the pump. The prediction performance of bionic YJSW335, obtained by computational fluid dynamics simulation, was improved compared with that of the original model, and then it could be proved that drag reduction had been achieved. The mechanism accounting for drag reduction of three factors was also investigated. After bionic design, the torque ratio and the highest efficiencies of YJSW335 were both advanced, which were very difficult to achieve through traditional design method. Moreover, the highest efficiency of the low speed area and high speed area is 85.65% and 86.32%, respectively. By economic matching analysis of the original and bionic powertrains, the latter can significantly reduce the fuel consumption and improve the operating economy of the loader.

  19. Drag Reduction and Performance Improvement of Hydraulic Torque Converters with Multiple Biological Characteristics

    PubMed Central

    Chunbao, Liu; Changsuo, Liu; Yubo, Zhang

    2016-01-01

    Fish-like, dolphin-like, and bionic nonsmooth surfaces were employed in a hydraulic torque converter to achieve drag reduction and performance improvement, which were aimed at reducing profile loss, impacting loss and friction loss, respectively. YJSW335, a twin turbine torque converter, was bionically designed delicately. The biological characteristics consisted of fish-like blades in all four wheels, dolphin-like structure in the first turbine and the stator, and nonsmooth surfaces in the pump. The prediction performance of bionic YJSW335, obtained by computational fluid dynamics simulation, was improved compared with that of the original model, and then it could be proved that drag reduction had been achieved. The mechanism accounting for drag reduction of three factors was also investigated. After bionic design, the torque ratio and the highest efficiencies of YJSW335 were both advanced, which were very difficult to achieve through traditional design method. Moreover, the highest efficiency of the low speed area and high speed area is 85.65% and 86.32%, respectively. By economic matching analysis of the original and bionic powertrains, the latter can significantly reduce the fuel consumption and improve the operating economy of the loader. PMID:27752220

  20. Born-Infeld extension of Lovelock brane gravity in the system of M0-branes and its application for the emergence of Pauli exclusion principle in BIonic superconductors

    NASA Astrophysics Data System (ADS)

    Sepehri, Alireza

    2016-07-01

    Recently, some authors (Cruz and Rojas, 2013 [1]) have constructed a Born-Infeld type action which may be written in terms of the Lovelock brane Lagrangians for a given dimension p. We reconsider their model in M-theory and study the process of birth and growth of nonlinear spinor and bosonic gravity during the construction of Mp-branes. Then, by application of this idea to BIonic system, we construct a BIonic superconductor in the background of nonlinear gravity. In this model, first, M0-branes link to each other and build an M5-brane and an anti-M5-brane connected by an M2-brane. M0-branes are zero dimensional objects that only scalars are attached to them. By constructing higher dimensional branes from M0-branes, gauge fields are produced. Also, if M0-branes don't link to each other completely, the symmetry of system is broken and fermions are created. The curvature produced by fermions has the opposite sign the curvature produced by gauge fields. Fermions on M5-branes and M2 plays the role of bridge between them. By passing time, M2 dissolves in M5's and nonlinear bosonic and spinor gravities are produced. By closing M5-branes towards each other, coupling of two identical fermions on two branes to each other causes that the square mass of their system becomes negative and some tachyonic states are created. For removing these tachyons, M5-branes compact, the sign of gravity between branes reverses, anti-gravity is produced which causes that branes and identical fermions get away from each other. This is the reason for the emergence of Pauli exclusion principle in Bionic system. Also, the spinor gravity vanishes and its energy builds a new M2 between M5-branes. We obtain the resistivity in this system and find that its value decreases by closing M5 branes to each other and shrinks to zero at colliding point of branes. This idea has different applications. For example, in cosmology, universes are located on M5-branes and M2-brane has the role of bridge between

  1. The EvoDevoCI: A Concept Inventory for Gauging Students’ Understanding of Evolutionary Developmental Biology

    PubMed Central

    Perez, Kathryn E.; Hiatt, Anna; Davis, Gregory K.; Trujillo, Caleb; French, Donald P.; Terry, Mark; Price, Rebecca M.

    2013-01-01

    The American Association for the Advancement of Science 2011 report Vision and Change in Undergraduate Biology Education encourages the teaching of developmental biology as an important part of teaching evolution. Recently, however, we found that biology majors often lack the developmental knowledge needed to understand evolutionary developmental biology, or “evo-devo.” To assist in efforts to improve evo-devo instruction among undergraduate biology majors, we designed a concept inventory (CI) for evolutionary developmental biology, the EvoDevoCI. The CI measures student understanding of six core evo-devo concepts using four scenarios and 11 multiple-choice items, all inspired by authentic scientific examples. Distracters were designed to represent the common conceptual difficulties students have with each evo-devo concept. The tool was validated by experts and administered at four institutions to 1191 students during preliminary (n = 652) and final (n = 539) field trials. We used student responses to evaluate the readability, difficulty, discriminability, validity, and reliability of the EvoDevoCI, which included items ranging in difficulty from 0.22–0.55 and in discriminability from 0.19–0.38. Such measures suggest the EvoDevoCI is an effective tool for assessing student understanding of evo-devo concepts and the prevalence of associated common conceptual difficulties among both novice and advanced undergraduate biology majors. PMID:24297293

  2. Wear resistance of machine tools' bionic linear rolling guides by laser cladding

    NASA Astrophysics Data System (ADS)

    Wang, Yiqiang; Liu, Botao; Guo, Zhengcai

    2017-06-01

    In order to improve the rolling wear resistance (RWR) of linear rolling guides (LRG) as well as prolong the life of machine tools, various shape samples with different units spaces ranged from 1 to 5 mm are designed through the observation of animals in the desert and manufactured by laser cladding. Wear resistance tests reproducing closely the real operational condition are conducted by using a homemade linear reciprocating wear test machine, and wear resistance is evaluated by means of weight loss measurement. Results indicate that the samples with bionic units have better RWR than the untreated one, of which the reticulate treated sample with unit space 3 mm present the best RWR. More specifically, among the punctuate treated samples, the mass loss increases with the increase of unit space; among the striate treated samples, the mass loss changes slightly with the increase of unit space, attaining a minimum at the unit space of 4 mm; among the reticulate treated samples, with the increase of unit space, the mass loss initially decreases, but turns to increase after reaching a minimum at the unit space of 3 mm. Additionally, the samples with striate shape perform better wear resistance than the other shape groups on the whole. From the ratio value of laser treated area to contacted area perspective, that the samples with ratio value between 0.15 and 0.3 possess better wear resistance is concluded.

  3. Comprehensive in vitro Proarrhythmia Assay (CiPA): Pending issues for successful validation and implementation.

    PubMed

    Cavero, Icilio; Guillon, Jean-Michel; Ballet, Veronique; Clements, Mike; Gerbeau, Jean-Frédéric; Holzgrefe, Henry

    2016-01-01

    The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a nonclinical Safety Pharmacology paradigm for discovering electrophysiological mechanisms that are likely to confer proarrhythmic liability to drug candidates intended for human use. Key talks delivered at the 'CiPA on my mind' session, held during the 2015 Annual Meeting of the Safety Pharmacology Society (SPS), are summarized. Issues and potential solutions relating to crucial constituents [e.g., biological materials (ion channels and pluripotent stem cell-derived cardiomyocytes), study platforms, drug solutions, and data analysis] of CiPA core assays are critically examined. In order to advance the CiPA paradigm from the current testing and validation stages to a research and regulatory drug development strategy, systematic guidance by CiPA stakeholders is necessary to expedite solutions to pending and newly arising issues. Once a study protocol is proved to yield robust and reproducible results within and across laboratories, it can be implemented as qualified regulatory procedure. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Advancing Water Science through Improved Cyberinfrastructure

    NASA Astrophysics Data System (ADS)

    Koch, B. J.; Miles, B.; Rai, A.; Ahalt, S.; Band, L. E.; Minsker, B.; Palmer, M.; Williams, M. R.; Idaszak, R.; Whitton, M. C.

    2012-12-01

    Major scientific advances are needed to help address impacts of climate change and increasing human-mediated environmental modification on the water cycle at global and local scales. However, such advances within the water sciences are limited in part by inadequate information infrastructures. For example, cyberinfrastructure (CI) includes the integrated computer hardware, software, networks, sensors, data, and human capital that enable scientific workflows to be carried out within and among individual research efforts and across varied disciplines. A coordinated transformation of existing CI and development of new CI could accelerate the productivity of water science by enabling greater discovery, access, and interoperability of data and models, and by freeing scientists to do science rather than create and manage technological tools. To elucidate specific ways in which improved CI could advance water science, three challenges confronting the water science community were evaluated: 1) How does ecohydrologic patch structure affect nitrogen transport and fate in watersheds?, 2) How can human-modified environments emulate natural water and nutrient cycling to enhance both human and ecosystem well-being?, 3) How do changes in climate affect water availability to support biodiversity and human needs? We assessed the approaches used by researchers to address components of these challenges, identified barriers imposed by limitations of current CI, and interviewed leaders in various water science subdisciplines to determine the most recent CI tools employed. Our preliminary findings revealed four areas where CI improvements are likely to stimulate scientific advances: 1) sensor networks, 2) data quality assurance/quality control, 3) data and modeling standards, 4) high performance computing. In addition, the full potential of a re-envisioned water science CI cannot be realized without a substantial training component. In light of these findings, we suggest that CI

  5. Family structure, experiences with end-of-life decision making, and who asked about advance directives impacts advance directive completion rates.

    PubMed

    Van Scoy, Lauren J; Howrylak, Judie; Nguyen, Anhthu; Chen, Melodie; Sherman, Michael

    2014-10-01

    Advance directives are an important but underutilized resource. Reasons for this underutilization need to be determined. We investigated factors associated with completion of advance directives among inpatients. We conducted prospective, structured interviews on family structure, health care, disease, and end-of-life experiences. We compared those with completed advance directives and those without. We interviewed 130 inpatients in an urban university hospital. We used bivariate analysis and logistic regression to identify characteristics of patients with living wills and health care proxies versus patients without them. Twenty-one percent of patients had a living will and 35% had a health care proxy. Patients with completed living wills were older (p≤0.0046), had more comorbidities (p=0.018), were widowed (p=0.02), and were more often admitted with chronic disease (p=0.009) compared to those without living wills. Patients with health care proxies were older (p<0.001), had religious affiliations (p=0.04), more children (p=0.03), and more often widowed (p≤0.001) than those without health care proxies. Patients were 10.8 times (95% confidence interval [CI] 4.59-25.3), 46.5 times (95% CI 15.1-139.4), and 68.6 times (95% CI 13.0-361.3) more likely to complete a living will when asked by medical staff, legal staff, or family and friends, respectively, than those not asked. Patients with health care proxies were 1.68 times (95% CI 0.81-3.47), 4.34 times (95% CI 1.50-12.6), and 18.0 times (95% CI 2.03-158.8) more likely to have been asked by the same groups. Patients with experience in end-of-life decision-making were 2.54 times more likely to possess a living will (95%CI 1.01-6.42) and 3.53 times more likely to possess a health care proxy (95% CI 1.51-8.25) than those without experiences. Having been asked about advance directives by medical staff, legal staff, or family and friends increases the likelihood that patients will possess an advance directive. Those with

  6. Design and development of a ferroelectric micro photo detector for the bionic eye

    NASA Astrophysics Data System (ADS)

    Song, Yang

    Driven by no effective therapy for Retinitis Pigmentosa and Age Related Macular Degeneration, artificial vision through the development of an artificial retina that can be implanted into the human eye, is being addressed by the Bionic Eye. This dissertation focuses on the study of a photoferroelectric micro photo detector as an implantable retinal prosthesis for vision restoration in patients with above disorders. This implant uses an electrical signal to trigger the appropriate ocular cells of the vision system without resorting to wiring or electrode implantation. The research work includes fabrication of photoferroelectric thin film micro detectors, characterization of these photoferroelectric micro devices as photovoltaic cells, and Finite Element Method (FEM) modeling of the photoferroelectrics and their device-neuron interface. A ferroelectric micro detector exhibiting the photovoltaic effect (PVE) directly adds electrical potential to the neuron membrane outer wall at the focal adhesion regions. The electrical potential then generates a retinal cell membrane potential deflection through a newly developed Direct-Electric-Field-Coupling (DEFC) model. This model is quite different from the traditional electric current model because instead of current directly working on the cell membrane, the PVE current is used to generate a localized high electric potential in the focal adhesion region by working together with the anisotropic high internal impedance of ferroelectric thin films. General electrodes and silicon photodetectors do not have such anisotropy and high impedance, and thus they cannot generate DEFC. This mechanism investigation is very valuable, because it clearly shows that our artificial retina works in a way that is totally different from the traditional current stimulation methods.

  7. Experiences of the use of FOX, an intelligent agent, for programming cochlear implant sound processors in new users.

    PubMed

    Vaerenberg, Bart; Govaerts, Paul J; de Ceulaer, Geert; Daemers, Kristin; Schauwers, Karen

    2011-01-01

    This report describes the application of the software tool "Fitting to Outcomes eXpert" (FOX) in programming the cochlear implant (CI) processor in new users. FOX is an intelligent agent to assist in the programming of CI processors. The concept of FOX is to modify maps on the basis of specific outcome measures, achieved using heuristic logic and based on a set of deterministic "rules". A prospective study was conducted on eight consecutive CI-users with a follow-up of three months. Eight adult subjects with postlingual deafness were implanted with the Advanced Bionics HiRes90k device. The implants were programmed using FOX, running a set of rules known as Eargroup's EG0910 advice, which features a set of "automaps". The protocol employed for the initial 3 months is presented, with description of the map modifications generated by FOX and the corresponding psychoacoustic test results. The 3 month median results show 25 dBHL as PTA, 77% (55 dBSPL) and 71% (70 dBSPL) phoneme score at speech audiometry and loudness scaling in or near to the normal zone at different frequencies. It is concluded that this approach is feasible to start up CI fitting and yields good outcome.

  8. Electron Attachment to Halomethanes at High Temperature: CH2CI2, CF2CI2, CH3CI, and CF3CI Attachment Rate Constants up to 1100 K

    DTIC Science & Technology

    2009-08-01

    hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...attachment reactions: 390i 50 meV (CH:Cl;). 124* 20 meV (CF2CI2), 670 + 70 meV (CH3CI), and 406±50 meV (CF,C1). Comparisons are made with existing data ...Research Laboratory, 29 Randolph Road, Hanscom Air Force Base . Massachusetts 01731-3010, USA (Received 15 May 2009; accepted 4 August 2009; published

  9. Mental health, treatment preferences, advance care planning, location, and quality of death in advanced cancer patients with dependent children.

    PubMed

    Nilsson, Matthew E; Maciejewski, Paul K; Zhang, Baohui; Wright, Alexi A; Trice, Elizabeth D; Muriel, Anna C; Friedlander, Robert J; Fasciano, Karen M; Block, Susan D; Prigerson, Holly G

    2009-01-15

    Clinicians observe that advanced cancer patients with dependent children agonize over the impact their death will have on their children. The objective of this study was to determine empirically whether advanced cancer patients with and without dependent children differ in treatment preferences, mental health, and end-of-life (EOL) outcomes. Coping with Cancer is a National Cancer Institute/National Institute of Mental Health-funded, multi-institutional, prospective cohort study of 668 patients with advanced cancer. Patients with and without dependent children were compared on rates of psychiatric disorders, advance care planning (ACP), EOL care, quality of their last week of life, and location of death. In adjusted analyses, patients with advanced cancer who had dependent children were more likely to meet panic disorder criteria (adjusted odds ratio [AOR], 5.41; 95% confidence interval [95% CI], 2.13-13.69), more likely to be worried (mean difference in standard deviations [delta], 0.09; P=.006), and more likely to prefer aggressive treatment over palliative care (AOR, 1.77; 95% CI, 1.07-2.93). Patients with dependent children were less likely to engage in ACP (eg, do not resuscitate orders: AOR, 0.44; 95% CI, 0.26-0.75) and had a worse quality of life in the last week of life (delta, 0.15; P=.007). Among spousal caregivers, those with dependent children were more likely to meet criteria for major depressive disorder (AOR, 4.53; 95% CI, 1.47-14) and generalized anxiety disorder (AOR, 3.95; 95% CI, 1.29-12.16). Patients with dependent children were more anxious, were less likely to engage in ACP, and were more likely to have a worse quality of life in their last week of life. Advanced cancer patients and spousal caregivers with dependent children represent a particularly distressed group that warrants further clinical attention, research, and support. Copyright (c) 2009 American Cancer Society.

  10. Characterization of Lignin Streams during Bionic Liquid-Based Pretreatment from Grass, Hardwood, and Softwood

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dutta, Tanmoy; Papa, Gabriella; Wang, Eileen

    Delignification as a function of ionic liquid (IL) pretreatment has potential in terms of recovering and converting the fractionated lignin streams to renewable products. Renewable biogenic ionic liquids, or bionic liquids (eg. cholinium lysinate, ([Ch][Lys])), provide opportunities in terms of effective, economic and sustainable lignocellulosic biomass pretreatment. We have evaluated [Ch][Lys] pretreatment in terms of sugar and lignin yields for three different feedstocks: switchgrass, eucalyptus, and pine. Four lignin streams isolated during [Ch][Lys] pretreatment and enzymatic hydrolysis were comprehensively analyzed, tracking their changes in physical-chemical structures. We observed changes in major lignin linkages and lignin aromatics units (p-hydroxyphenyl (H), guaiacylmore » (G), and syringil (S)) that occurred during pretreatment. A compositional analysis of the different process streams and a comprehensive mass balance in conjunction with multiple analytical techniques (Nuclear Magnetic Resonance (NMR), Mass Spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), Gel Permeation Chromatography (GPC)) is presented. Qualitative and quantitative analyses indicates that there are significantly more lignin-carbohydrate interactions for G-rich lignin in pine. The lignin removal and extent of lignin depolymerization for switchgrass and eucalyptus were higher than pine, and follows the order of switchgrass > eucalyptus > pine. The recovered lignin from pretreated liquid contained a lower relative amount of carbohydrate signals than raw biomass, indicating a high degree of dissociation of lignin carbohydrate complex (LCC) linkages for all samples analyzed. The insights gained from this work contribute to better understanding of physiochemical properties of lignin streams generated during [Ch][Lys] pretreatment, offering a starting point for lignin valorization strategies.« less

  11. Bionic limbs: clinical reality and academic promises.

    PubMed

    Farina, Dario; Aszmann, Oskar

    2014-10-08

    Three recent articles in Science Translational Medicine (Tan et al. and Ortiz-Catalan et al., this issue; Raspopovic et al., 5 Feb 2014 issue, 222ra19) present neuroprosthetic systems in which sensory information is delivered through direct nerve stimulation while controlling an action of the prosthesis--in all three cases, arm and hand movement. We discuss such sensory-motor integration and other key issues in prosthetic reconstruction, with an emphasis on the gap existing between clinically available systems and more advanced, custom-designed academic systems. In the near future, osseointegration, implanted muscle, and nerve electrodes for decoding and stimulation may be components of prosthetic systems for clinical use, available to a large patient population. Copyright © 2014, American Association for the Advancement of Science.

  12. Analysis of Advanced CI Applications

    DTIC Science & Technology

    1981-03-01

    rner Street Boston, ,/iA 021 10 Atcn« L,r. Fred Quelle AF^L/Of (ianscum AHB, MA 01/31 Atun « ./r. John Oanny AF..L/AL0 Kirtiand AHB...M d/11 / Atun « .jr. J. d. Hoyye ArJC/OL Andrew^ Ar’d, DO 20.334 Atv,n« oapt Oyole AFdC/X^rU Andrews Af-d, ÜO 20334 8 10 II...8217’■ ..:., ■■ . >. ■ — Ini Mil/Li;icoin Lab H. ). üux l-i Le ; in ji-on, MA U^l /.j Atun » iJr. ü. üreenwooj 4U Naval

  13. CI Controls for Energy and Environment

    NASA Technical Reports Server (NTRS)

    Biondo, Samuel J.

    1996-01-01

    Computational intelligence (CI) is a rapidly evolving field that utilizes life imitating metaphors for guiding model building including, but not limited to neural networks, fuzzy logic, genetic algorithms, artificial life, and hybrid CI paradigms. Although the boundaries between artificial intelligence (AI) and CI are not distinct, their research communities are separate and distinct. CI researchers tend to focus on processing numerical data from sensors, while the AI community generally relies on symbolic computing to capture human knowledge. In both areas, there is a great deal of interest and activity in hybrid systems that can offset the limitations of individual methods, extend their capabilities, and create new capabilities. Examples of the benefits that can accrue from hybrid systems are contained.

  14. [Inpatient rehabilitation of adult CI users: Results in dependency of duration of deafness, CI experience and age].

    PubMed

    Zeh, R; Baumann, U

    2015-08-01

    Cochlear implants (CI) have proven to be a highly effective treatment for severe hearing loss or deafness. Inpatient rehabilitation therapy is frequently discussed as a means to increase the speech perception abilities achieved by CI. However, thus far there exists no quantitative evaluation of the effect of these therapies. A retrospective analysis of audiometric data obtained from 1355 CI users compared standardized and qualitative speech intelligibility tests conducted at two time points (admission to and discharge from inpatient hearing therapy, duration 3-5 weeks). The test battery comprised examination of vowel/consonant identification, the Freiburg numbers and monosyllabic test (65 and 80 dB sound pressure level, SPL, free-field sound level), the Hochmair-Schulz-Moser (HSM) sentence test in quiet and in noise (65 dB SPL speech level; 15 dB signal-to-noise ratio, SNR), and a speech tracking test with and without lip-reading. An average increase of 20 percentage points was scored at discharge compared to the admission tests. Patients of all ages and duration of deafness demonstrated the same amount of benefit from the rehabilitation treatment. After completion of inpatient rehabilitation treatment, patients with short duration of CI experience (below 4 months) achieved test scores comparable to experienced long-term users. The demonstrated benefit of the treatment was independent of age and duration of deafness or CI experience. The rehabilitative training program significantly improved hearing abilities and speech perception in CI users, thus promoting their professional and social inclusion. The present results support the efficacy of inpatient rehabilitation for CI recipients. Integration of this or similar therapeutic concepts in the German catalog of follow-up treatment measures appears justified.

  15. Use of medications of questionable benefit in advanced dementia.

    PubMed

    Tjia, Jennifer; Briesacher, Becky A; Peterson, Daniel; Liu, Qin; Andrade, Susan E; Mitchell, Susan L

    2014-11-01

    Advanced dementia is characterized by severe cognitive impairment and complete functional dependence. Patients' goals of care should guide the prescribing of medication during such terminal illness. Medications that do not promote the primary goal of care should be minimized. To estimate the prevalence of medications with questionable benefit used by nursing home residents with advanced dementia, identify resident- and facility-level characteristics associated with such use, and estimate associated medication expenditures. Cross-sectional study of medication use by nursing home residents with advanced dementia using a nationwide long-term care pharmacy database linked to the Minimum Data Set (460 facilities) between October 1, 2009, and September 30, 2010. Use of medication deemed of questionable benefit in advanced dementia based on previously published criteria and mean 90-day expenditures attributable to these medications per resident. Generalized estimating equations using the logit link function were used to identify resident- and facility-related factors independently associated with the likelihood of receiving medications of questionable benefit after accounting for clustering within nursing homes. Of 5406 nursing home residents with advanced dementia, 2911 (53.9%) received at least 1 medication with questionable benefit (range, 44.7% in the Mid-Atlantic census region to 65.0% in the West South Central census region). Cholinesterase inhibitors (36.4%), memantine hydrochloride (25.2%), and lipid-lowering agents (22.4%) were the most commonly prescribed. In adjusted analyses, having eating problems (adjusted odds ratio [AOR], 0.68; 95% CI, 0.59-0.78), a feeding tube (AOR, 0.58; 95% CI, 0.48-0.70), or a do-not-resuscitate order (AOR, 0.65; 95% CI, 0.57-0.75), and enrolling in hospice (AOR, 0.69; 95% CI, 0.58-0.82) lowered the likelihood of receiving these medications. High facility-level use of feeding tubes increased the likelihood of receiving these

  16. Interventions Associated With the Management of Suspected Infections in Advanced Dementia.

    PubMed

    Yates, Elizabeth; Mitchell, Susan L; Habtemariam, Daniel; Dufour, Alyssa B; Givens, Jane L

    2015-12-01

    Nursing home (NH) residents with advanced dementia are commonly suspected of having infections. Most episodes are treated with antimicrobials, although evidence supporting bacterial infections is often lacking. The extent to which other interventions are used in managing suspected infections is unknown. To describe interventions used to manage suspected infections in advanced dementia and identify factors associated with greater intervention use. Residents with advanced dementia who experienced suspected infections in 35 Boston NHs were followed for 12 months. Data describing interventions used in managing each episode were ascertained, including blood draws, chest radiographs, procurement of urine samples, and hospital transfers. Resident and episode characteristics associated with greater intervention use were identified using mixed model regression. A total of 240 residents experienced 496 suspected infections involving the following interventions: any, n = 360 (72.6%); hospital transfer, n = 51 (10.3%); blood draw, n = 215 (43.3%); chest radiograph, n = 120 (24.2%); and urine sample, n = 222 (44.8%). Factors associated with greater intervention use included black race (adjusted odds ratio [AOR] 3.19; 95% CI, 1.37-7.44); no do not hospitalize order (AOR, 1.83; 95% CI, 1.16-2.90); not on hospice (AOR, 5.41; 95% CI, 2.14-13.70); and suspected source being respiratory (AOR, 10.67; 95% CI, 4.99-22.80), urine (AOR, 15.79; 95% CI, 7.41-33.66) or fever of unknown source (AOR, 20.26; 95% CI, 8.42-48.73) vs. skin/soft tissue. NH residents with advanced dementia frequently experience potentially burdensome interventions when suspected of having an infection. Advance directives to limit such interventions may be appropriate for residents whose goal of care is comfort. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  17. Use of advanced treatment technologies among men at low risk of dying from prostate cancer.

    PubMed

    Jacobs, Bruce L; Zhang, Yun; Schroeck, Florian R; Skolarus, Ted A; Wei, John T; Montie, James E; Gilbert, Scott M; Strope, Seth A; Dunn, Rodney L; Miller, David C; Hollenbeck, Brent K

    2013-06-26

    The use of advanced treatment technologies (ie, intensity-modulated radiotherapy [IMRT] and robotic prostatectomy) for prostate cancer is increasing. The extent to which these advanced treatment technologies have disseminated among patients at low risk of dying from prostate cancer is uncertain. To assess the use of advanced treatment technologies, compared with prior standards (ie, traditional external beam radiation treatment [EBRT] and open radical prostatectomy) and observation, among men with a low risk of dying from prostate cancer. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified a retrospective cohort of men diagnosed with prostate cancer between 2004 and 2009 who underwent IMRT (n = 23,633), EBRT (n = 3926), robotic prostatectomy (n = 5881), open radical prostatectomy (n = 6123), or observation (n = 16,384). Follow-up data were available through December 31, 2010. The use of advanced treatment technologies among men unlikely to die from prostate cancer, as assessed by low-risk disease (clinical stage ≤T2a, biopsy Gleason score ≤6, and prostate-specific antigen level ≤10 ng/mL), high risk of noncancer mortality (based on the predicted probability of death within 10 years in the absence of a cancer diagnosis), or both. In our cohort, the use of advanced treatment technologies increased from 32% (95% CI, 30%-33%) to 44% (95% CI, 43%-46%) among men with low-risk disease (P < .001) and from 36% (95% CI, 35%-38%) to 57% (95% CI, 55%-59%) among men with high risk of noncancer mortality (P < .001). The use of these advanced treatment technologies among men with both low-risk disease and high risk of noncancer mortality increased from 25% (95% CI, 23%-28%) to 34% (95% CI, 31%-37%) (P < .001). Among all patients diagnosed in SEER, the use of advanced treatment technologies for men unlikely to die from prostate cancer increased from 13% (95% CI, 12%-14%), or 129.2 per 1000 patients diagnosed with prostate cancer, to 24% (95

  18. Humanoid monocular stereo measuring system with two degrees of freedom using bionic optical imaging system

    NASA Astrophysics Data System (ADS)

    Du, Jia-Wei; Wang, Xuan-Yin; Zhu, Shi-Qiang

    2017-10-01

    Based on the process by which the spatial depth clue is obtained by a single eye, a monocular stereo vision to measure the depth information of spatial objects was proposed in this paper and a humanoid monocular stereo measuring system with two degrees of freedom was demonstrated. The proposed system can effectively obtain the three-dimensional (3-D) structure of spatial objects of different distances without changing the position of the system and has the advantages of being exquisite, smart, and flexible. The bionic optical imaging system we proposed in a previous paper, named ZJU SY-I, was employed and its vision characteristic was just like the resolution decay of the eye's vision from center to periphery. We simplified the eye's rotation in the eye socket and the coordinated rotation of other organs of the body into two rotations in the orthogonal direction and employed a rotating platform with two rotation degrees of freedom to drive ZJU SY-I. The structure of the proposed system was described in detail. The depth of a single feature point on the spatial object was deduced, as well as its spatial coordination. With the focal length adjustment of ZJU SY-I and the rotation control of the rotation platform, the spatial coordinates of all feature points on the spatial object could be obtained and then the 3-D structure of the spatial object could be reconstructed. The 3-D structure measurement experiments of two spatial objects with different distances and sizes were conducted. Some main factors affecting the measurement accuracy of the proposed system were analyzed and discussed.

  19. Clinical outcomes of TS-1 chemotherapy for advanced and recurrent gastric cancer.

    PubMed

    Lee, Sung Ryol; Kim, Hyung Ook; Yoo, Chang Hak

    2011-09-01

    Titanium silicate (TS)-1 chemotherapy has been widely used against gastric cancer in Japan. The aim of the present study was to assess the efficacy and hematological safety of TS-1 as treatment for advanced and recurrent gastric cancer. From September 2006 to February 2011, 51 advanced or recurrent gastric cancers were treated with TS-1. One course of treatment consisted of 40, 50, or 60 mg/m(2) of TS-1 twice a day for 28 days, followed by withdrawal for two weeks. The primary end point was progression-free survival (PFS), and the secondary end point was overall survival (OS). The disease control rate was 39.2% (complete response, 0/51; partial response, 6/51; stable disease, 14/51; progressive disease, 23/51; not evaluable, 8/51). The median PFS was 4.0 months (95% confidence interval [CI], 2.2 to 5.7); the median PFS of the advanced group was 6.0 months (95% CI, 2.8 to 9.1), and the median PFS of the recurrent group was 3.0 months (95% CI, 1.8 to 4.1). The median OS was 11.0 months (95% CI, 6.3 to 15.6); the median OS of the advanced group was 10.0 months (95% CI, 4.9 to 15.0), and the median OS of the recurrent group was 14.0 months (95% CI, 4.1 to 23.8). Grade 3 or 4 hematological toxicity occurred in three patients (5.9%), anemia occurred in two patients (3.9%), and thrombocytopenia occurred in one patient (2%). TS-1 chemotherapy was safe and effective, with relatively long PFS and OS in patients with advanced and recurrent gastric cancers.

  20. Racial disparities in advanced stage colorectal cancer survival

    PubMed Central

    Wallace, Kristin; Hill, Elizabeth G.; Lewin, David N.; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E.; Wargovich, Michael J.; Berger, Franklin G.; Bolick, Susan W.; Thomas, Melanie B.; Alberg, Anthony J.

    2013-01-01

    Purpose African Americans (AA) have a higher incidence and lower survival from colorectal cancer (CRC) compared to European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry (SCCCR) is used to investigate the relationship between race and age on advanced stage CRC survival. Methods The study population was comprised of 3865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2673 (69%) EA and 1192 (31%) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95% confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards (CPH) regression models to generate Hazard Ratios (HR) and 95% CI. Results We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (< 50 years), AA race was associated with a 1.34 (95% CI 1.06-1.71) higher risk of death compared to EA. Among older patients, we observed a modest increase risk of death among AA men compared to EA (HR 1.16 (95% CI 1.01-1.32) but no difference by race among women (HR 0.94 (95% CI 0.82-1.08)). Moreover, we observed that the disparity in survival has worsened over the past 15 years. Conclusions Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those < 50 years old. PMID:23296454

  1. Advancing the frontiers of silk fibroin protein-based materials for futuristic electronics and clinical wound-healing (Invited review).

    PubMed

    Koh, Leng-Duei; Yeo, Jingjie; Lee, Yeong Yuh; Ong, Qunya; Han, Mingyong; Tee, Benjamin C-K

    2018-05-01

    The present review will introduce the basic concepts of silk-based electronics/optoelectronics including the latest technological advances on the use of silk fibroin in combination with other functional components, with an emphasis on improving the performance of next-generation silk-based materials. It also highlights the patterning of silk fibroin to produce micro/nano-scale features, as well as the functionalization of silk fibroin to impart antimicrobial (i.e. antibacterial) properties. Silk-based bioelectronics have great potential for advanced or futuristic bio-applications including e-skins, e-bandages, biosensors, wearable displays, implantable devices, artificial muscles, etc. Notably, silk-based organic field-effect transistors have highly promising applications in e-skins and biosensors; silk-based electrodes/antennas are used for in vivo bioanalysis or sensing purpose (e.g., measurement of neurotransmitter such as dopamine) in addition to their use as food sensors; silk-based diodes can be applied as light sources for wound healing or tissue engineering, e.g., in cutaneous wound closure or induction of photothrombosis of corneal neovascularization; silk-based actuators have promising applications as artificial muscles; whereas silk-based memristors have exciting applications as logic or synaptic network for realizing e-skins or bionic brains. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Review of the research on “structural bionic” method of large sculpture

    NASA Astrophysics Data System (ADS)

    Yin, Jiang; Yang, Wenchang

    2017-09-01

    This paper presented the basic concept of bionic sculpture and summarized the application status of “structural bionic”theory in large bionic sculpture field. Introduced the development trend and challenges of large bionic sculpture and pointed out that the sculpture's “structural bionic” can bring higher mechanical performance of the new structure and system, The evaluation method and structure design for large bionic sculpture are urgently needed.Finally prospected the market of the large bionic sculpture.

  3. Technology that Touches Lives: Teleconsultation to Benefit Persons with Upper Limb Loss

    PubMed Central

    Whelan, Lynsay R.; Wagner, Nathan

    2011-01-01

    While over 1.5 million individuals are living with limb loss in the United States (Ziegler-Graham et al., 2008), only 10% of these individuals have a loss that affects an upper limb. Coincident with the relatively low incidence of upper limb loss, is a shortage of the community-based prosthetic rehabilitation experts that can help prosthetic users to more fully integrate their devices into their daily routines. This article describes how expert prosthetists and occupational therapists at Touch Bionics, a manufacturer of advanced upper limb prosthetic devices, employ Voice over the Internet Protocol (VoIP) videoconferencing software telehealth technologies to engage in remote consultation with users of prosthetic devices and/or their local practitioners. The Touch Bionics staff provide follow-up expertise to local prosthetists, occupational therapists, and other health professionals. Contrasted with prior telephone-based consultations, the video-enabled approach provides enhanced capabilities to benefit persons with upper limb loss. Currently, the opportunities for Touch Bionics occupational therapists to fully engage in patient-based services delivered through telehealth technologies are significantly reduced by their need to obtain and maintain professional licenses in multiple states. PMID:25945186

  4. An insect-inspired bionic sensor for tactile localization and material classification with state-dependent modulation

    PubMed Central

    Patanè, Luca; Hellbach, Sven; Krause, André F.; Arena, Paolo; Dürr, Volker

    2012-01-01

    Insects carry a pair of antennae on their head: multimodal sensory organs that serve a wide range of sensory-guided behaviors. During locomotion, antennae are involved in near-range orientation, for example in detecting, localizing, probing, and negotiating obstacles. Here we present a bionic, active tactile sensing system inspired by insect antennae. It comprises an actuated elastic rod equipped with a terminal acceleration sensor. The measurement principle is based on the analysis of damped harmonic oscillations registered upon contact with an object. The dominant frequency of the oscillation is extracted to determine the distance of the contact point along the probe and basal angular encoders allow tactile localization in a polar coordinate system. Finally, the damping behavior of the registered signal is exploited to determine the most likely material. The tactile sensor is tested in four approaches with increasing neural plausibility: first, we show that peak extraction from the Fourier spectrum is sufficient for tactile localization with position errors below 1%. Also, the damping property of the extracted frequency is used for material classification. Second, we show that the Fourier spectrum can be analysed by an Artificial Neural Network (ANN) which can be trained to decode contact distance and to classify contact materials. Thirdly, we show how efficiency can be improved by band-pass filtering the Fourier spectrum by application of non-negative matrix factorization. This reduces the input dimension by 95% while reducing classification performance by 8% only. Finally, we replace the FFT by an array of spiking neurons with gradually differing resonance properties, such that their spike rate is a function of the input frequency. We show that this network can be applied to detect tactile contact events of a wheeled robot, and how detrimental effects of robot velocity on antennal dynamics can be suppressed by state-dependent modulation of the input signals

  5. Racial disparities in advanced-stage colorectal cancer survival.

    PubMed

    Wallace, Kristin; Hill, Elizabeth G; Lewin, David N; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E; Wargovich, Michael J; Berger, Franklin G; Bolick, Susan W; Thomas, Melanie B; Alberg, Anthony J

    2013-03-01

    African-Americans (AA) have a higher incidence of and lower survival from colorectal cancer (CRC) compared with European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry are used to investigate the relationship between race and age on advanced-stage CRC survival. The study population was comprised of 3,865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2,673 (69 %) EA and 1,192 (31 %) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95 % confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards regression models to generate hazard ratios (HR) and 95 % CI. We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (<50 years), AA race was associated with a 1.34 times (95 % CI 1.06-1.71) higher risk of death compared with EA. Among older patients, we observed a modest increase in risk of death among AA men compared with EA [HR 1.16 (95 % CI 1.01-1.32)] but no difference by race between women [HR 0.94 (95 % CI 0.82-1.08)]. Moreover, we observed that the disparity in survival has worsened over the past 15 years. Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those <50 years old.

  6. Hospitalization Rates and Predictors of Rehospitalization Among Individuals With Advanced Cancer in the Year After Diagnosis.

    PubMed

    Whitney, Robin L; Bell, Janice F; Tancredi, Daniel J; Romano, Patrick S; Bold, Richard J; Joseph, Jill G

    2017-11-01

    Purpose Among individuals with advanced cancer, frequent hospitalization increasingly is viewed as a hallmark of poor-quality care. We examined hospitalization rates and individual- and hospital-level predictors of rehospitalization among individuals with advanced cancer in the year after diagnosis. Methods Individuals diagnosed with advanced breast, colorectal, non-small-cell lung, or pancreatic cancer from 2009 to 2012 (N = 25,032) were identified with data from the California Cancer Registry (CCR). After linkage with inpatient discharge data, multistate and log-linear Poisson regression models were used to calculate hospitalization rates and to model rehospitalization in the year after diagnosis, accounting for survival. Results In the year after diagnosis, 71% of individuals with advanced cancer were hospitalized, 16% had three or more hospitalizations, and 64% of hospitalizations originated in the emergency department. Rehospitalization rates were significantly associated with black non-Hispanic (incidence rate ratio [IRR], 1.29; 95% CI, 1.17 to 1.42) and Hispanic (IRR, 1.11; 95% CI, 1.03 to 1.20) race/ethnicity; public insurance (IRR, 1.37; 95% CI, 1.23 to 1.47) and no insurance (IRR, 1.17; 95% CI, 1.02 to 1.35); lower socioeconomic status quintiles (IRRs, 1.09 to 1.29); comorbidities (IRRs, 1.13 to 1.59); and pancreatic (IRR, 2.07; 95% CI, 1.95 to 2.20) and non-small-cell lung (IRR, 1.69; 95% CI, 1.54 to 1.86) cancers versus colorectal cancer. Rehospitalization rates were significantly lower after discharge from a hospital that had an outpatient palliative care program (IRR, 0.90; 95% CI, 0.83 to 0.97) and were higher after discharge from a for-profit hospital (IRR, 1.33; 95% CI, 1.14 to 1.56). Conclusion Individuals with advanced cancer experience a heavy burden of hospitalization in the year after diagnosis. Efforts to reduce hospitalization and provide care congruent with patient preferences might target individuals at higher risk. Future work might

  7. Patterns of Resuscitation Care and Survival After In-Hospital Cardiac Arrest in Patients With Advanced Cancer.

    PubMed

    Bruckel, Jeffrey T; Wong, Sandra L; Chan, Paul S; Bradley, Steven M; Nallamothu, Brahmajee K

    2017-10-01

    Little is known regarding patterns of resuscitation care in patients with advanced cancer who suffer in-hospital cardiac arrest (IHCA). In the Get With The Guidelines - Resuscitation registry, 47,157 adults with IHCA with and without advanced cancer (defined as the presence of metastatic or hematologic malignancy) were identified at 369 hospitals from April 2006 through June 2010. We compared rates of return of spontaneous circulation (ROSC) and survival to discharge between groups using multivariable models. We also compared duration of resuscitation effort and resuscitation quality measures. Overall, 6,585 patients with IHCA (14.0%) had advanced cancer. Patients with advanced cancer had lower multivariable-adjusted rates of ROSC (52.3% [95% CI, 49.5% to 55.3%] v 56.6% [95% CI, 53.8% to 59.5%]; P < .001) and survival to discharge (7.4% [95% CI, 6.6% to 8.4%] v 13.4% [95% CI, 12.1% to 14.8%]; P < .001). Among nonsurvivors who died during resuscitation, patients with advanced cancer had better performance on most resuscitation quality measures. Among patients with ROSC, patients with advanced cancer were made Do Not Attempt Resuscitation (DNAR) more frequently within 48 hours (adjusted relative risk, 1.30 [95% CI, 1.24 to 1.37]; P < .001). Adjustment for DNAR status explained some of the immediate effect of advanced cancer on survival; however, survival remained significantly lower in patients with cancer. Patients with advanced cancer can expect lower survival rates after IHCA compared with those without advanced cancer, and they are more frequently made DNAR within 48 hours of ROSC. These findings have important implications for discussions of resuscitation care wishes with patients and can better inform end-of-life discussions.

  8. Everyday listening questionnaire: correlation between subjective hearing and objective performance.

    PubMed

    Brendel, Martina; Frohne-Buechner, Carolin; Lesinski-Schiedat, Anke; Lenarz, Thomas; Buechner, Andreas

    2014-01-01

    Clinical experience has demonstrated that speech understanding by cochlear implant (CI) recipients has improved over recent years with the development of new technology. The Everyday Listening Questionnaire 2 (ELQ 2) was designed to collect information regarding the challenges faced by CI recipients in everyday listening. The aim of this study was to compare self-assessment of CI users using ELQ 2 with objective speech recognition measures and to compare results between users of older and newer coding strategies. During their regular clinical review appointments a group of representative adult CI recipients implanted with the Advanced Bionics implant system were asked to complete the questionnaire. The first 100 patients who agreed to participate in this survey were recruited independent of processor generation and speech coding strategy. Correlations between subjectively scored hearing performance in everyday listening situations and objectively measured speech perception abilities were examined relative to the speech coding strategies used. When subjects were grouped by strategy there were significant differences between users of older 'standard' strategies and users of the newer, currently available strategies (HiRes and HiRes 120), especially in the categories of telephone use and music perception. Significant correlations were found between certain subjective ratings and the objective speech perception data in noise. There is a good correlation between subjective and objective data. Users of more recent speech coding strategies tend to have fewer problems in difficult hearing situations.

  9. Advance Care Planning in an Accountable Care Organization Is Associated with Increased Advanced Directive Documentation and Decreased Costs

    PubMed Central

    Kim, Minchul; Franciskovich, Chris M.; Weinberg, Jason E.; Svendsen, Jessica D.; Fehr, Linda S.; Funk, Amy; Sawicki, Robert; Asche, Carl V.

    2018-01-01

    Abstract Background: Advance care planning (ACP) documents patient wishes and increases awareness of palliative care options. Objective: To study the association of outpatient ACP with advanced directive documentation, utilization, and costs of care. Design: This was a case–control study of cases with ACP who died matched 1:1 with controls. We used 12 months of data pre-ACP/prematch and predeath. We compared rates of documentation with logit model regression and conducted a difference-in-difference analysis using generalized linear models for utilization and costs. Setting/subjects: Medicare beneficiaries attributed to a large rural-suburban-small metro multisite accountable care organization from January 2013 to April 2016, with cross reference to ACP facilitator logs to find cases. Measurements: The presence of advance directive forms was verified by chart review. Cost analysis included all utilization and costs billed to Medicare. Results: We matched 325 cases and 325 controls (51.1% female and 48.9% male, mean age 81). 320/325 (98.5%) ACP versus 243/325 (74.8%) of controls had a Healthcare Power of Attorney (odds ratio [OR] 21.6, 95% CI 8.6–54.1) and 172/325(52.9%) ACP versus 145/325 (44.6%) controls had Practitioner Orders for Life Sustaining Treatment (OR 1.40, 95% CI 1.02–1.90) post-ACP/postmatch. Adjusted results showed ACP cases had fewer inpatient admissions (−0.37 admissions, 95% CI −0.66 to −0.08), and inpatient days (−3.66 days, 95% CI −6.23 to −1.09), with no differences in hospice, hospice days, skilled nursing facility use, home health use, 30-day readmissions, or emergency department visits. Adjusted costs were $9,500 lower in the ACP group (95% CI −$16,207 to −$2,793). Conclusions: ACP increases documentation and was associated with a reduction in overall costs driven primarily by a reduction in inpatient utilization. Our data set was limited by small numbers of minorities and cancer patients. PMID:29206564

  10. Advance Care Planning in an Accountable Care Organization Is Associated with Increased Advanced Directive Documentation and Decreased Costs.

    PubMed

    Bond, William F; Kim, Minchul; Franciskovich, Chris M; Weinberg, Jason E; Svendsen, Jessica D; Fehr, Linda S; Funk, Amy; Sawicki, Robert; Asche, Carl V

    2018-04-01

    Advance care planning (ACP) documents patient wishes and increases awareness of palliative care options. To study the association of outpatient ACP with advanced directive documentation, utilization, and costs of care. This was a case-control study of cases with ACP who died matched 1:1 with controls. We used 12 months of data pre-ACP/prematch and predeath. We compared rates of documentation with logit model regression and conducted a difference-in-difference analysis using generalized linear models for utilization and costs. Medicare beneficiaries attributed to a large rural-suburban-small metro multisite accountable care organization from January 2013 to April 2016, with cross reference to ACP facilitator logs to find cases. The presence of advance directive forms was verified by chart review. Cost analysis included all utilization and costs billed to Medicare. We matched 325 cases and 325 controls (51.1% female and 48.9% male, mean age 81). 320/325 (98.5%) ACP versus 243/325 (74.8%) of controls had a Healthcare Power of Attorney (odds ratio [OR] 21.6, 95% CI 8.6-54.1) and 172/325(52.9%) ACP versus 145/325 (44.6%) controls had Practitioner Orders for Life Sustaining Treatment (OR 1.40, 95% CI 1.02-1.90) post-ACP/postmatch. Adjusted results showed ACP cases had fewer inpatient admissions (-0.37 admissions, 95% CI -0.66 to -0.08), and inpatient days (-3.66 days, 95% CI -6.23 to -1.09), with no differences in hospice, hospice days, skilled nursing facility use, home health use, 30-day readmissions, or emergency department visits. Adjusted costs were $9,500 lower in the ACP group (95% CI -$16,207 to -$2,793). ACP increases documentation and was associated with a reduction in overall costs driven primarily by a reduction in inpatient utilization. Our data set was limited by small numbers of minorities and cancer patients.

  11. Bilateral globus pallidus internus deep brain stimulation for dyskinetic cerebral palsy supports success of cochlear implantation in a 5-year old ex-24 week preterm twin with absent cerebellar hemispheres.

    PubMed

    Lin, Jean-Pierre; Kaminska, Margaret; Perides, Sarah; Gimeno, Hortensia; Baker, Lesley; Lumsden, Daniel E; Britz, Anzell; Driver, Sandra; Fitzgerald-O'Connor, Alec; Selway, Richard

    2017-01-01

    Early onset dystonia (dyskinesia) and deafness in childhood pose significant challenges for children and carers and are the cause of multiple disability. It is particularly tragic when the child cannot make use of early cochlear implantation (CI) technology to relieve deafness and improve language and communication, because severe cervical and truncal dystonia brushes off the magnetic amplifier behind the ears. Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) neuromodulation can reduce dyskinesia, thus supporting CI neuromodulation success. We describe the importance of the order of dual neuromodulation surgery for dystonia and deafness. First with bilateral GPi DBS using a rechargeable ACTIVA-RC neurostimulator followed 5 months later by unilateral CI with a Harmony (BTE) Advanced Bionics Hi Res 90 K cochlear device. This double neuromodulation was performed in series in a 12.5 kg 5 year-old ex-24 week gestation-born twin without a cerebellum. Relief of dyskinesia enabled continuous use of the CI amplifier. Language understanding and communication improved. Dystonic storms abated. Tolerance of sitting increased with emergence of manual function. Status dystonicus ensued 10 days after ACTIVA-RC removal for infection-erosion at 3 years and 10 months. He required intensive care and DBS re-implantation 3 weeks later together with 8 months of hospital care. Today he is virtually back to the level of functioning before the DBS removal in 2012 and background medication continues to be slowly weaned. This case illustrates that early neuromodulation with DBS for dystonic cerebral palsy followed by CI for deafness is beneficial. Both should be considered early i.e. under the age of five years. The DBS should precede the CI to maximise dystonia reduction and thus benefits from CI. This requires close working between the paediatric DBS and CI services. Copyright © 2016. Published by Elsevier Ltd.

  12. A new high-resolution sediment record from Lake Gościąż (central Poland)

    NASA Astrophysics Data System (ADS)

    Bonk, Alicja; Błaszkiewicz, Mirosław; Brauer, Achim; Brykała, Dariusz; Gierszewski, Piotr; Kramkowski, Mateusz; Plessen, Brigit; Schwab, Markus; Słowiński, Michał; Tjallingii, Rik

    2017-04-01

    The varved sediments from Lake Gościąż, located in the Vistula Valley in Central Poland, are an iconic record for palaeoclimate and palaeoenvironmental reconstruction (Goslar et al. 2000, Hajdas et al. 1995, Ralska-Jasiewiczowa et al. 1998). Recently, we obtained a set of new sediment cores from Lake Gościąż and established a 21 m long sediment profile. Except of the topmost part of the core, it is continuously laminated down to glacial sands. We aim at applying a comprehensive multi-proxy core analyses combined with monitoring of present-day sedimentation processes. Sediment investigations will include new methods that have been developed or advanced since the previous studies on the Lake Gościąż sediments including continuous micro-facies analyses, μXRF core scanning and tephrochronology. The main aims of our new project are a revision of the existing floating chronology and to synchronise the Lake Gościąż sediment record based on independent isochrones with other European varved lake records like, e.g. Lake Meerfelder Maar, in order to investigate in detail proxy responses to climate change and to decipher regional leads and lags in climate change. Here, we will present (1) the objectives of our new project on this key record of past climate and environmental change and, (2) preliminary results including magnetic susceptibility, μ-XRF core scanning and microfacies images. This study is a contribution to scientific project financed by the National Science Centre, Poland - No DEC-2015/19/B/ST10/03039.

  13. CI chondrite-like clasts in the Nilpena polymict ureilite - Implications for aqueous alteration processes in CI chondrites

    NASA Technical Reports Server (NTRS)

    Brearley, Adrian J.; Prinz, Martin

    1992-01-01

    Petrographic studies of Nilpena polymict ureilite have revealed the presence of small quantities of carbonaceous chondrite matrix clasts. Detailed electron microprobe and TEM studies show that the chemistry and fine-scale mineralogy of one of these clasts is consistent with CI carbonaceous chondrite matrix. Compared to Orgeuil, the phyllosilicate, sulfide, and oxide mineralogy suggests that the Nilpena clasts may represent a less altered type of CI matrix. It is suggested that increased oxidation and aqueous alteration of Nilpena-type materials could result in the formation of the type of mineral assemblage observed in Orgueil. Increased alteration produces progressive more Mg-rich phyllosilicates and more Fe(3+)-rich iron oxides, such as ferrihydrite. As a function of increased alteration, Ca is also progressively leached from the matrix material to form carbonate veins. The depletion of Ca in CI chondrite matrices suggests the Ivuna and Alais may be intermediate in their degree of alteration to Nilpena and Orgueil.

  14. X-ray Reverberation Mapping of Ci Cam

    NASA Astrophysics Data System (ADS)

    Bartlett, Elizabeth; Garcia, M.

    2009-01-01

    We have analyzed the X-ray lightcurve of the star CI Cam, the optical counterpart of the X-ray transient XTE J0421+56 using data from XMM-Newton. Our motivation is based on evidence from ground based optical interferometry from the Keck and IOTA observatories which suggests that the dust surrounding CI CAM has a taurus morphology rather than a spherical distribution as previously hypothesized. By using a technique known as reverberation mapping we have constrained the time delay between the continuum of CI Cam and the Fe-K fluorescence line, corresponding to the reflection of the continuum off the dusty taurus. The time delay yields information on the size of the taurus.

  15. Vegetarianism as a protective factor for colorectal adenoma and advanced adenoma in Asians.

    PubMed

    Lee, Chang Geun; Hahn, Suk Jae; Song, Min Keun; Lee, Jun Kyu; Kim, Jae Hak; Lim, Yun Jeong; Koh, Moon-Soo; Lee, Jin Ho; Kang, Hyoun Woo

    2014-05-01

    Although epidemiologic and animal studies suggest a vegetarian diet protects against the development of colorectal cancer, the relationship between vegetarian diet and incidence of colorectal adenoma is not yet conclusive, especially for Asians. The purpose of this study was to examine the protective effect of a vegetarian diet against colorectal adenoma and advanced adenoma. This cross-sectional study compared the prevalence of colorectal adenoma among Buddhist priests, who are obligatory vegetarians, with that among age and sex-matched controls. All the subjects underwent health checkups in a health-promotion center in Korea. Colorectal adenoma and advanced adenoma were both more prevalent in the general population group than in the Buddhist priest group (25.2 vs. 17.9 %, 6.7 vs. 2.0 %). However, the prevalence of metabolic syndrome, high body mass index, and waist circumference were higher in the Buddhist priest group. According to univariate analysis, non-vegetarian diet (general population) significantly increased the prevalence of colorectal adenoma and advanced adenoma compared with a vegetarian diet (Buddhist priests) (OR 1.54, 95 % CI 1.08-2.21, P = 0.018; OR 3.60, 95 % CI 1.53-8.48, P = 0.003). In a conditional regression analysis model, non-vegetarian diet was also a significant risk factor for colorectal adenoma and advanced adenoma (OR 1.52, 95 % CI 0.75-2.07, P = 0.043; OR 2.94, CI 0.97-7.18, P = 0.036). Vegetarianism may be effective in preventing both colorectal adenoma and advanced adenoma in Asians.

  16. Fabrication of a bionic microstructure on a C/SiC brake lining surface: Positive applications of surface defects for surface wetting control

    NASA Astrophysics Data System (ADS)

    Wu, M. L.; Ren, C. Z.; Xu, H. Z.; Zhou, C. L.

    2018-05-01

    The material removal processes generate interesting surface topographies, unfortunately, that was usually considered to be surface defects. To date, little attention has been devoted to the positive applications of these interesting surface defects resulted from laser ablation to improve C/SiC surface wettability. In this study, the formation mechanism behind surface defects (residual particles) is discussed first. The results showed that the residual particles with various diameters experienced regeneration and migration, causing them to accumulate repeatedly. The effective accumulation of these residual particles with various diameters provides a new method about fabricating bionic microstructures for surface wetting control. The negligible influence of ablation processes on the chemical component of the subsurface was studied by comparing the C-O-Si weight percentage at the C/SiC subsurface. A group of microstructures were fabricated under different laser trace and different laser parameters. Surface wettability experimental results for different types of microstructures were compared. The results showed that the surface wettability increased as the laser scanning speed decreased. The surface wettability increased with the density of the laser scanning trace. We also demonstrated the application of optimized combination of laser parameters and laser trace to simulate a lotus leaf's microstructure on C/SiC surfaces. The parameter selection depends on the specific material properties.

  17. VELoCiRaPTORS.

    NASA Astrophysics Data System (ADS)

    Lundgren, J.; Esham, B.; Padalino, S. J.; Sangster, T. C.; Glebov, V.

    2007-11-01

    The Venting and Exhausting of Low Level Air Contaminants in the Rapid Pneumatic Transport of Radioactive Samples (VELoCiRaPTORS) system is constructed to transport radioactive materials quickly and safely at the NIF. A radioactive sample will be placed inside a carrier that is transported via an airflow system produced by controlled differential pressure. Midway through the transportation process, the carrier will be stopped and vented by a powered exhaust blower which will remove radioactive gases within the transport carrier. A Geiger counter will monitor the activity of the exhaust gas to ensure that it is below acceptable levels. If the radiation level is sufficient, the carrier will pass through the remainder of the system, pneumatically braking at the counting station. The complete design will run manually or automatically with control software. Tests were performed using an inactive carrier to determine possible transportation problems. The system underwent many consecutive trials without failure. VELoCiRaPTORS is a prototype of a system that could be installed at both the Laboratory for Laser Energetics at the University of Rochester and the National Ignition Facility at LLNL.

  18. Implications of CI therapy for visual deficit training

    PubMed Central

    Taub, Edward; Mark, Victor W.; Uswatte, Gitendra

    2014-01-01

    We address here the question of whether the techniques of Constraint Induced (CI) therapy, a family of treatments that has been employed in the rehabilitation of movement and language after brain damage might apply to the rehabilitation of such visual deficits as unilateral spatial neglect and visual field deficits. CI therapy has been used successfully for the upper and lower extremities after chronic stroke, cerebral palsy (CP), multiple sclerosis (MS), other central nervous system (CNS) degenerative conditions, resection of motor areas of the brain, focal hand dystonia, and aphasia. Treatments making use of similar methods have proven efficacious for amblyopia. The CI therapy approach consists of four major components: intensive training, training by shaping, a “transfer package” to facilitate the transfer of gains from the treatment setting to everyday activities, and strong discouragement of compensatory strategies. CI therapy is said to be effective because it overcomes learned nonuse, a learned inhibition of movement that follows injury to the CNS. In addition, CI therapy produces substantial increases in the gray matter of motor areas on both sides of the brain. We propose here that these mechanisms are examples of more general processes: learned nonuse being considered parallel to sensory nonuse following damage to sensory areas of the brain, with both having in common diminished neural connections (DNCs) in the nervous system as an underlying mechanism. CI therapy would achieve its therapeutic effect by strengthening the DNCs. Use-dependent cortical reorganization is considered to be an example of the more general neuroplastic mechanism of brain structure repurposing. If the mechanisms involved in these broader categories are involved in each of the deficits being considered, then it may be the principles underlying efficacious treatment in each case may be similar. The lessons learned during CI therapy research might then prove useful for the

  19. Evaluation of the Clinical Data Dictionary (CiDD)

    PubMed Central

    Lee, Myung Kyung; Min, Yul Ha; Kim, Younglan; Min, Hyo Ki; Ham, Sung Woo

    2010-01-01

    Objectives The purpose of the study was to evaluate content coverage and data quality of the Clinical Data Dictionary (CiDD) developed by the Center for Interoperable EHR (CiEHR). Methods A total of 12,994 terms were collected from 98 clinical forms of a tertiary cancer center hospital with 500 beds. After data cleaning, 9,418 terms were mapped with the data items of the CiDD by the research team, and validated by 30 doctors and nurses at the research hospital. Results Mapping results were classified into five categories: lexically mapped; semantically mapped; mapped to either a broader term or a narrower term; mapped to more than one term and not mapped. In terms of coverage, out of 9,418 terms, 6,750 (71.7%) terms were mapped; 4,319 (45.9%) terms were lexically mapped; 2,431 (25.8%) were semantically mapped; 281 (3.0%) terms were mapped to a broader term; 43 (0.5%) were mapped to a narrower term; and 550 (5.8%) were mapped to more than one term. In terms of data quality, the CiDD has problems such as errors in concept namingand representation, redundancy in synonyms, inadequate synonyms, and ambiguity in meaning. Conclusions Although the CiDD has terms covering 72% of local clinical terms, the CiDD can be improved by cleaning up errors and redundancies, adding textual definitions or use cases of the concept, and arranging the concepts in a hierarchy. PMID:21818428

  20. Rationale for Modernising Imaging in Advanced Prostate Cancer.

    PubMed

    Padhani, Anwar R; Lecouvet, Frederic E; Tunariu, Nina; Koh, Dow-Mu; De Keyzer, Frederik; Collins, David J; Sala, Evis; Fanti, Stefano; Vargas, H Alberto; Petralia, Giuseppe; Schlemmer, Heinz Peter; Tombal, Bertrand; de Bono, Johann

    2017-04-01

    To effectively manage patients with advanced prostate cancer (APC), it is essential to have accurate, reproducible, and validated methods for detecting and quantifying the burden of bone and soft tissue metastases and for assessing their response to therapy. Current standard of care imaging with bone and computed tomography (CT) scans have significant limitations for the assessment of bone metastases in particular. We aimed to undertake a critical comparative review of imaging methods used for diagnosis and disease monitoring of metastatic APC from the perspective of their availability and ability to assess disease presence, extent, and response of bone and soft tissue disease. An expert panel of radiologists, nuclear medicine physicians, and medical physicists with the greatest experience of imaging in advanced prostate cancer prepared a review of the practicalities, performance, merits, and limitations of currently available imaging methods. Meta-analyses showed that positron emission tomography (PET)/CT with different radiotracers and whole-body magnetic resonance imaging (WB-MRI) are more accurate for bone lesion detection than CT and bone scans (BSs). At a patient level, the pooled sensitivities for bone disease by using choline (CH)-PET/CT, WB-MRI, and BS were 91% (95% confidence interval [CI], 83-96%), 97% (95% CI, 91-99%), and 79% (95% CI, 73-83%), respectively. The pooled specificities for bone metastases detection using CH-PET/CT, WB-MRI, and BS were 99% (95% CI, 93-100%), 95% (95% CI, 90-97%), and 82% (95% CI, 78-85%), respectively. The ability of PET/CT and WB-MRI to assess therapeutic benefits is promising but has not been comprehensively evaluated. There is variability in the cost, availability, and quality of PET/CT and WB-MRI. Standardisation of acquisition, interpretation, and reporting of WB-MRI and PET/CT scans is required to assess the performance of these techniques in clinical trials of treatment approaches in APC. PET/CT and whole-body MRI

  1. FIRE_CI2_ETL_RADAR

    Atmospheric Science Data Center

    2015-11-25

    FIRE_CI2_ETL_RADAR Project Title:  FIRE II CIRRUS Discipline:  ... Platform:  Ground Station Instrument:  Radar Spatial Coverage:  (37.06, -95.34) Spatial ... Order Data Guide Documents:  ETL_RADAR Guide Readme Files:  Readme ETL_RADAR (PS) ...

  2. Proteobionics: biomimetics in proteomics.

    PubMed

    Sommer, Andrei P; Gheorghiu, Eleonora

    2006-03-01

    Proteomics was established 10 years ago by the analysis of microbial genomes via their protein complement or proteome. Bionics is an ancient art, which converts structures optimized by nature into advanced technical products. Previously, we analyzed survival modalities in nanobacteria and converted the interplay between survival-oriented protein functions and nanoscale mineral shells into models for advanced drug delivery. Exploiting protein functions observed in nature to design biomedical products and therapies could be named proteobionics. Here, we present examples for this new branch of nanoproteomics.

  3. CI Aql monitoring needed to support HST observations

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2016-10-01

    Dr. Edward Sion (Villanova University) has requested AAVSO observers' assistance in monitoring the recurrent nova CI Aql in support of observations with the Hubble Space Telescope Cosmic Origins Spectrograph scheduled for October 31 - November 2, 2016, and November 3 - November 5, 2016. These observations are part of a study on short orbital period recurrent novae as Supernovae Type Ia progenitors. It is essential to know 24 hours prior to the HST COS observations that CI Aql is not in outburst, in order to protect the instrumentation. Observers are asked to keep an eye on CI Aql with nightly snapshot images (V preferred) from now until November 12, and to report their observations promptly. It will be especially important to know the brightness of CI Aql each night for October 28 through November 7 UT. Visual observations are welcome. CI Aql (Nova Aql 1917) has had recurrent outbursts in 1941 and 2000, brightening to V 8.5. At minimum it is V 16-16.5 or fainter. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (https://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details.

  4. Diagnostic value of stool DNA testing for multiple markers of colorectal cancer and advanced adenoma: a meta-analysis.

    PubMed

    Yang, Hua; Xia, Bing-Qing; Jiang, Bo; Wang, Guozhen; Yang, Yi-Peng; Chen, Hao; Li, Bing-Sheng; Xu, An-Gao; Huang, Yun-Bo; Wang, Xin-Ying

    2013-08-01

    The diagnostic value of stool DNA (sDNA) testing for colorectal neoplasms remains controversial. To compensate for the lack of large-scale unbiased population studies, a meta-analysis was performed to evaluate the diagnostic value of sDNA testing for multiple markers of colorectal cancer (CRC) and advanced adenoma. The PubMed, Science Direct, Biosis Review, Cochrane Library and Embase databases were systematically searched in January 2012 without time restriction. Meta-analysis was performed using a random-effects model using sensitivity, specificity, diagnostic OR (DOR), summary ROC curves, area under the curve (AUC), and 95% CIs as effect measures. Heterogeneity was measured using the χ(2) test and Q statistic; subgroup analysis was also conducted. A total of 20 studies comprising 5876 individuals were eligible. There was no heterogeneity for CRC, but adenoma and advanced adenoma harboured considerable heterogeneity influenced by risk classification and various detection markers. Stratification analysis according to risk classification showed that multiple markers had a high DOR for the high-risk subgroups of both CRC (sensitivity 0.759 [95% CI 0.711 to 0.804]; specificity 0.883 [95% CI 0.846 to 0.913]; AUC 0.906) and advanced adenoma (sensitivity 0.683 [95% CI 0.584 to 0.771]; specificity 0.918 [95% CI 0.866 to 0.954]; AUC 0.946) but not for the average-risk subgroups of either. In the methylation subgroup, sDNA testing had significantly higher DOR for CRC (sensitivity 0.753 [95% CI 0.685 to 0.812]; specificity 0.913 [95% CI 0.860 to 0.950]; AUC 0.918) and advanced adenoma (sensitivity 0.623 [95% CI 0.527 to 0.712]; specificity 0.926 [95% CI 0.882 to 0.958]; AUC 0.910) compared with the mutation subgroup. There was no significant heterogeneity among studies for subgroup analysis. sDNA testing for multiple markers had strong diagnostic significance for CRC and advanced adenoma in high-risk subjects. Methylation makers had more diagnostic value than mutation

  5. Relationship Between Advanced Maternal Age, Hiesho (Sensitivity to Cold) and Abnormal Delivery in Japan

    PubMed Central

    Nakamura, Sachiyo; Horiuchi, Shigeko

    2013-01-01

    Background: In Japan, the proportion of women aged 35 and older giving birth has greatly increased in recent years, and maternal age is continuing to increase. Advanced maternal age is a risk factor for abnormal delivery, as is hiesho (sensitivity to cold). Research Question: This study aimed to assess whether advanced maternal age and hiesho precipitate premature delivery, premature rupture of membranes, weak labor pains, prolonged labor and atonic bleeding. Method: The study design was a descriptive comparative study with a retrospective cohort group design. Subjects in this study were 2,810 Japanese women in hospital after childbirth. The research methods employed were a paper questionnaire and extraction of data from medical records. Results: Comparing the rate of occurrence of abnormal delivery among women aged 35 to 39 according to whether or not they had hiesho, results were premature delivery OR: 3.51 (95% CI: 1.66-7.43), premature rupture of membranes OR: 1.25 (95% CI: 0.90-1.74), weak labor pains OR: 2.94 (95% CI: 1.65-5.24), prolonged labor OR: 2.56 (95% CI: 1.23-5.26), and atonic bleeding, OR: 1.65 (95% CI: 0.14-2.40) when hiesho was present. Among women aged 40 and over, results were premature delivery OR: 5.09 (95% CI: 1.16-22.20), premature rupture of membranes OR: 1.60 (95% CI: 0.73-3.46), weak labor pains OR: 7.02 (95% CI: 1.56-31.55), prolonged labor OR:7.19 (95% CI: 1.49-34.60) and atonic bleeding OR: 2.00 (95% CI: 0.64-6.23). Conclusions: Regardless of maternal age, the presence of hiesho is a risk factor that can precipitate premature delivery, premature rupture of membranes, weak labor pains, prolonged labor and atonic bleeding. Furthermore, hiesho coupled with advanced maternal age increases the incidence of premature delivery, weak labor pains and prolonged labor. PMID:24062862

  6. Evaluation of the 'Fitting to Outcomes eXpert' (FOX®) with established cochlear implant users.

    PubMed

    Buechner, Andreas; Vaerenberg, Bart; Gazibegovic, Dzemal; Brendel, Martina; De Ceulaer, Geert; Govaerts, Paul; Lenarz, Thomas

    2015-01-01

    To evaluate the possible impact of 'Fitting to Outcomes eXpert (FOX(®))' on cochlear implant (CI) fitting in a clinic with extensive experience of fitting a range of CI systems, as a way to assess whether a software tool such as FOX is able to complement standard clinical procedures. Ten adult post-lingually deafened and unilateral long-term users of the Advanced Bionics(TM) CI system (Clarion CII or HiRes 90K(TM)) underwent speech perception assessment with their current clinical program. One cycle 'iteration' of FOX optimization was performed and the program adjusted accordingly. After a month of using both clinical and FOX programs, a second iteration of FOX optimization was performed. Following this, the assessments were repeated without further acclimatization. FOX prescribed programming modifications in all subjects. Soundfield-aided thresholds were significantly lower for FOX than the clinical program. Group speech scores in noise were not significantly different between the two programs but three individual subjects had improved speech scores with the FOX MAP, two had worse speech scores, and five were the same. FOX provided a standardized approach to fitting based on outcome measures rather than comfort alone. The results indicated that for this group of well-fitted patients, FOX improved outcomes in some individuals. There were significant changes, both better and worse, in individual speech perception scores but median scores remained unchanged. Soundfield-aided thresholds were significantly improved for the FOX group.

  7. Increased risk of advanced neoplasms among asymptomatic siblings of patients with colorectal cancer.

    PubMed

    Ng, Siew C; Lau, James Y W; Chan, Francis K L; Suen, Bing Yee; Leung, Wai-Keung; Tse, Yee Kit; Ng, Simon S M; Lee, Janet F Y; To, Ka-Fai; Wu, Justin C Y; Sung, Joseph J Y

    2013-03-01

    Colorectal cancer (CRC) is the second-most common cancer in Hong Kong. Relatives of patients with CRC have an increased risk of colorectal neoplasm. We assessed the prevalence of advanced neoplasms among asymptomatic siblings of patients with CRC. Patients with CRC were identified from the Prince of Wales Hospital CRC Surgery Registry from 2001 to 2011. Colonoscopies were performed for 374 siblings of patients (age, 52.6 ± 7.4 y) and 374 age- and sex-matched siblings of healthy subjects who had normal colonoscopies and did not have a family history of CRC (controls, 52.7 ± 7.4 y). We identified individuals with advanced neoplasms (defined as cancers or adenomas of at least 10 mm in diameter, high-grade dysplasia, with villous or tubulovillous characteristics). The prevalence of advanced neoplasms was 7.5% among siblings of patients and 2.9% among controls (matched odds ratio [mOR], 3.07; 95% confidence interval [CI], 1.5-6.3; P = .002). The prevalence of adenomas larger than 10 mm was higher among siblings of patients than in controls (5.9% vs 2.1%; mOR, 3.34; 95% CI, 1.45-7.66; P = .004), as was the presence of colorectal adenomas (31.0% vs 18.2%; mOR, 2.19; 95% CI, 1.52-3.17; P < .001). Six cancers were detected among siblings of patients; no cancers were detected in controls. The prevalence of advanced neoplasms among siblings of patients was higher when their index case was female (mOR, 4.95; 95% CI, 1.81-13.55) and had distally located CRC (mOR, 3.10; 95% CI, 1.34-7.14). In Hong Kong, siblings of patients with CRC have a higher prevalence of advanced neoplasms, including CRC, than siblings of healthy individuals. Screening is indicated in this high-risk population. ClinicalTrials.gov number: NCT00164944. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. Predictors of advanced colorectal neoplasia for colorectal cancer screening.

    PubMed

    Wong, Martin C S; Lam, Thomas Y T; Tsoi, Kelvin K F; Chan, Victor C W; Hirai, Hoyee W; Ching, Jessica Y L; Sung, Joseph J Y

    2014-05-01

    The Asia-Pacific Colorectal Screening (APCS) score based on age, gender, family history, and smoking is useful to predict advanced colorectal neoplasia (ACN) in asymptomatic Asian subjects. To evaluate the factors in addition to those of APCS associated with ACN colonoscopic findings. Data from 5,220 asymptomatic subjects aged between 50 and 70 years who underwent screening colonoscopy in a community center between 2008 and 2012 were analyzed. One binary logistic regression analysis was conducted in 2013 with the presence of ACN or cancer as the outcome, controlling for APCS score, alcohol consumption, BMI, hypertension, and other chronic diseases as independent variables. The average participant age was 57.7 years (SD=4.9) and 47.5% were men. Advanced neoplasms or cancers were identified at colonoscopy in 5.6% of all screening participants. From multivariate regression analysis, APCS score≥4 (adjusted OR [AOR]=1.74, 95% CI=1.34, 2.25, p<0.001); overweight (BMI=23-24.9, AOR=1.52, 95% CI=1.12, 2.07, p=0.007); obesity (BMI≥25, AOR=1.56, 95% CI=1.15, 2.10, p=0.004); hypertension (AOR=1.58, 95% CI=1.21, 2.06, p=0.001); and alcohol consumption (AOR=1.47, 95% CI=1.05, 2.06, p=0.025) were associated with ACN. The c-statistic of APCS score alone was 0.560 (95% CI=0.524, 0.595, p=0.001) and that of APCS score plus BMI, hypertension, and alcohol consumption was 0.613 (95% CI=0.578, 0.648, p<0.001). Alcohol consumption, hypertension, and BMI are independent predictors of ACN, which could be incorporated into the APCS for prioritizing Asian asymptomatic subjects for colorectal cancer screening. Copyright © 2014. Published by Elsevier Inc.

  9. Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration

    PubMed Central

    Merle, Bénédicte M. J.; Silver, Rachel E.; Rosner, Bernard; Seddon, Johanna M.

    2017-01-01

    Purpose There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Methods Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. Results There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43–0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39–0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53–1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50–0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. Conclusions A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss. PMID:28892825

  10. Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration.

    PubMed

    Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

    2017-09-01

    There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43-0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39-0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53-1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50-0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss.

  11. Implications of Minimizing Trauma During Conventional Cochlear Implantation

    PubMed Central

    Carlson, Matthew L.; Driscoll, Colin L. W.; Gifford, René H.; Service, Geoffrey J.; Tombers, Nicole M.; Hughes-Borst, Becky J.; Neff, Brian A.; Beatty, Charles W.

    2014-01-01

    Objective To describe the relationship between implantation-associated trauma and postoperative speech perception scores among adult and pediatric patients undergoing cochlear implantation using conventional length electrodes and minimally traumatic surgical techniques. Study Design Retrospective chart review (2002–2010). Setting Tertiary academic referral center. Patients All subjects with significant preoperative low-frequency hearing (≤70 dB HL at 250 Hz) who underwent cochlear implantation with a newer generation implant electrode (Nucleus Contour Advance, Advanced Bionics HR90K [1J and Helix], and Med El Sonata standard H array) were reviewed. Intervention(s) Preimplant and postimplant audiometric thresholds and speech recognition scores were recorded using the electronic medical record. Main Outcome Measure(s) Postimplantation pure tone threshold shifts were used as a surrogate measure for extent of intracochlear injury and correlated with postoperative speech perception scores. Results Between 2002 and 2010, 703 cochlear implant (CI) operations were performed. Data from 126 implants were included in the analysis. The mean preoperative low-frequency pure-tone average was 55.4 dB HL. Hearing preservation was observed in 55% of patients. Patients with hearing preservation were found to have significantly higher postoperative speech perception performance in the cochlear implantation-only condition than those who lost all residual hearing. Conclusion Conservation of acoustic hearing after conventional length cochlear implantation is unpredictable but remains a realistic goal. The combination of improved technology and refined surgical technique may allow for conservation of some residual hearing in more than 50% of patients. Germane to the conventional length CI recipient with substantial hearing loss, minimizing trauma allows for improved speech perception in the electric condition. These findings support the use of minimally traumatic techniques in all CI

  12. Occupation and Bladder Cancer Phenotype: Identification of Workplace Patterns That Increase the Risk of Advanced Disease Beyond Overall Incidence.

    PubMed

    Noon, Aidan P; Martinsen, Jan Ivar; Catto, James W F; Pukkala, Eero

    2016-07-20

    We examined a national data set to determine if workers employed in specific occupations develop distinct bladder cancer (BCa) phenotypes. To compare the incidence and disease-specific mortality (DSM) of localized and advanced BCa in workers with different job titles. BCa incidence, stage at diagnosis, and DSM in 1.7 million Finnish men (13 717 with BCa) and 1.7 million women (4282 with BCa) with annotated occupational descriptions. Follow-up was 37 and 43 million person-years, respectively. The gender-specific incidence and BCa DSM within each occupational category was compared with the expected number of cases based on the entire Finnish population to generate standardized incidence ratios (SIRs) and standard mortality ratios (SMRs). Occupations were found that had significant differences in the incidence of localized (SIR loc ) and advanced (SIR adv , SMR adv ) BCa and DSM. Male chemical process workers (SIR loc /SIR adv : 5.19; 95% confidence interval [CI], 1.73-25.7), male military personnel (SIR loc /SIR adv : 6.4; 95% CI, 1.09-259.0), and male public safety workers (SIR loc /SIR adv : 1.77; 95% CI, 1.04-3.23) had significantly more localized than advanced tumors. In contrast, miscellaneous construction workers had more advanced than localized cancers for both genders (male SIR loc /SIR adv : 0.67; 95% CI, 0.53-0.86; female SIR loc /SIR adv : 0.12; 95% CI, 0.09-0.54). Male chemical process workers had fewer deaths from BCa than expected from advanced tumors (SMR adv : 0.32; 95% CI, 0.07-0.94), and miscellaneous constructions workers had more deaths from advanced tumors than expected (male SMR adv : 1.44; 95% CI, 1.10-1.85; female SMR adv : 3.35; 95% CI, 1.23-7.30). Limitations of this study are failure to control accurately for the effects of smoking and a lack of specific treatment information. Occupations exist that may differ in their risks for localized and advanced BCa and for DSM. Occupations have been identified that may have different patterns of

  13. The maternal genes Ci-p53/p73-a and Ci-p53/p73-b regulate zygotic ZicL expression and notochord differentiation in Ciona intestinalis embryos.

    PubMed

    Noda, Takeshi

    2011-12-01

    I isolated a Ciona intestinalis homolog of p53, Ci-p53/p73-a, in a microarray screen of rapidly degraded maternal mRNA by comparing the transcriptomes of unfertilized eggs and 32-cell stage embryos. Higher expression of the gene in eggs and lower expression in later embryonic stages were confirmed by whole-mount in situ hybridization (WISH) and quantitative reverse transcription-PCR (qRT-PCR); expression was ubiquitous in eggs and early embryos. Knockdown of Ci-p53/p73-a by injection of antisense morpholino oligonucleotides (MOs) severely perturbed gastrulation cell movements and expression of notochord marker genes. A key regulator of notochord differentiation in Ciona embryos is Brachyury (Ci-Bra), which is directly activated by a zic-like gene (Ci-ZicL). The expression of Ci-ZicL and Ci-Bra in A-line notochord precursors was downregulated in Ci-p53/p73-a knockdown embryos. Maternal expression of Ci-p53/p73-b, a homolog of Ci-p53/p73-a, was also detected. In Ci-p53/p73-b knockdown embryos, gastrulation cell movements, expression of Ci-ZicL and Ci-Bra in A-line notochord precursors, and expression of notochord marker gene at later stages were perturbed. The upstream region of Ci-ZicL contains putative p53-binding sites. Cis-regulatory analysis of Ci-ZicL showed that these sites are involved in expression of Ci-ZicL in A-line notochord precursors at the 32-cell and early gastrula stages. These results suggest that p53 genes are maternal factors that play a crucial role in A-line notochord differentiation in C. intestinalis embryos by regulating Ci-ZicL expression. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Clinical evaluation of music perception, appraisal and experience in cochlear implant users.

    PubMed

    Drennan, Ward R; Oleson, Jacob J; Gfeller, Kate; Crosson, Jillian; Driscoll, Virginia D; Won, Jong Ho; Anderson, Elizabeth S; Rubinstein, Jay T

    2015-02-01

    The objectives were to evaluate the relationships among music perception, appraisal, and experience in cochlear implant users in multiple clinical settings and to examine the viability of two assessments designed for clinical use. Background questionnaires (IMBQ) were administered by audiologists in 14 clinics in the United States and Canada. The CAMP included tests of pitch-direction discrimination, and melody and timbre recognition. The IMBQ queried users on prior musical involvement, music listening habits pre and post implant, and music appraisals. One-hundred forty-five users of Advanced Bionics and Cochlear Ltd cochlear implants. Performance on pitch direction discrimination, melody recognition, and timbre recognition tests were consistent with previous studies with smaller cohorts, as well as with more extensive protocols conducted in other centers. Relationships between perceptual accuracy and music enjoyment were weak, suggesting that perception and appraisal are relatively independent for CI users. Perceptual abilities as measured by the CAMP had little to no relationship with music appraisals and little relationship with musical experience. The CAMP and IMBQ are feasible for routine clinical use, providing results consistent with previous thorough laboratory-based investigations.

  15. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma.

    PubMed

    Bellmunt, Joaquim; de Wit, Ronald; Vaughn, David J; Fradet, Yves; Lee, Jae-Lyun; Fong, Lawrence; Vogelzang, Nicholas J; Climent, Miguel A; Petrylak, Daniel P; Choueiri, Toni K; Necchi, Andrea; Gerritsen, Winald; Gurney, Howard; Quinn, David I; Culine, Stéphane; Sternberg, Cora N; Mai, Yabing; Poehlein, Christian H; Perini, Rodolfo F; Bajorin, Dean F

    2017-03-16

    Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more. The median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P=0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also fewer events of grade 3, 4

  16. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma

    PubMed Central

    Bellmunt, J.; de Wit, R.; Vaughn, D.J.; Fradet, Y.; Lee, J.-L.; Fong, L.; Vogelzang, N.J.; Climent, M.A.; Petrylak, D.P.; Choueiri, T.K.; Necchi, A.; Gerritsen, W.; Gurney, H.; Quinn, D.I.; Culine, S.; Sternberg, C.N.; Mai, Y.; Poehlein, C.H.; Perini, R.F.; Bajorin, D.F.

    2017-01-01

    BACKGROUND Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. METHODS In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator’s choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1–expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more. RESULTS The median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P =0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were

  17. Surviving High-temperature Components in CI Chondrites

    NASA Technical Reports Server (NTRS)

    Zolensky, M.; Frank, D.

    2014-01-01

    The CI1 chondrites, while having the most solar-like compo-sition of any astromaterial available for laboratory analysis, have also been considerably altered by asteroidal processes including aqueous alteration. It is of fundamental importance to determine their pre-alteration mineralogy, so that the state of matter in the early Solar System can be better determined. In the course of a re-examination of the compositional range of olivine and low-Ca pyroxene in CI chondrites Orgueil, Ivuna and Alais [1] we found the first reported complete CAI, as already reported [2], with at-tached rock consisting mainly of olivine and low-Ca pyroxene. The range of residual olivine major element compositions we have determined in the CIs (Fig. 1) may now be directly com-pared with those of other astromaterials, including Wild 2 grains. The abundance of olivine and low-Ca pyroxene in CIs is higher than is generally appreciated, and in fact much higher than for some CMs [1]. We also noted numerous rounded objects varying in shape from spheres to oblate spheroids, and ranging up to 100µm in size (Fig. 2), which have been previously noted [3] but have not been well documented or appreciated. We characterized the mineralogy by transmission electron microscopy and found that they consist mainly of rather fine-grained, flaky single phase to intergrown serpentine and saponite. These two materials in fact dominate the bulk of the host CI1 chondrites. With the exception of sparse spinels, the rounded phyllosilicate objects are remarka-bly free of other minerals, suggesting that the precursor from which the phyllosilicates were derived was a homogeneous mate-rial. We suggest that these round phyllosilicates aggregates in CI1 chondrites were cryptocrystalline to glassy microchondrules. If so then CI chondrites cannot be considered chondrule-free. Small though they are, the abundance of these putative microchondrules is the same as that of chondrules in the Tagish Lake meteorite.

  18. Measurement of Small Values of Hydrostatic Pressure with the Compensation of Atmospheric Pressure Influence / Pomiar Małych Wartości Ciśnienia Hydrostatycznego Z Kompensacją Wpływu Ciśnienia Atmosferycznego

    NASA Astrophysics Data System (ADS)

    Broda, Krzysztof; Filipek, Wiktor

    2013-09-01

    structure has been simplified and the measurement accuracy has increased. Znajomość rozkładu ciśnienia (lub różnicy ciśnień) determinuje opis przepływu płynu przez ośrodek porowaty. W przypadku dużych liczb Reynoldsa nie nastręcza to większych trudności, lecz dla przepływów laminarnych (tj. dla liczb Re (Bear, 1988; Duckworth, 1983; Troskolański, 1957) z zakresu 0.01 do 3) jest to praktycznie niemożliwe w oparciu o dostępne na rynku przyrządy. Przyczyny powodujące taką sytuację zostały omówione w poprzednim opracowaniu (Broda i Filipek, 2012), w którym zwrócono uwagę na trudności pomiarów związane z napięciem powierzchniowym czy włoskowatością (Adamson, 1997). Zaproponowano (Broda i Filipek, 2012) nową, autorską metodę pomiaru bardzo małych różnic ciśnień oraz skonstruowano odpowiednie stanowisko składające się z dwóch oddzielnych zbiorników pomiarowych oraz przeprowadzono pomiary. Z przeprowadzonych badań (Broda i Filipek, 2012) wynikała konieczność zastosowania stabilizacji temperatury urządzenia oraz kompensacji wpływu ciśnienia atmosferycznego na proces pomiarowy. Niniejsza publikacja przedstawia wyniki kontynuacji badań nad metodami i aparaturą do pomiaru bardzo małych różnic ciśnień z uwzględnieniem zdobytych doświadczeń, w oparciu o nowe stanowisko pomiarowe, którego zasadę działania i budowę przedstawiono na rys. 1-5, kolejno przedstawiając koncepcję wykonania pomiaru małych wartości ciśnienia hydrodynamicznego z kompensacją wpływu ciśnienia atmosferycznego rys. 1; ilustrację obrazującą stan odpowiadający przypadkowi braku przepływu płynu przez badany obiekt rys. 2; omawiając stan odpowiadający przypadkowi przepływu płynu przez badany obiekt rys. 3. Kolejno omówiono stan odpowiadający pomiarowi spadku ciśnienia na badanym obiekcie rys. 4 oraz przedstawiono metodykę pomiaru (zależności (1) - (20)). Zdjęcie stanowiska badawczego oraz jego elementów ilustruje rys. 5. W

  19. Advance directives and outcomes of surrogate decision making before death.

    PubMed

    Silveira, Maria J; Kim, Scott Y H; Langa, Kenneth M

    2010-04-01

    Recent discussions about health care reform have raised questions regarding the value of advance directives. We used data from survey proxies in the Health and Retirement Study involving adults 60 years of age or older who had died between 2000 and 2006 to determine the prevalence of the need for decision making and lost decision-making capacity and to test the association between preferences documented in advance directives and outcomes of surrogate decision making. Of 3746 subjects, 42.5% required decision making, of whom 70.3% lacked decision-making capacity and 67.6% of those subjects, in turn, had advance directives. Subjects who had living wills were more likely to want limited care (92.7%) or comfort care (96.2%) than all care possible (1.9%); 83.2% of subjects who requested limited care and 97.1% of subjects who requested comfort care received care consistent with their preferences. Among the 10 subjects who requested all care possible, only 5 received it; however, subjects who requested all care possible were far more likely to receive aggressive care as compared with those who did not request it (adjusted odds ratio, 22.62; 95% confidence interval [CI], 4.45 to 115.00). Subjects with living wills were less likely to receive all care possible (adjusted odds ratio, 0.33; 95% CI, 0.19 to 0.56) than were subjects without living wills. Subjects who had assigned a durable power of attorney for health care were less likely to die in a hospital (adjusted odds ratio, 0.72; 95% CI, 0.55 to 0.93) or receive all care possible (adjusted odds ratio, 0.54; 95% CI, 0.34 to 0.86) than were subjects who had not assigned a durable power of attorney for health care. Between 2000 and 2006, many elderly Americans needed decision making near the end of life at a time when most lacked the capacity to make decisions. Patients who had prepared advance directives received care that was strongly associated with their preferences. These findings support the continued use of advance

  20. Optimal hydration volume among high-risk patients with advanced congestive heart failure undergoing coronary angiography

    PubMed Central

    Wang, Kun; Chen, Ping Yan; Chen, Ji-Yan; Tan, Ning; Li, Li-Wen

    2018-01-01

    We investigated the relationship between weight-adjusted hydration volumes and the risk of developing contrast-induced acute kidney injury (CI-AKI) and worsening heart failure (WHF) and explored the relative safety of optimal hydration volumes in patients with advanced congestive heart failure (CHF) undergoing coronary angiography (CAG) or percutaneous coronary intervention. We included 551 patients with advanced CHF (New York Heart Association class > 2 or history of pulmonary edema) undergoing CAG (follow-up period 2.62 ± 0.9 years). There was a significant association between hydration volume-to-weight ratio (HV/W) (quintile Q1, Q2, Q3, Q4, and Q5) and the incidence of CI-AKI (3.7%, 14.6%, 14.3%, 21.1%, and 31.5%, respectively) and WHF (3.6%, 5.4%, 8.3%, 13.6%, and 19.1%, respectively) (all P-trend < 0.001). Receiver operating curve analysis indicated that HV/W = 15 mL/kg and the mean HV/W (60.87% sensitivity and 64.96% specificity) were fair discriminators for CI-AKI (C-statistic 0.696). HV/W >15 mL/kg independently predicted CI-AKI (adjusted odds ratio [OR] 2.33; P = 0.016) and WHF (adjusted OR 2.13; P = 0.018). Moreover, both CI-AKI and WHF were independently associated with increased long-term mortality. Thus, for high-risk patients with advanced CHF undergoing CAG, HV/W > 15 mL/kg might be associated with an increased risk of developing CI-AKI and WHF. The potential benefits of a personalized limitation of hydration volume need further evaluation. PMID:29805771

  1. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer.

    PubMed

    Soria, Jean-Charles; Ohe, Yuichiro; Vansteenkiste, Johan; Reungwetwattana, Thanyanan; Chewaskulyong, Busyamas; Lee, Ki Hyeong; Dechaphunkul, Arunee; Imamura, Fumio; Nogami, Naoyuki; Kurata, Takayasu; Okamoto, Isamu; Zhou, Caicun; Cho, Byoung Chul; Cheng, Ying; Cho, Eun Kyung; Voon, Pei Jye; Planchard, David; Su, Wu-Chou; Gray, Jhanelle E; Lee, Siow-Ming; Hodge, Rachel; Marotti, Marcelo; Rukazenkov, Yuri; Ramalingam, Suresh S

    2018-01-11

    Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival. The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%). Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded

  2. Determinants of death anxiety in patients with advanced cancer.

    PubMed

    Neel, Caroline; Lo, Chris; Rydall, Anne; Hales, Sarah; Rodin, Gary

    2015-12-01

    To examine the presence of death anxiety in patients with advanced cancer and to identify the psychosocial and disease-related factors associated with it. Cross-sectional analysis of baseline data from a phase 2 pilot intervention trial. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. 60 adult outpatients with metastatic breast, endocrine, gastrointestinal, gynaecological, genitourinary and lung cancer. Death anxiety, as measured by the Death and Dying Distress Scale (DADDS). Thirty-two per cent of the sample reported death anxiety of at least moderate severity. The most distressing concern involved fears about the impact of one's death on others, and the least distressing concerns were related to dying alone or suddenly. According to regression analyses, death anxiety was negatively associated with self-esteem, b=-1.73, CI0.95 (-2.57 to -0.90) and positively associated with physical symptom burden, b=1.38, CI0.95 (0.44 to 2.31), having children under 18 years of age in the family, b=13.3, CI0.95 (2.15 to 24.5), and age, b=0.40, CI0.95 (0.0023 to 0.79). The physical symptoms most strongly associated with death anxiety were changes in physical appearance, b=18.8, CI0.95 (8.21 to29.5), and pain, b=10.1, CI0.95 (0.73 to 19.5). The findings suggest that death anxiety in patients with advanced cancer is common and determined by the interaction of individual factors, family circumstances and physical suffering. Multidimensional interventions that take into account these and other factors may be most likely to be effective to alleviate this death-related distress. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. KSC-2011-2271

    NASA Image and Video Library

    2011-03-11

    ORLANDO, Fla. –The Bionic Tigers robot participates in the regional FIRST robotics competition at the University of Central Florida in Orlando. The team is made up of students from Cocoa High School and Holy Trinity Episcopal Academy along the Space Coast in Florida. NASA's Launch Services Program based at Kennedy is a sponsor of the team. The Bionic Tigers finished seventh in the competition called "For Inspiration and Recognition of Science and Technology," or FIRST, among about 60 high school teams hoping to advance to the national robotics championship. FIRST, founded in 1989, is a non-profit organization that designs accessible, innovative programs to build self-confidence, knowledge and life skills while motivating young people to pursue academic opportunities. The robotics competition challenges teams of high school students and their mentors to solve a common problem in a six-week timeframe using a standard kit of parts and a common set of rules. Photo credit: NASA/Glenn Benson

  4. Factors influencing contraceptive use and non-use among women of advanced reproductive age in Nigeria.

    PubMed

    Solanke, Bola Lukman

    2017-01-07

    Factors influencing contraceptive use and non-use among women of advanced reproductive age have been insufficiently researched in Nigeria. This study examines factors influencing contraceptive use and non-use among women of advanced reproductive age in Nigeria. Secondary data were pooled and extracted from 2008 and 2013 Nigeria Demographic and Health Surveys (NDHS). The weighted sample size was 14,450 women of advanced reproductive age. The dependent variable was current contraceptive use. The explanatory variables were selected socio-demographic characteristics and three control variables. Analyses were performed using Stata version 12. Multinomial logistic regression was applied in four models. Majority of the respondents are not using any method of contraceptive; the expected risk of using modern contraceptive relative to traditional method reduces by a factor of 0.676 for multiparous women (rrr = 0.676; CI: 0.464-0.985); the expected risk of using modern contraceptive relative to traditional method reduces by a factor of 0.611 for women who want more children (rrr = 0.611; CI: 0.493-0.757); the relative risk for using modern contraceptive relative to traditional method increases by a factor of 1.637 as maternal education reaches secondary education (rrr = 1.637; CI: 1.173-2.285); the relative risk for using modern contraceptive relative to traditional method increases by a factor of 1.726 for women in richest households (rrr = 1.726; CI: 1.038-2.871); and the expected risk of using modern contraceptive relative to traditional method increases by a factor of 1.250 for southern women (rrr = 1.250; CI: 1.200-1.818). Socio-demographic characteristics exert more influence on non-use than modern contraceptive use. The scope, content and coverage of existing BCC messages should be extended to cover the contraceptive needs and challenges of women of advanced reproductive age in the country.

  5. Mortality among men with locally advanced prostate cancer managed with noncurative intent: a nationwide study in PCBaSe Sweden.

    PubMed

    Akre, Olof; Garmo, Hans; Adolfsson, Jan; Lambe, Mats; Bratt, Ola; Stattin, Pär

    2011-09-01

    There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment. To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent. We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis. We followed up the patient cohort in the Cause of Death Register for ≤ 11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics. The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25-32%) for Gleason score (GS) 2-6, 41% (95% CI, 38-44%) for GS 7, 52% (95% CI, 47-57%) for GS 8, and 64% (95% CI, 59-69%) for GS 9-10. Even for men aged >85 yr at diagnosis with GS 8-10, PCa was a major cause of death: 42% (95% CI, 37-47%). Men with locally advanced disease and a PSA<4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status. The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  6. Using the Web for Competitive Intelligence (CI) Gathering

    NASA Technical Reports Server (NTRS)

    Rocker, JoAnne; Roncaglia, George

    2002-01-01

    Businesses use the Internet as a way to communicate company information as a way of engaging their customers. As the use of the Web for business transactions and advertising grows, so too, does the amount of useful information for practitioners of competitive intelligence (CI). CI is the legal and ethical practice of information gathering about competitors and the marketplace. Information sources like company webpages, online newspapers and news organizations, electronic journal articles and reports, and Internet search engines allow CI practitioners analyze company strengths and weaknesses for their customers. More company and marketplace information than ever is available on the Internet and a lot of it is free. Companies should view the Web not only as a business tool but also as a source of competitive intelligence. In a highly competitive marketplace can any organization afford to ignore information about the other players and customers in that same marketplace?

  7. Multisensory emotion perception in congenitally, early, and late deaf CI users

    PubMed Central

    Nava, Elena; Villwock, Agnes K.; Büchner, Andreas; Lenarz, Thomas; Röder, Brigitte

    2017-01-01

    Emotions are commonly recognized by combining auditory and visual signals (i.e., vocal and facial expressions). Yet it is unknown whether the ability to link emotional signals across modalities depends on early experience with audio-visual stimuli. In the present study, we investigated the role of auditory experience at different stages of development for auditory, visual, and multisensory emotion recognition abilities in three groups of adolescent and adult cochlear implant (CI) users. CI users had a different deafness onset and were compared to three groups of age- and gender-matched hearing control participants. We hypothesized that congenitally deaf (CD) but not early deaf (ED) and late deaf (LD) CI users would show reduced multisensory interactions and a higher visual dominance in emotion perception than their hearing controls. The CD (n = 7), ED (deafness onset: <3 years of age; n = 7), and LD (deafness onset: >3 years; n = 13) CI users and the control participants performed an emotion recognition task with auditory, visual, and audio-visual emotionally congruent and incongruent nonsense speech stimuli. In different blocks, participants judged either the vocal (Voice task) or the facial expressions (Face task). In the Voice task, all three CI groups performed overall less efficiently than their respective controls and experienced higher interference from incongruent facial information. Furthermore, the ED CI users benefitted more than their controls from congruent faces and the CD CI users showed an analogous trend. In the Face task, recognition efficiency of the CI users and controls did not differ. Our results suggest that CI users acquire multisensory interactions to some degree, even after congenital deafness. When judging affective prosody they appear impaired and more strongly biased by concurrent facial information than typically hearing individuals. We speculate that limitations inherent to the CI contribute to these group differences. PMID:29023525

  8. Multisensory emotion perception in congenitally, early, and late deaf CI users.

    PubMed

    Fengler, Ineke; Nava, Elena; Villwock, Agnes K; Büchner, Andreas; Lenarz, Thomas; Röder, Brigitte

    2017-01-01

    Emotions are commonly recognized by combining auditory and visual signals (i.e., vocal and facial expressions). Yet it is unknown whether the ability to link emotional signals across modalities depends on early experience with audio-visual stimuli. In the present study, we investigated the role of auditory experience at different stages of development for auditory, visual, and multisensory emotion recognition abilities in three groups of adolescent and adult cochlear implant (CI) users. CI users had a different deafness onset and were compared to three groups of age- and gender-matched hearing control participants. We hypothesized that congenitally deaf (CD) but not early deaf (ED) and late deaf (LD) CI users would show reduced multisensory interactions and a higher visual dominance in emotion perception than their hearing controls. The CD (n = 7), ED (deafness onset: <3 years of age; n = 7), and LD (deafness onset: >3 years; n = 13) CI users and the control participants performed an emotion recognition task with auditory, visual, and audio-visual emotionally congruent and incongruent nonsense speech stimuli. In different blocks, participants judged either the vocal (Voice task) or the facial expressions (Face task). In the Voice task, all three CI groups performed overall less efficiently than their respective controls and experienced higher interference from incongruent facial information. Furthermore, the ED CI users benefitted more than their controls from congruent faces and the CD CI users showed an analogous trend. In the Face task, recognition efficiency of the CI users and controls did not differ. Our results suggest that CI users acquire multisensory interactions to some degree, even after congenital deafness. When judging affective prosody they appear impaired and more strongly biased by concurrent facial information than typically hearing individuals. We speculate that limitations inherent to the CI contribute to these group differences.

  9. Effect of technological advances on cochlear implant performance in adults.

    PubMed

    Lenarz, Minoo; Joseph, Gert; Sönmez, Hasibe; Büchner, Andreas; Lenarz, Thomas

    2011-12-01

    To evaluate the effect of technological advances in the past 20 years on the hearing performance of a large cohort of adult cochlear implant (CI) patients. Individual, retrospective, cohort study. According to technological developments in electrode design and speech-processing strategies, we defined five virtual intervals on the time scale between 1984 and 2008. A cohort of 1,005 postlingually deafened adults was selected for this study, and their hearing performance with a CI was evaluated retrospectively according to these five technological intervals. The test battery was composed of four standard German speech tests: Freiburger monosyllabic test, speech tracking test, Hochmair-Schulz-Moser (HSM) sentence test in quiet, and HSM sentence test in 10 dB noise. The direct comparison of the speech perception in postlingually deafened adults, who were implanted during different technological periods, reveals an obvious improvement in the speech perception in patients who benefited from the recent electrode designs and speech-processing strategies. The major influence of technological advances on CI performance seems to be on speech perception in noise. Better speech perception in noisy surroundings is strong proof for demonstrating the success rate of new electrode designs and speech-processing strategies. Standard (internationally comparable) speech tests in noise should become an obligatory part of the postoperative test battery for adult CI patients. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  10. Computed tomographic colonography for colorectal cancer screening: risk factors for the detection of advanced neoplasia.

    PubMed

    Hassan, Cesare; Pooler, B Dustin; Kim, David H; Rinaldi, Antonio; Repici, Alessandro; Pickhardt, Perry J

    2013-07-15

    The objective of this study was to determine whether age, sex, a positive family history of colorectal cancer, and body mass index (BMI) are important predictors of advanced neoplasia in the setting of screening computed tomographic colonography (CTC). Consecutive patients who were referred for first-time screening CTC from 2004 to 2011 at a single medical center were enrolled. Results at pathology were recorded for all patients who underwent polypectomy. Logistic regression was used to identify significant predictor variables for advanced neoplasia (any adenoma ≥ 10 mm or with villous component, high-grade dysplasia, or adenocarcinoma). Odds ratios (ORs) were used to express associations between the study variables (age, sex, BMI, and a positive family history of colorectal cancer) and advanced neoplasia. In total, 7620 patients underwent CTC screening. Of these, 276 patients (3.6%; 95% confidence interval [CI], 3.2%-4.1%) ultimately were diagnosed with advanced neoplasia. At multivariate analysis, age (mean OR per 10-year increase, 1.8; 95% CI, 1.6-2.0) and being a man (OR, 1.7; 95% CI, 1.3-2.2) were independent predictors of advanced neoplasia, whereas BMI and a positive family history of colorectal cancer were not. The number needed to screen to detect 1 case of advanced neoplasia varied from 51 among women aged ≤ 55 years to 10 among men aged >65 years. The number of post-CTC colonoscopies needed to detect 1 case of advanced neoplasia varied from 2 to 4. Age and sex were identified as important independent predictors of advanced neoplasia risk in individuals undergoing screening CTC, whereas BMI and a positive family history of colorectal cancer were not. These results have implications for appropriate patient selection. © 2013 American Cancer Society.

  11. Substance use disorder and its effects on outcomes in men with advanced-stage prostate cancer.

    PubMed

    Chhatre, Sumedha; Metzger, David S; Malkowicz, S Bruce; Woody, George; Jayadevappa, Ravishankar

    2014-11-01

    Substance use disorder in patients with cancer has implications for outcomes. The objective of this study was to analyze the effects of the type and timing of substance use on outcomes in elderly Medicare recipients with advanced prostate cancer. This was an observational cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2000 to 2009. Among men who were diagnosed with advanced prostate cancer between 2001 and 2004, we identified those who had a claim for substance use disorder in the year before cancer diagnosis, 1 year after cancer diagnosis, and an additional 4 years after diagnosis. The outcomes investigated were use of health services, costs, and mortality. The prevalence of substance use disorder was 10.6%. The category drug psychoses and related had greater odds of inpatient hospitalizations (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-2.8), outpatient hospital visits (OR, 2.6; 95% CI, 1.9-3.6), and emergency room visits (OR, 1.7; 95% CI, 1.2-2.4). Substance use disorder in the follow-up phase was associated with greater odds of inpatient hospitalizations (OR, 2.0; 95% CI, 1.8-2.2), outpatient hospital visits (OR, 2.0; 95% CI, 1.7-2.4), and emergency room visits (OR, 1.7; 95% CI, 1.5-2.1). Compared with men who did not have substance use disorder, those in the category drug psychoses and related had 70% higher costs, and those who had substance use disorder during the follow-up phase had 60% higher costs. The hazard of all-cause mortality was highest for patients in the drug psychoses and related category (hazard ratio, 1.3; 95% CI, 1.1-1.7) and the substance use disorder in treatment phase category (hazard ratio, 1.5; 95% CI, 1.3-1.7). The intersection of advanced prostate cancer and substance use disorder may adversely affect outcomes. Incorporating substance use screening and treatments into prostate cancer care guidelines and coordination of care is desirable. © 2014 American Cancer Society.

  12. Zebrafish CiA interneurons are late-born primary neurons.

    PubMed

    Yeo, Sang-Yeob

    2009-12-11

    Pax2 is a neural-related transcription factor downstream of Notch signaling and is expressed in the developing spinal cord of zebrafish, including in CiA interneurons. However, the characteristics of pax2-positive neurons are largely unknown. The goal of this study was to characterize Pax2-positive neurons by examining their expression in embryos in which Notch function had been knocked down by mutation or injection of a morpholino or mRNA. I found that Pax2-positive CiA interneurons were late-differentiating primary neurons. pax2.1 was expressed in CoPA commissural neurons and CiA interneurons at 26 hpf. The number of pax2.1-positive cells increased in mind bomb mutant embryos or embryos injected with Su(H)1-MO, but not in cells injected with Xenopus Delta or Delta(stu) mRNA. These observations imply that Notch signaling plays a role in regulating the number of CiA neurons by preventing uncommitted precursors from acquiring a neuronal fate during vertebrate development.

  13. Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas.

    PubMed

    Khalid-de Bakker, Carolina A J; Jonkers, Daisy M A E; Sanduleanu, Silvia; de Bruïne, Adriaan P; Meijer, Gerrit A; Janssen, Jan B M J; van Engeland, Manon; Stockbrügger, Reinhold W; Masclee, Ad A M

    2011-10-01

    Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance. FIT was collected prior to colonoscopy with a 50 ng/mL cutoff point. FIT results and complete colonoscopy findings were available from 329 subjects (mean age: 54.6 ± 3.7 years, 58.4% women). Advanced adenomas were detected in 38 (11.6%) of 329 subjects. Sensitivity for advanced adenomas of FIT and sigmoidoscopy were 15.8% (95% CI: 6.0-31.3) and 73.7% (95% CI: 56.9-86.6), respectively. No sensitivity improvement was obtained using the combination of sigmoidoscopy and FIT. Mean fecal hemoglobin in FIT positives was significantly lower for participants with only proximal adenomas versus those with distal ones (P = 0.008), for women versus men (P = 0.023), and for younger (<55 years) versus older (≥55 years) subjects (P = 0.029). Sensitivities of FIT were 0.0% (95% CI: 0.0-30.9) in subjects with only proximal versus 21.4% (95% CI: 8.3-41.0) in those with distal nonadvanced adenomas; 5.3% (95% CI: 0.0-26.0) in women versus 26.3% (95% CI: 9.2-51.2) in men; 9.5% (95% CI: 1.2-30.4) in younger versus 23.5% (95% CI: 6.8-49.9) in older subjects. Sigmoidoscopy had a significantly higher sensitivity for advanced adenomas than FIT. A single FIT showed very low sensitivity, especially in subjects with only proximal nonadvanced adenomas, in women, and in younger subjects. This points to the existence of "low" FIT performance in subgroups and the need for more tailored screening strategies.

  14. 21 CFR 73.3112 - C.I. Vat Orange 1.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false C.I. Vat Orange 1. 73.3112 Section 73.3112 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical Devices § 73.3112 C.I. Vat Orange 1. (a) Identity. The...

  15. 21 CFR 73.3112 - C.I. Vat Orange 1.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false C.I. Vat Orange 1. 73.3112 Section 73.3112 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical Devices § 73.3112 C.I. Vat Orange 1. (a) Identity. The...

  16. 21 CFR 73.3112 - C.I. Vat Orange 1.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false C.I. Vat Orange 1. 73.3112 Section 73.3112 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical Devices § 73.3112 C.I. Vat Orange 1. (a) Identity. The...

  17. 21 CFR 73.3112 - C.I. Vat Orange 1.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false C.I. Vat Orange 1. 73.3112 Section 73.3112 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical Devices § 73.3112 C.I. Vat Orange 1. (a) Identity. The...

  18. 21 CFR 73.3112 - C.I. Vat Orange 1.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false C.I. Vat Orange 1. 73.3112 Section 73.3112 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical Devices § 73.3112 C.I. Vat Orange 1. (a) Identity. The...

  19. Music Perception and Appraisal: Cochlear Implant Users and Simulated CI Listening

    PubMed Central

    Wright, Rose; Uchanski, Rosalie M.

    2012-01-01

    Background The inability to hear music well may contribute to decreased quality of life for cochlear implant (CI) users. Researchers have reported recently on the generally poor ability of CI users’ to perceive music, and a few researchers have reported on the enjoyment of music by CI users. However, the relation between music perception skills and music enjoyment is much less explored. Only one study has attempted to predict CI users’ enjoyment and perception of music from the users’ demographic variables and other perceptual skills (Gfeller et al., 2008). Gfeller’s results yielded different predictive relationships for music perception and music enjoyment, and the relationships were weak, at best. Purpose The first goal of this study is to clarify the nature and relationship between music perception skills and musical enjoyment for CI users, by employing a battery of music tests. The second goal is to determine whether normal hearing (NH) subjects, listening with a CI-simulation, can be used as a model to represent actual CI users for either music enjoyment ratings or music perception tasks. Research Design A prospective, cross-sectional observational study. Original music stimuli (unprocessed) were presented to CI users, and music stimuli processed with CI-simulation software were presented to twenty NH listeners (CIsim). As a control, original music stimuli were also presented to five other NH listeners. All listeners appraised twenty-four musical excerpts, performed music perception tests, and filled out a musical background questionnaire. Music perception tests were the Appreciation of Music in Cochlear Implantees (AMICI), Montreal Battery for Evaluation of Amusia (MBEA), Melodic Contour Identification (MCI), and University of Washington Clinical Assessment of Music Perception (UW-CAMP). Study Sample Twenty-five NH adults (22 – 56 years old), recruited from the local and research communities, participated in the study. Ten adult CI users (46 – 80

  20. SELECTED ANNOTATED BIBLIOGRAPHY ON SYSTEMS OF THEORETICAL DEVICES,

    DTIC Science & Technology

    BIONICS, BIBLIOGRAPHIES), (*BIBLIOGRAPHIES, BIONICS), (*CYBERNETICS, BIBLIOGRAPHIES), MATHEMATICS, COMPUTER LOGIC, NETWORKS, NERVOUS SYSTEM , THEORY , SEQUENCE SWITCHES, SWITCHING CIRCUITS, REDUNDANT COMPONENTS, LEARNING, MATHEMATICAL MODELS, BEHAVIOR, NERVES, SIMULATION, NERVE CELLS

  1. Semiempirical UNO-CAS and UNO-CI: method and applications in nanoelectronics.

    PubMed

    Dral, Pavlo O; Clark, Timothy

    2011-10-20

    Unrestricted Natural Orbital-Complete Active Space Configuration Interaction, abbreviated as UNO-CAS, has been implemented for NDDO-based semiempirical molecular-orbital (MO) theory. A computationally more economic technique, UNO-CIS, in which we use a configuration interaction (CI) calculation with only single excitations (CIS) to calculate excited states, has also been implemented and tested. The class of techniques in which unrestricted natural orbitals (UNOs) are used as the reference for CI calculations is denoted UNO-CI. Semiempirical UNO-CI gives good results for the optical band gaps of organic semiconductors such as polyynes and polyacenes, which are promising materials for nanoelectronics. The results of these semiempirical UNO-CI techniques are generally in better agreement with experiment than those obtained with the corresponding conventional semiempirical CI methods and comparable to or better than those obtained with far more computationally expensive methods such as time-dependent density-functional theory. We also show that symmetry breaking in semiempirical UHF calculations is very useful for predicting the diradical character of organic compounds in the singlet spin state.

  2. Prognostic role of pretreatment blood neutrophil-to-lymphocyte ratio in advanced cancer survivors: A systematic review and meta-analysis of 66 cohort studies.

    PubMed

    Mei, Zubing; Shi, Lu; Wang, Bo; Yang, Jizhen; Xiao, Zhihong; Du, Peixin; Wang, Qingming; Yang, Wei

    2017-07-01

    Neutrophil-to-lymphocyte ratio (NLR) is crucial for the incidence and mortality of various tumors. However, little is known on NLR and its association with prognosis in advanced tumors. Here we performed a meta-analysis to establish the prognostic significance of pretreatment blood NLR for advanced tumors. A systematic literature search through April 2016 was performed to evaluate the association between pretreatment blood NLR and overall survival (OS) or progression-free survival (PFS) in patients with advanced tumors. Data were extracted from studies reporting hazard ratios (HRs) and 95% confidence interval (CI) and pooled using the Mantel-Haenszel random-effect model. Sixty-six studies with a total of 24536 individuals were included in the meta-analysis. Pooled analyses revealed that elevated pretreatment NLR was associated with worse OS (HR 1.70, 95% CI 1.57-1.84, P<0.001) and PFS (HR 1.61, 95% CI 1.42-1.82, P<0.001) in advanced tumors. Subgroup analysis stratified by tumor type demonstrated that pancreatic cancer patients with high pretreatment NLR had the worst OS (HR 1.94, 95% CI 1.55-2.54, P<0.001) and colorectal cancer with the worst PFS (HR 1.74, 95% CI 1.04-2.90, P<0.001). When stratified by cut-off value for NLR, we found that cut-off value being five indicated the worst PFS (HR 2.23, 95% CI 1.54-3.23, P=0.019). Overall, high pretreatment blood NLR could be an adverse prognostic indicator for advanced tumor. Large-scale prospective studies investigating its survival outcomes in specific cancer type are strongly advocated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Depression and use of health care services in patients with advanced cancer

    PubMed Central

    Lo, Christopher; Calzavara, Andrew; Kurdyak, Paul; Barbera, Lisa; Shepherd, Frances; Zimmermann, Camilla; Moore, Malcolm J.; Rodin, Gary

    2013-01-01

    Abstract Objective To examine whether depression in patients with advanced cancer is associated with increased rates of physician visits, especially to primary care. Design Retrospective, observational study linking depression survey data to provincial health administration data. Setting Toronto, Ont. Participants A total of 737 patients with advanced cancer attending Princess Margaret Hospital, who participated in the Will to Live Study from 2002 to 2008. Main outcome measures Frequency of visits to primary care, oncology, surgery, and psychiatry services, before and after the depression assessment. Results Before the assessment, depression was associated with an almost 25% increase in the rate of primary care visits for reasons not related to mental health (rate ratio [RR] = 1.23, 95% CI 1.00 to 1.50), adjusting for medical morbidity and other factors. After assessment, depression was associated with a 2-fold increase in the rate of primary care visits for mental health–related reasons (RR = 2.35, 95% CI 1.18 to 4.66). However, depression was also associated during this time with an almost 25% reduction in the rate of oncology visits (RR = 0.78, 95% CI 0.65 to 0.94). Conclusion Depression affects health care service use in patients with advanced cancer. Individuals with depression were more likely to see primary care physicians but less likely to see oncologists, compared with individuals without depression. However, the frequent association of disease-related factors with depression in patients with advanced cancer highlights the need for communication between oncologists and primary care physicians about the medical and psychosocial care of these patients. PMID:23486819

  4. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables.

    PubMed

    Seddon, Johanna M; Reynolds, Robyn; Maller, Julian; Fagerness, Jesen A; Daly, Mark J; Rosner, Bernard

    2009-05-01

    The joint effects of genetic, ocular, and environmental variables were evaluated and predictive models for prevalence and incidence of AMD were assessed. Participants in the multicenter Age-Related Eye Disease Study (AREDS) were included in a prospective evaluation of 1446 individuals, of which 279 progressed to advanced AMD (geographic atrophy or neovascular disease) and 1167 did not progress during 6.3 years of follow-up. For prevalent AMD, 509 advanced cases were compared with 222 controls. Covariates for the incidence analysis included age, sex, education, smoking, body mass index (BMI), baseline AMD grade, and the AREDS vitamin-mineral treatment assignment. DNA specimens were evaluated for six variants in five genes related to AMD. Unconditional logistic regression analyses were performed for prevalent and incident advanced AMD. An algorithm was developed and receiver operating characteristic curves and C statistics were calculated to assess the predictive ability of risk scores to discriminate progressors from nonprogressors. All genetic polymorphisms were independently related to prevalence of advanced AMD, controlling for genetic factors, smoking, BMI, and AREDS treatment. Multivariate odds ratios (ORs) were 3.5 (95% confidence interval [CI], 1.7-7.1) for CFH Y402H; 3.7 (95% CI, 1.6-8.4) for CFH rs1410996; 25.4 (95% CI, 8.6-75.1) for LOC387715 A69S (ARMS2); 0.3 (95% CI, 0.1-0.7) for C2 E318D; 0.3 (95% CI, 0.1-0.5) for CFB; and 3.6 (95% CI, 1.4-9.4) for C3 R102G, comparing the homozygous risk/protective genotypes to the referent genotypes. For incident AMD, all these variants except CFB were significantly related to progression to advanced AMD, after controlling for baseline AMD grade and other factors, with ORs from 1.8 to 4.0 for presence of two risk alleles and 0.4 for the protective allele. An interaction was seen between CFH402H and treatment, after controlling for all genotypes. Smoking was independently related to AMD, with a multiplicative joint

  5. [Advance directives in patients with kidney disease or other general medical diagnoses].

    PubMed

    Driehorst, F; Keller, F

    2014-03-01

    After the law on living will was released in 2009 in Germany, an increased use of advance directives was observed. Since patients with kidney diseases are facing the potential or real need for expensive and invasive renal replacement therapy, one could speculate that they will either less or even more frequently state an advance directive than patients with other diseases. A structured interviewing was performed of all patients on a nephrology ward where also patients with other general medical conditions are treated. The study was approved by our local ethics committee (protocol # 303/08). All admitted patients were successively included who could give signed consent. The investigation was performed between July 2009 and April 2010 by a single interviewer (FD). Among 505 admitted patients, 211 were included but 11 patients did not consent to the investigation. Of the 200 investigated patients, 121 had a renal diagnosis and 79 other medical diseases. Compared to other European studies, the frequency of advance directives was high (26 %), underlining its clinical relevance. Upon multivariate logistic regression analysis the odds ratio (95 % confidence interval, CI) for the presence of an advance directive was significantly increased only by the age (1.06; CI 1.03-1.09; p = 0.001), but not by the underlying diagnosis (1.47; CI 0.72-2.97; p = 0.287). Significantly more patients did forego resuscitation than did dialysis in their living will (16 vs. 4) while the majority was undecided (36 vs. 47; p = 0.01). Age was found the more impacting variable than the renal diagnosis on the prevalence of advance directives. Patients with a renal diagnosis should be encouraged to make a statement on dialysis in their living will. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Physician Decision-Making in the Setting of Advanced Illness: An Examination of Patient Disposition and Physician Religiousness.

    PubMed

    Frush, Benjamin W; Brauer, Simon G; Yoon, John D; Curlin, Farr A

    2018-03-01

    Little is known about patient and physician factors that affect decisions to pursue more or less aggressive treatment courses for patients with advanced illness. This study sought to determine how patient age, patient disposition, and physician religiousness affect physician recommendations in the context of advanced illness. A survey was mailed to a stratified random sample of U.S. physicians, which included three vignettes depicting advanced illness scenarios: 1) cancer, 2) heart failure, and 3) dementia with acute infection. One vignette included experimental variables to test how patient age and patient disposition affected physician recommendations. After each vignette, physicians indicated their likelihood to recommend disease-directed medical care vs. hospice care. Among eligible physicians (n = 1878), 62% (n = 1156) responded. Patient age and stated patient disposition toward treatment did not significantly affect physician recommendations. Compared with religious physicians, physicians who reported that religious importance was "not applicable" were less likely to recommend chemotherapy (adjusted odds ratio [OR] 0.39, 95% CI 0.23-0.66) and more likely to recommend hospice (OR 1.90, 95% CI 1.15-3.16) for a patient with cancer. Compared with physicians who ever attended religious services, physicians who never attended were less likely to recommend left ventricular assist device placement for a patient with congestive heart failure (OR 0.57, 95% CI 0.35-0.92). In addition, Asian ethnicity was independently associated with recommending chemotherapy (OR 1.72, 95% CI 1.13-2.61) and being less likely to recommend hospice (OR 0.59, 95% CI 0.40-0.91) for the patient with cancer; and it was associated with recommending antibiotics for the patient with dementia and pneumonia (OR 1.64, 95% CI 1.08-2.50). This study provides preliminary evidence that patient disposition toward more and less aggressive treatment in advanced illness does not substantially factor

  7. Immune Checkpoint Inhibitors for Patients With Advanced Non-Small-Cell Lung Cancer: A Systematic Review.

    PubMed

    Ellis, Peter M; Vella, Emily T; Ung, Yee C

    2017-09-01

    Second-line treatment options are limited for patients with advanced non-small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC. Medline, Embase, and PubMed were searched for randomized controlled trials comparing treatment with immune checkpoint inhibitors against treatment with chemotherapy in patients with stage IIIB or IV NSCLC. Nine randomized controlled trials with 15 publications were included. A significant overall survival benefit of second-line nivolumab (nonsquamous: hazard ratio [HR] = 0.72, 95% confidence interval [CI], 0.60-0.77; P < .001; squamous: HR = 0.59, 95% CI, 0.44-0.79; P < .001) or second-line atezolizumab (HR = 0.73, 95% CI, 0.62-0.87; P = .0003) or second-line pembrolizumab (in patients with programmed cell death ligand 1 [PD-L1]-positive tumors) (pembrolizumab 2 mg/kg HR = 0.71, 95% CI, 0.58-0.88; P = .0008; pembrolizumab 10 mg/kg HR = 0.61, 95% CI, 0.49-0.75; P < .0001) or first-line pembrolizumab (HR = 0.60, 95% CI, 0.41-0.89; P = .005) compared with chemotherapy was found. The adverse effects were mainly higher in the chemotherapy arms. For patients with advanced stage IIIB/IV NSCLC, the improvement in overall survival outweighed the harms and supported the use of first-line pembrolizumab (in patients with ≥ 50% PD-L1-positive tumors) or second-line nivolumab, atezolizumab, or pembrolizumab (in patients with PD-L1-positive tumors). Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Association of Hospital Volume With Racial and Ethnic Disparities in Locally Advanced Cervical Cancer Treatment.

    PubMed

    Uppal, Shitanshu; Chapman, Christina; Spencer, Ryan J; Jolly, Shruti; Maturen, Kate; Rauh-Hain, J Alejandro; delCarmen, Marcela G; Rice, Laurel W

    2017-02-01

    To evaluate racial-ethnic disparities in guideline-based care in locally advanced cervical cancer and their relationship to hospital case volume. Using the National Cancer Database, we performed a retrospective cohort study of women diagnosed between 2004 and 2012 with locally advanced squamous or adenocarcinoma of the cervix undergoing definitive primary radiation therapy. The primary outcome was the race-ethnicity-based rates of adherence to the National Comprehensive Cancer Network guideline-based care. The secondary outcome was the effect of guideline-based care on overall survival. Multivariable models and propensity matching were used to compare the hospital risk-adjusted rates of guideline-based adherence and overall survival based on hospital case volume. The final cohort consisted of 16,195 patients. The rate of guideline-based care was 58.4% (95% confidence interval [CI] 57.4-59.4%) for non-Hispanic white, 53% (95% CI 51.4-54.9%) for non-Hispanic black, and 51.5% (95% CI 49.4-53.7%) for Hispanic women (P<.001). From 2004 to 2012, the rate of guideline-based care increased from 49.5% (95% CI 47.1-51.9%) to 59.1% (95% CI 56.9-61.2%) (Ptrend<.001). Based on a propensity score-matched analysis, patients receiving guideline-based care had a lower risk of mortality (adjusted hazard ratio 0.65, 95% CI 0.62-0.68). Compared with low-volume hospitals, the increase in adherence to guideline-based care in high-volume hospitals was 48-63% for non-Hispanic white, 47-53% for non-Hispanic black, and 41-54% for Hispanic women. Racial and ethnic disparities in the delivery of guideline-based care are the highest in high-volume hospitals. Guideline-based care in locally advanced cervical cancer is associated with improved survival.

  9. Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martinez, Steve R., E-mail: steve.martinez@ucdmc.ucdavis.ed; Beal, Shannon H.; Chen, Steven L.

    2010-11-01

    Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and {>=}10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximatelymore » half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.« less

  10. Gefitinib provides similar effectiveness and improved safety than erlotinib for advanced non-small cell lung cancer: A meta-analysis.

    PubMed

    Zhang, Wenxiong; Wei, Yiping; Yu, Dongliang; Xu, Jianjun; Peng, Jinhua

    2018-04-01

    The epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib are effective for advanced non-small cell lung cancer (NSCLC). This meta-analysis compared their effectiveness and safety. We searched systematically in PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar for relevant clinical trials regarding gefitinib versus erlotinib for NSCLC. Antitumor effectiveness (overall survival [OS], progression-free survival [PFS], objective response rate [ORR] and disease control rate [DCR]) and adverse effects [AEs]) were assessed. Forty studies comprising 9376 participants were included. The results suggested that gefitinib and erlotinib are effective for advanced NSCLC with comparable PFS (95% confidence intervals [CI]: 0.98-1.11, P = .15), OS (95% CI: 0.93-1.19, P = .45), ORR (95% CI: 0.99-1.16, P = .07), and DCR (95% CI: 0.92-1.03, P = .35). For erlotinib, dose reduction was significantly more frequent (95% CI: 0.10-0.57, P = .001) as were grade 3 to 5 AEs (95% CI: 0.36-0.79, P = .002). In the subgroup analysis, the erlotinib group had a significant higher rate and severity of skin rash, nausea/vomiting, fatigue, and stomatitis. Gefitinib was proven to be the better choice for advanced NSCLC, with equal antitumor effectiveness and fewer AEs compared with erlotinib. Further large-scale, well-designed randomized controlled trials are warranted to confirm our validation.

  11. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

    PubMed

    Thigpen, T; Brady, M F; Homesley, H D; Soper, J T; Bell, J

    2001-01-15

    In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents.

  12. Interferon after surgery for women with advanced (Stage II-IV) epithelial ovarian cancer.

    PubMed

    Lawal, Aramide O; Musekiwa, Alfred; Grobler, Liesl

    2013-06-06

    Epithelial ovarian cancer (EOC) is a life-threatening disease. Most often women become symptomatic only in the advanced stages of the disease, increasing the difficulty of treatment. Whilst the disease responds well to surgery and chemotherapy, the relapse rate is high. New treatments to prevent disease recurrence or progression, prolong survival, and increase the quality of life are needed. To assess the effectiveness and safety of interferon after surgery in the treatment of advanced (stage II-IV) EOC. The Cochrane Gynaecological Cancer Review Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2012, MEDLINE and EMBASE were searched to January 2012. Handsearching of conference proceedings was also undertaken. Reference lists of reviews and included trials were screened and experts in the field were contacted for additional trials. Clinical trials registers were searched for ongoing trials. Randomised controlled trials (RCTs) involving participants with advanced EOC that compared post-operative chemotherapy alone with post-operative interferon therapy in combination with chemotherapy or post-operative chemotherapy followed by interferon or observation alone Two review authors (AL and AM) independently screened the search results for relevant trials and extracted pre-specified information from each included trial. Data were managed using Review Manager 5.1. Hazard ratios (HR) were calculated for time-to-event outcomes and risk ratios (RR) for dichotomous outcomes, with corresponding 95% confidence intervals (CI). Five trials, including 1476 participants, were included in the review. Two trials compared interferon with observation alone and three trials compared interferon plus chemotherapy with chemotherapy alone. A meta-analysis of two trials involving 370 participants found no significant difference in both overall survival (HR 1.14, 95% CI 0.84 to 1.55) and progression free survival (HR 0.99, 95% CI 0.79 to 1.24) between

  13. BRAF Mutations in Advanced Cancers: Clinical Characteristics and Outcomes

    PubMed Central

    El-Osta, Hazem; Falchook, Gerald; Tsimberidou, Apostolia; Hong, David; Naing, Aung; Kim, Kevin; Wen, Sijin; Janku, Filip; Kurzrock, Razelle

    2011-01-01

    Background Oncogenic BRAF mutations have been found in diverse malignancies and activate RAF/MEK/ERK signaling, a critical pathway of tumorigenesis. We examined the clinical characteristics and outcomes of patients with mutant (mut) BRAF advanced cancer referred to phase 1 clinic. Methods We reviewed the records of 80 consecutive patients with mutBRAF advanced malignancies and 149 with wild-type (wt) BRAF (matched by tumor type) referred to the Clinical Center for Targeted Therapy and analyzed their outcome. Results Of 80 patients with mutBRAF advanced cancer, 56 had melanoma, 10 colorectal, 11 papillary thyroid, 2 ovarian and 1 esophageal cancer. Mutations in codon 600 were found in 77 patients (62, V600E; 13, V600K; 1, V600R; 1, unreported). Multivariate analysis showed less soft tissue (Odds ratio (OR) = 0.39, 95%CI: 0.20–0.77, P = 0.007), lung (OR = 0.38, 95%CI: 0.19–0.73, p = 0.004) and retroperitoneal metastases (OR = 0.34, 95%CI: 0.13–0.86, p = 0.024) and more brain metastases (OR = 2.05, 95%CI: 1.02–4.11, P = 0.043) in patients with mutBRAF versus wtBRAF. Comparing to the corresponding wtBRAF, mutBRAF melanoma patients had insignificant trend to longer median survival from diagnosis (131 vs. 78 months, p = 0.14), while mutBRAF colorectal cancer patients had an insignificant trend to shorter median survival from diagnosis (48 vs. 53 months, p = 0.22). In melanoma, V600K mutations in comparison to other BRAF mutations were associated with more frequent brain (75% vs. 36.3%, p = 0.02) and lung metastases (91.6% vs. 47.7%, p = 0.007), and shorter time from diagnosis to metastasis and to death (19 vs. 53 months, p = 0.046 and 78 vs. 322 months, p = 0.024 respectively). Treatment with RAF/MEK targeting agents (Hazard ratio (HR) = 0.16, 95%CI: 0.03–0.89, p = 0.037) and any decrease in tumor size after referral (HR = 0.07, 95%CI: 0.015–0.35, p = 0.001) correlated with longer

  14. CI2 for creating and comparing confidence-intervals for time-series bivariate plots.

    PubMed

    Mullineaux, David R

    2017-02-01

    Currently no method exists for calculating and comparing the confidence-intervals (CI) for the time-series of a bivariate plot. The study's aim was to develop 'CI2' as a method to calculate the CI on time-series bivariate plots, and to identify if the CI between two bivariate time-series overlap. The test data were the knee and ankle angles from 10 healthy participants running on a motorised standard-treadmill and non-motorised curved-treadmill. For a recommended 10+ trials, CI2 involved calculating 95% confidence-ellipses at each time-point, then taking as the CI the points on the ellipses that were perpendicular to the direction vector between the means of two adjacent time-points. Consecutive pairs of CI created convex quadrilaterals, and any overlap of these quadrilaterals at the same time or ±1 frame as a time-lag calculated using cross-correlations, indicated where the two time-series differed. CI2 showed no group differences between left and right legs on both treadmills, but the same legs between treadmills for all participants showed differences of less knee extension on the curved-treadmill before heel-strike. To improve and standardise the use of CI2 it is recommended to remove outlier time-series, use 95% confidence-ellipses, and scale the ellipse by the fixed Chi-square value as opposed to the sample-size dependent F-value. For practical use, and to aid in standardisation or future development of CI2, Matlab code is provided. CI2 provides an effective method to quantify the CI of bivariate plots, and to explore the differences in CI between two bivariate time-series. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Restoration of vision in blind individuals using bionic devices: a review with a focus on cortical visual prostheses.

    PubMed

    Lewis, Philip M; Ackland, Helen M; Lowery, Arthur J; Rosenfeld, Jeffrey V

    2015-01-21

    The field of neurobionics offers hope to patients with sensory and motor impairment. Blindness is a common cause of major sensory loss, with an estimated 39 million people worldwide suffering from total blindness in 2010. Potential treatment options include bionic devices employing electrical stimulation of the visual pathways. Retinal stimulation can restore limited visual perception to patients with retinitis pigmentosa, however loss of retinal ganglion cells precludes this approach. The optic nerve, lateral geniculate nucleus and visual cortex provide alternative stimulation targets, with several research groups actively pursuing a cortically-based device capable of driving several hundred stimulating electrodes. While great progress has been made since the earliest works of Brindley and Dobelle in the 1960s and 1970s, significant clinical, surgical, psychophysical, neurophysiological, and engineering challenges remain to be overcome before a commercially-available cortical implant will be realized. Selection of candidate implant recipients will require assessment of their general, psychological and mental health, and likely responses to visual cortex stimulation. Implant functionality, longevity and safety may be enhanced by careful electrode insertion, optimization of electrical stimulation parameters and modification of immune responses to minimize or prevent the host response to the implanted electrodes. Psychophysical assessment will include mapping the positions of potentially several hundred phosphenes, which may require repetition if electrode performance deteriorates over time. Therefore, techniques for rapid psychophysical assessment are required, as are methods for objectively assessing the quality of life improvements obtained from the implant. These measures must take into account individual differences in image processing, phosphene distribution and rehabilitation programs that may be required to optimize implant functionality. In this review, we

  16. HoPaCI-DB: host-Pseudomonas and Coxiella interaction database

    PubMed Central

    Bleves, Sophie; Dunger, Irmtraud; Walter, Mathias C.; Frangoulidis, Dimitrios; Kastenmüller, Gabi; Voulhoux, Romé; Ruepp, Andreas

    2014-01-01

    Bacterial infectious diseases are the result of multifactorial processes affected by the interplay between virulence factors and host targets. The host-Pseudomonas and Coxiella interaction database (HoPaCI-DB) is a publicly available manually curated integrative database (http://mips.helmholtz-muenchen.de/HoPaCI/) of host–pathogen interaction data from Pseudomonas aeruginosa and Coxiella burnetii. The resource provides structured information on 3585 experimentally validated interactions between molecules, bioprocesses and cellular structures extracted from the scientific literature. Systematic annotation and interactive graphical representation of disease networks make HoPaCI-DB a versatile knowledge base for biologists and network biology approaches. PMID:24137008

  17. Interest and preferences for using advanced physical activity tracking devices: results of a national cross-sectional survey

    PubMed Central

    Alley, Stephanie; Schoeppe, Stephanie; Guertler, Diana; Jennings, Cally; Vandelanotte, Corneel

    2016-01-01

    Objectives Pedometers are an effective self-monitoring tool to increase users' physical activity. However, a range of advanced trackers that measure physical activity 24 hours per day have emerged (eg, Fitbit). The current study aims to determine people's current use, interest and preferences for advanced trackers. Design and participants A cross-sectional national telephone survey was conducted in Australia with 1349 respondents. Outcome measures Regression analyses were used to determine whether tracker interest and use, and use of advanced trackers over pedometers is a function of demographics. Preferences for tracker features and reasons for not wanting to wear a tracker are also presented. Results Over one-third of participants (35%) had used a tracker, and 16% are interested in using one. Multinomial regression (n=1257) revealed that the use of trackers was lower in males (OR=0.48, 95% CI 0.36 to 0.65), non-working participants (OR=0.43, 95% CI 0.30 to 0.61), participants with lower education (OR=0.52, 95% CI 0.38 to 0.72) and inactive participants (OR=0.52, 95% CI 0.39 to 0.70). Interest in using a tracker was higher in younger participants (OR=1.73, 95% CI 1.15 to 2.58). The most frequently used tracker was a pedometer (59%). Logistic regression (n=445) revealed that use of advanced trackers compared with pedometers was higher in males (OR=1.67, 95% CI 1.01 to 2.79) and younger participants (OR=2.96, 95% CI 1.71 to 5.13), and lower in inactive participants (OR=0.35, 95% CI 0.19 to 0.63). Over half of current or interested tracker users (53%) prefer to wear it on their wrist, 31% considered counting steps the most important function and 30% regarded accuracy as the most important characteristic. The main reasons for not wanting to use a tracker were, ‘I don't think it would help me’ (39%), and ‘I don't want to increase my activity’ (47%). Conclusions Activity trackers are a promising tool to engage people in self-monitoring a physical activity

  18. Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis.

    PubMed

    Caussy, Cyrielle; Soni, Meera; Cui, Jeffrey; Bettencourt, Ricki; Schork, Nicholas; Chen, Chi-Hua; Ikhwan, Mahdi Al; Bassirian, Shirin; Cepin, Sandra; Gonzalez, Monica P; Mendler, Michel; Kono, Yuko; Vodkin, Irine; Mekeel, Kristin; Haldorson, Jeffrey; Hemming, Alan; Andrews, Barbara; Salotti, Joanie; Richards, Lisa; Brenner, David A; Sirlin, Claude B; Loomba, Rohit

    2017-06-30

    The risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis. This is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE). The prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438). Using a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients. 140084. National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.

  19. APEX 3: a multi-purpose test platform for auditory psychophysical experiments.

    PubMed

    Francart, Tom; van Wieringen, Astrid; Wouters, Jan

    2008-07-30

    APEX 3 is a software test platform for auditory behavioral experiments. It provides a generic means of setting up experiments without any programming. The supported output devices include sound cards and cochlear implants from Cochlear Corporation and Advanced Bionics Corporation. Many psychophysical procedures are provided and there is an interface to add custom procedures. Plug-in interfaces are provided for data filters and external controllers. APEX 3 is supported under Linux and Windows and is available free of charge.

  20. C.I. Disperse Blue; Testing Consent Order

    EPA Pesticide Factsheets

    This notice announces that EPA has signed an enforceable Testing Consent Order with eight companies who have agreed to perform certain health and environmental effects tests with C.I. Disperse Blue 79:1(1)8-79:1)(CAS No. 3618-72-2.

  1. Occurrence of CYP1B1 Mutations in Juvenile Open-Angle Glaucoma With Advanced Visual Field Loss.

    PubMed

    Souzeau, Emmanuelle; Hayes, Melanie; Zhou, Tiger; Siggs, Owen M; Ridge, Bronwyn; Awadalla, Mona S; Smith, James E H; Ruddle, Jonathan B; Elder, James E; Mackey, David A; Hewitt, Alex W; Healey, Paul R; Goldberg, Ivan; Morgan, William H; Landers, John; Dubowsky, Andrew; Burdon, Kathryn P; Craig, Jamie E

    2015-07-01

    Juvenile open-angle glaucoma (JOAG) is a severe neurodegenerative eye disorder in which most of the genetic contribution remains unexplained. To assess the prevalence of pathogenic CYP1B1 sequence variants in an Australian cohort of patients with JOAG and severe visual field loss. For this cohort study, we recruited 160 patients with JOAG classified as advanced (n = 118) and nonadvanced (n = 42) through the Australian and New Zealand Registry of Advanced Glaucoma from January 1, 2007, through April 1, 2014. Eighty individuals with no evidence of glaucoma served as a control group. We defined JOAG as diagnosis before age 40 years and advanced JOAG as visual field loss in 2 of the 4 central fixation squares on a reliable visual field test result. We performed direct sequencing of the entire coding region of CYP1B1. Data analysis was performed in October 2014. Identification and characterization of CYP1B1 sequence variants. We identified 7 different pathogenic variants among 8 of 118 patients with advanced JOAG (6.8%) but none among the patients with nonadvanced JOAG. Three patients were homozygous or compound heterozygous for CYP1B1 pathogenic variants, which provided a likely basis for their disease. Five patients were heterozygous. The allele frequency among the patients with advanced JOAG (11 in 236 [4.7%]) was higher than among our controls (1 in 160 [0.6%]; P = .02; odds ratio, 7.8 [95% CI, 0.02-1.0]) or among the control population from the Exome Aggregation Consortium database (2946 of 122 960 [2.4%]; P = .02; odds ratio, 2.0 [95% CI, 0.3-0.9]). Individuals with CYP1B1 pathogenic variants, whether heterozygous or homozygous, had worse mean (SD) deviation on visual fields (-24.5 [5.1] [95% CI, -31.8 to -17.2] vs -15.6 [10.0] [95% CI, -17.1 to -13.6] dB; F1,126 = 5.90; P = .02; partial ηp2 = 0.05) and were younger at diagnosis (mean [SD] age, 23.1 [8.4] [95% CI, 17.2-29.1] vs 31.5 [8.0] [95% CI, 30.1-33.0] years; F1,122 = 7

  2. Recombinant Botulinum Neurotoxin Hc Subunit (BoNT Hc) and Catalytically Inactive Clostridium botulinum Holoproteins (ciBoNT HPs) as Vaccine Candidates for the Prevention of Botulism

    PubMed Central

    Webb, Robert P.; Smith, Theresa J.; Smith, Leonard A.; Wright, Patrick M.; Guernieri, Rebecca L.; Brown, Jennifer L.; Skerry, Janet C.

    2017-01-01

    There are few available medical countermeasures against botulism and the discontinuation of the pentavalent botulinum toxoid vaccine by the Centers for Disease Control and Prevention in 2011 has resulted in the need for a safe and effective prophylactic alternative. Advances in genetic engineering have resulted in subsequent vaccine efforts being primarily focused on the production of highly purified recombinant protein antigens representing one or more domains of the botulinum neurotoxin. Recombinant subunit vaccines based on the carboxy one-third of the toxin (Hc) developed in our lab against serotypes A-F have been shown to be safe and effective. However, in response to the identification of an ever increasing number of BoNT subtypes with significant amino acid heterogeneity, we have developed catalytically inactive BoNT holoproteins (ciBoNT HPs) in an attempt to elicit greater protective immunity to address these toxin variants. Here we report the production of ciBoNT/B1 HP, ciBoNT/C1 HP, ciBoNT/E1 HP and ciBoNT/F1 HP and compare the immunological and protective abilities of ciBoNT HPs and BoNT/A Hc, BoNT/B Hc, BoNT/C Hc, BoNT/E Hc and BoNT/F Hc vaccines when challenged with homologous and heterologous toxins. Our results suggest the ciBoNT HP vaccines exhibit superior potency after single vaccinations but multiple vaccinations with BoNT/Hc antigens resulted in increased survival rates at the toxin challenge levels used. PMID:28869522

  3. Association of prehospital advanced airway management with neurologic outcome and survival in patients with out-of-hospital cardiac arrest.

    PubMed

    Hasegawa, Kohei; Hiraide, Atsushi; Chang, Yuchiao; Brown, David F M

    2013-01-16

    It is unclear whether advanced airway management such as endotracheal intubation or use of supraglottic airway devices in the prehospital setting improves outcomes following out-of-hospital cardiac arrest (OHCA) compared with conventional bag-valve-mask ventilation. To test the hypothesis that prehospital advanced airway management is associated with favorable outcome after adult OHCA. Prospective, nationwide, population-based study (All-Japan Utstein Registry) involving 649,654 consecutive adult patients in Japan who had an OHCA and in whom resuscitation was attempted by emergency responders with subsequent transport to medical institutions from January 2005 through December 2010. Favorable neurological outcome 1 month after an OHCA, defined as cerebral performance category 1 or 2. Of the eligible 649,359 patients with OHCA, 367,837 (57%) underwent bag-valve-mask ventilation and 281,522 (43%) advanced airway management, including 41,972 (6%) with endotracheal intubation and 239,550 (37%) with use of supraglottic airways. In the full cohort, the advanced airway group incurred a lower rate of favorable neurological outcome compared with the bag-valve-mask group (1.1% vs 2.9%; odds ratio [OR], 0.38; 95% CI, 0.36-0.39). In multivariable logistic regression, advanced airway management had an OR for favorable neurological outcome of 0.38 (95% CI, 0.37-0.40) after adjusting for age, sex, etiology of arrest, first documented rhythm, witnessed status, type of bystander cardiopulmonary resuscitation, use of public access automated external defibrillator, epinephrine administration, and time intervals. Similarly, the odds of neurologically favorable survival were significantly lower both for endotracheal intubation (adjusted OR, 0.41; 95% CI, 0.37-0.45) and for supraglottic airways (adjusted OR, 0.38; 95% CI, 0.36-0.40). In a propensity score-matched cohort (357,228 patients), the adjusted odds of neurologically favorable survival were significantly lower both for

  4. Pitch ranking, electrode discrimination, and physiological spread of excitation using current steering in cochlear implants

    PubMed Central

    Goehring, Jenny L.; Neff, Donna L.; Baudhuin, Jacquelyn L.; Hughes, Michelle L.

    2014-01-01

    The first objective of this study was to determine whether adaptive pitch-ranking and electrode-discrimination tasks with cochlear-implant (CI) recipients produce similar results for perceiving intermediate “virtual-channel” pitch percepts using current steering. Previous studies have not examined both behavioral tasks in the same subjects with current steering. A second objective was to determine whether a physiological metric of spatial separation using the electrically evoked compound action potential spread-of-excitation (ECAP SOE) function could predict performance in the behavioral tasks. The metric was the separation index (Σ), defined as the difference in normalized amplitudes between two adjacent ECAP SOE functions, summed across all masker electrodes. Eleven CII or 90 K Advanced Bionics (Valencia, CA) recipients were tested using pairs of electrodes from the basal, middle, and apical portions of the electrode array. The behavioral results, expressed as d′, showed no significant differences across tasks. There was also no significant effect of electrode region for either task. ECAP Σ was not significantly correlated with pitch ranking or electrode discrimination for any of the electrode regions. Therefore, the ECAP separation index is not sensitive enough to predict perceptual resolution of virtual channels. PMID:25480063

  5. Clinical evaluation of music perception, appraisal and experience in cochlear implant users

    PubMed Central

    Drennan, Ward. R.; Oleson, Jacob J.; Gfeller, Kate; Crosson, Jillian; Driscoll, Virginia D.; Won, Jong Ho; Anderson, Elizabeth S.; Rubinstein, Jay T.

    2014-01-01

    Objectives The objectives were to evaluate the relationships among music perception, appraisal, and experience in cochlear implant users in multiple clinical settings and to examine the viability of two assessments designed for clinical use. Design Background questionnaires (IMBQ) were administered by audiologists in 14 clinics in the United States and Canada. The CAMP included tests of pitch-direction discrimination, and melody and timbre recognition. The IMBQ queried users on prior musical involvement, music listening habits pre and post implant, and music appraisals. Study sample One-hundred forty-five users of Advanced Bionics and Cochlear Ltd cochlear implants. Results Performance on pitch direction discrimination, melody recognition, and timbre recognition tests were consistent with previous studies with smaller cohorts, as well as with more extensive protocols conducted in other centers. Relationships between perceptual accuracy and music enjoyment were weak, suggesting that perception and appraisal are relatively independent for CI users. Conclusions Perceptual abilities as measured by the CAMP had little to no relationship with music appraisals and little relationship with musical experience. The CAMP and IMBQ are feasible for routine clinical use, providing results consistent with previous thorough laboratory-based investigations. PMID:25177899

  6. Nursing domain of CI governance: recommendations for health IT adoption and optimization.

    PubMed

    Collins, Sarah A; Alexander, Dana; Moss, Jacqueline

    2015-05-01

    There is a lack of recommended models for clinical informatics (CI) governance that can facilitate successful health information technology implementation. To understand existing CI governance structures and provide a model with recommended roles, partnerships, and councils based on perspectives of nursing informatics leaders. We conducted a cross-sectional study through administering a survey via telephone to facilitate semistructured interviews from June 2012 through November 2012. We interviewed 12 nursing informatics leaders, across the United States, currently serving in executive- or director-level CI roles at integrated health care systems that have pioneered electronic health records implementation projects. We found the following 4 themes emerge: (1) Interprofessional partnerships are essential. (2) Critical role-based levels of practice and competencies need to be defined. (3) Integration into existing clinical infrastructure facilitates success. (4) CI governance is an evolving process. We described specific lessons learned and a model of CI governance with recommended roles, partnerships, and councils from the perspective of nursing informatics leaders. Applied CI work is highly interprofessional with patient safety implications that heighten the need for best practice models for governance structures, adequate resource allocation, and role-based competencies. Overall, there is a notable lack of a centralized CI group comprised of formally trained informaticians to provide expertise and promote adherence to informatics principles within EHR implementation governance structures. Our model of the nursing domain of CI governance with recommended roles, partnerships, and councils provides a starting point that should be further explored and validated. Not only can the model be used to understand, shape, and standardize roles, competencies, and structures within CI practice for nursing, it can be used within other clinical domains and by other informaticians

  7. [Technical advancements in cochlear implants : State of the art].

    PubMed

    Büchner, A; Gärtner, L

    2017-04-01

    Twenty years ago, cochlear implants (CI) were indicated only in cases of profound hearing loss or complete deafness. While from today's perspective the technology was clumsy and provided patients with only limited speech comprehension in quiet scenarios, successive advances in CI technology and the consequent substantial hearing improvements over time have since then resulted in continuous relaxation of indication criteria toward residual hearing. While achievements in implant and processor electronics have been one key factor for the ever-improving hearing performance, development of electro-acoustic CI systems-together with atraumatic implantation concepts-has led to enormous improvements in patients with low-frequency residual hearing. Manufactures have designed special processors with integrated hearing aid components for this patient group, which are capable of conveying acoustic and electric stimulation. A further milestone in improvement of hearing in challenging listening environments was the adoption of signal enhancement algorithms and assistive listening devices from the hearing aid industry. This article gives an overview of the current state of the art in the abovementioned areas of CI technology.

  8. Clinical features and response to systemic therapy in a historical cohort of advanced or unresectable mucosal melanoma.

    PubMed

    Shoushtari, Alexander N; Bluth, Mark J; Goldman, Debra A; Bitas, Christiana; Lefkowitz, Robert A; Postow, Michael A; Munhoz, Rodrigo R; Buchar, Gauri; Hester, Robert H; Romero, Jacqueline A; Fitzpatrick, Laura J; Weiser, Martin R; Panageas, Katherine S; Wolchok, Jedd D; Chapman, Paul B; Carvajal, Richard D

    2017-02-01

    There are very few data available regarding the pattern of first metastases in resected mucosal melanomas (MMs) as well as the response of advanced MM to cytotoxic therapy. A retrospective, single-institution cohort was assembled of all patients with advanced/unresectable MM between 1995 and 2012 who had received systemic therapy with available imaging (N=81). Responses to first-line and second-line systemic therapy were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The relationship between response, overall survival, and clinical covariates was investigated using Cox proportional hazards regression. Primary sites included anorectal (N=31, 38%), vulvovaginal (N=28, 35%), head and neck (N=21, 26%), and gallbladder (N=1, 1%) mucosa. Seven percent of patients had their first relapse in the brain. Cytotoxic therapy represented 82 and 51% of first-line and second-line regimens. The best response achieved in the first-line setting was similar for single-agent [10%; 95% confidence interval (CI): 1-32%] and combination alkylator therapy (8%; 95% CI: 2-21%). Median overall survival from first-line treatment was 10.3 months (95% CI: 8.7-13.9 months). Patients with elevated lactic dehydrogenase [hazard ratio (HR): 1.87, 95% CI: 1.10-3.19, P=0.020] and Eastern Cooperative Oncology Group performance status 1-2 (HR: 1.69, 95% CI: 1.05-2.72, P=0.030) had a higher risk of death, whereas patients with 12-week objective responses had a lower risk of death (HR: 0.12, 95% CI: 0.04-0.41, P<0.001). Cytotoxic systemic therapy has modest activity in advanced/unresectable MM, belying its adjuvant benefit. Patients whose tumors have an objective response to therapy have a lower probability of death. Brain imaging should be considered in routine surveillance.

  9. KSC-2011-2263

    NASA Image and Video Library

    2011-03-11

    ORLANDO, Fla. – NASA Kennedy Space Center Director Bob Cabana checks out the robot designed by the Bionic Tigers team at the regional FIRST robotics competition at the University of Central Florida in Orlando. The team is made up of students from Cocoa High School and Holy Trinity Episcopal Academy along the Space Coast in Florida. NASA's Launch Services Program based at Kennedy is a sponsor of the team. The Bionic Tigers finished seventh in the competition called "For Inspiration and Recognition of Science and Technology," or FIRST, among about 60 high school teams hoping to advance to the national robotics championship. FIRST, founded in 1989, is a non-profit organization that designs accessible, innovative programs to build self-confidence, knowledge and life skills while motivating young people to pursue academic opportunities. The robotics competition challenges teams of high school students and their mentors to solve a common problem in a six-week timeframe using a standard kit of parts and a common set of rules. Photo credit: NASA/Glenn Benson

  10. Ci8 short, a novel LPS-induced peptide from the ascidian Ciona intestinalis, modulates responses of the human immune system.

    PubMed

    Bonura, Angela; Vizzini, Aiti; Vlah, Sara; Gervasi, Francesco; Longo, Alessandra; Melis, Mario R; Schildberg, Frank A; Colombo, Paolo

    2018-02-01

    The selective modulation of immunity is an emerging concept driven by the vast advances in our understanding of this crucial host defense system. Invertebrates have raised researchers' interest as potential sources of new bioactive molecules owing to their antibacterial, anticancer and immunomodulatory activities. A LipoPolySaccharide (LPS) challenge in the ascidian Ciona intestinalis generates the transcript, Ci8 short, with cis-regulatory elements in the 3' UTR region that are essential for shaping innate immune responses. The derived amino acidic sequence in silico analysis showed specific binding to human Major Histocompatibility Complex (MHC) Class I and Class II alleles. The role of Ci8 short peptide was investigated in a more evolved immune system using human Peripheral Blood Mononuclear Cells (PBMCs) as in vitro model. The biological activities of this molecule include the activation of 70kDa TCR ζ chain Associated Protein kinase (ZAP-70) and T Cell Receptor (TCR) Vβ oligo clonal selection on CD4 + T lymphocytes as well as increased proliferation and IFN-γ secretion. Furthermore Ci8 short affects CD4 + /CD25 high induced regulatory T cells (iTreg) subset selection which co-expressed the functional markers TGF-β1/Latency Associated Protein (LAP) and CD39/CD73. This paper describes a new molecule that modulates important responses of the human adaptive immune system. Copyright © 2017 Elsevier GmbH. All rights reserved.

  11. Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer.

    PubMed

    Ramalingam, Suresh S; Yang, James C-H; Lee, Chee Khoon; Kurata, Takayasu; Kim, Dong-Wan; John, Thomas; Nogami, Naoyuki; Ohe, Yuichiro; Mann, Helen; Rukazenkov, Yuri; Ghiorghiu, Serban; Stetson, Daniel; Markovets, Aleksandra; Barrett, J Carl; Thress, Kenneth S; Jänne, Pasi A

    2018-03-20

    Purpose The AURA study ( ClinicalTrials.gov identifier: NCT01802632) included two cohorts of treatment-naïve patients to examine clinical activity and safety of osimertinib (an epidermal growth factor receptor [EGFR] -tyrosine kinase inhibitor selective for EGFR-tyrosine kinase inhibitor sensitizing [ EGFRm] and EGFR T790M resistance mutations) as first-line treatment of EGFR-mutated advanced non-small-cell lung cancer (NSCLC). Patients and Methods Sixty treatment-naïve patients with locally advanced or metastatic EGFRm NSCLC received osimertinib 80 or 160 mg once daily (30 patients per cohort). End points included investigator-assessed objective response rate (ORR), progression-free survival (PFS), and safety evaluation. Plasma samples were collected at or after patients experienced disease progression, as defined by Response Evaluation Criteria in Solid Tumors (RECIST), to investigate osimertinib resistance mechanisms. Results At data cutoff (November 1, 2016), median follow-up was 19.1 months. Overall ORR was 67% (95% CI, 47% to 83%) in the 80-mg group, 87% (95% CI, 69% to 96%) in the 160-mg group, and 77% (95% CI, 64% to 87%) across doses. Median PFS time was 22.1 months (95% CI, 13.7 to 30.2 months) in the 80-mg group, 19.3 months (95% CI, 13.7 to 26.0 months) in the 160-mg group, and 20.5 months (95% CI, 15.0 to 26.1 months) across doses. Of 38 patients with postprogression plasma samples, 50% had no detectable circulating tumor DNA. Nine of 19 patients had putative resistance mechanisms, including amplification of MET (n = 1); amplification of EGFR and KRAS (n = 1); MEK1, KRAS, or PIK3CA mutation (n = 1 each); EGFR C797S mutation (n = 2); JAK2 mutation (n = 1); and HER2 exon 20 insertion (n = 1). Acquired EGFR T790M was not detected. Conclusion Osimertinib demonstrated a robust ORR and prolonged PFS in treatment-naïve patients with EGFRm advanced NSCLC. There was no evidence of acquired EGFR T790M mutation in postprogression plasma samples.

  12. Gemcitabine-cisplatin versus gemcitabine-oxaliplatin doublet chemotherapy in advanced gallbladder cancers: a match pair analysis.

    PubMed

    Ramaswamy, Anant; Ostwal, Vikas; Pinninti, Rakesh; Kannan, Sadhana; Bhargava, Prabhat; Nashikkar, Chaitali; Mirani, Jimmy; Banavali, Shripad

    2017-05-01

    Gemcitabine-cisplatin (GC) and gemcitabine-oxaliplatin (GO) are the most commonly used regimens in advanced gallbladder cancer (GBC). The data of patients with advanced GBC, treated between January 2013 and June 2015 were retrieved. A 1:1 matching without replacement was performed by using nearest neighbor matching method. A total of 326 patients (163 GC and 163 GO), were matched 1:1 by age and gender. The response rates for GC and GO were 31.2% and 36.3% (P = 0.350). The overall median event free survival (EFS) was 4.34 months (95% CI 4.030-4.644 months). The median EFS was 4.67 months (95% CI 4.060-5.271 months) in GC cohort and 3.88 months (95% CI 3.369-4.385 months) in GO cohort (P = 0.023). The overall median OS was 8.016 months (95% CI 7.361-8.672 months). The median OS was 8.02 months (95% CI 7.257-8.776 months) in GC cohort and 7.79 months (95% CI 6.690-8.88 months) in GO cohort (P = 0.455). The incidence of Grade 2/3 peripheral neuropathy (9.2% vs. 3.1%; P = 0.445) and Grade 3/4 transamintis (14.7% vs. 6.1%) was higher with GO while the incidence of anemia (22.1% vs. 6.7%; P < 0.001), neutropenia (7.3% vs. 2.4%; P = 0.49) and thrombocytopenia (9.8% vs. 3.7%; P = 0.033) was higher with GC. Gemcitabine-cisplatin or gemcitabine-oxaliplatin can be used as an initial regimen in advanced GBC. Higher EFS, potentially lower costs, lower incidence of peripheral neuropathy and hepatotoxicity favor the use of GC, whereas a lower incidence of hematological toxicities, and potential ease of administration in patients with borderline renal and cardiac functions favor GO. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  13. Sensitivity of 2-[18F]fluoro-2-deoxyglucose positron emission tomography for advanced colorectal neoplasms: a large-scale analysis of 7505 asymptomatic screening individuals.

    PubMed

    Sekiguchi, Masau; Kakugawa, Yasuo; Terauchi, Takashi; Matsumoto, Minori; Saito, Hiroshi; Muramatsu, Yukio; Saito, Yutaka; Matsuda, Takahisa

    2016-12-01

    The sensitivity of 2-[ 18 F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET) for advanced colorectal neoplasms among healthy subjects is not yet fully understood. The present study aimed to clarify the sensitivity by analyzing large-scale data from an asymptomatic screening population. A total of 7505 asymptomatic screenees who underwent both FDG-PET and colonoscopy at our Cancer Screening Division between February 2004 and March 2013 were analyzed. FDG-PET and colonoscopy were performed on consecutive days, and each examination was interpreted in a blinded fashion. The results of the two examinations were compared for each of the divided six colonic segments, with those from colonoscopy being set as the reference. The relationships between the sensitivity of FDG-PET and clinicopathological features of advanced neoplasms were also evaluated. Two hundred ninety-one advanced neoplasms, including 24 invasive cancers, were detected in 262 individuals. Thirteen advanced neoplasms (advanced adenomas) were excluded from the analysis because of the coexistence of lesions in the same colonic segment. The sensitivity, specificity, and positive and negative predictive values of FDG-PET for advanced neoplasms were 16.9 % [95 % confidence interval (CI) 12.7-21.8 %], 99.3 % (95 % CI 99.2-99.4 %), 13.5 % (95 % CI 10.1-17.6 %), and 99.4 % (95 % CI 99.3-99.5 %), respectively. The sensitivity was lower for lesions with less advanced histological grade, of smaller size, and flat-type morphology, and for those located in the proximal part of the colon. FDG-PET is believed to be difficult to use as a primary screening tool in population-based colorectal cancer screening because of its low sensitivity for advanced neoplasms. Even when it is used in opportunistic cancer screening, the limit of its sensitivity should be considered.

  14. Predictors of Timely Access of Oncology Services and Advanced-Stage Cancer in an HIV-Endemic Setting

    PubMed Central

    Suneja, Gita; Tapela, Neo; Mapes, Abigail; Pusoentsi, Malebogo; Mmalane, Mompati; Hodgeman, Ryan; Boyer, Matthew; Musimar, Zola; Ramogola-Masire, Doreen; Grover, Surbhi; Nsingo-Bvochora, Memory; Kayembe, Mukendi; Efstathiou, Jason; Lockman, Shahin; Dryden-Peterson, Scott

    2016-01-01

    Background. Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. Methods. Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). Results. Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0–185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59–653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79–1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09–1.40) and those with advanced cancer entered care earlier (aHR 1.48, 95% CI 1.30–1.70). Factors significantly associated with advanced cancer included income <$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05–1.75), male sex (aOR 1.45, 95% CI 1.12–1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03–1.88). Conclusion. Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. Implications for Practice: The majority (54%) of patients in this large cohort from Botswana presented with advanced-stage cancer despite universal access to free health care. Median time from first symptom to

  15. Predictors of Timely Access of Oncology Services and Advanced-Stage Cancer in an HIV-Endemic Setting.

    PubMed

    Brown, Carolyn A; Suneja, Gita; Tapela, Neo; Mapes, Abigail; Pusoentsi, Malebogo; Mmalane, Mompati; Hodgeman, Ryan; Boyer, Matthew; Musimar, Zola; Ramogola-Masire, Doreen; Grover, Surbhi; Nsingo-Bvochora, Memory; Kayembe, Mukendi; Efstathiou, Jason; Lockman, Shahin; Dryden-Peterson, Scott

    2016-06-01

    Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0-185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59-653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79-1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09-1.40) and those with advanced cancer entered care earlier (aHR 1.48, 95% CI 1.30-1.70). Factors significantly associated with advanced cancer included income <$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05-1.75), male sex (aOR 1.45, 95% CI 1.12-1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03-1.88). Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. The majority (54%) of patients in this large cohort from Botswana presented with advanced-stage cancer despite universal access to free health care. Median time from first symptom to specialized oncology care was 13 months. For HIV-infected patients (51% of total

  16. Quantitative detection of RO2 radicals and other products from cyclohexene ozonolysis with ammonium-CI3-TOF and acetate-CI-API-TOF

    NASA Astrophysics Data System (ADS)

    Hansel, A.; Scholz, W.; Mentler, B.; Fischer, L.; Berndt, T.

    2017-12-01

    The performance of the novel ammonium-CI3-TOF utilizing NH4+ adduct ion chemistry to measure quantitatively first generation oxidized product molecules (OMs) as well as highly oxidized organic molecules (HOMs) was investigated for the first time. The gas-phase ozonolysis of cyclohexene served as a test system in order to evaluate the capability of the detection systems. Experiments have been carried out in the TROPOS free-jet flow system at close to atmospheric conditions. Product ion signals were simultaneously observed by the ammonium-CI3-TOF and the acetate-CI-API-TOF. Both instruments are in remarkable good agreement within a factor of two for HOMs. For OMs not containing an OOH group the acetate technique can considerably underestimate OM concentrations by 2-3 orders of magnitude. First steps of cyclohexene ozonolysis generate ten different (m/z product peaks) main products comprising 92% of observed OMs. The remaining 8% are distributed over several (m/z peaks) minor products that can be attributed to HOMs, predominately to highly oxidized RO2 radicals. Summing up, observed ammonium-CI3-TOF products yield 4.9 x 109 molecules cm-³ in excellent agreement with the amount of reacted cyclohexene of 5.0 x 109 molecules cm-³ for reactant concentrations of [O3] = 2.25 x 1012 molecules cm-³ and [cyclohexene] = 2.0 x 1012 molecules cm-³ and a reaction time of 7.9 s. NH4+ adduct ion chemistry based CIMS techniques offer a unique opportunity for complete detection of the whole product distribution, and consequently, for a much better understanding of atmospheric oxidation processes.

  17. Preferential interactions in pigmented, polymer blends - C.I. Pigment Blue 15:4 and C.I. Pigment Red 122 - as used in a poly(carbonate)-poly(butylene terephthalate) polymer blend.

    PubMed

    Fagelman, K E; Guthrie, J T

    2005-11-18

    Some important characteristics of selected pigments have been evaluated, using the inverse gas chromatography (IGC) technique, that indicate the occurrence of preferential interactions in pigmented polymer blends. Attention has been given to copper phthalocyanine pigments and to quinacridone pigments incorporated in polycarbonate-poly(butylene terephthalate) blends. Selected supporting techniques were used to provide supplementary information concerning the pigments of interest, C.I. Pigment Blue 15:4 and C.I. Pigment Red 122. For C.I. Pigment Red 122 and for C.I. Pigment Blue, the dispersive component of the surface free energy decreases as the temperature increases, indicating the relative ease with which the molecules can be removed from the surface.

  18. Inhibition of the Growth of Papillary Thyroid Carcinoma Cells by CI-1040

    PubMed Central

    Henderson, Ying C.; Ahn, Soon-Hyun; Clayman, Gary L.

    2015-01-01

    Background Papillary thyroid carcinoma (PTC), the most common type of thyroid malignancy, usually possesses mutations, either RET/PTC rearrangement or BRAF mutation. Both mutations can activate the mitogen-activated protein kinase kinase/extracellular signal–related kinase signaling transduction pathway, which results in activation of transcription factors that regulate cellular proliferation, differentiation, and apoptosis. Objective To test the effects of CI-1040 (PD184352), a specific MEK1/2 inhibitor, on PTC cells carrying either an RET/PTC1 rearrangement or a BRAF mutation. Design The effects of CI-1040 on PTC cells were evaluated in vitro and in vivo. Main Outcome Measures The effects of CI-1040 on PTC cells were evaluated in vitro using a cell proliferation assay, cell cycle analysis, and immunoblotting. The antitumor effects of CI-1040 in vivo were evaluated in an orthotopic mouse model. Results The concentrations of CI-1040 needed to inhibit 50% cell growth were 0.052μM for PTC cells with a BRAF mutation and 1.1μM for PTC cells with the RET/PTC1 rearrangement. After 3 weeks of oral administration of CI-1040 (300 mg/kg/d) to mice with orthotopic tumor implants of PTC cells, the mean tumor volume of implants bearing the RET/PTC1 rearrangement (n=5) was reduced 47.5% compared with untreated mice (from 701.9 to 368.5 mm3), and the mean volume of implants with a BRAF mutation (n=8) was reduced 31.3% (from 297.3 to 204.2 mm3). Conclusions CI-1040 inhibits PTC cell growth in vitro and in vivo. Because RET/PTC rearrangements are unique to thyroid carcinomas and a high percentage of PTCs possess either mutation, these findings support the clinical evaluation of CI-1040 for patients with PTC. PMID:19380355

  19. Knee Instability and Basic and Advanced Function Decline in Knee Osteoarthritis.

    PubMed

    Sharma, Leena; Chmiel, Joan S; Almagor, Orit; Moisio, Kirsten; Chang, Alison H; Belisle, Laura; Zhang, Yunhui; Hayes, Karen W

    2015-08-01

    Manifestations of instability in knee osteoarthritis (OA) include low overall knee confidence, low confidence that the knees will not buckle, buckling, and excessive motion during gait. Confidence and buckling may particularly influence activity choices, contributing to events leading to disability. Buckling is more likely to affect advanced than basic functional tasks. In this prospective longitudinal study, we tested the hypothesis that overall knee confidence, buckling confidence, buckling, and frontal plane motion during gait are associated with advanced 2-year function outcomes in persons with knee OA. Persons with knee OA were queried about overall knee confidence (higher score = worse confidence), buckling confidence, and knee buckling, and underwent quantitative gait analysis to quantify varus-valgus excursion and angular velocity. Physical function was assessed using the Late-Life Function and Disability Instrument Basic and Advanced Lower Extremity Domain scores. Logistic regression was used to evaluate the relationship between baseline instability measures and baseline-to-2-year function outcome, adjusting for potential confounders. The sample was comprised of 212 persons (mean age 64.6 years, 76.9% women). Buckling was significantly associated with poor advanced function outcome (adjusted odds ratio [OR] 2.08, 95% confidence interval [95% CI] 1.03-4.20) but not basic function outcome. Overall knee confidence was significantly associated with advanced outcome (adjusted OR 1.65, 95% CI 1.01-2.70), while associations between buckling confidence and both outcomes approached significance. Neither varus-valgus excursion nor angular velocity during gait was associated with either outcome. Knee buckling and low knee confidence were each associated with poor 2-year advanced function outcomes. Current treatment does not address these modifiable factors; interventions to address them may improve outcome in knee OA. © 2015, American College of Rheumatology.

  20. Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis

    PubMed Central

    Caussy, Cyrielle; Soni, Meera; Cui, Jeffrey; Bettencourt, Ricki; Schork, Nicholas; Chen, Chi-Hua; Ikhwan, Mahdi Al; Bassirian, Shirin; Cepin, Sandra; Gonzalez, Monica P.; Mendler, Michel; Vodkin, Irine; Mekeel, Kristin; Haldorson, Jeffrey; Hemming, Alan; Andrews, Barbara; Salotti, Joanie; Richards, Lisa; Brenner, David A.; Sirlin, Claude B.

    2017-01-01

    BACKGROUND. The risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis. METHODS. This is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE). RESULTS. The prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8–126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1–146.1, P = 0.0438). CONCLUSION. Using a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients. TRIAL REGISTRATION. UCSD IRB: 140084. FUNDING. National Institute of Diabetes and Digestive and Kidney Diseases and

  1. Detection of CI line emission towards the oxygen-rich AGB star omi Ceti

    NASA Astrophysics Data System (ADS)

    Saberi, M.; Vlemmings, W. H. T.; De Beck, E.; Montez, R.; Ramstedt, S.

    2018-05-01

    We present the detection of neutral atomic carbon CI(3P1-3P0) line emission towards omi Cet. This is the first time that CI is detected in the envelope around an oxygen-rich M-type asymptotic giant branch (AGB) star. We also confirm the previously tentative CI detection around V Hya, a carbon-rich AGB star. As one of the main photodissociation products of parent species in the circumstellar envelope (CSE) around evolved stars, CI can be used to trace sources of ultraviolet (UV) radiation in CSEs. The observed flux density towards omi Cet can be reproduced by a shell with a peak atomic fractional abundance of 2.4 × 10-5 predicted based on a simple chemical model where CO is dissociated by the interstellar radiation field. However, the CI emission is shifted by 4 km s-1 from the stellar velocity. Based on this velocity shift, we suggest that the detected CI emission towards omi Cet potentially arises from a compact region near its hot binary companion. The velocity shift could, therefore, be the result of the orbital velocity of the binary companion around omi Cet. In this case, the CI column density is estimated to be 1.1 × 1019 cm-2. This would imply that strong UV radiation from the companion and/or accretion of matter between two stars is most likely the origin of the CI enhancement. However, this hypothesis can be confirmed by high-angular resolution observations.

  2. Lapatinib for treatment of advanced or metastasized breast cancer: systematic review.

    PubMed

    Riera, Rachel; Soárez, Patrícia Coelho de; Puga, Maria Eduarda Dos Santos; Ferraz, Marcos Bosi

    2009-09-01

    Around 16% to 20% of women with breast cancer have advanced, metastasized breast cancer. At this stage, the disease is treatable, but not curable. The objective here was to assess the effectiveness of lapatinib for treating patients with advanced or metastasized breast cancer. Systematic review of the literature, developed at Centro Paulista de Economia da Saúde (CPES), Universidade Federal de São Paulo (Unifesp). Systematic review with searches in virtual databases (PubMed, Lilacs [Literatura Latino-Americana e do Caribe em Ciências da Saúde], Cochrane Library, Scirus and Web of Science) and manual search. Only one clinical trial that met the selection criteria was found. This study showed that lapatinib in association with capecitabine reduced the risk of cancer progression by 51% (95% confidence interval, CI: 0.34-0.71; P < 0.001), compared with capecitabine alone, without any increase in severe adverse effects. The combination of lapatinib plus capecitabine was more effective than capecitabine alone for reducing the risk of cancer progression. Further randomized clinical trials need to be carried out with the aim of assessing the effectiveness of lapatinib as monotherapy or in association for first-line or second-line treatment of advanced breast cancer.

  3. [CI] and CO in local galaxies from the Beyond the Peak Project

    NASA Astrophysics Data System (ADS)

    Crocker, Alison F.; Pellegrini, E. W.; Smith, J. T.; Beyond The Peak Team

    2014-01-01

    From simple plane-parallel photodissociation region (PDR) models, neutral carbon ([CI]) is predicted to exist in a thin layer between C+ and CO on the surface of molecular clouds (e.g. (Hollenbach & Tielens 1999, Kaufman et al. 1999). However, observations of the Milky Way and the Magellanic Clouds indicate that [CI] may instead be a better tracer of the entire cold gas reservoir, often very well correlated with emission from 12CO(1-0) or 13CO(1-0) (e.g. Keene et al. 1996, Bolatto et al. 2000, Shimajiri et al. 2013). Here, we present the observed [CI] fluxes from the Beyond the Peak sample of 22 nearby galaxies observed with the Herschel FTS spectrometer. We first attempt to model all CO transitions and the [CI] lines as a single plane-parallel PDR, but this fails in all cases. Instead, a two-component PDR model is able to fit the CO SLED of nearly all galaxies. We investigate correlations of the [CI] fluxes and line ratio with properties of the cooler component determined from the PDR fits.

  4. Palbociclib and Letrozole in Advanced Breast Cancer.

    PubMed

    Finn, Richard S; Martin, Miguel; Rugo, Hope S; Jones, Stephen; Im, Seock-Ah; Gelmon, Karen; Harbeck, Nadia; Lipatov, Oleg N; Walshe, Janice M; Moulder, Stacy; Gauthier, Eric; Lu, Dongrui R; Randolph, Sophia; Diéras, Véronique; Slamon, Dennis J

    2016-11-17

    A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication. In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety. The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib-letrozole group vs. 1.4% in the placebo-letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib-letrozole group and in 13 patients (5.9%) in the placebo-letrozole group. Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib combined with letrozole resulted in

  5. Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in locally advanced and metastatic biliary tract carcinoma - a retrospective study.

    PubMed

    Croitoru, Adina; Gramaticu, Iulia; Dinu, Ioana; Gheorghe, Liana; Alexandrescu, Sorin; Buica, Florina; Luca, Ioana; Becheanu, Gabriel; Herlea, Vlad; Simionov, Iulia; Hrehoret, Doina; Lupescu, Ioana; Popescu, Irinel; Diculescu, Mircea

    2012-09-01

    This is a retrospective study of patients with advanced biliary tract carcinoma (BTC), who were treated with different regimens of chemotherapy. We studied patients with advanced BTC registered at the Department of Oncology at the Fundeni Clinical Institute between 2004 and 2008. The following data were analyzed: rate of response, progression free survival (PFS) to first and second line of chemotherapy, overall survival (OS) and drug toxicity. Ninety-six patients were eligible having either advanced intra or extrahepatic cholangiocarcinoma, or gallbladder cancer with no prior chemotherapy. Out of 96 patients, 57 (59.4%) received fluoropyrimidines (FP)+cisplatin and 39 (40.6%) gemcitabine (Gem)+/-cisplatin. The median PFS for FP+cisplatin was 5.9 months (95%CI 5-6.9) and for Gem+/-cisplatin 6.3 months (95%CI 5.4-7.1), p=0.661. Median OS for FP+cisplatin was 10.3 months (95%CI 7.5-13.1) and for Gem+/-cisplatin 9.1 months (95%CI 7.0-11.2), p=0.098. On disease progression, 46 patients received second line CT (Gem or FP+/-platinum compounds). Median OS for patients with FP based first line and Gem+/-cisplatin in second line was 19 months (95%CI 8.9-29) higher than for the reverse sequence: 13.2 months (95%CI 12-14.4), but not statistically significant (p=0.830). All patients were evaluated for toxicities. Most patients (75.5%) reported at least one adverse event. Our results through direct comparison of FP+cisplatin with Gem+/-cisplatin as first line treatment did not show any statistical differences in terms of rate of response, PFS and OS. However, our study showed that FP+cisplatin as first line and Gem based second line therapy gave a better OS rate.

  6. Availability of Advanced Breast Imaging at Screening Facilities Serving Vulnerable Populations.

    PubMed

    Lee, Christoph I; Bogart, Andy; Germino, Jessica C; Goldman, L Elizabeth; Hubbard, Rebecca A; Haas, Jennifer S; Hill, Deirdre A; Tosteson, Anna Na; Alford-Teaster, Jennifer A; DeMartini, Wendy B; Lehman, Constance D; Onega, Tracy L

    2016-03-01

    Among vulnerable women, unequal access to advanced breast imaging modalities beyond screening mammography may lead to delays in cancer diagnosis and unfavourable outcomes. We aimed to compare on-site availability of advanced breast imaging services (ultrasound, magnetic resonance imaging [MRI], and image-guided biopsy) between imaging facilities serving vulnerable patient populations and those serving non-vulnerable populations. 73 imaging facilities across five Breast Cancer Surveillance Consortium regional registries in the United States during 2011 and 2012. We examined facility and patient characteristics across a large, national sample of imaging facilities and patients served. We characterized facilities as serving vulnerable populations based on the proportion of mammograms performed on women with lower educational attainment, lower median income, racial/ethnic minority status, and rural residence.We performed multivariable logistic regression to determine relative risks of on-site availability of advanced imaging at facilities serving vulnerable women versus facilities serving non-vulnerable women. Facilities serving vulnerable populations were as likely (Relative risk [RR] for MRI = 0.71, 95% Confidence Interval [CI] 0.42, 1.19; RR for MRI-guided biopsy = 1.07 [0.61, 1.90]; RR for stereotactic biopsy = 1.18 [0.75, 1.85]) or more likely (RR for ultrasound = 1.38 [95% CI 1.09, 1.74]; RR for ultrasound-guided biopsy = 1.67 [1.30, 2.14]) to offer advanced breast imaging services as those serving non-vulnerable populations. Advanced breast imaging services are physically available on-site for vulnerable women in the United States, but it is unknown whether factors such as insurance coverage or out-of-pocket costs might limit their use. © The Author(s) 2015.

  7. Availability of Advanced Breast Imaging at Screening Facilities Serving Vulnerable Populations

    PubMed Central

    Lee, Christoph I.; Bogart, Andy; Germino, Jessica C.; Goldman, L. Elizabeth; Hubbard, Rebecca A.; Haas, Jennifer S.; Hill, Deirdre A.; Tosteson, Anna N.A.; Alford-Teaster, Jennifer A.; DeMartini, Wendy B.; Lehman, Constance D.; Onega, Tracy L.

    2015-01-01

    Objective Among vulnerable women, unequal access to advanced breast imaging modalities beyond screening mammography may lead to delays in cancer diagnosis and unfavorable outcomes. We aimed to compare on-site availability of advanced breast imaging services (ultrasound (US), magnetic resonance imaging (MRI), and image-guided biopsy) between imaging facilities serving vulnerable patient populations and those serving non-vulnerable populations. Setting 73 United States imaging facilities across five Breast Cancer Surveillance Consortium regional registries during calendar years 2011–2012. Methods We examined facility and patient characteristics across a large, national sample of imaging facilities and patients served. We characterized facilities as serving vulnerable populations based on the proportion of mammograms performed on women with lower educational attainment, lower median income, racial/ethnic minority status, and rural residence. We performed multivariable logistic regression to determine relative risks of on-site availability of advanced imaging at facilities serving vulnerable women versus facilities serving non-vulnerable women. Results Facilities serving vulnerable populations were as likely (RR for MRI = 0.71 [95% CI 0.42, 1.19]; RR for MRI-guided biopsy = 1.07 [0.61, 1.90]; RR for stereotactic biopsy = 1.18 [0.75, 1.85]) or more likely (RR for US = 1.38 [95% CI 1.09, 1.74]; RR for US-guided biopsy = 1.67 [1.30, 2.14]) to offer advanced breast imaging services as those serving non-vulnerable populations. Conclusions Advanced breast imaging services are physically available on-site for vulnerable women in the United States, but it is unknown whether factors such as insurance coverage or out-of-pocket costs might limit their use. PMID:26078275

  8. Health insurance status and the care of nursing home residents with advanced dementia.

    PubMed

    Goldfeld, Keith S; Grabowski, David C; Caudry, Daryl J; Mitchell, Susan L

    Nursing home residents with advanced dementia commonly experience burdensome and costly hospitalizations that may not extend survival or improve the quality of life. Fragmentation in health care has contributed to poor coordination of care for acutely ill nursing home residents. To compare patterns of care and quality outcomes for nursing home residents with advanced dementia covered by managed care with those covered by traditional fee-for-service Medicare. Choices, Attitudes, and Strategies for Care of Advanced Dementia at the End-of-Life (CASCADE) was a prospective cohort study including 22 nursing homes in the Boston, Massachusetts, area that monitored 323 nursing home residents for 18 months to better understand the course of advanced dementia at or near the end of life. Data from CASCADE and Medicare were linked to determine the health insurance status of study participants. The health insurance status of the resident, either managed care or traditional fee for service. The outcomes included survival, symptoms related to comfort, treatment of pain and dyspnea, presence of pressure ulcers, presence of a do-not-hospitalize order, treatment of pneumonia, hospital transfer (admission or emergency department visit) for an acute illness, hospice referral, primary care visits, and family satisfaction with care. Residents enrolled in managed care (n = 133) were more likely to have do-not-hospitalize orders compared with those in traditional Medicare fee for service (n = 158) (63.7% vs 50.9%; adjusted odds ratio, 1.9; 95% CI, 1.1-3.4), were less likely to be transferred to the hospital for acute illness (3.8% vs 15.7%; adjusted odds ratio, 0.2; 95% CI, 0.1-0.5), had more primary care visits per 90 days (mean [SD], 4.8 [2.6] vs 4.2 [5.0]; adjusted rate ratio, 1.3; 95% CI, 1.1-1.6), and had more nurse practitioner visits (3.0 [2.1] vs 0.8 [2.6]; adjusted rate ratio, 3.0; 95% CI, 2.2-4.1). Survival, comfort, and other treatment outcomes did not differ significantly

  9. Music-Based Training for Pediatric CI Recipients: A Systematic Analysis of Published Studies

    PubMed Central

    Gfeller, Kate

    2016-01-01

    In recent years, there has been growing interest in the use of music-based training to enhance speech and language development in children with normal hearing and some forms of communication disorders, including pediatric CI users. The use of music training for CI users may initially seem incongruous given that signal processing for CIs presents a degraded version of pitch and timbre, both key elements in music. Furthermore, empirical data of systematic studies of music training, particularly in relation to transfer to speech skills are limited. This study describes the rationale for music training of CI users, describes key features of published studies of music training with CI users, and highlights some developmental and logistical issues that should be taken into account when interpreting or planning studies of music training and speech outcomes with pediatric CI recipients. PMID:27246744

  10. Sorafenib With and Without Transarterial Chemoembolization for Advanced Hepatocellular Carcinoma With Main Portal Vein Tumor Thrombosis: A Retrospective Analysis.

    PubMed

    Zhang, Yingqiang; Fan, Wenzhe; Wang, Yu; Lu, Ligong; Fu, Sirui; Yang, Jianyong; Huang, Yonghui; Yao, Wang; Li, Jiaping

    2015-12-01

    The survival benefit of combining sorafenib and transarterial chemoembolization (TACE) therapy compared with sorafenib monotherapy for patients with advanced hepatocellular carcinoma (HCC) and main portal vein tumor thrombosis (MPVTT) is unclear. Between January 2009 and June 2013, 183 consecutive patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) and MPVTT were retrospectively reviewed. Of these, 89 patients with advanced HCC and MPVTT were enrolled in this study: 45 were treated with combination therapy (sorafenib-TACE group), and the other 44 treated with sorafenib monotherapy (sorafenib group). The mean number of TACE sessions per patient was 2.6 (range: 1-5). The median duration of sorafenib in the sorafenib-TACE group and sorafenib group was 5.6 months and 5.4 months, respectively. The disease control rate was similar between the two groups. Median time to progression was 3.0 months (95% confidence interval [CI]: 2.2, 3.7) in the sorafenib-TACE group, and 3.0 months (95% CI: 2.1, 3.8) in the sorafenib group (p = .924). Median overall survival was 7.0 months (95% CI: 6.1, 7.8) and 6.0 months (95% CI: 4.7, 7.3) in the sorafenib-TACE group and the sorafenib group, respectively (p = .544). The adverse events related to sorafenib were comparable between the two groups. Twenty-one adverse events of grade 3-4 related to TACE occurred in 12 patients (26.7%), and 2 of them died (4.4%). This study demonstrated no advantage of combination therapy over sorafenib monotherapy. Considering the patients' morbidity after TACE, sorafenib monotherapy is appropriate for managing patients with advanced HCC and MPVTT. ©AlphaMed Press.

  11. Inclusion of populations at risk of advanced melanoma in an opportunistic targeted screening project involving general practitioners

    PubMed Central

    Rat, Cédric; Quereux, Gaelle; Grimault, Charlotte; Fernandez, Jérémy; Poiraud, Mickael; Gaultier, Aurélie; Chaslerie, Anicet; Pivette, Jacques; Khammari, Amir; Dreno, Brigitte; Nguyen, Jean-Michel

    2016-01-01

    Objective The study objective was to measure the rates of inclusion of populations at risk of advanced melanoma in a pilot targeted screening project involving general practitioners. Design This cross-sectional database study compared the inclusion rates of patients who signed inclusion in a targeted screening project with those of patients who did not, during a period in which both groups of patients consulted investigators. Setting Data were extracted from the national healthcare insurance records in western France from 11 April to 30 October 2011. Patients Patients, older than 18, considered for the data extraction had consulted one of the 78 participating GPs during the study period, and were affiliated with the national healthcare insurance. Main outcome measures Inclusion in the screening was the main outcome measure. Patients at risk of advanced melanoma were characterized by male gender, age over 50, low income, rural residence, farmer, and presence of chronic disease. Results A total of 57,279 patients consulted GPs during the inclusion period and 2711 (4.73%) were included in the targeted screening. Populations at risk of advanced melanoma were less included: men (OR = 0.67; 95%CI [0.61–0.73]; p < 0.001), older than 50 (OR = 0.67; 95%CI [0.60–0.74]; p < 0.001), low income (OR = 0.65; 95%CI [0.55–0.77]; p < 0.001), farmer (OR = 0.23; 95%CI [0.17–0.30]; p < 0.001) and presence of a chronic disease (OR = 0.87; 95%CI [0.77–0.98]; p < 0.028). Conclusion This study demonstrated inequalities in the inclusion of patients in a melanoma screening. Patients at risk of advanced cancer were screened less often. Further studies should focus on GPs ability to identify and screen these patients. Key Points Advanced melanoma is more frequently diagnosed in men, older patients and socioeconomically disadvantaged populations, which leads to survival inequalities.• Despite the involvement of general practitioners, the

  12. IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD - a pilot study.

    PubMed

    Hagström, Hannes; Stål, Per; Hultcrantz, Rolf; Brismar, Kerstin; Ansurudeen, Ishrath

    2017-12-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. Advanced fibrosis (stage 3-4) is the most robust marker for future mortality, but diagnosis requires liver biopsy. Current non-invasive scoring systems aimed to identify advanced fibrosis are imperfect. Insulin-like growth factor I (IGF-I) and its binding protein IGFBP-1 are liver derived proteins, that are involved in various liver disorders. The aim of this study was to examine the possible association between advanced fibrosis and IGF-I and IGFBP-1 in NAFLD. Fasting blood samples were obtained from 52 patients diagnosed with NAFLD by liver biopsy. Total IGF-I and IGFBP-1 concentrations were determined in serum by in-house radio-immuno-assays. IGF-I levels were age-standardized (IGF-SD). A logistic regression model was used to investigate the association of IGF-SD and IGFBP-1 with advanced fibrosis (stage 3-4). Patients with advanced fibrosis (stage 3-4 vs. 0-2) had lower IGF-SD (-1.17 vs. 0.11, p = .01) and higher mean levels of IGFBP-1 (29.9 vs. 18.8 µg/l, p = .02). IGFBP-1 was associated with presence of advanced fibrosis (OR 1.04 per unit increase, 95%CI 1.0-1.07, p = .05), while IGF-1 was negatively associated with advanced fibrosis (OR 0.63 per standard deviation, 95%CI 0.44-0.92, p = .02). This pilot study suggests an association between serum IGFBP-1 and IGF-I levels with advanced fibrosis in NAFLD patients. IGFBP1 and IGF-1 could be of interest as future biomarkers. Similar studies in larger cohorts are needed.

  13. Effect of advanced age and vital signs on admission from an ED observation unit.

    PubMed

    Caterino, Jeffrey M; Hoover, Emily M; Moseley, Mark G

    2013-01-01

    The primary objective was to determine the relationship between advanced age and need for admission from an emergency department (ED) observation unit. The secondary objective was to determine the relationship between initial ED vital signs and admission. We conducted a prospective, observational cohort study of ED patients placed in an ED-based observation unit. Multivariable penalized maximum likelihood logistic regression was used to identify independent predictors of need for hospital admission. Age was examined continuously and at a cutoff of 65 years or more. Vital signs were examined continuously and at commonly accepted cutoffs.We additionally controlled for demographics, comorbid conditions, laboratory values, and observation protocol. Three hundred patients were enrolled, 12% (n = 35) were 65 years or older, and 11% (n = 33) required admission. Admission rates were 2.9% (95% confidence interval [CI], 0.07%-14.9%) in older adults and 12.1% (95% CI, 8.4%-16.6%) in younger adults. In multivariable analysis, age was not associated with admission (odds ratio [OR], 0.30; 95% CI, 0.05-1.67). Predictors of admission included systolic pressure 180 mm Hg or greater (OR, 4.19; 95% CI, 1.08-16.30), log Charlson comorbidity score (OR, 2.93; 95% CI, 1.57-5.46), and white blood cell count 14,000/mm(3) or greater (OR, 11.35; 95% CI, 3.42-37.72). Among patients placed in an ED observation unit, age 65 years or more is not associated with need for admission. Older adults can successfully be discharged from these units. Systolic pressure 180 mm Hg or greater was the only predictive vital sign. In determining appropriateness of patients selected for an ED observation unit, advanced age should not be an automatic disqualifying criterion. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Prognosis in advanced lung cancer--A prospective study examining key clinicopathological factors.

    PubMed

    Simmons, Claribel P; Koinis, Filippos; Fallon, Marie T; Fearon, Kenneth C; Bowden, Jo; Solheim, Tora S; Gronberg, Bjorn Henning; McMillan, Donald C; Gioulbasanis, Ioannis; Laird, Barry J

    2015-06-01

    In patients with advanced incurable lung cancer deciding as to the most appropriate treatment (e.g., chemotherapy or supportive care only) is challenging. In such patients the TNM classification system has reached its ceiling therefore other factors are used to assess prognosis and as such, guide treatment. Performance status (PS), weight loss and inflammatory biomarkers (Glasgow Prognostic Score (mGPS)) predict survival in advanced lung cancer however these have not been compared. This study compares key prognostic factors in advanced lung cancer. Patients with newly diagnosed advanced lung cancer were recruited and demographics, weight loss, other prognostic factors (mGPS, PS) were collected. Kaplan-Meier and Cox regression methods were used to compare these prognostic factors. 390 patients with advanced incurable lung cancer were recruited; 341 were male, median age was 66 years (IQR 59-73) and patients had stage IV non-small cell (n=288) (73.8%) or extensive stage small cell lung cancer (n=102) (26.2%). The median survival was 7.8 months. On multivariate analysis only performance status (HR 1.74 CI 1.50-2.02) and mGPS (HR 1.67, CI 1.40-2.00) predicted survival (p<0.001). Survival at 3 months ranged from 99% (ECOG 0-1) to 74% (ECOG 2) and using mGPS, from 99% (mGPS0) to 71% (mGPS2). In combination, survival ranged from 99% (mGPS 0, ECOG 0-1) to 33% (mGPS2, ECOG 3). Performance status and the mGPS are superior prognostic factors in advanced lung cancer. In combination, these improved survival prediction compared with either alone. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Prognostic Value of Plasma Epstein-Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era.

    PubMed

    Chen, Wen-Hui; Tang, Lin-Quan; Guo, Shan-Shan; Chen, Qiu-Yan; Zhang, Lu; Liu, Li-Ting; Qian, Chao-Nan; Guo, Xiang; Xie, Dan; Zeng, Mu-Sheng; Mai, Hai-Qiang

    2016-02-01

    This study aimed to evaluate the prognostic value of plasma Epstein-Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level < 4000  copies/mL, patients with an EBV DNA ≥ 4000  copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68-84]) versus (93%, 95% CI [90-96], P < 0.001), DMFS (83%, 95% CI [76-89]) versus (97%, 95% CI [94-99], P < 0.001), and OS (85%, 95% CI [78-92]) versus (98%, 95% CI [95-100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80-6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036-3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647-14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701-8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252-5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized

  16. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction.

    PubMed

    Li, Jin; Qin, Shukui; Xu, Jianming; Xiong, Jianping; Wu, Changping; Bai, Yuxian; Liu, Wei; Tong, Jiandong; Liu, Yunpeng; Xu, Ruihua; Wang, Zhehai; Wang, Qiong; Ouyang, Xuenong; Yang, Yan; Ba, Yi; Liang, Jun; Lin, Xiaoyan; Luo, Deyun; Zheng, Rongsheng; Wang, Xin; Sun, Guoping; Wang, Liwei; Zheng, Leizhen; Guo, Hong; Wu, Jingbo; Xu, Nong; Yang, Jianwei; Zhang, Honggang; Cheng, Ying; Wang, Ningju; Chen, Lei; Fan, Zhining; Sun, Piaoyang; Yu, Hao

    2016-05-01

    There is currently no standard treatment strategy for patients with advanced metastatic gastric cancer experiencing progression after two or more lines of chemotherapy. We assessed the efficacy and safety of apatinib, a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, in patients with advanced gastric or gastroesophageal junction adenocarcinoma for whom at least two lines of prior chemotherapy had failed. This was a randomized, double-blind, placebo-controlled phase III trial. Patients from 32 centers in China with advanced gastric or gastroesophageal junction adenocarcinoma, for whom two or more prior lines of chemotherapy had failed, were enrolled. Patients were randomly assigned to oral apatinib 850 mg or placebo once daily. The primary end points were overall (OS) and progression-free survival (PFS). Between January 2011 and November 2012, 267 patients were enrolled. Median OS was significantly improved in the apatinib group compared with the placebo group (6.5 months; 95% CI, 4.8 to 7.6 v 4.7 months; 95% CI, 3.6 to 5.4; P = .0149; hazard ratio, 0.709; 95% CI, 0.537 to 0.937; P = .0156). Similarly, apatinib significantly prolonged median PFS compared with placebo (2.6 months; 95% CI, 2.0 to 2.9 v 1.8 months; 95% CI, 1.4 to 1.9; P < .001; hazard ratio, 0.444; 95% CI, 0.331 to 0.595; P < .001). The most common grade 3 to 4 nonhematologic adverse events were hand-foot syndrome, proteinuria, and hypertension. These data show that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. © 2016 by American Society of Clinical Oncology.

  17. Subgroup effects of occupational therapy-based intervention for people with advanced cancer.

    PubMed

    Sampedro Pilegaard, Marc; Oestergaard, Lisa Gregersen; la Cour, Karen; Thit Johnsen, Anna; Brandt, Åse

    2018-03-23

    Many people with advanced cancer have decreased ability to perform activities of daily living (ADL). We recently performed a randomized, controlled trial (RCT) assessing the efficacy of an occupational therapy-based program, the 'Cancer Home-Life Intervention' in people with advanced cancer (N = 242) and found no overall effects on ADL ability. However, heterogeneity of treatment effect may disguise subgroup differences. To investigate whether subgroups of people with advanced cancer gain positive effects from the 'Cancer Home-Life Intervention' on ADL ability. An exploratory subgroup analysis including 191 participants from a RCT. The outcome was ADL motor ability measured by the Assessment of Motor and Process Skills (AMPS). Subgroups were defined by age, gender, years of education, type of primary tumor, functional level, and activity problems. The 'Cancer Home-Life Intervention' had no statistically significant effect in the six subgroups. Modifying effects of age (0.30 [95% CI: -0.05 to 0.64]) and gender (0.23 [95% CI: -0.11 to 0.57]) were not found. There were no subgroup effects of the 'Cancer Home-Life Intervention'on ADL motor ability. Some indications suggest greater effects for those aged below 69 years; however, this result should be interpreted with caution.

  18. Electro-chemical coupling in the voltage-dependent phosphatase Ci-VSP

    PubMed Central

    Kohout, Susy C.; Bell, Sarah C.; Liu, Lijun; Xu, Qiang; Minor, Daniel L.; Isacoff, Ehud Y.

    2010-01-01

    In the voltage sensing phosphatase, Ci-VSP, a voltage sensing domain (VSD) controls a lipid phosphatase domain (PD). The mechanism by which the domains are allosterically coupled is not well understood. Using an in vivo assay, we find that the inter-domain linker that connects the VSD to the PD is essential for coupling the full-length protein. Biochemical assays show that the linker is also needed for activity in the isolated PD. We identify a late step of VSD motion in the full-length protein that depends on the linker. Strikingly, this VSD motion is found to require PI(4,5)P2, a substrate of Ci-VSP. These results suggest that the voltage-driven motion of the VSD turns the enzyme on by rearranging the linker into an activated conformation, and that this activated conformation is stabilized by PI(4,5)P2. We propose that Ci-VSP activity is self-limited because its decrease of PI(4,5)P2 levels decouples the VSD from the enzyme. PMID:20364128

  19. Expression, purification, and reconstitution of the voltage-sensing domain from Ci-VSP.

    PubMed

    Li, Qufei; Jogini, Vishwanath; Wanderling, Sherry; Cortes, D Marien; Perozo, Eduardo

    2012-10-16

    The voltage-sensing domain (VSD) is the common scaffold responsible for the functional behavior of voltage-gated ion channels, voltage sensitive enzymes, and proton channels. Because of the position of the voltage dependence of the available VSD structures, at present, they all represent the activated state of the sensor. Yet in the absence of a consensus resting state structure, the mechanistic details of voltage sensing remain controversial. The voltage dependence of the VSD from Ci-VSP (Ci-VSD) is dramatically right shifted, so that at 0 mV it presumably populates the putative resting state. Appropriate biochemical methods are an essential prerequisite for generating sufficient amounts of Ci-VSD protein for high-resolution structural studies. Here, we present a simple and robust protocol for the expression of eukaryotic Ci-VSD in Escherichia coli at milligram levels. The protein is pure, homogeneous, monodisperse, and well-folded after solubilization in Anzergent 3-14 at the analyzed concentration (~0.3 mg/mL). Ci-VSD can be reconstituted into liposomes of various compositions, and initial site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopic measurements indicate its first transmembrane segment folds into an α-helix, in agreement with the homologous region of other VSDs. On the basis of our results and enhanced relaxation EPR spectroscopy measurement, Ci-VSD reconstitutes essentially randomly in proteoliposomes, precluding straightforward application of transmembrane voltages in combination with spectroscopic methods. Nevertheless, these results represent an initial step that makes the resting state of a VSD accessible to a variety of biophysical and structural approaches, including X-ray crystallography, spectroscopic methods, and electrophysiology in lipid bilayers.

  20. Expression, Purification and Reconstitution of the Voltage Sensing Domain from Ci-VSP

    PubMed Central

    Li, Qufei; Jogini, Vishwanath; Wanderling, Sherry; Cortes, D. Marien; Perozo, Eduardo

    2013-01-01

    The voltage-sensing domain (VSD) is the common scaffold responsible for the functional behavior of voltage gated ion channels, voltage sensitive enzymes and proton channels. Because of the position of the voltage dependence of the available VSD structures, at present, they all represent the activated state of the sensor. Yet, in the absence of a consensus resting state structure, the mechanistic details of voltage sensing remain controversial. The voltage dependence of the VSD from Ci-VSP (Ci-VSD) is dramatically right shifted, so that at 0 mV It presumably populates the putative resting state. Appropriate biochemical methods are an essential prerequisite to generate sufficient amounts of Ci-VSD protein for high-resolution structural studies. Here, we present a simple and robust protocol for the Escherichia coli expression of eukaryotic Ci-VSD at milligram levels. The protein is pure, homogeneous, mono-disperse and well folded after solubilization in Anzergent 3-14 at the analyzed concentration (~ 0.3 mg/mL). Ci-VSD can be reconstituted into liposomes of various compositions and initial site-directed spin labeling and EPR spectroscopic measurements indicate its first transmembrane segment folds into an α-helix, in agreement to the homologous region of other VSDs. Based on current results and enhanced relaxation EPR spectroscopy measurement, Ci-VSD reconstitutes essentially randomly in proteo-liposomes, precluding straightforward application of transmembrane voltages in combination with spectroscopic methods. Nevertheless, the present results represent an initial step that makes the resting state of a VSD accessible to a variety of biophysical and structural approaches, including X-ray crystallography, spectroscopic methods and electrophysiology in lipid bilayers. PMID:22989304

  1. Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration.

    PubMed

    Roh, Miin; Selivanova, Alexandra; Shin, Hyun Joon; Miller, Joan W; Jackson, Mary Lou

    2018-01-01

    Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL.

  2. First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer.

    PubMed

    Vaccaro, Vanja; Bria, Emilio; Sperduti, Isabella; Gelibter, Alain; Moscetti, Luca; Mansueto, Giovanni; Ruggeri, Enzo Maria; Gamucci, Teresa; Cognetti, Francesco; Milella, Michele

    2013-07-28

    To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m(2), infused at 10 mg/m(2) per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA

  3. First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

    PubMed Central

    Vaccaro, Vanja; Bria, Emilio; Sperduti, Isabella; Gelibter, Alain; Moscetti, Luca; Mansueto, Giovanni; Ruggeri, Enzo Maria; Gamucci, Teresa; Cognetti, Francesco; Milella, Michele

    2013-01-01

    AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS: We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m2, infused at 10 mg/m2 per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of

  4. Cell-Based Strategies for Meniscus Tissue Engineering

    PubMed Central

    Niu, Wei; Guo, Weimin; Han, Shufeng; Zhu, Yun; Liu, Shuyun; Guo, Quanyi

    2016-01-01

    Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering. PMID:27274735

  5. Effect of advanced age and vital signs on admission from an emergency department observation unit

    PubMed Central

    Caterino, Jeffrey M.; Hoover, Emily; Moseley, Mark G.

    2012-01-01

    Objectives The primary objective was to determine the relationship between advanced age and need for admission from an emergency department (ED) observation unit. The secondary objective was to determine the relationship between initial ED vital signs and admission. Methods We conducted a prospective, observational cohort study of ED patients placed in an ED-based observation unit. Multivariable penalized maximum likelihood logistic regression was used to identify independent predictors of need for hospital admission. Age was examined continuously and at a cutoff of ≥65 years. Vital signs were examined continuously and at commonly accepted cutoffs. We additionally controlled for demographics, co-morbid conditions, laboratory values, and observation protocol. Results Three hundred patients were enrolled, 12% (n=35) ≥65 years old and 11% (n=33) requiring admission. Admission rates were 2.9% (95% confidence interval [CI], 0.07-14.9%) in older adults and 12.1% (95% CI, 8.4-16.6%) in younger adults. In multivariable analysis, age was not associated with admission (odds ratio [OR] 0.30, 95% CI 0.05-1.67). Predictors of admission included: systolic pressure ≥180 mmHg (OR 4.19, 95% CI 1.08-16.30), log Charlson co-morbidity score (OR 2.93, 95% CI 1.57-5.46), and white blood cell count ≥14,000/mm3 (OR11.35, 95% CI 3.42-37.72). Conclusions Among patients placed in an ED observation unit, age ≥65 years is not associated with need for admission. Older adults can successfully be discharged from these units. Systolic pressure≥180 mmHg was the only predictive vital sign. In determining appropriateness of patients selected for an ED observation unit, advanced age should not be an automatic disqualifying criterion. PMID:22386358

  6. Massage therapy versus simple touch to improve pain and mood in patients with advanced cancer: a randomized trial.

    PubMed

    Kutner, Jean S; Smith, Marlaine C; Corbin, Lisa; Hemphill, Linnea; Benton, Kathryn; Mellis, B Karen; Beaty, Brenda; Felton, Sue; Yamashita, Traci E; Bryant, Lucinda L; Fairclough, Diane L

    2008-09-16

    Small studies of variable quality suggest that massage therapy may relieve pain and other symptoms. To evaluate the efficacy of massage for decreasing pain and symptom distress and improving quality of life among persons with advanced cancer. Multisite, randomized clinical trial. Population-based Palliative Care Research Network. 380 adults with advanced cancer who were experiencing moderate-to-severe pain; 90% were enrolled in hospice. Six 30-minute massage or simple-touch sessions over 2 weeks. Primary outcomes were immediate (Memorial Pain Assessment Card, 0- to 10-point scale) and sustained (Brief Pain Inventory [BPI], 0- to 10-point scale) change in pain. Secondary outcomes were immediate change in mood (Memorial Pain Assessment Card) and 60-second heart and respiratory rates and sustained change in quality of life (McGill Quality of Life Questionnaire, 0- to 10-point scale), symptom distress (Memorial Symptom Assessment Scale, 0- to 4-point scale), and analgesic medication use (parenteral morphine equivalents [mg/d]). Immediate outcomes were obtained just before and after each treatment session. Sustained outcomes were obtained at baseline and weekly for 3 weeks. 298 persons were included in the immediate outcome analysis and 348 in the sustained outcome analysis. A total of 82 persons did not receive any allocated study treatments (37 massage patients, 45 control participants). Both groups demonstrated immediate improvement in pain (massage, -1.87 points [95% CI, -2.07 to -1.67 points]; control, -0.97 point [CI, -1.18 to -0.76 points]) and mood (massage, 1.58 points [CI, 1.40 to 1.76 points]; control, 0.97 point [CI, 0.78 to 1.16 points]). Massage was superior for both immediate pain and mood (mean difference, 0.90 and 0.61 points, respectively; P < 0.001). No between-group mean differences occurred over time in sustained pain (BPI mean pain, 0.07 point [CI, -0.23 to 0.37 points]; BPI worst pain, -0.14 point [CI, -0.59 to 0.31 points]), quality of life (Mc

  7. Imaging the asymmetric dust shell around CI Cam with long baseline optical interferometry

    NASA Astrophysics Data System (ADS)

    Thureau, N. D.; Monnier, J. D.; Traub, W. A.; Millan-Gabet, R.; Pedretti, E.; Berger, J.-P.; Garcia, M. R.; Schloerb, F. P.; Tannirkulam, A.-K.

    2009-09-01

    We present the first high angular resolution observation of the B[e] star/X-ray transient object CI Cam, performed with the two-telescope Infrared Optical Telescope Array (IOTA), its upgraded three-telescope version (IOTA3T) and the Palomar Testbed Interferometer (PTI). Visibilities and closure phases were obtained using the IONIC-3 integrated optics beam combiner. CI Cam was observed in the near-infrared H and K spectral bands, wavelengths well suited to measure the size and study the geometry of the hot dust surrounding CI Cam. The analysis of the visibility data over an 8yr period from soon after the 1998 outburst to 2006 shows that the dust visibility has not changed over the years. The visibility data show that CI Cam is elongated which confirms the disc-shape of the circumstellar environment and totally rules out the hypothesis of a spherical dust shell. Closure phase measurements show direct evidence of asymmetries in the circumstellar environment of CI Cam and we conclude that the dust surrounding CI Cam lies in an inhomogeneous disc seen at an angle. The near-infrared dust emission appears as an elliptical skewed Gaussian ring with a major axis a = 7.58 +/- 0.24mas, an axis ratio r = 0.39 +/- 0.03 and a position angle θ = 35° +/- 2°.

  8. Certification procedures for nuclear fast red (Kernechtrot), CI 60760.

    PubMed

    Frank, M; Dapson, Rw; Wickersham, Tw; Kiernan, Ja

    2007-02-01

    Nuclear fast red (CI 60760), also known as Kernechtrot, is commonly used in conjunction with an excess of aluminum ions as a red nuclear counterstain following histochemical procedures that yield blue products. The dye has also been used as a histochemical and colorimetric reagent for calcium. Unsatisfactory samples of nuclear fast red are encountered occasionally, and confusion has resulted from applying the name of the dye to neutral red (CI 50040), an unrelated compound with different properties. Tests for the identity and performance of nuclear fast red have been developed in the laboratory of the Biological Stain Commission. The Commission will now accept samples submitted by vendors for certification. We describe here the spectrophotometric, chromatographic and biological staining methods that are used to identify and test nuclear fast red.

  9. High attrition among HIV-infected patients with advanced disease treated in an intermediary referral center in Maputo, Mozambique.

    PubMed

    Molfino, Lucas; Kumar, Ajay M V; Isaakidis, Petros; Van den Bergh, Rafael; Khogali, Mohamed; Hinderaker, Sven G; Magaia, Alice; Lobo, Sheila; Edwards, Celeste Gracia; Walter, Jan

    2014-01-01

    In Mozambique, antiretroviral therapy (ART) scale-up has been successfully implemented. However, attrition in care remains a major programmatic challenge. In 2009, an intermediary-level HIV referral center was created in Maputo to ensure access to specialized care for HIV-infected patients with complications (advanced clinical-immunological stage, Kaposi sarcoma, or suspected ART failure). To determine the attrition from care and to identify risk factors that lead to high attrition among patients referred to an intermediary-level HIV referral center. This was a retrospective cohort study from 2009 to 2011. A total of 1,657 patients were enrolled, 847 (51%) were men, the mean age was 36 years (standard deviation: 11), the mean CD4 count was 27 cells/µl (interquartile range: 11-44), and one-third were severely malnourished. The main reasons for referral were advanced clinical stages (WHO stages 3 and 4, and CD4 count <50 cells/µl) in 70% of the cases, and 19% had Kaposi sarcoma. The overall attrition rate was 28.7 per 100 person-years (PYs) - the mortality rate was 5.0 (95% confidence interval [CI]: 4.2-5.9) per 100 PYs, and the loss-to-follow-up rate was 23.7 (95% CI: 21.9-25.6) per 100 PYs. There were 793 attritions - 137 deaths and 656 lost to follow-up (LTFU); 77% of all attrition happened within the first year. The factors independently associated with attrition were male sex (adjusted hazard ratio [aHR]: 1.15, 95% CI: 1.0-1.3), low body mass index (aHR: 1.51, 95% CI: 1.2-1.8), WHO clinical stage 3 or 4 (aHR: 1.30, 95% CI: 1.0-1.6; and aHR: 1.91, 95% CI: 1.4-2.5), later year of enrollment (aHR 1.61, 95% CI 1.3-1.9), and 'being already on ART' at enrollment (aHR 13.71, 95% CI 11.4-16.4). Attrition rates among HIV-infected patients enrolled in an intermediary referral center were high, mainly related to advanced stage of clinical disease. Measures are required to address this, including innovative strategies for HIV-testing uptake, earlier ART initiation and

  10. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3.

    PubMed

    Slamon, Dennis J; Neven, Patrick; Chia, Stephen; Fasching, Peter A; De Laurentiis, Michelino; Im, Seock-Ah; Petrakova, Katarina; Bianchi, Giulia Val; Esteva, Francisco J; Martín, Miguel; Nusch, Arnd; Sonke, Gabe S; De la Cruz-Merino, Luis; Beck, J Thaddeus; Pivot, Xavier; Vidam, Gena; Wang, Yingbo; Rodriguez Lorenc, Karen; Miller, Michelle; Taran, Tetiana; Jerusalem, Guy

    2018-06-03

    Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. Results A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001). Consistent treatment effects were observed in patients who were treatment naïve in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in ≥ 5% of patients was neutropenia (6.8% v 0%). Conclusion Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.

  11. NHERI: Advancing the Research Infrastructure of the Multi-Hazard Community

    NASA Astrophysics Data System (ADS)

    Blain, C. A.; Ramirez, J. A.; Bobet, A.; Browning, J.; Edge, B.; Holmes, W.; Johnson, D.; Robertson, I.; Smith, T.; Zuo, D.

    2017-12-01

    The Natural Hazards Engineering Research Infrastructure (NHERI), supported by the National Science Foundation (NSF), is a distributed, multi-user national facility that provides the natural hazards research community with access to an advanced research infrastructure. Components of NHERI are comprised of a Network Coordination Office (NCO), a cloud-based cyberinfrastructure (DesignSafe-CI), a computational modeling and simulation center (SimCenter), and eight Experimental Facilities (EFs), including a post-disaster, rapid response research facility (RAPID). Utimately NHERI enables researchers to explore and test ground-breaking concepts to protect homes, businesses and infrastructure lifelines from earthquakes, windstorms, tsunamis, and surge enabling innovations to help prevent natural hazards from becoming societal disasters. When coupled with education and community outreach, NHERI will facilitate research and educational advances that contribute knowledge and innovation toward improving the resiliency of the nation's civil infrastructure to withstand natural hazards. The unique capabilities and coordinating activities over Year 1 between NHERI's DesignSafe-CI, the SimCenter, and individual EFs will be presented. Basic descriptions of each component are also found at https://www.designsafe-ci.org/facilities/. Additionally to be discussed are the various roles of the NCO in leading development of a 5-year multi-hazard science plan, coordinating facility scheduling and fostering the sharing of technical knowledge and best practices, leading education and outreach programs such as the recent Summer Institute and multi-facility REU program, ensuring a platform for technology transfer to practicing engineers, and developing strategic national and international partnerships to support a diverse multi-hazard research and user community.

  12. Causes of antepartum stillbirth in women of advanced maternal age.

    PubMed

    Walker, Kate F; Bradshaw, Lucy; Bugg, George J; Thornton, Jim G

    2016-02-01

    To breakdown the causes of antepartum stillbirth by maternal age. Observational study. UK. Anonymised national data on 2850 cases of antepartum stillbirth in 2009. The association between cause of stillbirth and maternal age was examined using an adjusted multinomial logistic regression model. Risk ratios were calculated relative to stillbirth due to haemorrhage. Antepartum stillbirths classified by the Centre for Maternal and Child Enquiries (CMACE) classification. Stillbirths in women aged 35 years and over are more likely to be due to major congenital anomalies (relative risk ratio (RRR) 2.0, 95% CI 1.3-3.0), mechanical causes (RRR 1.6, 95% CI 1.0-2.6), maternal disorders (RRR 2.1, 95% CI 1.2-3.6) or associated obstetric factors (RRR 2.1, 95% CI 1.1-3.9) than women less than 35. Women aged 35 years and over have a statistically significant increased risk of stillbirth due to major congenital anomalies (OR relative to live birth 1.6, 95% CI 1.3-1.9) and maternal disorders (OR 1.7, 95% CI 1.2-2.4) than younger women. Women aged 35 years and over were 30% more likely to experience a term stillbirth than women <35 years (OR 1.3, 95% CI 1.1-1.5). Stillbirth due to congenital anomaly was statistically significantly more likely in women ≥ 35 years. Advanced maternal age is a significant risk factor for antepartum stillbirth particularly at term. Attention should be given to stillbirth due to mechanical causes, maternal disorders and associated obstetric factors in such women. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Dual inhibitory action of enadoline (CI977) on release of amino acids in the rat hippocampus.

    PubMed

    Millan, M H; Chapman, A G; Meldrum, B S

    1995-06-06

    The effect of the kappa-opioid receptor agonist enadoline (CI977, (5R)-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1-pyrrilidinyl)-1-oxaspiro [4,5]dec-8-yl-4-benzofuranacetamide monohydrochloride), on the release of amino acids was studied in the hippocampus of freely moving rats. K+, 100 mM, or veratrine, 100 microM, were applied for 10 min via the dialysis probe, either alone (control groups) or together with CI977 (after a 10 min pretreatment with CI977 in the perfusion medium). To test the specificity of the response to CI977, nor-binaltorphimine, a selective kappa-opioid receptor antagonist, was delivered together with CI977 in two groups of animals. To test the effect of systemic injection, CI977 was given subcutaneously 30 min prior to either stimulus. K(+)-induced release of glutamate and aspartate was significantly reduced by CI977, 2.5 mM; release of gamma-aminobutyric acid (GABA) was reduced by 250 microM CI977 in the probe. The effect of CI977 on release of glutamate and aspartate, but not of GABA, was reversed by nor-binaltorphimine (45 microM). Systemic treatment with CI977, 1 or 10 mg/kg, did not reduce K(+)-induced release of glutamate. Veratrine-induced release of aspartate and glutamate was significantly inhibited by 25 microM and release of GABA by 250 microM CI977 in the probe, and this effect was not modified by nor-binaltorphimine (58 microM). Systemic injection of CI977 1 mg/kg significantly reduced veratrine-induced release of glutamate. These results indicate that CI977 regulates release of amino acids by two independent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. [The Heidelberg CI database module : Quality control in hearing restoration with cochlear implants].

    PubMed

    Herisanu, I T; Hoth, S; Praetorius, M

    2016-12-01

    Cochlear implants (CI) have been established as the therapy of choice for functional deafness. The number of CI-rehabilitated patients is continuously growing. The resulting data can provide important information for physicians, health insurance companies, and scientists. Assessment and structuring of data becomes more feasible with the application of modern database systems. In collaboration with Innoforce Est., Liechtenstein, the authors developed a database module for the specific needs of CI patients. Data of 100 patients were included and evaluated. The main features of the module and an example data analysis are presented. Analysis of data from these 100 patients reveals 50 men and 50 women aged between 1 and 87 years, with a maximum value in the 51-60-years age group. More than 50% of the patients were also severely hearing impaired in the contralateral ear and fitted the CI indication criteria. Functional deafness in the ear subsequently fitted with CI in most of the patients had arisen more than 20 years previously. Preoperative diagnostic electrical stimulation of the cochlear nerve was positive in 67 patients. All 100 patients perceived auditory sensations with the CI. The presented patient cohort is representative of patients at the Department of Otorhinolaryngology, University of Heidelberg Medical Center, Germany, and the demographic distribution is in accordance with the literature. The state of the contralateral ear, often also fitting the CI indication, is not surprising, as cochlear implantation is a comparatively new procedure. Preoperative electrical stimulation turned out not to be significant by itself. The hearing results and overview of complications were easy to calculate in comparison to a pure data storage system such as i.s.h.med.

  15. Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma.

    PubMed

    Kaseb, Ahmed O; Morris, Jeffrey S; Iwasaki, Michiko; Al-Shamsi, Humaid O; Raghav, Kanwal Pratap Singh; Girard, Lauren; Cheung, Sheree; Nguyen, Van; Elsayes, Khaled M; Xiao, Lianchun; Abdel-Wahab, Reham; Shalaby, Ahmed S; Hassan, Manal; Hassabo, Hesham M; Wolff, Robert A; Yao, James C

    2016-01-01

    Clinicaltrials.gov #NCT01180959. Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib. For this single-arm, Phase II study, we recruited patients with Child-Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0-2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib). Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival. A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months - not defined). The 16-week progression-free survival rate was 43% (95% CI: 28%-59%), median time to progression was 3.9 months (95% CI: 2.0-8.3 months), and median overall survival duration was 9.9 months (95% CI: 8.3-15.5 months). Grade 3-4 adverse events included fatigue (13%), acne (11%), diarrhea (9%), anemia (7%), and upper gastrointestinal hemorrhage (7%). Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted.

  16. Advanced imaging technologies increase detection of dysplasia and neoplasia in patients with Barrett's esophagus: a meta-analysis and systematic review.

    PubMed

    Qumseya, Bashar J; Wang, Haibo; Badie, Nicole; Uzomba, Rosemary N; Parasa, Sravanthi; White, Donna L; Wolfsen, Herbert; Sharma, Prateek; Wallace, Michael B

    2013-12-01

    US guidelines recommend surveillance of patients with Barrett's esophagus (BE) to detect dysplasia. BE conventionally is monitored via white-light endoscopy (WLE) and a collection of random biopsy specimens. However, this approach does not definitively or consistently detect areas of dysplasia. Advanced imaging technologies can increase the detection of dysplasia and cancer. We investigated whether these imaging technologies can increase the diagnostic yield for the detection of neoplasia in patients with BE, compared with WLE and analysis of random biopsy specimens. We performed a systematic review, using Medline and Embase, to identify relevant peer-review studies. Fourteen studies were included in the final analysis, with a total of 843 patients. Our metameter (estimate) of interest was the paired-risk difference (RD), defined as the difference in yield of the detection of dysplasia or cancer using advanced imaging vs WLE. The estimated paired-RD and 95% confidence interval (CI) were obtained using random-effects models. Heterogeneity was assessed by means of the Q statistic and the I(2) statistic. An exploratory meta-regression was performed to look for associations between the metameter and potential confounders or modifiers. Overall, advanced imaging techniques increased the diagnostic yield for detection of dysplasia or cancer by 34% (95% CI, 20%-56%; P < .0001). A subgroup analysis showed that virtual chromoendoscopy significantly increased the diagnostic yield (RD, 0.34; 95% CI, 0.14-0.56; P < .0001). The RD for chromoendoscopy was 0.35 (95% CI, 0.13-0.56; P = .0001). There was no significant difference between virtual chromoendoscopy and chromoendoscopy, based on Student t test analysis (P = .45). Based on a meta-analysis, advanced imaging techniques such as chromoendoscopy or virtual chromoendoscopy significantly increase the diagnostic yield for identification of dysplasia or cancer in patients with BE. Copyright © 2013 AGA Institute. Published by

  17. Trichomonas vaginalis infection and risk of advanced prostate cancer.

    PubMed

    Shui, Irene M; Kolb, Suzanne; Hanson, Christi; Sutcliffe, Siobhan; Rider, Jennifer R; Stanford, Janet L

    2016-05-01

    The epidemiologic evidence for an association of Trichomonas vaginalis (Tv) with overall prostate cancer is mixed, but some studies suggest Tv may increase risk of more aggressive disease. The aim of this study was to assess whether Tv serostatus is associated with advanced or fatal prostate cancer. A total of 146 men with advanced (metastatic or fatal) prostate cancer and 181 age-matched controls were selected from two prior population-based, case-control studies. Tv serostatus was determined with the same laboratory methods used in previous epidemiologic studies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression to compare Tv serostatus in prostate cancer cases and controls adjusted for potential confounders. The seroprevalence of Tv in controls was 23%. Tv serostatus was not associated with an increased risk of metastatic or fatal prostate cancer (ORs < 1). Our study does not support an increased risk of advanced or fatal prostate cancer in men seropositive for Tv. © 2016 Wiley Periodicals, Inc.

  18. 10 CFR 709.4 - Notification of a CI evaluation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... person, in accordance with § 709.21 of this part. (b) Any job announcement or posting with respect to any... retention in that position (709.3(b) and (c)) upon his or her successful completion of a CI evaluation...

  19. Reliable prediction of clinical outcome in patients with chronic HCV infection and compensated advanced hepatic fibrosis: a validated model using objective and readily available clinical parameters.

    PubMed

    van der Meer, Adriaan J; Hansen, Bettina E; Fattovich, Giovanna; Feld, Jordan J; Wedemeyer, Heiner; Dufour, Jean-François; Lammert, Frank; Duarte-Rojo, Andres; Manns, Michael P; Ieluzzi, Donatella; Zeuzem, Stefan; Hofmann, W Peter; de Knegt, Robert J; Veldt, Bart J; Janssen, Harry L A

    2015-02-01

    Reliable tools to predict long-term outcome among patients with well compensated advanced liver disease due to chronic HCV infection are lacking. Risk scores for mortality and for cirrhosis-related complications were constructed with Cox regression analysis in a derivation cohort and evaluated in a validation cohort, both including patients with chronic HCV infection and advanced fibrosis. In the derivation cohort, 100/405 patients died during a median 8.1 (IQR 5.7-11.1) years of follow-up. Multivariate Cox analyses showed age (HR=1.06, 95% CI 1.04 to 1.09, p<0.001), male sex (HR=1.91, 95% CI 1.10 to 3.29, p=0.021), platelet count (HR=0.91, 95% CI 0.87 to 0.95, p<0.001) and log10 aspartate aminotransferase/alanine aminotransferase ratio (HR=1.30, 95% CI 1.12 to 1.51, p=0.001) were independently associated with mortality (C statistic=0.78, 95% CI 0.72 to 0.83). In the validation cohort, 58/296 patients with cirrhosis died during a median of 6.6 (IQR 4.4-9.0) years. Among patients with estimated 5-year mortality risks <5%, 5-10% and >10%, the observed 5-year mortality rates in the derivation cohort and validation cohort were 0.9% (95% CI 0.0 to 2.7) and 2.6% (95% CI 0.0 to 6.1), 8.1% (95% CI 1.8 to 14.4) and 8.0% (95% CI 1.3 to 14.7), 21.8% (95% CI 13.2 to 30.4) and 20.9% (95% CI 13.6 to 28.1), respectively (C statistic in validation cohort = 0.76, 95% CI 0.69 to 0.83). The risk score for cirrhosis-related complications also incorporated HCV genotype (C statistic = 0.80, 95% CI 0.76 to 0.83 in the derivation cohort; and 0.74, 95% CI 0.68 to 0.79 in the validation cohort). Prognosis of patients with chronic HCV infection and compensated advanced liver disease can be accurately assessed with risk scores including readily available objective clinical parameters. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Specific Inhibition of the transcription factor Ci by a Cobalt(III)-Schiff base-DNA conjugate

    PubMed Central

    Hurtado, Ryan R.; Harney, Allison S.; Heffern, Marie C.; Holbrook, Robert J.; Holmgren, Robert A.; Meade, Thomas J.

    2012-01-01

    We describe the use of Co(III) Schiff base-DNA conjugates, a versatile class of research tools that target C2H2 transcription factors, to inhibit the Hedgehog (Hh) pathway. In developing mammalian embryos, Hh signaling is critical for the formation and development of many tissues and organs. Inappropriate activation of the Hedgehog (Hh) pathway has been implicated in a variety of cancers including medulloblastomas and basal cell carcinomas. It is well known that Hh regulates the activity of the Gli family of C2H2 zinc finger transcription factors in mammals. In Drosophila the function of the Gli proteins is performed by a single transcription factor with an identical DNA binding consensus sequence, Cubitus Interruptus (Ci). We have demonstrated previously that conjugation of a specific 17 base-pair oligonucleotide to a Co(III) Schiff base complex results in a targeted inhibitor of the Snail family C2H2 zinc finger transcription factors. Modification of the oligonucleotide sequence in the Co(III) Schiff base-DNA conjugate to that of Ci’s consensus sequence (Co(III)-Ci) generates an equally selective inhibitor of Ci. Co(III)-Ci irreversibly binds the Ci zinc finger domain and prevents it from binding DNA in vitro. In a Ci responsive tissue culture reporter gene assay, Co(III)-Ci reduces the transcriptional activity of Ci in a concentration dependent manner. In addition, injection of wild-type Drosophila embryos with Co(III)-Ci phenocopies a Ci loss of function phenotype, demonstrating effectiveness in vivo. This study provides evidence that Co(III) Schiff base-DNA conjugates are a versatile class of specific and potent tools for studying zinc finger domain proteins and have potential applications as customizable anti-cancer therapeutics. PMID:22214326

  1. The Exon Junction Complex and Srp54 Contribute to Hedgehog Signaling via ci RNA Splicing in Drosophila melanogaster.

    PubMed

    Garcia-Garcia, Elisa; Little, Jamie C; Kalderon, Daniel

    2017-08-01

    Hedgehog (Hh) regulates the Cubitus interruptus (Ci) transcription factor in Drosophila melanogaster by activating full-length Ci-155 and blocking processing to the Ci-75 repressor. However, the interplay between the regulation of Ci-155 levels and activity, as well as processing-independent mechanisms that affect Ci-155 levels, have not been explored extensively. Here, we identified Mago Nashi (Mago) and Y14 core Exon Junction Complex (EJC) proteins, as well as the Srp54 splicing factor, as modifiers of Hh pathway activity under sensitized conditions. Mago inhibition reduced Hh pathway activity by altering the splicing pattern of ci to reduce Ci-155 levels. Srp54 inhibition also affected pathway activity by reducing ci RNA levels but additionally altered Ci-155 levels and activity independently of ci splicing. Further tests using ci transgenes and ci mutations confirmed evidence from studying the effects of Mago and Srp54 that relatively small changes in the level of Ci-155 primary translation product alter Hh pathway activity under a variety of sensitized conditions. We additionally used ci transgenes lacking intron sequences or the presumed translation initiation codon for an alternatively spliced ci RNA to provide further evidence that Mago acts principally by modulating the levels of the major ci RNA encoding Ci-155, and to show that ci introns are necessary to support the production of sufficient Ci-155 for robust Hh signaling and may also be important mediators of regulatory inputs. Copyright © 2017 by the Genetics Society of America.

  2. The Impact of Renin-Angiotensin System Blockade on Renal Outcomes and Mortality in Pre-Dialysis Patients with Advanced Chronic Kidney Disease.

    PubMed

    Oh, Yun Jung; Kim, Sun Moon; Shin, Byung Chul; Kim, Hyun Lee; Chung, Jong Hoon; Kim, Ae Jin; Ro, Han; Chang, Jae Hyun; Lee, Hyun Hee; Chung, Wookyung; Lee, Chungsik; Jung, Ji Yong

    2017-01-01

    Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071-1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123-1.500; P < 0.001). The risk of composite outcomes was higher in RAS blockade users in IPTW (HR, 1.154; 95% CI, 1.016-1.310; P = 0.027), but was marginal significance in PS matched analysis (HR, 1.243; 95% CI, 0.996-1.550; P = 0.054). The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.

  3. Endoscopic versus Percutaneous Biliary Drainage in Palliation of Advanced Malignant Hilar Obstruction: A Meta-Analysis and Systematic Review

    PubMed Central

    Dharmapuri, Sirish; Duvvuri, Abhiram; Dharmapuri, Sowmya; Boddireddy, Raghuveer; Moole, Vishnu; Yedama, Prathyusha; Bondalapati, Naveen; Uppu, Achuta

    2016-01-01

    Background. Palliation in advanced unresectable hilar malignancies can be achieved by endoscopic (EBD) or percutaneous transhepatic biliary drainage (PTBD). It is unclear if one approach is superior to the other in this group of patients. Aims. Compare clinical outcomes of EBD versus PTBD. Methods. (i) Study Selection Criterion. Studies using PTBD and EBD for palliation of advanced unresectable hilar malignancies. (ii) Data Collection and Extraction. Articles were searched in Medline, PubMed, and Ovid journals. (iii) Statistical Method. Fixed and random effects models were used to calculate the pooled proportions. Results. Initial search identified 786 reference articles, in which 62 articles were selected and reviewed. Data was extracted from nine studies (N = 546) that met the inclusion criterion. The pooled odds ratio for successful biliary drainage in PTBD versus EBD was 2.53 (95% CI = 1.57 to 4.08). Odds ratio for overall adverse effects in PTBD versus EBD groups was 0.81 (95% CI = 0.52 to 1.26). Odds ratio for 30-day mortality rate in PTBD group versus EBD group was 0.84 (95% CI = 0.37 to 1.91). Conclusions. In patients with advanced unresectable hilar malignancies, palliation with PTBD seems to be superior to EBD. PTBD is comparable to EBD in regard to overall adverse effects and 30-day mortality. PMID:27648439

  4. Associations between advanced cancer patients' survival and family caregiver presence and burden.

    PubMed

    Dionne-Odom, J Nicholas; Hull, Jay G; Martin, Michelle Y; Lyons, Kathleen Doyle; Prescott, Anna T; Tosteson, Tor; Li, Zhongze; Akyar, Imatullah; Raju, Dheeraj; Bakitas, Marie A

    2016-05-01

    We conducted a randomized controlled trial (RCT) of an early palliative care intervention (ENABLE: Educate, Nurture, Advise, Before Life Ends) for persons with advanced cancer and their family caregivers. Not all patient participants had a caregiver coparticipant; hence, we explored whether there were relationships between patient survival, having an enrolled caregiver, and caregiver outcomes prior to death. One hundred and twenty-three patient-caregiver dyads and 84 patients without a caregiver coparticipant participated in the ENABLE early versus delayed (12 weeks later) RCT. We collected caregiver quality-of-life (QOL), depression, and burden (objective, stress, and demand) measures every 6 weeks for 24 weeks and every 3 months thereafter until the patient's death or study completion. We conducted survival analyses using log-rank and Cox proportional hazards models. Patients with a caregiver coparticipant had significantly shorter survival (Wald = 4.31, HR = 1.52, CI: 1.02-2.25, P = 0.04). After including caregiver status, marital status (married/unmarried), their interaction, and relevant covariates, caregiver status (Wald = 6.25, HR = 2.62, CI: 1.23-5.59, P = 0.01), being married (Wald = 8.79, HR = 2.92, CI: 1.44-5.91, P = 0.003), and their interaction (Wald = 5.18, HR = 0.35, CI: 0.14-0.87, P = 0.02) were significant predictors of lower patient survival. Lower survival in patients with a caregiver was significantly related to higher caregiver demand burden (Wald = 4.87, CI: 1.01-1.20, P = 0.03) but not caregiver QOL, depression, and objective and stress burden. Advanced cancer patients with caregivers enrolled in a clinical trial had lower survival than patients without caregivers; however, this mortality risk was mostly attributable to higher survival by unmarried patients without caregivers. Higher caregiver demand burden was also associated with decreased patient survival. © 2016 The Authors. Cancer Medicine published by

  5. Reduction in advanced breast cancer after introduction of a mammography screening program in Tyrol/Austria.

    PubMed

    Oberaigner, W; Geiger-Gritsch, Sabine; Edlinger, M; Daniaux, M; Knapp, R; Hubalek, M; Siebert, U; Marth, C; Buchberger, W

    2017-06-01

    We analysed all female breast cancer (BC) cases in Tyrol/Austria regarding the shift in cancer characteristics, especially the shift in advanced BC, for the group exposed to screening as compared to the group unexposed to screening. The analysis was based on all BC cases diagnosed in women aged 40-69 years, resident in Tyrol, and diagnosed between 2009 and 2013. The data were linked to the Tyrolean mammography screening programme database to classify BC cases as "exposed to screening" or "unexposed to screening". Age-adjusted relative risks (RR) were estimated by relating the exposed to the unexposed group. In a total of about 145,000 women aged 40-69 years living in Tyrol during the study period, 1475 invasive BC cases were registered. We estimated an age-adjusted relative risk (RR) for tumour size ≥ 21 mm of 0.72 (95% confidence interval (CI) 0.60 to 0.86), for metastatic BC of 0.27 (95% CI 0.17 to 0.46) and for advanced BC of 0.83 (95% CI 0.71 to 0.96), each comparing those exposed to those unexposed to screening, respectively. In our population-based registry analysis we observed that participation in the mammography screening programme in Tyrol is associated with a 28% decrease in risk for BC cases with tumour size ≥ 21 mm and a 17% decrease in risk for advanced BC. We therefore expect the Tyrolean mammography programme to show a reduction in BC mortality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Communication: CDFT-CI couplings can be unreliable when there is fractional charge transfer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mavros, Michael G.; Van Voorhis, Troy, E-mail: tvan@mit.edu

    2015-12-21

    Constrained density functional theory with configuration interaction (CDFT-CI) is a useful, low-cost tool for the computational prediction of electronic couplings between pseudo-diabatic constrained electronic states. Such couplings are of paramount importance in electron transfer theory and transition state theory, among other areas of chemistry. Unfortunately, CDFT-CI occasionally fails significantly, predicting a coupling that does not decay exponentially with distance and/or overestimating the expected coupling by an order of magnitude or more. In this communication, we show that the eigenvalues of the difference density matrix between the two constrained states can be used as an a priori metric to determine whenmore » CDFT-CI are likely to be reliable: when the eigenvalues are near 0 or ±1, transfer of a whole electron is occurring, and CDFT-CI can be trusted. We demonstrate the utility of this metric with several illustrative examples.« less

  7. Communication: CDFT-CI couplings can be unreliable when there is fractional charge transfer

    NASA Astrophysics Data System (ADS)

    Mavros, Michael G.; Van Voorhis, Troy

    2015-12-01

    Constrained density functional theory with configuration interaction (CDFT-CI) is a useful, low-cost tool for the computational prediction of electronic couplings between pseudo-diabatic constrained electronic states. Such couplings are of paramount importance in electron transfer theory and transition state theory, among other areas of chemistry. Unfortunately, CDFT-CI occasionally fails significantly, predicting a coupling that does not decay exponentially with distance and/or overestimating the expected coupling by an order of magnitude or more. In this communication, we show that the eigenvalues of the difference density matrix between the two constrained states can be used as an a priori metric to determine when CDFT-CI are likely to be reliable: when the eigenvalues are near 0 or ±1, transfer of a whole electron is occurring, and CDFT-CI can be trusted. We demonstrate the utility of this metric with several illustrative examples.

  8. Non-CI refractory lithophile abundances in bulk planetary materials

    NASA Astrophysics Data System (ADS)

    Dauphas, N.

    2015-12-01

    Refractory inclusions in meteorites show evidence for fractionation of refractory lithophile elements relative to one another. For bulk planetary materials, it is most often assumed that refractory lithophile elements (e.g., Ca, Al, Ti, REEs) are in proportions similar to CI carbonaceous chondrites, which is taken to be a proxy for solar composition. A diagnostic feature of REE patterns in refractory inclusions in meteorites is the presence of thulium anomalies, arising from the fact that this heavy REE is more volatile than the highly refractory HREEs surrounding it (Tm/Tm* is defined relative to either Er-Yb or Er-Lu). Tm anomalies thus represent an excellent diagnostic tool to test the assumption that refractory lithophile elements have uniform relative abundances at a bulk planetary scale. Prior to this work, high precision Tm measurements were lacking because it is mono-isotopic and as such is not amenable to high-precision single spike measurements. We have developed a multi-collector REE abundance measurement technique to measure all REEs at high precision, including the mono-isotopic ones. This technique was used to revise the abundance of CI and PAAS REE abundances (Pourmand et al. 2012) and the CI composition agrees well with an independent study (Barrat et al. 2012). The same technique was applied to measure REE patterns in 41 chondrites as well as terrestrial rocks (Dauphas and Pourmand, 2015). Our results reveal the presence of Tm anomalies of about -4.5 % in terrestrial rocks, enstatite and ordinary chondrites, relative to carbonaceous chondrites including CIs. This demonstrates that the assumption that refractory lithophile elements are in constant proportions among planetary bodies is unwarranted. It also shows that carbonaceous chondrites cannot be a major constituent of the Earth. The presence of Tm anomalies in meteorites and terrestrial rocks suggests that either (i) the material in the inner part of the solar system was formed from a gas

  9. PAT: From Western solid dosage forms to Chinese materia medica preparations using NIR-CI.

    PubMed

    Zhou, Luwei; Xu, Manfei; Wu, Zhisheng; Shi, Xinyuan; Qiao, Yanjiang

    2016-01-01

    Near-infrared chemical imaging (NIR-CI) is an emerging technology that combines traditional near-infrared spectroscopy with chemical imaging. Therefore, NIR-CI can extract spectral information from pharmaceutical products and simultaneously visualize the spatial distribution of chemical components. The rapid and non-destructive features of NIR-CI make it an attractive process analytical technology (PAT) for identifying and monitoring critical control parameters during the pharmaceutical manufacturing process. This review mainly focuses on the pharmaceutical applications of NIR-CI in each unit operation during the manufacturing processes, from the Western solid dosage forms to the Chinese materia medica preparations. Finally, future applications of chemical imaging in the pharmaceutical industry are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Ciênsação: gaining a feeling for sciences

    NASA Astrophysics Data System (ADS)

    Abreu de Oliveira, Marcos Henrique; Fischer, Robert

    2017-03-01

    Ciênsação, an open online repository for hands-on experiments, has been developed to convince teachers in Latin America that science is best experienced first hand. Permitting students to experiment autonomously in small groups can be a challenging endeavour for educators in these countries. We analyse the reasons that cause hesitation of teachers appling hands-on experiments in class, and discuss how Ciênsação was implemented to overcome these obstacles. The resulting student research activities are specifically designed to be easily integrated in formal science education at school, to foster research skills and, most importantly, to let young people get to know science as an engaging creative activity.

  11. Coupling between the voltage-sensing and phosphatase domains of Ci-VSP.

    PubMed

    Villalba-Galea, Carlos A; Miceli, Francesco; Taglialatela, Maurizio; Bezanilla, Francisco

    2009-07-01

    The Ciona intestinalis voltage sensor-containing phosphatase (Ci-VSP) shares high homology with the phosphatidylinositol phosphatase enzyme known as PTEN (phosphatase and tensin homologue deleted on chromosome 10). We have taken advantage of the similarity between these proteins to inquire about the coupling between the voltage sensing and the phosphatase domains in Ci-VSP. Recently, it was shown that four basic residues (R11, K13, R14, and R15) in PTEN are critical for its binding onto the membrane, required for its catalytic activity. Ci-VSP has three of the basic residues of PTEN. Here, we show that when R253 and R254 (which are the homologues of R14 and R15 in PTEN) are mutated to alanines in Ci-VSP, phosphatase activity is disrupted, as revealed by a lack of effect on the ionic currents of KCNQ2/3, where current decrease is a measure of phosphatase activity. The enzymatic activity was not rescued by the introduction of lysines, indicating that the binding is an arginine-specific interaction between the phosphatase binding domain and the membrane, presumably through the phosphate groups of the phospholipids. We also found that the kinetics and steady-state voltage dependence of the S4 segment movement are affected when the arginines are not present, indicating that the interaction of R253 and R254 with the membrane, required for the catalytic action of the phosphatase, restricts the movement of the voltage sensor.

  12. Comparison of single agent versus combined chemotherapy in previously treated patients with advanced urothelial carcinoma: a meta-analysis.

    PubMed

    Wu, Xiao-Jun; Zhi, Yi; He, Peng; Zhou, Xiao-Zhou; Zheng, Ji; Chen, Zhi-Wen; Zhou, Zhan-Song

    2016-01-01

    Platinum-based chemotherapy is the standard treatment for advanced urothelial cancer (UC) and is generally used in the first-line setting. However, the optimal salvage treatment for previously treated UC patients is unclear. We conducted a systematic review of published clinical trials of single agent versus combined chemotherapy as salvage treatment in previously treated UC patients. Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All relevant studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS), and grade 3/4 toxicities were extracted and analyzed using Comprehensive Meta Analysis software (Version 2.0). Fifty cohorts with 1,685 patients were included for analysis: 814 patients were treated with single agent chemotherapy and 871 with combined chemotherapy. Pooled OS was significantly higher at 1 year for combined chemotherapy than for single agent (relative risk [RR] 1.52; 95% CI: 1.01-2.37; P=0.03) but not for 2-year OS (RR 1.31; 95% CI: 0.92-1.85; P=0.064). Additionally, combined chemotherapy significantly improved ORR (RR 2.25; 95% CI: 1.60-3.18; P<0.001) and DCR (RR 1.12; 95% CI: 1.01-1.25, P=0.033) compared to single agent for advanced UC patients. As for grade 3 and 4 toxicities, more frequencies of leukopenia and thrombocytopenia were observed in the combined chemotherapy than in single agent group, while equivalent frequencies of anemia, nausea, vomiting, and diarrhea were found between the two groups. In comparison with single agent alone, combined chemotherapy as salvage treatment for advanced UC patients significantly improved ORR, DCR, and 1-year OS, but not 2-year OS. Our findings support the need to compare combined chemotherapy with single agent alone in the salvage setting in large prospective

  13. Horizontal sound localization in cochlear implant users with a contralateral hearing aid.

    PubMed

    Veugen, Lidwien C E; Hendrikse, Maartje M E; van Wanrooij, Marc M; Agterberg, Martijn J H; Chalupper, Josef; Mens, Lucas H M; Snik, Ad F M; John van Opstal, A

    2016-06-01

    Interaural differences in sound arrival time (ITD) and in level (ILD) enable us to localize sounds in the horizontal plane, and can support source segregation and speech understanding in noisy environments. It is uncertain whether these cues are also available to hearing-impaired listeners who are bimodally fitted, i.e. with a cochlear implant (CI) and a contralateral hearing aid (HA). Here, we assessed sound localization behavior of fourteen bimodal listeners, all using the same Phonak HA and an Advanced Bionics CI processor, matched with respect to loudness growth. We aimed to determine the availability and contribution of binaural (ILDs, temporal fine structure and envelope ITDs) and monaural (loudness, spectral) cues to horizontal sound localization in bimodal listeners, by systematically varying the frequency band, level and envelope of the stimuli. The sound bandwidth had a strong effect on the localization bias of bimodal listeners, although localization performance was typically poor for all conditions. Responses could be systematically changed by adjusting the frequency range of the stimulus, or by simply switching the HA and CI on and off. Localization responses were largely biased to one side, typically the CI side for broadband and high-pass filtered sounds, and occasionally to the HA side for low-pass filtered sounds. HA-aided thresholds better than 45 dB HL in the frequency range of the stimulus appeared to be a prerequisite, but not a guarantee, for the ability to indicate sound source direction. We argue that bimodal sound localization is likely based on ILD cues, even at frequencies below 1500 Hz for which the natural ILDs are small. These cues are typically perturbed in bimodal listeners, leading to a biased localization percept of sounds. The high accuracy of some listeners could result from a combination of sufficient spectral overlap and loudness balance in bimodal hearing. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Electrical stimulation of the brain and the development of cortical visual prostheses: An historical perspective.

    PubMed

    Lewis, Philip M; Rosenfeld, Jeffrey V

    2016-01-01

    Rapid advances are occurring in neural engineering, bionics and the brain-computer interface. These milestones have been underpinned by staggering advances in micro-electronics, computing, and wireless technology in the last three decades. Several cortically-based visual prosthetic devices are currently being developed, but pioneering advances with early implants were achieved by Brindley followed by Dobelle in the 1960s and 1970s. We have reviewed these discoveries within the historical context of the medical uses of electricity including attempts to cure blindness, the discovery of the visual cortex, and opportunities for cortex stimulation experiments during neurosurgery. Further advances were made possible with improvements in electrode design, greater understanding of cortical electrophysiology and miniaturisation of electronic components. Human trials of a new generation of prototype cortical visual prostheses for the blind are imminent. This article is part of a Special Issue entitled Hold Item. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial.

    PubMed

    Tröger, Wilfried; Galun, Danijel; Reif, Marcus; Schumann, Agnes; Stanković, Nikola; Milićević, Miroslav

    2014-07-21

    The treatment of cancer patients with mistletoe extract is said to prolong their survival and, above all, improve their quality of life. We studied whether the quality of life of patients with advanced pancreatic cancer could be improved by mistletoe extract. An open, single-center, group-sequential, randomized phase III trial (ISRCTN70760582) was conducted. From January 2009 to December 2010, 220 patients with locally advanced or metastatic pancreatic cancer who were receiving no further treatment for pancreatic cancer other than best supportive care were included in this trial. They were stratified by prognosis and randomly allocated either to a group that received mistletoe treatment or to one that did not. Mistletoe extract was given in escalating doses by subcutaneous injection three times a week. The planned interim evaluation of data from 220 patients indicated that mistletoe treatment was associated with longer overall survival, and the trial was terminated prematurely. After termination of the study, the results with respect to quality of life (assessed with the QLO-C30 scales of the European Organisation for Research and Treatment of Cancer) and trends in body weight were evaluated. Data on quality of life and body weight were obtained from 96 patients treated with mistletoe and 72 control patients. Those treated with mistletoe did better on all 6 functional scales and on 7 of 9 symptom scales, including pain (95% confidence interval [CI] -29 to -17), fatigue (95% CI -36.1 to -25.0), appetite loss (95% CI -51 to -36.7), and insomnia (95% CI -45.8 to -28.6). This is reflected by the trend in body weight during the trial. In patients with locally advanced or metastatic pancreatic carcinoma, mistletoe treatment significantly improves the quality of life in comparison to best supportive care alone. Mistletoe is an effective second-line treatment for this disease.

  16. Nivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

    PubMed Central

    Rizvi, Naiyer A.; Chow, Laura Q.; Borghaei, Hossein; Brahmer, Julie; Ready, Neal; Gerber, David E.; Shepherd, Frances A.; Antonia, Scott; Goldman, Jonathan W.; Juergens, Rosalyn A.; Laurie, Scott A.; Nathan, Faith E.; Shen, Yun; Harbison, Christopher T.; Hellmann, Matthew D.

    2016-01-01

    Purpose Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non–small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. Methods Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. Results Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD–ligand 1 expression and 14% (two of 14) in patients with no PD–ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively. Conclusion First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC. PMID:27354485

  17. Building the bionic eye: an emerging reality and opportunity.

    PubMed

    Merabet, Lotfi B

    2011-01-01

    Once the topic of folklore and science fiction, the notion of restoring vision to the blind is now approaching a tractable reality. Technological advances have inspired numerous multidisciplinary groups worldwide to develop visual neuroprosthetic devices that could potentially provide useful vision and improve the quality of life of profoundly blind individuals. While a variety of approaches and designs are being pursued, they all share a common principle of creating visual percepts through the stimulation of visual neural elements using appropriate patterns of electrical stimulation. Human clinical trials are now well underway and initial results have been met with a balance of excitement and cautious optimism. As remaining technical and surgical challenges continue to be solved and clinical trials move forward, we now enter a phase of development that requires careful consideration of a new set of issues. Establishing appropriate patient selection criteria, methods of evaluating long-term performance and effectiveness, and strategies to rehabilitate implanted patients will all need to be considered in order to achieve optimal outcomes and establish these devices as viable therapeutic options. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Characteristics of Social Support Among Teenage, Optimal Age, and Advanced Age Women in Canada: An Analysis of the National Longitudinal Survey of Children and Youth.

    PubMed

    Kim, Theresa H M; Rotondi, Michael; Connolly, Jennifer; Tamim, Hala

    2017-06-01

    Background Social support is highly valued and beneficial for women, especially after childbirth. The objective was to examine the differences of social support reported among teen, optimal age, and advanced age women, and to identify the characteristics associated with social support separately for each age group. Methods This was a cross-sectional analysis of the National Longitudinal Survey of Children and Youth. Primiparous women with infants were grouped into: teen (15-19 years), optimal age (20-34 years), and advanced age (35 years and older). The outcome was social support (Social Provisions Scale), and demographic, socio-economic, health, community, and infant characteristics were considered for stepwise linear regression, separately for the groups. Results Total of 455,022 mothers was analyzed. Teens had the lowest social support (Mean = 17.56) compared to other groups (Means = 19.07 and 19.05; p < 0.001). Teens' volunteer involvement was associated with an increase in social support (Adjβ 2.77; 95%CI 0.86, 4.68), and depression was associated with a decrease (Adjβ -0.12; 95%CI -0.22, -0.02). Optimal age women's support significantly increased with maternal age (Adjβ 0.07; 95%CI 0.02,0.12), working status (Adjβ 0.60; 95%CI 0.13,1.07), and with chronic condition(s) (Adjβ 0.59; 95%CI 0.16,1.02), while it decreased with depression (Adjβ -0.05; 95%CI -0.10, -0.01) and ever-immigrants (Adjβ -1.67; 95%CI -2.29, -1.04). Use of childcare was associated with increased support among women in advanced age group (Adjβ 1.58; 95%CI 0.12, 3.04). For all groups, social support was significantly associated with neighbourhood safety. Conclusion The characteristics associated with social support varied among the three age groups. The findings may help promote awareness of the essential needs to increase support, especially for teens.

  19. FIB-TEM Investigations of Fe-NI-Sulfides in the CI Chondrites Alais and Orgueil

    NASA Technical Reports Server (NTRS)

    Berger, Eve L.; Lauretta, D. S.; Zega, T. J.; Keller, L. P.

    2013-01-01

    The CI chondrites are primitive meteorites with bulk compositions matching the solar photosphere for all but the lightest elements. They have been extensively aqueously altered, and are composed primarily of fine-grained phyllosilicate matrix material which is host to carbonates, sulfates, sulfides, and minor amounts of olivine and pyroxene. The alteration, while extensive, is heterogeneous. For example, CI-chondrite cubanite and carbonate grains differ on mm to sub-mm scales, demonstrating multiple aqueous episodes. CI-chondrite variability is also evidenced by degree of brecciation, abundance and size of coarse-grained phyllosilicates, olivine and pyroxene abundance, as well as Ni-content and size of sulfide grains. Our previous work revealed Orgueil sulfide grains with variable Ni-contents, metal:S ratios, crystal structures and textures. We continue to explore the variability of CI-chondrite pyrrhotite (Po, (FeNi)1-xS) and pentlandite (Pn, (Fe,Ni)9S8) grains. We investigate the microstructure of sulfides within and among CI-chondrite meteorites in order to place constraints on the conditions under which they formed.

  20. Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer

    PubMed Central

    Enzinger, Andrea C.; Zhang, Baohui; Schrag, Deborah; Prigerson, Holly G.

    2015-01-01

    Purpose To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer. Patients and Methods This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences. Results Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses. Conclusion Prognostic disclosures are associated with more realistic

  1. Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer.

    PubMed

    Enzinger, Andrea C; Zhang, Baohui; Schrag, Deborah; Prigerson, Holly G

    2015-11-10

    To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer. This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences. Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses. Prognostic disclosures are associated with more realistic patient expectations of LE, without decrements to

  2. Refining Low Physical Activity Measurement Improves Frailty Assessment in Advanced Lung Disease and Survivors of Critical Illness.

    PubMed

    Baldwin, Matthew R; Singer, Jonathan P; Huang, Debbie; Sell, Jessica; Gonzalez, Wendy C; Pollack, Lauren R; Maurer, Mathew S; D'Ovidio, Frank F; Bacchetta, Matthew; Sonett, Joshua R; Arcasoy, Selim M; Shah, Lori; Robbins, Hilary; Hays, Steven R; Kukreja, Jasleen; Greenland, John R; Shah, Rupal J; Leard, Lorriana; Morrell, Matthew; Gries, Cynthia; Katz, Patricia P; Christie, Jason D; Diamond, Joshua M; Lederer, David J

    2017-08-01

    The frail phenotype has gained popularity as a clinically relevant measure in adults with advanced lung disease and in critical illness survivors. Because respiratory disease and chronic illness can greatly limit physical activity, the measurement of participation in traditional leisure time activities as a frailty component may lead to substantial misclassification of frailty in pulmonary and critical care patients. To test and validate substituting the Duke Activity Status Index (DASI), a simple 12-item questionnaire, for the Minnesota Leisure Time Physical Activity (MLTA) questionnaire, a detailed questionnaire covering 18 leisure time activities, as the measure of low activity in the Fried frailty phenotype (FFP) instrument. In separate multicenter prospective cohort studies of adults with advanced lung disease who were candidates for lung transplant and older survivors of acute respiratory failure, we assessed the FFP using either the MLTA or the DASI. For both the DASI and MLTA, we evaluated content validity by testing floor effects and construct validity through comparisons with conceptually related factors. We tested the predictive validity of substituting the DASI for the MLTA in the FFP assessment using Cox models to estimate associations between the FFP and delisting/death before transplant in those with advanced lung disease and 6-month mortality in older intensive care unit (ICU) survivors. Among 618 adults with advanced lung disease and 130 older ICU survivors, the MLTA had a substantially greater floor effect than the DASI (42% vs. 1%, and 49% vs. 12%, respectively). The DASI correlated more strongly with strength and function measures than did the MLTA in both cohorts. In models adjusting for age, sex, comorbidities, and illness severity, substitution of the DASI for the MLTA led to stronger associations of the FFP with delisting/death in lung transplant candidates (FFP-MLTA hazard ratio [HR], 1.42; 95% confidence interval [CI], 0.55-3.65; FFP

  3. Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration

    PubMed Central

    Selivanova, Alexandra; Shin, Hyun Joon; Miller, Joan W.; Jackson, Mary Lou

    2018-01-01

    Purpose Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. Methods We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. Results Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). Conclusion In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL. PMID:29746512

  4. [Advances of studies on new technology and method for identifying traditional Chinese medicinal materials].

    PubMed

    Chen, Shilin; Guo, Baolin; Zhang, Guijun; Yan, Zhuyun; Luo, Guangming; Sun, Suqin; Wu, Hezhen; Huang, Linfang; Pang, Xiaohui; Chen, Jianbo

    2012-04-01

    In this review, the authors summarized the new technologies and methods for identifying traditional Chinese medicinal materials, including molecular identification, chemical identification, morphological identification, microscopic identification and identification based on biological effects. The authors introduced the principle, characteristics, application and prospect on each new technology or method and compared their advantages and disadvantages. In general, new methods make the result more objective and accurate. DNA barcoding technique and spectroscopy identification have their owner obvious strongpoint in universality and digitalization. In the near future, the two techniques are promising to be the main trend for identifying traditional Chinese medicinal materials. The identification techniques based on microscopy, liquid chromatography, PCR, biological effects and DNA chip will be indispensable supplements. However, the bionic identification technology is just placed in the developing stage at present.

  5. The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials.

    PubMed

    Zhang, L L; Cao, F F; Wang, Y; Meng, F L; Zhang, Y; Zhong, D S; Zhou, Q H

    2015-05-01

    The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically. Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects. Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64-0.99) and disease control rate (RR 0.90; 95 % CI 0.82-0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91-1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86-1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups. The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.

  6. Observational Approach to Molecular Cloud Evolutation with the Submillimeter-Wave CI Lines

    NASA Astrophysics Data System (ADS)

    Oka, T.; Yamamoto, S.

    Neutral carbon atoms (CI) play important roles both in chemistry and cooling processes of interstellar molecular clouds. It is thus crucial to explore its large area distribution to obtain information on formation processes and thermal balance of molecular clouds. However, observations of the submillimeter-wave CI lines have been limited to small areas around some representative objects. We have constructed a 1.2 m submillimeter-wave telescope at the summit of Mt.Fuji. The telescope was designed for the exclusive use of surveying molecular clouds in two submillimeter-wave CI lines, 3 P1 -3 P0 (492GHz) and 3 P2 -3 P1 (809 GHz), of atomic carbon. A superconductor-insulator-superconductor (SIS) mixer receiver was equipped on the Nasmyth focus of the telescope. The receiver noise temperatures [Trx(DSB)] are 300 K and 1000 K for the 492 GHz and the 809 GHz mixers, respectively. The intermediate frequency is centered at 2 GHz, having a 700 MHz bandwidth. An acousto-optical spectrometer (AOS) with 1024 channel outputs is used as a receiver backend. The telescope was installed at Nishi-yasugawara (alt. 3725 m), which is 200 m north of the highest peak, Kengamine (3776 m), in July 1998. It has b en operatede successfully during 4 observing seasons in a remote way from the Hongo campus of the University of Tokyo. We have already observed more than 40 square degrees of the sky with the CI 492 GHz line. The distribution of CI emission is found to be different from those of the 13 CO or C1 8 O emission in some clouds. These differences are discussed in relation to formation processes of molecular clouds.

  7. AHRQ series on complex intervention systematic reviews-paper 7: PRISMA-CI elaboration and explanation.

    PubMed

    Guise, Jeanne-Marie; Butler, Mary; Chang, Christine; Viswanathan, Meera; Pigott, Terri; Tugwell, Peter

    2017-10-01

    Complex interventions are widely used in health care, public health, education, criminology, social work, business, and welfare. They have increasingly become the subject of systematic reviews and are challenging to effectively report. The Complex Interventions Methods Workgroup developed an extension to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Complex Interventions (PRISMA-CI). Following the EQUATOR Network guidance for Preferred Reporting Items for Systematic Reviews and Meta-Analysis extensions, this Explanation and Elaboration (EE) document accompanies the PRISMA-CI checklist to promote consistency in reporting of systematic reviews of complex interventions. The EE document explains the meaning and rationale for each unique PRISMA-CI checklist item and provides examples to assist systematic review authors in operationalizing PRISMA-CI guidance. The Complex Interventions Workgroup developed PRISMA-CI as an important start toward increased consistency in reporting of systematic reviews of complex interventions. Because the field is rapidly expanding, the Complex Interventions Methods Workgroup plans to re-evaluate periodically for the need to add increasing specificity and examples as the field matures. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Research into topology optimization and the FDM method for a space cracked membrane

    NASA Astrophysics Data System (ADS)

    Hu, Qingxi; Li, Wanyuan; Zhang, Haiguang; Liu, Dali; Peng, Fujun; Duan, Yongchao

    2017-07-01

    The problem that the space membranes are easily torn open is the main focus in this paper, and a bionic strengthening-ribs structure is proposed for a space membrane based on interdisciplinary strengths, such as topology optimization, composite materials, and rapid prototyping. The optimization method and modeling method of membranes with bionic strengthening-ribs was studied. The PEEK and SCF/PEEK composite material which are applied to the space environment are chosen, and FDM technology is used. Through topology optimization, bionic strengthening-ribs with good tensile and tear capacities were obtained. Cracked membranes, cracked membranes with PEEK strengthening-ribs and SCF/PEEK strengthening-ribs were tested and test data were obtained. An extension situation and tension fracture were compared for three cases. The experimental results showed that membranes with the bionic strengthening-ribs structure have better mechanical properties, and the strength of the membranes with PEEK and SCF/PEEK strengthening-ribs were raised, respectively, up to 266.9% and 185.9%. The strengthening-ribs structure greatly improves the capacity to halt membrane crack-growth, which has an important significance to avoid membrane tear, and to ensure the spacecraft orbital lifetime.

  9. The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib

    PubMed Central

    Zhou, Jian-Guo; Tian, Xu; Cheng, Long; Zhou, Quan; Liu, Yuan; Zhang, Yu; Bai, Yu-ju; Ma, Hu

    2015-01-01

    Abstract Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a critical member of systemic therapy for advanced non-small-cell lung cancer (NSCLC). Erlotinib is the first-generation EGFR-TKIs, the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations. However, the safety of erlotinib plus chemotherapy (CT) or erlotinib alone for advanced NSCLC remains controversial. We carried out a systematic meta-analysis to determine the overall risk of neutropenia and leukopenia associated with erlotinib. PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. RR with 95% CIs for neutropenia and leukopenia were all extracted. The random-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were conducted. We identified 12 eligible studies involving 3932 patients. Erlotinib plus CT or alone relative to CT is associated with significantly decreased risks of neutropenia and leukopenia in patients with advanced NSCLC (RR, 0.38; 95% CI, 0.21–0.71; P = 0.00; incidence: 9.9 vs. 35.2%) and (RR, 0.32; 95% CI, 0.11–0.93; P = 0.04; incidence: 3.5 vs. 11.6%), respectively. The subgroup analysis by erlotinb with or without CT showed that erlotinib combine with CT have no significance decrease the relative risks of neutropenia or leukopenia (RR, 0.98; 95% CI, 0.78–1.23; P = 0.87; incidence: 26.2 vs. 30.5%) and (RR, 0.81; 95% CI, 0.34–1.95; P = 0.64; incidence: 6.5 vs. 9.3%), respectively. However, erlotinib alone could decrease incidence of neutropenia (RR, 0.14; 95% CI, 0.07–0.27; P = 0.00; incidence: 3.7 vs. 40.8%) or leukopenia (RR, 0.07; 95% CI, 0.01–0.45; P = 0.01; incidence: 0.8 vs. 15.7%). The power analysis

  10. Increasing likelihood of advanced pulmonary tuberculosis at initial diagnosis in a low-incidence US state.

    PubMed

    Yang, Z-H; Gorden, T; Liu, D-P; Mukasa, L; Patil, N; Bates, J H

    2018-06-01

    Arkansas, USA. To investigate the relationship between an increase in the proportion of cases with advanced disease at first diagnosis and the recently observed slowing of the decline in tuberculosis (TB) incidence in low-incidence US states. We conducted descriptive statistical analyses of de-identified surveillance data of 1246 culture-confirmed TB patients reported in Arkansas during 1996-2013. We then fitted stepwise, multivariate logistic regression models to identify predictors for advanced disease at diagnosis, defined as having either smear-positive sputum or lung cavitation. From 1996 to 2013, the proportion of new cases with positive sputum smear and cases with lung cavitation increased from 51.6% to 75% and from 37.7% to 50%, respectively. Patients diagnosed during 2006-2013 were more likely to have positive sputum smears (adjusted odds ratio [aOR] 2.55, 95%CI 1.95-3.35) or lung cavitation (aOR 1.49, 95%CI 1.14-1.95) than those diagnosed during 1996-2005. During 1996-2013, age 15-64 years and excessive alcohol use were predictive of positive sputum smear or lung cavitation. Measures to reduce the proportion of cases with advanced disease at first diagnosis may be helpful to achieve further decline in TB incidence in low-incidence settings.

  11. CI as a Tracer of Gas Mass in Star Forming Galaxies

    NASA Astrophysics Data System (ADS)

    Bourne, Nathan

    2018-01-01

    Research in galaxy evolution aims to understand the cosmic industry of converting gas into stars. While SFR and stellar mass evolution are well constrained by current data, our knowledge of gas in galaxies throughout cosmic time is comparatively lacking. Almost all high-redshift gas measurements to date rely on CO as a tracer, but this is subject to systematic uncertainties due to optically thick emission and poorly constrained dependences on gas density, distribution and metallicity. Recently, some attention has been given to dust continuum as an alternative gas tracer, which shows promise for large samples but still requires accurate calibration on a direct gas tracer at high redshift. The [CI] 492GHz emission line could overcome much of the systematic uncertainty, as it is optically thin and has similar excitation conditions to CO(1-0), but observational limitations have so far restricted CI measurements to very small samples. I will presen t some new data from ALMA, for the first time testing the CI/dust correlation in a representative sample of star-forming galaxies at z=1, and discuss how future observations could be designed to more widely exploit this independent gas tracer.

  12. Circulating CD147 predicts mortality in advanced hepatocellular carcinoma.

    PubMed

    Lee, Aimei; Rode, Anthony; Nicoll, Amanda; Maczurek, Annette E; Lim, Lucy; Lim, Seok; Angus, Peter; Kronborg, Ian; Arachchi, Niranjan; Gorelik, Alexandra; Liew, Danny; Warner, Fiona J; McCaughan, Geoffrey W; McLennan, Susan V; Shackel, Nicholas A

    2016-02-01

    The glycoprotein CD147 has a role in tumor progression, is readily detectable in the circulation, and is abundantly expressed in hepatocellular carcinoma (HCC). Advanced HCC patients are a heterogeneous group with some individuals having dismal survival. The aim of this study was to examine circulating soluble CD147 levels as a prognostic marker in HCC patients. CD147 was measured in 277 patients (110 HCC, 115 chronic liver disease, and 52 non-liver disease). Clinical data included etiology, tumor progression, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment response. Patients with HCC were stratified into two groups based upon the 75th percentile of CD147 levels (24 ng/mL). CD147 in HCC correlated inversely with poor survival (P = 0.031). Increased CD147 predicted poor survival in BCLC stages C and D (P = 0.045), and CD147 levels >24 ng/mL predicted a significantly diminished 90-day and 180-day survival time (hazard ratio [HR] = 6.1; 95% confidence interval [CI]: 2.1-63.2; P = 0.0045 and HR = 2.8; 95% CI: 1.2-12.6; P = 0.028, respectively). In BCLC stage C, CD147 predicted prognosis; levels >24 ng/mL were associated with a median survival of 1.5 months compared with 6.5 months with CD147 levels ≤24 ng/mL (P = 0.03). CD147 also identified patients with a poor prognosis independent from treatment frequency, modality, and tumor size. Circulating CD147 is an independent marker of survival in advanced HCC. CD147 requires further evaluation as a potential new prognostic measure in HCC to identify patients with advanced disease who have a poor prognosis. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  13. Predictors of Responses to Corticosteroids for Cancer-Related Fatigue in Advanced Cancer Patients: A Multicenter, Prospective, Observational Study.

    PubMed

    Matsuo, Naoki; Morita, Tatsuya; Matsuda, Yoshinobu; Okamoto, Kenichiro; Matsumoto, Yoshihisa; Kaneishi, Keisuke; Odagiri, Takuya; Sakurai, Hiroki; Katayama, Hideki; Mori, Ichiro; Yamada, Hirohide; Watanabe, Hiroaki; Yokoyama, Taro; Yamaguchi, Takashi; Nishi, Tomohiro; Shirado, Akemi; Hiramoto, Shuji; Watanabe, Toshio; Kohara, Hiroyuki; Shimoyama, Satofumi; Aruga, Etsuko; Baba, Mika; Sumita, Koki; Iwase, Satoru

    2016-07-01

    Although corticosteroids are widely used to relieve cancer-related fatigue (CRF), information regarding the factors predicting responses to corticosteroids remains limited. The aim of this study was to identify potential factors predicting responses to corticosteroids for CRF in advanced cancer patients. Inclusion criteria for this multicenter, prospective, observational study were patients who had metastatic or locally advanced cancer and had a fatigue intensity score of 4 or more on a 0-10 Numerical Rating Scale (NRS). Univariate and multivariate analyses were conducted to identify the factors predicting two-point reduction or more in NRS on day 3. Among 179 patients who received corticosteroids, 86 (48%; 95% CI 41%-56%) had a response with two-point reduction or more. Factors that significantly predicted responses were performance status score of 3 or more, Palliative Performance Scale score more than 40, absence of ascites, absence of drowsiness, absence of depression, serum albumin level greater than 3 mg/dL, serum sodium level greater than 135 mEq/L, and baseline NRS score greater than 5. A multivariate analysis showed that the independent factors predicting responses were baseline NRS score greater than 5 (odds ratio [OR] 6.6, 95% CI 2.8-15.4), Palliative Performance Scale score more than 40 (OR 4.4, 95% CI 2.1-9.3), absence of drowsiness (OR 3.4, 95% CI 1.7-6.9), absence of ascites (OR 2.3, 95% CI 1.1-4.7), and absence of pleural effusion (OR 2.2, 95% CI 1.0-5.0). Treatment responses to corticosteroids for CRF may be predicted by baseline symptom intensity, performance status, drowsiness, and severity of fluid retention symptoms. Larger prospective studies are needed to confirm these results. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  14. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: A randomized controlled open-label trial

    PubMed Central

    Adenis, A.; Blay, J.-Y.; Bui-Nguyen, B.; Bouché, O.; Bertucci, F.; Isambert, N.; Bompas, E.; Chaigneau, L.; Domont, J.; Ray-Coquard, I.; Blésius, A.; Van Tine, B. A.; Bulusu, V. R.; Dubreuil, P.; Mansfield, C. D.; Acin, Y.; Moussy, A.; Hermine, O.; Le Cesne, A.

    2014-01-01

    Background Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. Patients and methods Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. Results Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09–0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16–0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6–2.2, P

  15. Evaluation of Advanced Access in the National Primary Care Collaborative

    PubMed Central

    Pickin, Mark; O'Cathain, Alicia; Sampson, Fiona C; Dixon, Simon

    2004-01-01

    Background: An aim of the National Primary Care Collaborative is to improve quality and access for patients in primary care using principles of Advanced Access. Aims: To determine whether Advanced Access led to improved availability of appointments with general practitioners (GPs) and to examine GPs' views of the process. Design: Observational study. Setting: Four hundred and sixty-two general practices in England participating in four waves of the collaborative during 2000 and 2001. Method: Regression analysis of the collaborative's monthly data on the availability of GP appointments for the 352 practices in waves 1–3, and a postal survey of lead GPs in all four waves. The main outcome measures were the change in mean time to the third available appointment with GPs, and the proportion of GPs thinking it worthwhile participating in the collaborative. Results: The time to the third available appointment improved from a mean of 3.6 to 1.9 days, difference = 1.7 days, 95% confidence interval (CI) = 1.4 to 2.0 days. It improved in two-thirds of practices (66% [219/331]), remained the same in 16% (53/331), and worsened in 18% (59/331). The majority of GPs in all four waves, 83% (308/371, 95% CI = 79 to 87), felt that it was worthwhile participating in the collaborative, although one in 12 practices would not recommend it. One-fifth of GPs cited a lack of resources as a constraint, and some expressed concerns about the trade-off between immediate access and continuity of care. Conclusion: Advanced Access helped practices to improve availability of GP appointments, and was well received by the majority of practices. PMID:15113514

  16. The radiation shielding potential of CI and CM chondrites

    NASA Astrophysics Data System (ADS)

    Pohl, Leos; Britt, Daniel T.

    2017-03-01

    Galactic Cosmic Rays (GCRs) and Solar Energetic Particles (SEPs) pose a serious limit on the duration of deep space human missions. A shield composed of a bulk mass of material in which the incident particles deposit their energy is the simplest way to attenuate the radiation. The cost of bringing the sufficient mass from the Earth's surface is prohibitive. The shielding properties of asteroidal material, which is readily available in space, are investigated. Solution of Bethe's equation is implemented for incident protons and the application in composite materials and the significance of various correction terms are discussed; the density correction is implemented. The solution is benchmarked and shows good agreement with the results in literature which implement more correction terms within the energy ranges considered. The shielding properties of CI and CM asteroidal taxonomy groups and major asteroidal minerals are presented in terms of stopping force. The results show that CI and CM chondrites have better stopping properties than Aluminium. Beneficiation is discussed and is shown to have a significant effect on the stopping power.

  17. The Bionic Amoeba.

    ERIC Educational Resources Information Center

    Wright, Emmett L.

    1979-01-01

    A demonstration is described that encourages students to engage in inquiry in biology. Using chemicals and an overhead projector, the instructor can simulate a living organism projected onto a screen. The reaction can aid students in defining the characteristics of life. (SA)

  18. Efficacy of Addition of Antiangiogenic Agents to Taxanes-Containing Chemotherapy in Advanced Nonsmall-Cell Lung Cancer

    PubMed Central

    Sheng, Jin; Yang, Yun-Peng; Yang, Bi-Jun; Zhao, Yuan-Yuan; Ma, Yu-Xiang; Hong, Shao-Dong; Zhang, Ya-Xiong; Zhao, Hong-Yun; Huang, Yan; Zhang, Li

    2015-01-01

    Abstract Preclinical researches indicated a potential synergistic effect of taxanes-containing chemotherapy (TCC) and antiangiogenic agents (AAs) on the treatment of advanced nonsmall-cell lung cancer (NSCLC). The advantage of adding AA to TCC in the real world remains confusing. We summarized the current evidences from relevant phase II/III randomized controlled trials (RCTs) by performing this meta-analyses. Electronic databases were searched for eligible literatures. The primary endpoint was overall survival (OS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were calculated using RevMan 5.2. A total of 14 phase II/III RCTs involving 9703 participants were included. Compared to standard TCC, the addition of AA was associated with the significant better OS (HR 0.92, 95% CI 0.87–0.97, P = 0.002), prolonged progression-free survival (HR 0.79, 95% CI 0.71–0.87, P < 0.00001), superior response rate (risk ratio [RR] 1.69, 95% CI 1.47–1.95, P < 0.0001), and disease control rate (RR 1.19, 95% CI 1.08–1.32, P < 0.00001). Subgroup analyses indicated that patient treated with monoclonal antibodies (HR 0.89, 95% CI 0.82–0.96, P = 0.02) as well as application in second-line (HR 0.91, 95% CI 0.85–0.96, P = 0.02) acquired significant OS improvement. Other clinical factors directing significant OS improvement by the combination strategy included nonsquamous cancer (P = 0.002), nonsmokers (P = 0.0005), and female (P = 0.02). Toxicities were greater but generally mild or moderate in the combination group, and were mostly manageable. In summary, the addition of AAs to TCC could improve prognosis of advanced NSCLC. Furthermore, proper selection of patient population and AAs is crucial for clinical trials design and clinical practice in the future. PMID:26252298

  19. Missed opportunities for earlier diagnosis of HIV in patients who presented with advanced HIV disease: a retrospective cohort study

    PubMed Central

    Levy, Itzchak; Maor, Yasmin; Mahroum, Naim; Olmer, Liraz; Wieder, Anat; Litchevski, Vladislav; Mor, Orna; Rahav, Galia

    2016-01-01

    Objective To quantify and characterise missed opportunities for earlier HIV diagnosis in patients diagnosed with advanced HIV. Design A retrospective observational cohort study. Setting A central tertiary medical centre in Israel. Measures The proportion of patients with advanced HIV, the proportion of missed opportunities to diagnose them earlier, and the rate of clinical indicator diseases (CIDs) in those patients. Results Between 2010 and 2015, 356 patients were diagnosed with HIV, 118 (33.4%) were diagnosed late, 57 (16%) with advanced HIV disease. Old age (OR=1.45 (95% CI 1.16 to 1.74)) and being heterosexual (OR=2.65 (95% CI 1.21 to 5.78)) were significant risk factors for being diagnosed late. All patients with advanced disease had at least one CID that did not lead to an HIV test in the 5 years prior to AIDS diagnosis. The median time between CID and AIDS diagnosis was 24 months (IQR 10–30). 60% of CIDs were missed by a general practitioner and 40% by a specialist. Conclusions Missed opportunities to early diagnosis of HIV occur in primary and secondary care. Lack of national guidelines, lack of knowledge regarding CIDs and communication barriers with patients may contribute to a late diagnosis of HIV. PMID:28186940

  20. Feasibility of cytological specimens for ALK fusion detection in patients with advanced NSCLC using the method of RT-PCR.

    PubMed

    Wang, Yan; Liu, Yu; Zhao, Chao; Li, Xuefei; Wu, Chunyan; Hou, Likun; Zhang, Shijia; Jiang, Tao; Chen, Xiaoxia; Su, Chunxia; Gao, Guanghui; Li, Wei; Wu, Fengying; Li, Aiwu; Ren, Shengxiang; Zhou, Caicun; Zhang, Jun

    2016-04-01

    Histological tissues are preferred for anaplastic lymphoma kinase (ALK) fusion detection in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the feasibility of cytological sample as an alternative specimen for ALK fusion testing in patients with advanced NSCLC. Advanced NSCLC patients with cytological specimens or tumor tissue who had their ALK fusion status detected by the method of reverse transcriptase polymerase chain reaction (RT-PCR) in Shanghai Pulmonary Hospital, Tongji University were included into this study. The efficacy was evaluated in those with ALK fusion positive and received the therapy of crizotinib. 1274 patients were included in this study. Among them, 108 patients were ALK RT-PCR positive and 69 of them received crizotinib treatment. Among 1002 patients with cytological specimens, the average concentration of RNA extracted from cytological specimens was 60.99 ng/μl (95% confidence interval [CI], 55.56-66.60) and the incidence rate of ALK fusion was 8.3% (83/1002), which were similar to 63.16 ng/μl (95% CI, 51.88-76.34) (p=0.727) and 9.2% (25/272, p=0.624) in 272 patients with tumor tissue. Also, there were no statistically significant differences regarding to the objective response rate (ORR) (62.0% vs. 42.1%, p=0.177) and the median progression free survival (mPFS) [8.6 months (95% CI 7.30-9.84) vs. 7.0 months (95% CI 4.54-9.47), p=0.736] in patients of cytological group and tissue group after the treatment of crizotinib. Cytological specimens showed a high feasibility to detect ALK fusion status, which could be regarded as alternative samples for ALK fusion detection by the method of RT-PCR in patients with advanced NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Ingress observations of the 1980 eclipse of the symbiotic star CI Cyngni

    NASA Technical Reports Server (NTRS)

    Stencel, R. E.; Michalitsianos, A. G.; Kafatos, M.; Boyarchuk, A. A.

    1981-01-01

    One of the major results from the IUE may prove to be the knowledge gained by studies of the ultraviolet spectra of symbiotic stars. Symbiotics combine spectral features of a cool M giant like photosphere with strong high excitation emission lines of nebular origin, superposed. The UV spectra are dominated by intense permitted and semiforbidden emission lines and weak continua indicative of hot compact objects and accretion disks. Two symbiotics, AR Pav and CI Cyg are thought to be eclipsing binaries and IUE observations during the 1980 eclipse of CI Cygni are discussed.

  2. In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia.

    PubMed

    Radujkovic, Aleksandar; Luft, Thomas; Dreger, Peter; Ho, Anthony D; Jens Zeller, W; Fruehauf, Stefan; Topaly, Julian

    2014-08-01

    The prognosis of patients with advanced-phase chronic myeloid leukemia (CML) remains dismal despite the availability of targeted therapies and allogeneic stem cell transplantation (allo-SCT). Increasing the antileukemic efficacy of the pretransplant conditioning regimen may be a strategy to increase remission rates and duration. We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan. Drug combinations were tested in vitro in different imatinib-sensitive and imatinib-resistant BCR-ABL-positive cell lines. A tetrazolium-based MTT assay was used for the assessment and quantification of growth inhibition after exposure to alkylating agents alone or to combinations with nilotinib. Drug interaction was analyzed using the median-effect method of Chou and Talalay, and combination index (CI) values were calculated according to the classic isobologram equation. Treatment of imatinib-sensitive, BCR-ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI < 1), additive (CI ~ 1), and predominantly antagonistic (CI > 1) effects, respectively. In imatinib-resistant K562-R and LAMA84-R cells, all applied drug combinations were synergistic (CI < 1) at higher growth inhibition levels. Our in vitro data warrant further investigation and may provide the basis for nilotinib-supplemented conditioning regimens for allo-SCT in advanced-phase CML.

  3. Simple score to predict risk of hepatocellular carcinoma in chronic hepatitis C patients with advanced fibrosis after pegylated interferon and ribavirin therapy.

    PubMed

    Hu, Ching-Chih; Weng, Cheng-Hao; Chang, Liang-Che; Lin, Chih-Lang; Chen, Yen-Ting; Hu, Ching-Fang; Hua, Man-Chin; Chen, Li-Wei; Chien, Rong-Nan

    2018-01-01

    Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups. The median observation duration was 6.0 years (range: 0.9-12.6 years). The HCC prevalence after pegIFN and RBV therapy in CHC patients with sustained virologic response (SVR) and without SVR was 14.7% and 32.2%, respectively. Multivariate Cox regression showed age ≥59.5 years old at initiation of therapy (HR: 2.542, 95% CI: 1.390-4.650, P =0.002), pretreatment total bilirubin ≥1.1 mg/dL (HR: 2.630, 95% CI: 1.420-4.871, P =0.002), pretreatment platelet counts <146.5 × 10 3 /μL (HR: 2.751, 95% CI: 1.373-5.511, P =0.004), no achievement of SVR (HR: 2.331, 95% CI: 1.277-4.253, P =0.006), and no diabetes at treatment initiation (HR: 3.085, 95% CI: 1.283-7.418, P =0.012) were significant predictors of HCC development. The scoring model consisted of the five categorical predictors and had an optimal cutoff point of 2.5. The area under receiver operating characteristic (AUROC) of the scoring model was 0.774±0.035 ( P <0.001). The sensitivity and specificity of the cutoff value to detect HCC were 81.3% and 57.5%. The 5-year and 10-year cumulative incidence of HCC was 4.9% and 10.0% in patients with simple score ≤2; and 25.9% and 44.6% in patients with simple score ≥3 ( P <0.001). The simple clinical-guided score has high discriminatory power for HCC prediction in advanced fibrotic CHC patients after pegIFN and RBV therapy.

  4. Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas

    PubMed Central

    de Masson, Adèle; Beylot-Barry, Marie; Bouaziz, Jean-David; de Latour, Régis Peffault; Aubin, François; Garciaz, Sylvain; d’Incan, Michel; Dereure, Olivier; Dalle, Stéphane; Dompmartin, Anne; Suarez, Felipe; Battistella, Maxime; Vignon-Pennamen, Marie-Dominique; Rivet, Jacqueline; Adamski, Henri; Brice, Pauline; François, Sylvie; Lissandre, Séverine; Turlure, Pascal; Wierzbicka-Hainaut, Ewa; Brissot, Eolia; Dulery, Rémy; Servais, Sophie; Ravinet, Aurélie; Tabrizi, Reza; Ingen-Housz-Oro, Saskia; Joly, Pascal; Socié, Gérard; Bagot, Martine

    2014-01-01

    The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38–0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41–0.77) and progression-free survival 31% (95%CI: 0.19–0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1–0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3–6.2; P=0.01) but also transplant-related mortality (HR=10−7, 95%CI: 4.10−8–2.10−7; P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides. PMID:24213148

  5. Protein-energy wasting syndrome in advanced chronic kidney disease: prevalence and specific clinical characteristics.

    PubMed

    Pérez-Torres, Almudena; González Garcia, M Elena; San José-Valiente, Belén; Bajo Rubio, M Auxiliadora; Celadilla Diez, Olga; López-Sobaler, Ana M; Selgas, Rafael

    Protein-energy wasting (PEW) is associated with increased mortality and differs depending on the chronic kidney disease (CKD) stage and the dialysis technique. The prevalence in non-dialysis patients is understudied and ranges from 0 to 40.8%. To evaluate the nutritional status of a group of Spanish advanced CKD patients by PEW criteria and subjective global assessment (SGA). Cross-sectional study of 186 patients (101 men) with a mean age of 66.1±16 years. The nutritional assessment consisted of: SGA, PEW criteria, 3-day dietary records, anthropometric parameters and bioelectrical impedance vector analysis. The prevalence of PEW was 30.1%, with significant differences between men and women (22.8 vs. 33.8%, p < 0.005), while 27.9% of SGA values were within the range of malnutrition. No differences were found between the 2methods. Men had higher proteinuria, percentage of muscle mass and nutrient intake. Women had higher levels of total cholesterol, HDL and a higher body fat percentage. The characteristics of patients with PEW were low albumin levels and a low total lymphocyte count, high proteinuria, low fat and muscle mass and a high Na/K ratio. The multivariate analysis found PEW to be associated with: proteinuria (OR: 1.257; 95% CI: 1.084-1.457, p=0.002), percentage of fat intake (OR: 0.903; 95% CI: 0.893-0.983, p=0.008), total lymphocyte count (OR: 0.999; 95% CI: 0.998-0.999, p=0.001) and cell mass index (OR: 0.995; 95% CI: 0.992-0.998). Malnutrition was identified in Spanish advanced CKD patients measured by different tools. We consider it appropriate to adapt new diagnostic elements to PEW criteria. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  6. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer.

    PubMed

    Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

    2016-01-01

    Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi'an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2-11.8 months), and median overall survival was 21.0 months (95% CI: 20.1-21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation.

  7. SLA: A Time for New Initiatives-- CI Division Formed, Fundraising Goal Set, Certification Coming

    ERIC Educational Resources Information Center

    DiMattia, Susan; Blumenstein, Lynn

    2004-01-01

    Several initiatives were announced at the Special Libraries Association (d.b.a. SLA) conference, June 4-9, at the Gaylord Opryland Hotel in Nashville. A petition drive resulted in formation of a Competitive Intelligence (CI) Division from the former CI Section of the Leadership and Management Division. The board encouraged the member-driven…

  8. Apatinib for advanced nonsmall-cell lung cancer: A retrospective case series analysis.

    PubMed

    Yang, Chengxi; Feng, Wen; Wu, Di

    2018-01-01

    Apatinib, a tyrosine kinase inhibitor which selectively inhibits vascular endothelial growth factor receptor-2, has been shown to be beneficial to patients with a variety of cancers, including advanced nonsmall-cell lung cancer (NSCLC). Thus, this study was aimed to retrospectively assess the efficacy and safety of apatinib in patients with advanced/metastatic NSCLC who failed more than two lines of treatment. Twenty-three NSCLC patients were involved in this study, who received oral apatinib at a daily dose of 250/500/750 mg, with the progression after the failure of second-line therapy. Treatment was continued until disease progression. The tumor assessments were determined according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Safety was evaluated with adverse reactions and toxicities based on the Common Terminology Criteria for Adverse Events (version 4.0). Response and safety for the included patients were evaluated every 8 weeks. In this study, 23 NSCLC patients were followed from January 2015 to December 2016. Available image efficacy was obtained in 22 patients, including 4 identified as partial responses, 17 stable disease, and 1 progressive disease; no complete responses was observed. The objective response rate was 18.2%, and the disease control rate was 95.5%. Median progression free survival and overall survival for apatinib were 203 days (95% CI, 120-269) and 227 days (95% CI, 146-294), respectively. The most frequent treatment-related adverse events were hypertension, gastrointestinal reactions, and hand-foot skin reaction. Apatinib exhibited modest activity and acceptable toxicity for advanced NSCLC after the failure of chemotherapy or other targeted therapy.

  9. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp; Ioka, Tatsuya; Ito, Yoshinori

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received amore » maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.« less

  10. Effects of Exercise on Functional Performance and Fall Rate in Subjects with Mild or Advanced Alzheimer's Disease: Secondary Analyses of a Randomized Controlled Study.

    PubMed

    Öhman, Hannareeta; Savikko, Niina; Strandberg, Timo; Kautiainen, Hannu; Raivio, Minna; Laakkonen, Marja-Liisa; Tilvis, Reijo; Pitkälä, Kaisu H

    2016-01-01

    Exercise improves functional performance in subjects with dementia. However, whether the benefits of exercise are evident in all stages of dementia remains uncertain. This study examines how people in different stages of Alzheimer's disease (AD) benefit from exercise intervention in their physical functioning and risk of falling. The present study is a subanalysis of a randomized controlled trial examining the effects of exercise intervention (twice a week for 12 months) in AD patients (n = 194). We studied the effects separately in participants with mild dementia and in participants with advanced dementia. In subjects with mild dementia, the deterioration in physical functioning was slower in the intervention group than in the controls. Changes in Functional Independence Measure at 12 months were -2.7 (95% CI -0.5 to -4.9) in the intervention group and -10.1 (95% CI -7.0 to -13.3) in the control group (p < 0.001). The exercise intervention proved effective in preventing falls among patients with advanced AD, with an incidence rate ratio of 0.47 (95% CI 0.37-0.60; p < 0.001). Regular exercise may slow the rate of functional deterioration in mild AD and reduce falls in patients suffering from advanced AD. © 2016 S. Karger AG, Basel.

  11. Oxygen, Magnesium, and Aluminum Isotopes in the Ivuna CAI: Re-Examining High-Temperature Fractionations in CI Chondrites

    NASA Astrophysics Data System (ADS)

    Frank, D. R.; Huss, G. R.; Nagashima, K.; Zolensky, M. E.; Le, L.

    2017-07-01

    The only whole CAI preserved in the aqueously altered CI chondrites is 16O-rich and has no resolvable radiogenic Mg. Accretion of CAIs by the CI parent object(s) may limit the precision of cosmochemical models that require a CI starting composition.

  12. A comparison of diagnostic imaging ordering patterns between advanced practice clinicians and primary care physicians following office-based evaluation and management visits.

    PubMed

    Hughes, Danny R; Jiang, Miao; Duszak, Richard

    2015-01-01

    Little is known about the use of diagnostic testing, such as medical imaging, by advanced practice clinicians (APCs), specifically, nurse practitioners and physician assistants. To examine the use of diagnostic imaging ordered by APCs relative to that of primary care physicians (PCPs) following office-based encounters. Using 2010-2011 Medicare claims for a 5% sample of beneficiaries, we compared diagnostic imaging ordering between APC and PCP episodes of care, controlling for geographic variation, patient demographics, and Charlson Comorbidity Index scores. Provider specialty codes were used to identify PCPs and APCs (general practice, family practice, or internal medicine for PCP; nurse practitioner or physician assistant for APC). Episodes were constructed using evaluation and management (E&M) office visits without any claims 30 days prior to the index visit and (1) no claims at all within the subsequent 30 days; (2) no claims within the subsequent 30 days other than a single imaging event; or (3) claims for any nonimaging services in that subsequent 30-day period. The primary outcome was whether an imaging event followed a qualifying E&M visit. Advanced practice clinicians and PCPs ordered imaging in 2.8% and 1.9% episodes of care, respectively. In adjusted estimates and across all patient groups and imaging services, APCs were associated with more imaging than PCPs (odds ratio [OR], 1.34 [95% CI, 1.27-1.42]), ordering 0.3% more images per episode. Advanced practice clinicians were associated with increased radiography orders on both new (OR, 1.36 [95% CI, 1.13-1.66]) and established (OR, 1.33 [95% CI, 1.24-1.43]) patients, ordering 0.3% and 0.2% more images per episode of care, respectively. For advanced imaging, APCs were associated with increased imaging on established patients (OR, 1.28 [95% CI, 1.14-1.44]), ordering 0.1% more images, but were not significantly different from PCPs ordering imaging on new patients. Advanced practice clinicians are associated

  13. Prognostic role of cardiac power index in ambulatory patients with advanced heart failure.

    PubMed

    Grodin, Justin L; Mullens, Wilfried; Dupont, Matthias; Wu, Yuping; Taylor, David O; Starling, Randall C; Tang, W H Wilson

    2015-07-01

    Cardiac pump function is often quantified by left ventricular ejection fraction by various imaging modalities. As the heart is commonly conceptualized as a hydraulic pump, cardiac power describes the hydraulic function of the heart. We aim to describe the prognostic value of resting cardiac power index (CPI) in ambulatory patients with advanced heart failure. We calculated CPI in 495 sequential ambulatory patients with advanced heart failure who underwent invasive haemodynamic assessment with longitudinal follow-up of adverse outcomes (all-cause mortality, cardiac transplantation, or ventricular assist device placement). The median CPI was 0.44 W/m(2) (interquartile range 0.37, 0.52). Over a median of 3.3 years, there were 117 deaths, 104 transplants, and 20 ventricular assist device placements in our cohort. Diminished CPI (<0.44 W/m(2) ) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P < 0.0001). The prognostic value of CPI remained significant after adjustment for age, gender, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, left ventricular ejection fraction, and creatinine [HR 1.5, 95% CI 1.03-2.3, P = 0.04). Furthermore, CPI can risk stratify independently of peak oxygen consumption (HR 2.2, 95% CI 1.4-3.4, P = 0.0003). Resting cardiac power index provides independent and incremental prediction in adverse outcomes beyond traditional haemodynamic and cardio-renal risk factors. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

  14. The Accuracy of Physicians' Clinical Predictions of Survival in Patients With Advanced Cancer.

    PubMed

    Amano, Koji; Maeda, Isseki; Shimoyama, Satofumi; Shinjo, Takuya; Shirayama, Hiroto; Yamada, Takeshi; Ono, Shigeki; Yamamoto, Ryo; Yamamoto, Naoki; Shishido, Hideki; Shimizu, Mie; Kawahara, Masanori; Aoki, Shigeru; Demizu, Akira; Goshima, Masahiro; Goto, Keiji; Gyoda, Yasuaki; Hashimoto, Kotaro; Otomo, Sen; Sekimoto, Masako; Shibata, Takemi; Sugimoto, Yuka; Morita, Tatsuya

    2015-08-01

    Accurate prognoses are needed for patients with advanced cancer. To evaluate the accuracy of physicians' clinical predictions of survival (CPS) and assess the relationship between CPS and actual survival (AS) in patients with advanced cancer in palliative care units, hospital palliative care teams, and home palliative care services, as well as those receiving chemotherapy. This was a multicenter prospective cohort study conducted in 58 palliative care service centers in Japan. The palliative care physicians evaluated patients on the first day of admission and followed up all patients to their death or six months after enrollment. We evaluated the accuracy of CPS and assessed the relationship between CPS and AS in the four groups. We obtained a total of 2036 patients: 470, 764, 404, and 398 in hospital palliative care teams, palliative care units, home palliative care services, and chemotherapy, respectively. The proportion of accurate CPS (0.67-1.33 times AS) was 35% (95% CI 33-37%) in the total sample and ranged from 32% to 39% in each setting. While the proportion of patients living longer than CPS (pessimistic CPS) was 20% (95% CI 18-22%) in the total sample, ranging from 15% to 23% in each setting, the proportion of patients living shorter than CPS (optimistic CPS) was 45% (95% CI 43-47%) in the total sample, ranging from 43% to 49% in each setting. Physicians tend to overestimate when predicting survival in all palliative care patients, including those receiving chemotherapy. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  15. Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.

    PubMed

    Gettinger, Scott; Rizvi, Naiyer A; Chow, Laura Q; Borghaei, Hossein; Brahmer, Julie; Ready, Neal; Gerber, David E; Shepherd, Frances A; Antonia, Scott; Goldman, Jonathan W; Juergens, Rosalyn A; Laurie, Scott A; Nathan, Faith E; Shen, Yun; Harbison, Christopher T; Hellmann, Matthew D

    2016-09-01

    Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD-ligand 1 expression and 14% (two of 14) in patients with no PD-ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively. First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC. © 2016 by American Society of Clinical Oncology.

  16. Staging laparoscopy improves treatment decision-making for advanced gastric cancer.

    PubMed

    Hu, Yan-Feng; Deng, Zhen-Wei; Liu, Hao; Mou, Ting-Yu; Chen, Tao; Lu, Xin; Wang, Da; Yu, Jiang; Li, Guo-Xin

    2016-02-07

    To evaluate the clinical value of staging laparoscopy in treatment decision-making for advanced gastric cancer (GC). Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A χ(2) test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics. Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P < 0.05) for staging laparoscopy; compared with CT and EUS, which was in fair agreement. The strength of agreement between preoperative M stage and final M stage was in almost perfect agreement (Kw = 0.990; 95% CI: 0.977-1.000; P < 0.05) for staging laparoscopy; compared with CT, which was in slight agreement. Multivariate analysis revealed that tumor size (≥ 40 mm), depth of tumor invasion (T4b), and Borrmann type (III or IV) were significantly correlated with either peritoneal metastasis or positive cytology. The best performance in diagnosing P-positive was obtained when two or three risk factors existed. Staging laparoscopy can improve treatment decision-making for advanced GC and decrease unnecessary exploratory laparotomy.

  17. An efficient approach to CI: General matrix element formulas for spin-coupled particle-hole excitations

    NASA Astrophysics Data System (ADS)

    Tavan, Paul; Schulten, Klaus

    1980-03-01

    A new, efficient algorithm for the evaluation of the matrix elements of the CI Hamiltonian in the basis of spin-coupled ν-fold excitations (over orthonormal orbitals) is developed for even electron systems. For this purpose we construct an orthonormal, spin-adapted CI basis in the framework of second quantization. As a prerequisite, spin and space parts of the fermion operators have to be separated; this makes it possible to introduce the representation theory of the permutation group. The ν-fold excitation operators are Serber spin-coupled products of particle-hole excitations. This construction is also designed for CI calculations from multireference (open-shell) states. The 2N-electron Hamiltonian is expanded in terms of spin-coupled particle-hole operators which map any ν-fold excitation on ν-, and ν±1-, and ν±2-fold excitations. For the calculation of the CI matrix this leaves one with only the evaluation of overlap matrix elements between spin-coupled excitations. This leads to a set of ten general matrix element formulas which contain Serber representation matrices of the permutation group Sν×Sν as parameters. Because of the Serber structure of the CI basis these group-theoretical parameters are kept to a minimum such that they can be stored readily in the central memory of a computer for ν?4 and even for higher excitations. As the computational effort required to obtain the CI matrix elements from the general formulas is very small, the algorithm presented appears to constitute for even electron systems a promising alternative to existing CI methods for multiply excited configurations, e.g., the unitary group approach. Our method makes possible the adaptation of spatial symmetries and the selection of any subset of configurations. The algorithm has been implemented in a computer program and tested extensively for ν?4 and singlet ground and excited states.

  18. Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury.

    PubMed

    James, Matthew T; Pannu, Neesh; Hemmelgarn, Brenda R; Austin, Peter C; Tan, Zhi; McArthur, Eric; Manns, Braden J; Tonelli, Marcello; Wald, Ron; Quinn, Robert R; Ravani, Pietro; Garg, Amit X

    2017-11-14

    serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%). A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research.

  19. Determinants of Patient-Oncologist Prognostic Discordance in Advanced Cancer

    PubMed Central

    Gramling, Robert; Fiscella, Kevin; Xing, Guibo; Hoerger, Michael; Duberstein, Paul; Plumb, Sandy; Mohile, Supriya; Fenton, Joshua J.; Tancredi, Daniel J.; Kravitz, Richard L.; Epstein, Ronald M.

    2018-01-01

    IMPORTANCE Patients with advanced cancer often report expectations for survival that differ from their oncologists’ expectations. Whether patients know that their survival expectations differ from those of their oncologists remains unknown. This distinction is important because knowingly expressing differences of opinion is important for shared decision making, whereas patients not knowing that their understanding differs from that of their treating physician is a potential marker of inadequate communication. OBJECTIVE To describe the prevalence, distribution, and proportion of prognostic discordance that is due to patients’ knowingly vs unknowingly expressing an opinion that differs from that of their oncologist. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study conducted at academic and community oncology practices in Rochester, New York, and Sacramento, California. The sample comprises 236 patients with advanced cancer and their 38 oncologists who participated in a randomized trial of an intervention to improve clinical communication. Participants were enrolled from August 2012 to June 2014 and followed up until October 2015. MAIN OUTCOMES AND MEASURES We ascertained discordance by comparing patient and oncologist ratings of 2-year survival probability. For discordant pairs, we determined whether patients knew that their opinions differed from those of their oncologists by asking the patients to report how they believed their oncologists rated their 2-year survival. RESULTS Among the 236 patients (mean [SD] age, 64.5 [11.4] years; 54%female), 161 patient-oncologist survival prognosis ratings (68%; 95%CI, 62%–75%) were discordant. Discordance was substantially more common among nonwhite patients compared with white patients (95%[95%CI, 86%–100%] vs 65%[95%CI, 58%–73%], respectively; P = .03). Among 161 discordant patients, 144 (89%) did not know that their opinions differed from that of their oncologists and nearly all of them (155 of 161 [96

  20. Observations of CI Cam needed to support spectroscopy

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2016-10-01

    Kelly Gourdji and Marcella Wijngaarden (graduate students at the University of Amsterdam/Anton Pannekoek Institute for Astronomy) have requested AAVSO observers' assistance in providing optical photometry of CI Cam in support of their high-resolution spectroscopy from now through January 2017. They write: "...We are currently observing the variable star CI Cam (the B[e] optical counterpart of a HMXB system) with the HERMES spectrograph at the Mercator Telescope in La Palma. Having observed the star for three nights now, the object appears to be in outburst. In particular, H alpha was measured to be 80 times the continuum flux, and increasing between Oct. 9 and 12. This is similar to the previous outburst in 2004/5. Photometric data obtained during the 2004/5 outburst suggested an outburst duration of about 3 months and a peak brightness of 11.2 in the V band." More information is available in ATel #9634 (Wijngaarden et al.). Multiple snapshot observations per night in BVRI are requested beginning immediately and continuing through January 2017. Time series are not necessary unless requested later via an AAVSO Special Notice. Observations made using other filters will be useful as well as long as there are multiple observations in these bands. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (https://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details.

  1. Clinical response to apatinib monotherapy in advanced non-small cell lung cancer.

    PubMed

    Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

    2018-06-01

    Apatinib, an oral tyrosine kinase inhibitor mainly targeting VEGFR-2, exerts both antiangiogenesis and antiproliferation effects. Apatinib shows clinical benefit in advanced non-small cell lung cancer (NSCLC) at an initial dose of 750 mg qd. We further assessed the efficacy and safety of apatinib at a more frequently used dose of 500 mg qd. The preliminary clinical outcome of apatinib in patients with brain metastases was also reported. We retrospectively reviewed the clinical data of 25 patients who received apatinib between August 2015 and May 2016. Progression-free survival (PFS) was calculated by using the Kaplan-Meier method. The objective response rate and disease control rate were 8.0% and 68.0%, respectively. The median PFS was 5.17 (95% confidence interval [CI]: 0.76-9.57) months. In the second-line setting (n = 13), the median PFS was 7.37 (95% CI: 0.01-14.72) months, whereas the median PFS for the 12 patients treated with apatinib as third line or beyond therapy was 5.17 (95% CI: 1.78-8.55) months. Of the seven patients with brain metastases, four patients had stable disease. All patients were well tolerant to apatinib without any grade 3 or 4 adverse events. The most common grade 1 or 2 adverse events included hypertension (72.0%), hand-foot-skin reaction (24.0%), fatigue (24.0%) and abnormal liver function (20.0%). Apatinib is effective and well tolerated in patients with advanced NSCLC, even at a dosage of 500 mg qd, and might offer a new option for the treatment of such patients with brain metastases. © 2017 John Wiley & Sons Australia, Ltd.

  2. High-volume ovarian cancer care: survival impact and disparities in access for advanced-stage disease.

    PubMed

    Bristow, Robert E; Chang, Jenny; Ziogas, Argyrios; Randall, Leslie M; Anton-Culver, Hoda

    2014-02-01

    To characterize the impact of hospital and physician ovarian cancer case volume on survival for advanced-stage disease and investigate socio-demographic variables associated with access to high-volume providers. Consecutive patients with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) were identified from the California Cancer Registry. Disease-specific survival analysis was performed using Cox-proportional hazards model. Multivariate logistic regression analyses were used to evaluate for differences in access to high-volume hospitals (HVH) (≥20 cases/year), high-volume physicians (HVP) (≥10 cases/year), and cross-tabulations of high- or low-volume hospital (LVH) and physician (LVP) according to socio-demographic variables. A total of 11,865 patients were identified. The median ovarian cancer-specific survival for all patients was 28.2 months, and on multivariate analysis the HVH/HVP provider combination (HR = 1.00) was associated with superior ovarian cancer-specific survival compared to LVH/LVP (HR = 1.31, 95%CI = 1.16-1.49). Overall, 2119 patients (17.9%) were cared for at HVHs, and 1791 patients (15.1%) were treated by HVPs. Only 4.3% of patients received care from HVH/HVP, while 53.1% of patients were treated by LVH/LVP. Both race and socio-demographic characteristics were independently associated with an increased likelihood of being cared for by the LVH/LVP combination and included: Hispanic race (OR = 1.72, 95%CI = 1.22-2.42), Asian/Pacific Islander race (OR = 1.57, 95%CI = 1.07-2.32), Medicaid insurance (OR = 2.51, 95%CI = 1.46-4.30), and low socioeconomic status (OR = 2.84, 95%CI = 1.90-4.23). Among patients with advanced-stage ovarian cancer, the provider combination of HVH/HVP is an independent predictor of improved disease-specific survival. Access to high-volume ovarian cancer providers is limited, and barriers are more pronounced for patients with low socioeconomic status, Medicaid insurance, and racial minorities. Copyright © 2013

  3. SWOG S0722: phase II study of mTOR inhibitor everolimus (RAD001) in advanced malignant pleural mesothelioma (MPM).

    PubMed

    Ou, Sai-Hong Ignatius; Moon, James; Garland, Linda L; Mack, Philip C; Testa, Joseph R; Tsao, Anne S; Wozniak, Antoniette J; Gandara, David R

    2015-02-01

    The PI3K/Akt/mammalian target of rapamycin pathway is activated in a majority of malignant pleural mesotheliomas (MPM). We evaluated the activity of everolimus, an oral mammalian target of rapamycin inhibitor, in patients with unresectable MPM. MPM patients who had received at least one but no more than two prior chemotherapy regimens, which must have been platinum-based, were treated with 10 mg of everolimus daily. The primary endpoint was 4-month progression-free survival (PFS) by RECIST 1.1. A total of 59 evaluable patients were included in the analysis. The median duration of treatment was 2 cycles (56 days). Overall response rate was 2% [95% confidence interval (CI): 0-12%] by RECIST 1.1 and 0% (0-10%) by modified RECIST for MPM. The 4-month PFS rate was 29% (95% CI: 17-41%) by RECIST 1.1, and 27% (95% CI: 16-39%) by modified RECIST. The median PFS was 2.8 months (95% CI: 1.8-3.4) by RECIST 1.1. The median overall survival was 6.3 months (95% CI: 4.0-8.0). There was no difference in PFS among patients who received one or two prior chemotherapy regimens (p = 0.74). There was no difference in overall survival between patients with epithelioid histology versus other types (p = 0.47). The most common toxicities were fatigue (59%), hypertriglyceridemia (44%), anemia (42%), oral mucositis (34%), nausea (32%), and anorexia (32%). The most common grade 3 to 4 toxicities were fatigue (10.2%), anemia (6.8%), and lung infection (6.8%). Everolimus has limited clinical activity in advanced MPM patients. Additional studies of single-agent everolimus in advanced MPM are not warranted.

  4. CI+MBPT calculations of Ar I energies, g factors, and transition line strengths

    NASA Astrophysics Data System (ADS)

    Savukov, I. M.

    2018-03-01

    Excited states of noble gas atoms present certain challenges to atomic theory for several reasons: first, relativistic effects are important and LS coupling is not optimal; second, energy intervals can be quite small, leading to strong mixing of states; third, many-body perturbation theory for hole states does not converge well. Previously, some attempts were made to solve this problem, using for example the all-order coupled-cluster approach and particle-hole configuration-interaction many-body perturbation theory (CI-MBPT) with modified denominators. However, while these approaches were promising, the accuracy was still limited. In this paper, we calculate Ar I energies, g factors, and transition amplitudes using ab initio CI-MBPT with eight valence electrons to avoid the problem of slow convergence of MBPT due to strong interaction between 3p and 3s states. We also included in CI many dominant states obtained by double excitations of the ground state configuration. Thus perturbation corrections were needed only for 1s, 2s, 2p core electrons non-included in valence-valence CI, which are quite small. We found that energy, g factors, and electric dipole matrix elements are in reasonable agreement with experiments. It is noteworthy that the theory agreed well with accurately measured g factors. Experimental oscillator strengths have large uncertainty, so in some cases we made a comparison with average values.

  5. Frequency and Correlates of Advance Planning Among Cognitively Impaired Older Adults

    PubMed Central

    Lingler, Jennifer Hagerty; Hirschman, Karen B.; Garand, Linda; Dew, Mary Amanda; Becker, James T.; Schulz, Richard; DeKosky, Steven T.

    2009-01-01

    Objective To examine the prevalence and sociodemographic correlates of written advance planning among patients with or at risk for dementia-imposed decisional incapacity. Design Retrospective, cross-sectional. Setting University-based memory disorders clinic. Participants Persons with a consensus-based diagnosis of mild cognitive impairment (N = 112), probable or possible Alzheimer disease (AD; N = 549), and nondemented comparison subjects (N = 84). Intervention N/A. Measurements Semistructured interviews to assess durable power of attorney (DPOA) and living will (LW) status upon initial presentation for a dementia evaluation. Results Sixty-five percent of participants had a DPOA and 56% had a LW. Planning rates did not vary by diagnosis. European Americans (adjusted odds ratio = 4.75; 95% CI, 2.40-9.38), older adults (adjusted odds ratio = 1.05; 95% CI, 1.03-1.07) and college graduates (adjusted odds ratio = 2.06; 95% CI, 1.33-3.20) were most likely to have a DPOA. Findings were similar for LW rates. Conclusions Although a majority of persons with and at risk for the sustained and progressive decisional incapacity of AD are formally planning for the future, a substantial minority are not. PMID:18669942

  6. Clinical predictors of advanced sellar masses.

    PubMed

    Rambaldini, Gloria M; Butalia, Sonia; Ezzat, Shereen; Kucharczyk, Walter; Sawka, Anna M

    2007-10-01

    To identify clinical variables associated with the presence of a structurally advanced sellar mass (ASM). We performed a retrospective study of patients referred for evaluation of suspected new pituitary disease or sellar mass to the Endocrine Oncology Unit of Mount Sinai Hospital in Toronto, Ontario, Canada. By multivariate analysis, we examined predictors of a structurally ASM (a sellar lesion with any of the following characteristics: diameter of >or=1 cm on magnetic resonance imaging [MRI], optic chiasmal compression on MRI, or clinical or biochemical evidence of hypopituitarism). Data from 152 patients were analyzed. Of the 152 sellar masses, 142 (93%) were pituitary adenomas. An ASM was noted in 85 of the 152 patients (56%). In the final multivariate model, male sex (odds ratio [OR], 6.23; 95% confidence interval [CI], 2.84 to 13.56; P<0.001) and self-reported visual field defect (OR, 3.62; 95% CI, 1.07 to 12.25; P = 0.039) were significantly independently associated with the presence of an ASM. The presence of new or changed headaches also tended to be associated with an ASM (OR, 2.11; 95% CI, 0.96 to 4.64; P = 0.063). Age and self-reported galactorrhea were not independently associated with the presence of an ASM and were conditionally removed from the final model. In patients with suspected sellar or pituitary disease, male sex and self-reported visual field defects independently predict the presence of an ASM. New or changed headaches also tend to be related to the presence of an ASM. The presence of predictors of an ASM should prompt expedited sellar MRI and biochemical evaluation.

  7. Jenkins-CI, an Open-Source Continuous Integration System, as a Scientific Data and Image-Processing Platform.

    PubMed

    Moutsatsos, Ioannis K; Hossain, Imtiaz; Agarinis, Claudia; Harbinski, Fred; Abraham, Yann; Dobler, Luc; Zhang, Xian; Wilson, Christopher J; Jenkins, Jeremy L; Holway, Nicholas; Tallarico, John; Parker, Christian N

    2017-03-01

    High-throughput screening generates large volumes of heterogeneous data that require a diverse set of computational tools for management, processing, and analysis. Building integrated, scalable, and robust computational workflows for such applications is challenging but highly valuable. Scientific data integration and pipelining facilitate standardized data processing, collaboration, and reuse of best practices. We describe how Jenkins-CI, an "off-the-shelf," open-source, continuous integration system, is used to build pipelines for processing images and associated data from high-content screening (HCS). Jenkins-CI provides numerous plugins for standard compute tasks, and its design allows the quick integration of external scientific applications. Using Jenkins-CI, we integrated CellProfiler, an open-source image-processing platform, with various HCS utilities and a high-performance Linux cluster. The platform is web-accessible, facilitates access and sharing of high-performance compute resources, and automates previously cumbersome data and image-processing tasks. Imaging pipelines developed using the desktop CellProfiler client can be managed and shared through a centralized Jenkins-CI repository. Pipelines and managed data are annotated to facilitate collaboration and reuse. Limitations with Jenkins-CI (primarily around the user interface) were addressed through the selection of helper plugins from the Jenkins-CI community.

  8. Jenkins-CI, an Open-Source Continuous Integration System, as a Scientific Data and Image-Processing Platform

    PubMed Central

    Moutsatsos, Ioannis K.; Hossain, Imtiaz; Agarinis, Claudia; Harbinski, Fred; Abraham, Yann; Dobler, Luc; Zhang, Xian; Wilson, Christopher J.; Jenkins, Jeremy L.; Holway, Nicholas; Tallarico, John; Parker, Christian N.

    2016-01-01

    High-throughput screening generates large volumes of heterogeneous data that require a diverse set of computational tools for management, processing, and analysis. Building integrated, scalable, and robust computational workflows for such applications is challenging but highly valuable. Scientific data integration and pipelining facilitate standardized data processing, collaboration, and reuse of best practices. We describe how Jenkins-CI, an “off-the-shelf,” open-source, continuous integration system, is used to build pipelines for processing images and associated data from high-content screening (HCS). Jenkins-CI provides numerous plugins for standard compute tasks, and its design allows the quick integration of external scientific applications. Using Jenkins-CI, we integrated CellProfiler, an open-source image-processing platform, with various HCS utilities and a high-performance Linux cluster. The platform is web-accessible, facilitates access and sharing of high-performance compute resources, and automates previously cumbersome data and image-processing tasks. Imaging pipelines developed using the desktop CellProfiler client can be managed and shared through a centralized Jenkins-CI repository. Pipelines and managed data are annotated to facilitate collaboration and reuse. Limitations with Jenkins-CI (primarily around the user interface) were addressed through the selection of helper plugins from the Jenkins-CI community. PMID:27899692

  9. Fractionated Radioimmunotherapy With 90Y-Clivatuzumab Tetraxetan and Low-Dose Gemcitabine Is Active in Advanced Pancreatic Cancer

    PubMed Central

    Ocean, Allyson J.; Pennington, Kenneth L.; Guarino, Michael J.; Sheikh, Arif; Bekaii-Saab, Tanios; Serafini, Aldo N.; Lee, Daniel; Sung, Max W.; Gulec, Seza A.; Goldsmith, Stanley J.; Manzone, Timothy; Holt, Michael; O’Neil, Bert H.; Hall, Nathan; Montero, Alberto J.; Kauh, John; Gold, David V.; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2014-01-01

    BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at

  10. Prevalence and risk factors of advanced colorectal neoplasms in asymptomatic Korean people between 40 and 49 years of age.

    PubMed

    Koo, Ja Eun; Kim, Kyung-Jo; Park, Hye Won; Kim, Hong-Kyu; Choe, Jae Won; Chang, Hye-Sook; Lee, Ji Young; Myung, Seung-Jae; Yang, Suk-Kyun; Kim, Jin-Ho

    2017-01-01

    Current guidelines recommend colon cancer screening for persons aged over 50 years. However, there are few data on colorectal cancer screening in 40- to 49-year-olds. This study assessed the prevalence and risk factors of colorectal neoplasms in 40- to 49-year-old Koreans. We analyzed the results of screening colonoscopies of 6680 persons 40-59 years of age (2206 aged 40-49 and 4474 aged 50-59 years). The prevalence of overall and advanced neoplasms in the 40- to 49-year age group was lower than in the 50- to 59-year age group (26.7% and 2.4% vs 37.8% and 3.5%, respectively). However, the prevalence of overall and advanced neoplasms increased to 39.1% and 5.4%, respectively, in 45- to 49-year-old individuals with metabolic syndrome. In the 40- to 49-year age group, age, current smoking, and metabolic syndrome were associated with an increased risk of advanced neoplasms (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.30; OR 3.12, 95% CI 1.20-8.12; and OR 2.00, 95% CI 1.09-3.67, respectively). Individuals aged 40-49 years had a lower prevalence of colorectal neoplasms than those aged 50-59 years, but some 40- to 49-year-olds showed a similar prevalence to those aged 50-59 years. Age, current smoking habits, and metabolic syndrome are associated with an increased risk of advanced neoplasms in subjects aged 40-49 years. Further studies are needed to stratify the risks of colon cancer and guide targeted screening in persons younger than 50 years old. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  11. Impact of Blood Transfusions on Survival of Locally Advanced Cervical Cancer Patients Undergoing Neoadjuvant Chemotherapy Plus Radical Surgery.

    PubMed

    Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Lopez, Carlos; Indini, Alice; Leone Roberti Maggiore, Umberto; Sabatucci, Ilaria; Lorusso, Domenica; Raspagliesi, Francesco

    2017-03-01

    Transfusions represent one of the main progresses of modern medicine. However, accumulating evidence supports that transfusions correlate with worse survival outcomes in patients affected by solid cancers. In the present study, we aimed to investigate the effects of perioperative blood transfusion in locally advanced cervical cancer. Data of consecutive patients affected by locally advanced cervical cancer scheduled to undergo neoadjuvant chemotherapy plus radical surgery were retrospectively searched to test the impact of perioperative transfusions on survival outcomes. Five-year survival outcomes were evaluated using Kaplan-Meier and Cox models. The study included 275 patients. Overall, 170 (62%) patients had blood transfusion. Via univariate analysis, we observed that transfusion correlated with an increased risk of developing recurrence (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.09-4.40; P = 0.02). Other factors associated with 5-year disease-free survival were noncomplete clinical response after neoadjuvant chemotherapy (HR, 2.99; 95% CI, 0.92-9.63; P = 0.06) and pathological (P = 0.03) response at neoadjuvant chemotherapy as well as parametrial (P = 0.004), vaginal (P < 0.001), and lymph node (P = 0.002) involvements. However, via multivariate analysis, only vaginal (HR, 3.07; 95% CI, 1.20-7.85; P = 0.01) and lymph node involvements (HR, 2.4; 95% CI, 1.00-6.06; P = 0.05) correlate with worse disease-free survival. No association with worse outcomes was observed for patients undergoing blood transfusion (HR, 2.71; 95% CI, 0.91-8.03; P = 0.07). Looking at factors influencing overall survival, we observed that lymph node status (P = 0.01) and vaginal involvement (P = 0.06) were independently associated with survival. The role of blood transfusions in increasing the risk of developing recurrence in LAAC patients treated by neoadjuvant chemotherapy plus radical surgery remains unclear; further prospective studies are warranted.

  12. Screening for depression in advanced disease: psychometric properties, sensitivity, and specificity of two items of the Palliative Care Outcome Scale (POS).

    PubMed

    Antunes, Bárbara; Murtagh, Fliss; Bausewein, Claudia; Harding, Richard; Higginson, Irene J

    2015-02-01

    Depression is common among patients with advanced disease but often difficult to detect. To assess the Palliative care Outcome Scale (POS) (10 items) against the Geriatric Depression Scale (GDS)-10 total score and the Hospital Anxiety and Depression Scale (HADS)-Depression subscale total score and determine if the POS has appropriate items to screen for depression among people with advanced disease. This was a secondary analysis performed on five studies. Four psychometric properties were assessed: data quality, scaling assumptions, acceptability, and internal consistency (reliability). Receiver operating characteristic (ROC) curves were used to determine the area under the curve. Sensitivity, specificity, positive and negative predictive values, false positive and negative rates, and positive and negative likelihood ratios were computed. The overall sample had 416 patients from Germany and England: 144 had cancer and 267 had nonmalignant conditions. Prevalence of depression across the sample was 17.5%. Floor and ceiling effects were rare. Cronbach's alpha coefficients for POS items 7 and 8 summed, GDS-10 and HADS-Depression items varied: 0.61 (heart failure) and 0.80 (cancer). Two items combined (Item 7-feeling depressed and Item 8-feeling good about yourself) consistently presented the highest area under the ROC curve, ranging from 0.76 (95% CI 0.60, 0.93) (Germany, lung cancer) to 0.97 (95% CI 0.91, 1.0) (heart failure), highest negative predictive value, and lowest false negative rate. For the overall sample, the cutoff 2/3 presented a negative predictive value of 89.4% (95% CI 84.7, 92.8) and false negative rate of 10.6 (95% CI 7.2, 15.3). POS items 7 and 8 summed are potentially useful to screen for depression in advanced disease populations. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  13. Prior cancer does not adversely affect survival in locally advanced lung cancer: A national SEER-medicare analysis.

    PubMed

    Laccetti, Andrew L; Pruitt, Sandi L; Xuan, Lei; Halm, Ethan A; Gerber, David E

    2016-08-01

    Management of locally advanced non-small cell lung cancer is among the most highly contested areas in thoracic oncology. In this population, a history of prior cancer frequently results in exclusion from clinical trials and may influence therapeutic decisions. We therefore determined prevalence and prognostic impact of prior cancer among these patients. We identified patients>65years of age diagnosed 1992-2009 with locally advanced lung cancer in the Surveillance, Epidemiology, and End Results-Medicare linked dataset. We characterized prior cancer by prevalence, type, stage, and timing. We compared all-cause and lung cancer-specific survival between patients with and without prior cancer using propensity score-adjusted Cox regression. 51,542 locally advanced lung cancer patients were included; 15.8% had a history of prior cancer. Prostate (25%), gastrointestinal (17%), breast (16%), and other genitourinary (15%) were the most common types of prior cancer, and 76% percent of prior cancers were localized or in situ stage. Approximately half (54%) of prior cancers were diagnosed within 5 years of the index lung cancer date. Patients with prior cancer had similar (propensity-score adjusted hazard ratio [HR] 0.96; 95% CI, 0.94-0.99; P=0.005) and improved lung cancer-specific (HR 0.84; 95% CI, 0.81-0.86; P<0.001) survival compared to patients with no prior cancer. For patients with locally advanced lung cancer, prior cancer does not adversely impact clinical outcomes. Patients with locally advanced lung cancer and a history of prior cancer should not be excluded from clinical trials, and should be offered aggressive, potentially curative therapies if otherwise appropriate. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Regulation of notochord-specific expression of Ci-Bra downstream genes in Ciona intestinalis embryos.

    PubMed

    Takahashi, Hiroki; Hotta, Kohji; Takagi, Chiyo; Ueno, Naoto; Satoh, Nori; Shoguchi, Eiichi

    2010-02-01

    Brachyury, a T-box transcription factor, is expressed in ascidian embryos exclusively in primordial notochord cells and plays a pivotal role in differentiation of notochord cells. Previously, we identified approximately 450 genes downstream of Ciona intestinalis Brachyury (Ci-Bra), and characterized the expression profiles of 45 of these in differentiating notochord cells. In this study, we looked for cisregulatory sequences in minimal enhancers of 20 Ci-Bra downstream genes by electroporating region within approximately 3 kb upstream of each gene fused with lacZ. Eight of the 20 reporters were expressed in notochord cells. The minimal enchancer for each of these eight genes was narrowed to a region approximately 0.5-1.0-kb long. We also explored the genome-wide and coordinate regulation of 43 Ci-Bra-downstream genes. When we determined their chromosomal localization, it became evident that they are not clustered in a given region of the genome, but rather distributed evenly over 13 of the 14 pairs of chromosomes, suggesting that gene clustering does not contribute to coordinate control of the Ci-Bra downstream gene expression. Our results might provide Insights Into the molecular mechanisms underlying notochord formation in chordates.

  15. Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan.

    PubMed

    Chao, Kuan-Chong; Chen, Yi-Jen; Juang, Chi-Mou; Lau, Hei-Yu; Wen, Kuo-Chang; Sung, Pi-Lin; Fang, Feng-Ying; Twu, Nae-Fang; Yen, Ming-Shyen

    2013-03-01

    To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3-16.7] and PSOC groups (median 16.7 months, 95% CI 12.9-20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6-104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7-85.2; p = 0.006, log-rank statistic). PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ. Copyright © 2013. Published by Elsevier B.V.

  16. The use of antidepressants in patients with advanced cancer--results from an international multicentre study.

    PubMed

    Janberidze, Elene; Hjermstad, Marianne Jensen; Brunelli, Cinzia; Loge, Jon Håvard; Lie, Hanne Cathrine; Kaasa, Stein; Knudsen, Anne Kari

    2014-10-01

    Depression is common in patients with advanced cancer; however, it is not often recognized and therefore not treated. The aims of this study were to examine the prevalence of the use of antidepressants (ADs) in an international cross-sectional study sample and to identify sociodemographic and medical variables associated with their use. The study was conducted in patients with advanced cancer from 17 centres across eight countries. Healthcare professionals registered patient and disease-related characteristics. A dichotomous score (no/yes) was used to assess the use of ADs other than as adjuvant for pain. Self-report questionnaires from patients were used for the assessment of functioning and symptom intensity. Of 1051 patient records with complete data on ADs, 1048 were included (M:540/F:508, mean age 62 years, standard deviation [SD] 12). The majority were inpatients, and 85% had metastatic disease. The prevalence of AD use was 14%. Multivariate logistic regression analyses showed that younger age (odds ratio [OR] 2.46; confidence interval [CI] 1.32-4.55), female gender (OR 1.59; CI 1.09-2.33), current medication for pain (OR 2.68; CI 1.65-4.33) and presence of three or more co-morbidities (OR 4.74; CI 2.27-9.91) were associated with AD use for reasons other than pain. Disease-related variables (diagnoses, stage, Karnofsky Performance Status and survival) were not associated with the use of ADs. Female gender, younger age, analgesic use and multiple co-morbidities were associated with the use of ADs. However, information is still limited on which variables guide physicians in prescribing AD medication. Further longitudinal studies including details on psychiatric and medication history are needed to improve the identification of patients in need of ADs. Copyright © 2014 John Wiley & Sons, Ltd.

  17. The perception and experience of gender-based discrimination related to professional advancement among Japanese physicians.

    PubMed

    Yasukawa, Kosuke; Nomura, Kyoko

    2014-01-01

    Previous studies from the US have found that female physicians often experience gender-based discrimination related to professional advancement. In Japan, female physicians are underrepresented in leadership positions but little is known about the prevalence of gender discrimination. We investigated the perception and prevalence of gender-based career obstacles and discrimination among Japanese physicians. The study was based on surveys of alumnae from 13 medical schools and alumni from 3 medical schools. In total, 1,684 female and 808 male physicians completed a self-administered questionnaire (response rate 83% and 58%). More women than men had the perception of gender-based career obstacles for women (77% vs. 55%; p < 0.0001). Women with part-time positions were more likely to have the perception of gender-based career obstacles than women working full-time (OR 1.32, 95% CI: 1.01-1.73). More women than men reported experience of gender discrimination related to professional advancement (21% vs. 3%; p < 0.0001). Factors associated with experience of gender discrimination included age (p < 0.0001), marital status (p < 0.0001), academic positions (p < 0.0001), subspecialty board certification (p = 0.0011), and PhD status (p < 0.0001). Women older than 40 years were more likely to experience gender discrimination compared with younger women (OR 5.77, 95% CI: 1.83-18.24 for women above 50, and OR 3.2, 95% CI: 1.48-7.28 for women between 40 and 49) and women with PhD were more likely to experience gender discrimination (OR 4.23, 95% CI: 1.81-9.89). Our study demonstrated that a significant proportion of Japanese women experienced gender-based discrimination and perceived gender-based career obstacles compared with male physicians.

  18. Influence of Institutional Experience and Technological Advances on Outcome of Stereotactic Body Radiation Therapy for Oligometastatic Lung Disease.

    PubMed

    Rieber, Juliane; Abbassi-Senger, Nasrin; Adebahr, Sonja; Andratschke, Nicolaus; Blanck, Oliver; Duma, Marciana; Eble, Michael J; Ernst, Iris; Flentje, Michael; Gerum, Sabine; Hass, Peter; Henkenberens, Christoph; Hildebrandt, Guido; Imhoff, Detlef; Kahl, Henning; Klass, Nathalie Desirée; Krempien, Robert; Lohaus, Fabian; Lohr, Frank; Petersen, Cordula; Schrade, Elsge; Streblow, Jan; Uhlmann, Lorenz; Wittig, Andrea; Sterzing, Florian; Guckenberger, Matthias

    2017-07-01

    Many technological and methodical advances have made stereotactic body radiotherapy (SBRT) more accurate and more efficient during the last years. This study aims to investigate whether experience in SBRT and technological innovations also translated into improved local control (LC) and overall survival (OS). A database of 700 patients treated with SBRT for lung metastases in 20 German centers between 1997 and 2014 was used for analysis. It was the aim of this study to investigate the impact of fluorodeoxyglucose positron-emission tomography (FDG-PET) staging, biopsy confirmation, image guidance, immobilization, and dose calculation algorithm, as well as the influence of SBRT experience, on LC and OS. Median follow-up time was 14.3 months (range, 0-131.9 months), with 2-year LC and OS of 81.2% (95% confidence interval [CI] 75.8%-85.7%) and 54.4% (95% CI 50.2%-59.0%), respectively. In multivariate analysis, all treatment technologies except FDG-PET staging did not significantly influence outcome. Patients who received pre-SBRT FDG-PET staging showed superior 1- and 2-year OS of 82.7% (95% CI 77.4%-88.6%) and 64.8% (95% CI 57.5%-73.3%), compared with patients without FDG-PET staging resulting in 1- and 2-year OS rates of 72.8% (95% CI 67.4%-78.8%) and 52.6% (95% CI 46.0%-60.4%), respectively (P=.012). Experience with SBRT was identified as the main prognostic factor for LC: institutions with higher SBRT experience (patients treated with SBRT within the last 2 years of the inclusion period) showed superior LC compared with less-experienced centers (P≤.001). Experience with SBRT within the last 2 years was independent from known prognostic factors for LC. Investigated technological and methodical advancements other than FDG-PET staging before SBRT did not significantly improve outcome in SBRT for pulmonary metastases. In contrast, LC was superior with increasing SBRT experience of the individual center. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Advanced Beamformers for Cochlear Implant Users: Acute Measurement of Speech Perception in Challenging Listening Conditions

    PubMed Central

    Buechner, Andreas; Dyballa, Karl-Heinz; Hehrmann, Phillipp; Fredelake, Stefan; Lenarz, Thomas

    2014-01-01

    Objective To investigate the performance of monaural and binaural beamforming technology with an additional noise reduction algorithm, in cochlear implant recipients. Method This experimental study was conducted as a single subject repeated measures design within a large German cochlear implant centre. Twelve experienced users of an Advanced Bionics HiRes90K or CII implant with a Harmony speech processor were enrolled. The cochlear implant processor of each subject was connected to one of two bilaterally placed state-of-the-art hearing aids (Phonak Ambra) providing three alternative directional processing options: an omnidirectional setting, an adaptive monaural beamformer, and a binaural beamformer. A further noise reduction algorithm (ClearVoice) was applied to the signal on the cochlear implant processor itself. The speech signal was presented from 0° and speech shaped noise presented from loudspeakers placed at ±70°, ±135° and 180°. The Oldenburg sentence test was used to determine the signal-to-noise ratio at which subjects scored 50% correct. Results Both the adaptive and binaural beamformer were significantly better than the omnidirectional condition (5.3 dB±1.2 dB and 7.1 dB±1.6 dB (p<0.001) respectively). The best score was achieved with the binaural beamformer in combination with the ClearVoice noise reduction algorithm, with a significant improvement in SRT of 7.9 dB±2.4 dB (p<0.001) over the omnidirectional alone condition. Conclusions The study showed that the binaural beamformer implemented in the Phonak Ambra hearing aid could be used in conjunction with a Harmony speech processor to produce substantial average improvements in SRT of 7.1 dB. The monaural, adaptive beamformer provided an averaged SRT improvement of 5.3 dB. PMID:24755864

  20. Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer

    PubMed Central

    Zhou, Guo-Wu; Xiong, Ye; Chen, Si; Xia, Fan; Li, Qiang; Hu, Jia

    2016-01-01

    Abstract Background: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC. Methods: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software. Results: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08–2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61–0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65–1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher. Conclusion: Anti-PD-1/PD-L1 antibody therapy may significantly improve

  1. Advance Care Planning for Older Homeless-Experienced Adults: Results from the Health Outcomes of People Experiencing Homelessness in Older Middle Age Study.

    PubMed

    Sudore, Rebecca L; Cuervo, Isabel Arellano; Tieu, Lina; Guzman, David; Kaplan, Lauren M; Kushel, Margot

    2018-05-09

    Older homeless-experienced adults have low engagement in advance care planning (ACP) despite high morbidity and mortality. We conducted a cross-sectional analysis of a cohort of 350 homeless-experienced adults aged 50 and older in Oakland, California. We assessed the prevalence of potential surrogate decision-makers, ACP contemplation, discussions, and ACP documentation (surrogate designation, advance directives). We used multivariable logistic regression to examine factors associated with ACP discussions and documentation. The median age of the cohort was 59 (range 52-82), 75.2% were male, and 82.1% were black. Sixty-one percent reported a potential surrogate, 21.5% had discussed ACP, and 19.0% reported ACP documentation. In multivariable models, having 1 to 5 confidants versus none (adjusted odds ratio (aOR)=5.8, 95% confidence interval (CI)=1.7-20.0), 3 or more chronic conditions versus none (aOR=2.3, 95% CI=0.9-5.6), and a recent primary care visit (aOR=2.1, 95% CI=1.0-4.4) were associated with higher odds of ACP discussions and each additional 5 years of homelessness (aOR=0.7, 95% CI=0.5-0.9) with lower odds. Having 1 to 5 confidants (aOR=5.0, 95% CI=1.4-17.5), being black (aOR=5.5, 95% CI=1.5-19.5), and having adequate versus limited literacy (aOR=7.0, 95% CI=1.5-32.4) were associated with higher odds of ACP documentation and illicit drug use (aOR=0.3, 95% CI=0.1-0.9) with lower odds. Although the majority of older homeless-experienced adults have a potential surrogate, few have discussed or documented their ACP wishes; the odds of both were greater with larger social networks. Future interventions must be customized for individuals with limited social networks and address the instability of homelessness, health literacy, and the constraints of safety-net healthcare settings. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

  2. Identification of two CiGADs from Caragana intermedia and their transcriptional responses to abiotic stresses and exogenous abscisic acid.

    PubMed

    Ji, Jing; Zheng, Lingyu; Yue, Jianyun; Yao, Xiamei; Chang, Ermei; Xie, Tiantian; Deng, Nan; Chen, Lanzhen; Huang, Yuwen; Jiang, Zeping; Shi, Shengqing

    2017-01-01

    Glutamate decarboxylase (GAD), as a key enzyme in the γ -aminobutyric acid (GABA) shunt, catalyzes the decarboxylation of L-glutamate to form GABA. This pathway has attracted much interest because of its roles in carbon and nitrogen metabolism, stress responses, and signaling in higher plants. The aim of this study was to isolate and characterize genes encoding GADs from Caragana intermedia , an important nitrogen-fixing leguminous shrub. Two full-length cDNAs encoding GADs (designated as CiGAD1 and CiGAD2 ) were isolated and characterized. Multiple alignment and phylogenetic analyses were conducted to evaluate their structures and identities to each other and to homologs in other plants. Tissue expression analyses were conducted to evaluate their transcriptional responses to stress (NaCl, ZnSO 4 , CdCl 2 , high/low temperature, and dehydration) and exogenous abscisic acid. The CiGAD s contained the conserved PLP domain and calmodulin (CaM)-binding domain in the C-terminal region. The phylogenetic analysis showed that they were more closely related to the GADs of soybean, another legume, than to GADs of other model plants. According to Southern blotting analysis, CiGAD1 had one copy and CiGAD2 -related genes were present as two copies in C. intermedia . In the tissue expression analyses, there were much higher transcript levels of CiGAD2 than CiGAD1 in bark, suggesting that CiGAD2 might play a role in secondary growth of woody plants. Several stress treatments (NaCl, ZnSO 4 , CdCl 2 , high/low temperature, and dehydration) significantly increased the transcript levels of both CiGAD s, except for CiGAD2 under Cd stress. The CiGAD1 transcript levels strongly increased in response to Zn stress (74.3-fold increase in roots) and heat stress (218.1-fold increase in leaves). The transcript levels of both CiGAD s significantly increased as GABA accumulated during a 24-h salt treatment. Abscisic acid was involved in regulating the expression of these two CiGAD s under salt

  3. Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD

    PubMed Central

    Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A.; Kleiner, David; Brunt, Elizabeth M.; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James

    2015-01-01

    OBJECTIVE Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. RESEARCH DESIGN AND METHODS This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. RESULTS The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m2, respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75–0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit

  4. The Body-Machine Interface: A new perspective on an old theme

    PubMed Central

    Casadio, Maura; Ranganathan, Rajiv; Mussa-Ivaldi, Ferdinando A.

    2012-01-01

    Body-machine interfaces establish a way to interact with a variety of devices, allowing their users to extend the limits of their performance. Recent advances in this field, ranging from computer-interfaces to bionic limbs, have had important consequences for people with movement disorders. In this article, we provide an overview of the basic concepts underlying the body-machine interface with special emphasis on their use for rehabilitation and for operating assistive devices. We outline the steps involved in building such an interface and we highlight the critical role of body-machine interfaces in addressing theoretical issues in motor control as well as their utility in movement rehabilitation. PMID:23237465

  5. Oxygen, Magnesium, and Aluminum Isotopes in the Ivuna CAI: Re-Examining High-Temperature Fractionations in CI Chondrites

    NASA Technical Reports Server (NTRS)

    Frank, D. R.; Huss, G. R.; Nagashima, K.; Zolensky, M. E.; Le, L.

    2017-01-01

    CI chondrites are thought to approximate the bulk solar system composition since they closely match the composition of the solar photosphere. Thus, chemical differences between a planetary object and the CI composition are interpreted to result from fractionations of a CI starting composition. This interpretation is often made despite the secondary mineralogy of CI chondrites, which resulted from low-T aqueous alteration on the parent asteroid(s). Prevalent alteration and the relatively large uncertainties in the photospheric abundances (approx. +/-5-10%) permit chemical fractionation of CI chondrites from the bulk solar system, if primary chondrules and/or CAIs have been altered beyond recognition. Isolated olivine and pyroxene grains that range from approx. 5 microns to several hundred microns have been reported in CI chondrites, and acid residues of Orgueil were found to contain refractory oxides with oxygen isotopic compositions matching CAIs. However, the only CAI found to be unambiguously preserved in a CI chondrite was identified in Ivuna. The Ivuna CAI's primary mineralogy, small size (approx.170 microns), and fine-grained igneous texture classify it as a compact type A. Aqueous alteration infiltrated large portions of the CAI, but other regions remain pristine. The major primary phases are melilite (Ak 14-36 ), grossmanite (up to 20.8 wt.% TiO 2 ), and spinel. Both melilite and grossmanite have igneous textures and zoning patterns. An accretionary rim consists primarily of olivine (Fa 2-17 ) and low-Ca pyroxene (Fs 2-10 ), which could be either surviving CI2 material or a third lithology.

  6. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer.

    PubMed

    Turner, Nicholas C; Ro, Jungsil; André, Fabrice; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Loibl, Sibylle; Huang Bartlett, Cynthia; Zhang, Ke; Giorgetti, Carla; Randolph, Sophia; Koehler, Maria; Cristofanilli, Massimo

    2015-07-16

    Growth of hormone-receptor-positive breast cancer is dependent on cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), which promote progression from the G1 phase to the S phase of the cell cycle. We assessed the efficacy of palbociclib (an inhibitor of CDK4 and CDK6) and fulvestrant in advanced breast cancer. This phase 3 study involved 521 patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that had relapsed or progressed during prior endocrine therapy. We randomly assigned patients in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant. Premenopausal or perimenopausal women also received goserelin. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, objective response, rate of clinical benefit, patient-reported outcomes, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 195 events of disease progression or death had occurred. The median progression-free survival was 9.2 months (95% confidence interval [CI], 7.5 to not estimable) with palbociclib-fulvestrant and 3.8 months (95% CI, 3.5 to 5.5) with placebo-fulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 to 0.56; P<0.001). The most common grade 3 or 4 adverse events in the palbociclib-fulvestrant group were neutropenia (62.0%, vs. 0.6% in the placebo-fulvestrant group), leukopenia (25.2% vs. 0.6%), anemia (2.6% vs. 1.7%), thrombocytopenia (2.3% vs. 0%), and fatigue (2.0% vs. 1.2%). Febrile neutropenia was reported in 0.6% of palbociclib-treated patients and 0.6% of placebo-treated patients. The rate of discontinuation due to adverse events was 2.6% with palbociclib and 1.7% with placebo. Among patients with hormone-receptor-positive metastatic breast cancer who had progression of disease during prior endocrine therapy, palbociclib combined with fulvestrant resulted

  7. Tumor deposits counted as positive lymph nodes in TNM staging for advanced colorectal cancer: a retrospective multicenter study.

    PubMed

    Li, Jun; Yang, Shengke; Hu, Junjie; Liu, Hao; Du, Feng; Yin, Jie; Liu, Sai; Li, Ci; Xing, Shasha; Yuan, Jiatian; Lv, Bo; Fan, Jun; Leng, Shusheng; Zhang, Xin; Wang, Bing

    2016-04-05

    We investigated the possibility of counting tumor deposits (TDs) as positive lymph nodes (pLNs) in the pN category and evaluated its prognostic value for colorectal cancer (CRC) patients. A new pN category (npN category) was calculated using the numbers of pLNs plus TDs. The npN category included 4 tiers: npN1a (1 tumor node), npN1b (2-3 tumor nodes), npN2a (4-6 tumor nodes), and npN2b (≥7 tumor nodes). We identified 4,121 locally advanced CRC patients, including 717 (11.02%) cases with TDs. Univariate and multivariate analyses were performed to evaluate the disease-free and overall survival (DFS and OS) for npN and pN categories. Multivariate analysis showed that the npN and pN categories were both independent prognostic factors for DFS (HR 1.614, 95% CI 1.541 to 1.673; HR 1.604, 95% CI 1.533 to 1.679) and OS (HR 1.633, 95% CI 1.550 to 1.720; HR 1.470, 95% CI 1.410 to 1.532). However, the npN category was superior to the pN category by Harrell's C statistic. We conclude that it is thus feasible to consider TDs as positive lymph nodes in the pN category when evaluating the prognoses of CRC patients, and the npN category is potentially superior to the TNM (7th edition) pN category for predicting DFS and OS among advanced CRC patients.

  8. Study of single nucleotide polymorphisms of FBW7 and its substrate genes revealed a predictive factor for paclitaxel plus cisplatin chemotherapy in Chinese patients with advanced esophageal squamous cell carcinoma.

    PubMed

    Liu, Ying; Xu, Shu Ning; Chen, Yong Shun; Wu, Xiao Yuan; Qiao, Lei; Li, Ke; Yuan, Long

    2016-07-12

    Paclitaxel plays a major role in the treatment of advanced esophageal squamous cell carcinoma. However, there is no biomarker that could be used to predict the clinical response of paclitaxel. This work was conducted to investigate the association of genetic polymorphisms in FBW7 and its substrate genes and the clinical response of paclitaxel. Patients with advanced esophageal squamous cell carcinoma were treated with paclitaxel 175 mg/m2 over 3 hours day 1 and cisplatin 75 mg/m2 day 1, every 3 weeks. The genotypes of 11 FBW7 and its substrate gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis revealed that patients with mTOR rs1057079 AG (ORadjusted: 4.59; 95% CI: 1.78-11.86) genotype had significant correlation with the clinical response of paclitaxel when compared with AA genotype after adjustment for sex, age, and chemotherapy cycle. The median progression-free survival (PFS) of patients with advanced ESCC who received paclitaxel plus cisplatin (TP) as first-line treatment is 14.3 months (95% CI: 9.0-19.60 months). The median PFS (mPFS) of AG genotypes and AA genotypes in mTOR rs1057079 were 17.31 months (95% CI: 15.9-18.67 months) and 9.8 months (95% CI: 8.58-11.02 months) (p=0.019), respectively.

  9. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Appelt, Ane L., E-mail: ane.lindegaard.appelt@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

    2013-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from themore » histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.« less

  10. Outcomes of Basic Versus Advanced Life Support for Out-of-Hospital Medical Emergencies.

    PubMed

    Sanghavi, Prachi; Jena, Anupam B; Newhouse, Joseph P; Zaslavsky, Alan M

    2015-11-03

    Most Medicare patients seeking emergency medical transport are treated by ambulance providers trained in advanced life support (ALS). Evidence supporting the superiority of ALS over basic life support (BLS) is limited, but some studies suggest ALS may harm patients. To compare outcomes after ALS and BLS in out-of-hospital medical emergencies. Observational study with adjustment for propensity score weights and instrumental variable analyses based on county-level variations in ALS use. Traditional Medicare. 20% random sample of Medicare beneficiaries from nonrural counties between 2006 and 2011 with major trauma, stroke, acute myocardial infarction (AMI), or respiratory failure. Neurologic functioning and survival to 30 days, 90 days, 1 year, and 2 years. Except in cases of AMI, patients showed superior unadjusted outcomes with BLS despite being older and having more comorbidities. In propensity score analyses, survival to 90 days among patients with trauma, stroke, and respiratory failure was higher with BLS than ALS (6.1 percentage points [95% CI, 5.4 to 6.8 percentage points] for trauma; 7.0 percentage points [CI, 6.2 to 7.7 percentage points] for stroke; and 3.7 percentage points [CI, 2.5 to 4.8 percentage points] for respiratory failure). Patients with AMI did not exhibit differences in survival at 30 days but had better survival at 90 days with ALS (1.0 percentage point [CI, 0.1 to 1.9 percentage points]). Neurologic functioning favored BLS for all diagnoses. Results from instrumental variable analyses were broadly consistent with propensity score analyses for trauma and stroke, showed no survival differences between BLS and ALS for respiratory failure, and showed better survival at all time points with BLS than ALS for patients with AMI. Only Medicare beneficiaries from nonrural counties were studied. Advanced life support is associated with substantially higher mortality for several acute medical emergencies than BLS. National Science Foundation, Agency for

  11. Adriamycin and cis-platinum as first-line treatment in unresectable locally advanced or metastatic adult soft-tissue sarcomas.

    PubMed

    Kalofonos, Haralabos P; Bafaloukos, Dimitrios; Kourelis, Theodoros G; Karamouzis, Michalis V; Megas, Panagiotis; Iconomou, Grigorios; Tsiata, Ekaterini; Dimitropoulos, Dimitrios; Kosmidis, Paris; Lampiris, E

    2004-06-01

    Standard chemotherapy in advanced adult soft-tissue sarcomas (STS) has not yet been established. We evaluated the efficacy and toxicity of the combination of adriamycin (ADR) and cis-platinum (CDDP) as first-line treatment in nonoperable locally advanced or metastatic adult STS. Thirty patients were treated with CDDP 100 mg/m2 on day 1 and ADR 75 mg/m2 equally divided on days 1 to 3, every 3 weeks for 6 cycles. Patients were evaluated for response, toxicity, and survival, while resectability of residual disease was also assessed after the third cycle and the end of chemotherapy. No complete response was observed. Five patients (16.7%, 95% CI: 2.5%-31%) achieved partial response, 16 patients (53.3%, 95% CI: 34%-72%) had stable disease and 9 patients (30%, 95% CI: 13%-47%) had progressive disease. The overall median survival was 11.5 months (range, 4-96 months), and the median time to disease progression was 6 months (range, 0-96 months). Furthermore, two patients with PR and six patients with stable disease underwent further surgery followed by radiotherapy in four of them. At present, 5 patients remain free of relapse for 96, 90, 72, 60, and 48 months, respectively. Treatment-related toxicity was acceptable, with moderate myelosuppression and alopecia as the main adverse events. The ADR/CDDP regimen was well tolerated, but it did not achieve a high response rate. However, patients with resectable disease after chemotherapy achieved long-term survival. Further studies are needed to evaluate the role of combined-modality treatments in the management of patients with advanced STS.

  12. Dietary intake of advanced glycation endproducts is associated with higher levels of advanced glycation endproducts in plasma and urine: The CODAM study.

    PubMed

    Scheijen, Jean L J M; Hanssen, Nordin M J; van Greevenbroek, Marleen M; Van der Kallen, Carla J; Feskens, Edith J M; Stehouwer, Coen D A; Schalkwijk, Casper G

    2018-06-01

    Advanced glycation endproducts (AGEs) are formed by the reaction between reducing sugars and proteins. AGEs in the body have been associated with several age-related diseases. High-heat treated and most processed foods are rich in AGEs. The aim of our study was to investigate whether dietary AGEs, are associated with plasma and urinary AGE levels. In 450 participants of the Cohort on Diabetes and Atherosclerosis Maastricht study (CODAM study) we measured plasma and urine concentrations of the AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) using UPLC-MS/MS. We also estimated dietary intake of CML, CEL and MG-H1 with the use of a dietary AGE database and a food frequency questionnaire (FFQ). We used linear regression to investigate the association between standardized dietary AGE intake and standardized plasma or urinary AGE levels, after adjustment for age, sex, glucose metabolism status, waist circumference, kidney function, energy- and macro-nutrient intake, smoking status, physical activity, alcohol intake, LDL-cholesterol and markers of oxidative stress. We found that higher intake of dietary CML, CEL and MG-H1 was associated with significantly higher levels of free plasma and urinary CML, CEL and MG-H1 (βCML = 0.253 (95% CI 0.086; 0.415), βCEL = 0.194 (95% CI 0.040; 0.339), βMG-H1 = 0.223 (95% CI 0.069; 0.373) for plasma and βCML = 0.223 (95% CI 0.049; 0.393), βCEL = 0.180 (95% CI 0.019; 0.332), βMG-H1 = 0.196 (95% CI 0.037; 0.349) for urine, respectively). In addition, we observed non-significant associations of dietary AGEs with their corresponding protein bound plasma AGEs. We demonstrate that higher intake of dietary AGEs is associated with higher levels of AGEs in plasma and urine. Our findings may have important implications for those who ingest a diet rich in AGEs. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and

  13. Herbal medicines for advanced colorectal cancer.

    PubMed

    Guo, Zhongning; Jia, Xiaoqiang; Liu, Jian Ping; Liao, Juan; Yang, Yufei

    2012-05-16

    Herbal medicine has been widely used in patients with advanced colorectal cancer in China, but its efficacy has not been confirmed. To evaluate the beneficial effect and safety on Chinese herbal medicine therapy for advanced stage colorectal cancer, and it's influence on the patients' quality of life. The following electronic databases were searched: BIOSIS Previews, Cochrane Controlled Trials Register, Medline EMBASE, Biological Abstracts, until Aug. 2011. Manual searching was performed on 16 types of Chinese journals which started from their respective first publication dates, as well as unpublished conference proceedings. No language restriction was applied. Randomized or quasi-randomised controlled trials on the treatment of advanced stage colorectal cancer by herbal medicines or herbal medicines combined with chemotherapy, regardless of blinding. The data were extracted independently by two reviewers. Methodological quality of the included in trials was assessed according to the following parameters: randomisation, allocation concealment, double blinding, and drop-out rates. A total of 20 randomised controlled trials with 1304 participants were identified. All the 20 trials compared the use of herbal medicines with chemotherapy and chemotherapy alone in the treatment of advanced stage colorectal cancers.Compared with chemotherapy alone, the use of Quxie capsule combined with chemotherapy could decrease mortality rate (RR 0.17, 95% CI 0.03 to 0.97); the use of Jianpi Jiedu formula, Xiaozheng formula and Yiqi Huoxue herbal medicine combined with chemotherapy respectively could improve 1-year survival rate significantly; the use of Xiaozheng Formula in conjunction with chemotherapy could improve 3-year survival rate. There were 10 herbal medicines showing benefit in improving quality of life. Herbal medicines did not show additional benefit in response rate or stability rate. No trials reported serious adverse effect from herbal medicine. Some herbal medicines

  14. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer

    PubMed Central

    Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

    2016-01-01

    Background and objective Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Patients and methods Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi’an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2–11.8 months), and median overall survival was 21.0 months (95% CI: 20.1–21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Conclusion Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation. PMID:26966381

  15. Vemurafenib for BRAF V600 mutated advanced melanoma: results of treatment beyond progression.

    PubMed

    Scholtens, A; Geukes Foppen, M H; Blank, C U; van Thienen, J V; van Tinteren, H; Haanen, J B

    2015-03-01

    Selective BRAF inhibition (BRAFi) by vemurafenib or dabrafenib has become approved standard treatment in BRAF V600 mutated advanced stage melanoma. While the response rate is high, the response duration is limited with a progression-free survival (PFS) of 5-6months. Our observation of accelerated disease progression within some patients after stopping vemurafenib treatment has fostered the idea of treatment beyond progression (BRAFi TBP). In this retrospective study, we analysed 70 metastatic melanoma patients, treated at our institute, who experienced progression after prior objective response upon treatment with vemurafenib. Thirty-five patients that continued treatment beyond progression are compared with 35 patients who stopped BRAFi treatment at disease progression. Median overall survival beyond documented progression was found to be 5.2months versus 1.4months (95% confidence interval (CI): 3.8-7.4 versus 0.6-3.4; Log-Rank p=0.002) in favour of BRAFi TBP. In the multivariate survival analysis, stopping treatment at disease progression was significantly associated with shorter survival (hazard ratio: 1.92; 95% CI: 1.04-3.55; p=0.04). Our results suggest that continuing vemurafenib treatment beyond progression may be beneficial in advanced melanoma patients, who prior to progression responded to vemurafenib. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

    PubMed Central

    Quintero, Enrique; Gargallo, Carla; Lanas, Angel; Bujanda, Luis; Gimeno-García, Antonio Z.; Hernández-Guerra, Manuel; Nicolás-Pérez, David; Alonso-Abreu, Inmaculada; Morillas, Juan Diego; Balaguer, Francesc; Muriel, Alfonso

    2016-01-01

    Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). Methods and Findings This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced

  17. SAC-CI methodology applied to molecular spectroscopy and photo-biology

    NASA Astrophysics Data System (ADS)

    Hasegawa, J.; Miyahara, T.; Nakashima, H.; Nakatsuji, H.

    2012-06-01

    The SAC-CI method was applied to the spectroscopy of radical cations and anions of various organic molecules. It was also applied to photo-biology, in particular, to elucidate the bio-molecular color-tuning mechanism of human visions and to the circular dichroism spectroscopy that is used to understand the helical structures of DNA and RNA.

  18. Ciênsação: Gaining a Feeling for Sciences

    ERIC Educational Resources Information Center

    de Oliveira, Marcos Henrique Abreu; Fischer, Robert

    2017-01-01

    Ciênsação, an open online repository for hands-on experiments, has been developed to convince teachers in Latin America that science is best experienced first hand. Permitting students to experiment autonomously in small groups can be a challenging endeavour for educators in these countries. We analyse the reasons that cause hesitation of teachers…

  19. Programmable and functional electrothermal bimorph actuators based on large-area anisotropic carbon nanotube paper

    NASA Astrophysics Data System (ADS)

    Li, Qingwei; Liu, Changhong; Fan, Shoushan

    2018-04-01

    Electro-active polymer (EAP) actuators, such as electronic, ionic and electrothermal (ET) actuators, have become an important branch of next-generation soft actuators in bionic robotics. However, most reported EAP actuators could realize only simple movements, being restricted by the small area of flexible electrodes and simple designs. We prepared large-area flexible electrodes of high anisotropy, made of oriented carbon nanotube (CNT) paper, and carried out artful graphic designs and processing on the electrodes to make functional ET bimorph actuators which can realize large bending deformations (over 220°, curvature > 1.5 cm-1) and bionic movements driven by electricity. The anisotropy of CNT paper benefits electrode designs and multiform actuations for complex actuators. Based on the large-area CNT paper, more interesting and functional actuators can be designed and prepared which will have practical applications in the fields of artificial muscles, complicated actuations, and soft and bionic robotics.

  20. Direct Simple Shear Test Data Analysis using Jupyter Notebooks on DesignSafe-CI

    NASA Astrophysics Data System (ADS)

    Eslami, M.; Esteva, M.; Brandenberg, S. J.

    2017-12-01

    Due to the large number of files and their complex structure, managing data generated during natural hazards experiments requires scalable and specialized tools. DesignSafe-CI (https://www.designsafe-ci.org/) is a web-based research platform that provides computational tools to analyze, curate, and publish critical data for natural hazards research making it understandable and reusable. We present a use case from a series of Direct Simple Shear (DSS) experiments in which we used DS-CI to post-process, visualize, publish, and enable further analysis of the data. Current practice in geotechnical design against earthquakes relies on the soil's plasticity index (PI) to assess liquefaction susceptibility, and cyclic softening triggering procedures, although, quite divergent recommendations on recommended levels of plasticity can be found in the literature for these purposes. A series of cyclic and monotonic direct simple shear experiments was conducted on three low-plasticity fine-grained mixtures at the same plasticity index to examine the effectiveness of the PI in characterization of these types of materials. Results revealed that plasticity index is an insufficient indicator of the cyclic behavior of low-plasticity fine-grained soils, and corrections for pore fluid chemistry and clay minerology may be necessary for future liquefaction susceptibility and cyclic softening assessment procedures. Each monotonic, or cyclic experiment contains two stages; consolidation and shear, which include time series of load, displacement, and corresponding stresses and strains, as well as equivalent excess pore-water pressure. Using the DS-CI curation pipeline we categorized the data to display and describe the experiment's structure and files corresponding to each stage of the experiments. Two separate notebooks in Python 3 were created using the Jupyter application available in DS-CI. A data plotter aids visualizing the experimental data in relation to the sensor from which it was

  1. A phase II study of flavopiridol in patients with advanced renal cell carcinoma: results of Southwest Oncology Group Trial 0109.

    PubMed

    Van Veldhuizen, Peter J; Faulkner, James R; Lara, Primo N; Gumerlock, Paul H; Goodwin, J Wendall; Dakhil, Shaker R; Gross, Howard M; Flanigan, Robert C; Crawford, E David

    2005-07-01

    Flavopiridol is a cyclin-dependent kinase inhibitor that prevents cell cycle progression and tumor growth. In initial phase I studies, encouraging responses were seen in advanced renal cell cancer (RCC). In a phase II study of flavopiridol given as a 72-h continuous infusion every 2 weeks in RCC, a response rate of 6% was seen but with considerable grade 3 or 4 asthenia, diarrhea, and thrombosis. Subsequently, an alternative 1-h bolus schedule was reported to have enhanced tolerability in a phase I trial. We therefore conducted a phase II study of this bolus regimen. A total of 38 patients with advanced RCC were entered into this multi-institutional phase II study. Flavopiridol (50 mg/m(2) per day) was administered by bolus intravenous injection daily for three consecutive days, repeated every 3 weeks. Out of 34 eligible patients, one complete response and three partial responses were observed, for an overall response rate of 12% (95% CI 3-27%). Of the 34 patients, 14 (41%) had stable disease (SD). The probability of not failing treatment by 6 months was 21% (95% CI 9-35%). Median overall survival time was 9 months (95% CI 8-18 months). The most common grade 3 or 4 toxicities were diarrhea (35%) and tumor pain (12%) along with anemia, dyspnea, and fatigue (9% each). Flavopiridol at this dose and schedule is feasible with an acceptable toxicity profile. Flavopiridol has some modest biologic activity against advanced RCC, as evidenced by its single-agent objective response and SD rates.

  2. Identification and Validation of Novel Hedgehog-Responsive Enhancers Predicted by Computational Analysis of Ci/Gli Binding Site Density

    PubMed Central

    Richards, Neil; Parker, David S.; Johnson, Lisa A.; Allen, Benjamin L.; Barolo, Scott; Gumucio, Deborah L.

    2015-01-01

    The Hedgehog (Hh) signaling pathway directs a multitude of cellular responses during embryogenesis and adult tissue homeostasis. Stimulation of the pathway results in activation of Hh target genes by the transcription factor Ci/Gli, which binds to specific motifs in genomic enhancers. In Drosophila, only a few enhancers (patched, decapentaplegic, wingless, stripe, knot, hairy, orthodenticle) have been shown by in vivo functional assays to depend on direct Ci/Gli regulation. All but one (orthodenticle) contain more than one Ci/Gli site, prompting us to directly test whether homotypic clustering of Ci/Gli binding sites is sufficient to define a Hh-regulated enhancer. We therefore developed a computational algorithm to identify Ci/Gli clusters that are enriched over random expectation, within a given region of the genome. Candidate genomic regions containing Ci/Gli clusters were functionally tested in chicken neural tube electroporation assays and in transgenic flies. Of the 22 Ci/Gli clusters tested, seven novel enhancers (and the previously known patched enhancer) were identified as Hh-responsive and Ci/Gli-dependent in one or both of these assays, including: Cuticular protein 100A (Cpr100A); invected (inv), which encodes an engrailed-related transcription factor expressed at the anterior/posterior wing disc boundary; roadkill (rdx), the fly homolog of vertebrate Spop; the segment polarity gene gooseberry (gsb); and two previously untested regions of the Hh receptor-encoding patched (ptc) gene. We conclude that homotypic Ci/Gli clustering is not sufficient information to ensure Hh-responsiveness; however, it can provide a clue for enhancer recognition within putative Hedgehog target gene loci. PMID:26710299

  3. A multicenter randomized controlled trial evaluating balneotherapy in patients with advanced chronic venous insufficiency.

    PubMed

    Carpentier, Patrick H; Blaise, Sophie; Satger, Bernadette; Genty, Céline; Rolland, Carole; Roques, Christian; Bosson, Jean-Luc

    2014-02-01

    Apart from compression therapy, physical therapy has scarcely been evaluated in the treatment of chronic venous disorders (CVDs). Spa treatment is a popular way to administer physical therapy for CVDs in France, but its efficacy has not yet been assessed in a large trial. The objective was to assess the efficacy of spa therapy for patients with advanced CVD (CEAP clinical classes C4-C5). This was a single-blind (treatment concealed to the investigators) randomized, multicenter, controlled trial (French spa resorts). Inclusion criteria were primary or post-thrombotic CVD with skin changes but no active ulcer (C4a, C4b, or C5). The treated group had the usual 3-week spa treatment course soon after randomization; the control group had spa treatment after the 1-year comparison period. All patients continued their usual medical care including wearing compression stockings. Treatment consisted of four balneotherapy sessions per day for 6 days a week. Follow-up was performed at 6, 12 and 18 months by independent blinded investigators. The main outcome criterion was the incidence of leg ulcers at 12 months. Secondary criteria were a modified version of the Venous Clinical Severity Score, a visual analog scale for leg symptoms, and the Chronic Venous Insufficiency Questionnaire 2 and EuroQol 5D quality-of-life autoquestionnaires. Four hundred twenty-five subjects were enrolled: 214 in the treatment group (Spa) and 211 in the control group (Ctr); they were similar at baseline regarding their demographic characteristics, the severity of the CVD, and the outcome variables. At 1 year, the incidence of leg ulcers was not statistically different (Spa: +9.3%; 95% confidence interval [CI], +5.6 - +14.3; Ctr: +6.1%; 95% CI, +3.2 - +10.4), whereas the Venous Clinical Severity Score improved significantly in the treatment group (Spa: -1.2; 95% CI, -1.6 - -0.8; Ctr: -0.6; 95% CI, -1.0 - -0.2; P = .04). A significant difference favoring spa treatment was found regarding symptoms after 1

  4. New places and phases of CO-poor/CI-rich molecular gas in the Universe

    NASA Astrophysics Data System (ADS)

    Papadopoulos, Padelis P.; Bisbas, Thomas G.; Zhang, Zhiyu

    2018-04-01

    In this work we extend the work on the recently discovered role of Cosmic Rays (CRs) in regulating the average CO/H_2 abundance ratio in molecular clouds (and thus their CO line visibility) in starburst galaxies, and find that it can lead to a CO-poor/CI-rich H_2 gas phase even in environments with Galactic or in only modestly enhanced CR backgrounds expected in ordinary star-forming galaxies. Furthermore, the same CR-driven astro-chemistry raises the possibility of a widespread phase transition of molecular gas towards a CO-poor/CI-rich phase in: a) molecular gas outflows found in star-forming galaxies, b) active galactic nuclei (AGNs), and c) near synchrotron-emitting radio jets and the radio-loud cores of powerful radio galaxies. For main sequence galaxies we find that CRs can render some of their molecular gas mass CO-invisible, compounding the effects of low metallicities. Imaging the two fine structure lines of atomic carbon with resolution high enough to search beyond the CI/CO-bright line regions associated with central starbursts can reveal such a CO-poor/CI-rich molecular gas phase, provided that relative brightness sensitivity levels of Tb(CI 1 - 0)/Tb(CO J = 1 - 0) ˜0.15 are reached. The capability to search for such gas in the Galaxy is now at hand with the new high-frequency survey telescope HEAT deployed in Antarctica and future ones to be deployed in Dome A. ALMA can search for such gas in star-forming spiral disks, galactic molecular gas outflows and the CR-intense galactic and circumgalactic gas-rich environments of radio-loud objects.

  5. Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree.

    PubMed

    Gelibter, Alain; Malaguti, Paola; Di Cosimo, Serena; Bria, Emilio; Ruggeri, Enzo Maria; Carlini, Paolo; Carboni, Fabio; Ettorre, Giuseppe Maria; Pellicciotta, Mario; Giannarelli, Diana; Terzoli, Edmondo; Cognetti, Francesco; Milella, Michele

    2005-09-15

    Gemcitabine infusion at the fixed dose rate of 10 mg/m(2) per minute (FDR-gemcitabine) has pharmacokinetic advantages and may result in improved therapeutic efficacy. Between April 2002 and September 2003, 40 patients with advanced-stage pancreatic adenocarcinoma (PDAC; n = 27) or biliary tree carcinoma (BTC; n = 13) were treated with weekly FDR-gemcitabine (1000 mg/m(2)). The primary end point was the response rate. The secondary end points were progression-free and overall survival (PFS and OS), tumor marker response, and clinical benefit response (CBR). The overall response rate (ORR) on an intent-to-treat basis was 15% (95% confidence interval [95% CI], 4-26%). A positive CBR was obtained in 14 of 29 (48%) patients. Seventeen of 25 (68%) patients had a reduction in carbohydrate antigen 19-9 (CA 19-9) of > 25%. The median time to treatment failure and the median PFS were 17 weeks (95% CI, 13-22 weeks) and 19 weeks (95% CI, 15-23 weeks), respectively. The median OS was 40 weeks (95% CI, 36-45 weeks) and the 1-year actuarial survival rate was 25.8%. Multivariate analysis showed that a performance status score of 0-1 at study entry and locally advanced disease were the only independent predictors of longer PFS and OS, whereas a reduction in CA 19-9 serum levels > 75% was an independent predictor of longer PFS, but had no impact on OS. Toxicity was mild with Grade 3-4 neutropenia (according to the National Cancer Institute-Common Toxicity Criteria [version 2.0]) in 18 of 427 treatment weeks (4.2%), and Grade 3 anemia and thrombocytopenia in 6 of 427 treatment weeks (1.4%) and 9 of 427 treatment weeks (2.1%), respectively, and asymptomatic Grade 3-4 transaminase elevation in 21 of 427 treatment weeks (4.9%). FDR-gemcitabine at the weekly dose of 1000 mg/m(2) demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC. Copyright 2005 American Cancer Society.

  6. Combination Chemotherapy with S-1 and Oxaliplatin (SOX) as First-Line Treatment in Elderly Patients with Advanced Gastric Cancer.

    PubMed

    Zhong, Dong-ta; Wu, Ri-ping; Wang, Xin-li; Huang, Xiao-bing; Lin, Meng-xin; Lan, Yan-qin; Chen, Qiang

    2015-09-01

    This study is a retrospective analysis evaluating the efficacy and toxicity of combination chemotherapy with S-1 and oxaliplatin (SOX) as first-line treatment in elderly patients with advanced gastric cancer. One hundred and twenty-nine patients with recurrent or metastatic gastric adenocarcinoma were treated with SOX; S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily on days 1 to 14 followed by a 7-day rest period, 130 mg/m(2) oxaliplatin was given as an intravenous infusion over 2-hours on day one. The cycle was repeated every three weeks. All of the patients were older than 65 years. Among 129 patients enrolled, nine patients could not be evaluated for responses because of the absence of any measurable lesions or early discontinuation of therapy. Assessment of the response of 120 patients was made. The overall objective response rate was 54.2 % (95 %CI, 45.3-63.1 %), with three complete responses and 62 partial responses. The disease control rate was 80.8 % (95 %CI, 73.8-87.8 %). The median follow-up period was 23 months (range, 5-42 months). The median time to progression was 6.9 months (95 %CI, 5.5-8.3 months) and the median overall survival was 12.8 months (95 %CI, 11.4-14.2 months). The one-year survival rate was 57.5 % (95 %CI, 48.7-66.3 %). In 129 patients assessed safety, grade 3 and 4 toxicities included leucopenia (20.9 %), neutropenia (24.0 %), anemia (10.9 %), thrombocytopenia (10.1 %), anorexia (3.1 %), peripheral neurotoxicity (15.5 %), and fatigue (12.4 %). No treatment-related deaths occurred. Combination chemotherapy with SOX offers an effective, safe and well-tolerated regimen for elderly patients with advanced gastric cancer.

  7. Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice.

    PubMed

    Almeida-Reis, Rafael; Theodoro-Junior, Osmar A; Oliveira, Bruno T M; Oliva, Leandro V; Toledo-Arruda, Alessandra C; Bonturi, Camila R; Brito, Marlon V; Lopes, Fernanda D T Q S; Prado, Carla M; Florencio, Ariana C; Martins, Mílton A; Owen, Caroline A; Leick, Edna A; Oliva, Maria L V; Tibério, Iolanda F L C

    2017-01-01

    Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.  C57BL / 6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNF α -, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2 α , collagen, and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNF α -positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease.

  8. Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice

    PubMed Central

    Theodoro-Junior, Osmar A.; Oliveira, Bruno T. M.; Oliva, Leandro V.; Toledo-Arruda, Alessandra C.; Bonturi, Camila R.; Brito, Marlon V.; Prado, Carla M.; Florencio, Ariana C.; Martins, Mílton A.; Owen, Caroline A.; Oliva, Maria L. V.

    2017-01-01

    Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.  C57BL/6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNFα-, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2α, collagen, and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNFα-positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease. PMID:28466019

  9. Dose-dense weekly chemotherapy in advanced ovarian cancer: An updated meta-analysis of randomized controlled trials.

    PubMed

    Marchetti, C; De Felice, F; Di Pinto, A; D'Oria, O; Aleksa, N; Musella, A; Palaia, I; Muzii, L; Tombolini, V; Benedetti Panici, P

    2018-05-01

    The use of dose-dense weekly chemotherapy in the management of advanced ovarian cancer (OC) remains controversial. The aim of this meta-analysis was to evaluate the efficacy of dose-dense regimen to improve clinical outcomes in OC patients with the inclusion of new trials. For this updated meta-analysis, PubMed Medline and Scopus databases and meeting proceedings were searched for eligible studies with the limitation of randomized controlled trials, comparing dose-dense chemotherapy versus standard treatment. Trials were grouped in two types of dose-dense chemotherapy: weekly dose-dense (both paclitaxel and carboplatin weekly administration) and semi-weekly dose-dense (weekly paclitaxel and three weekly carboplatin administration). Data were extracted independently and were analyzed using RevMan statistical software version 5.3 (http://www.cochrane.org). Primary end-point was progression-free survival (PFS). Four randomized controlled trials comprising 3698 patients were identified as eligible. Dose-dense chemotherapy had not a significant benefit on PFS (HR 0.92, 95% CI 0.81-1.04, p = 0.20). When the analysis was restricted to both weekly and semi-weekly dose-dense data, a no significant interaction between dose-dense and standard regimen was confirmed (HR 1.01, 95% CI 0.93-1.10 and HR 0.82, 95% CI 0.63-1.08, respectively). In the absence of PFS superiority of dose-dense schedule, three weekly schedule should remain the standard of care for advanced OC. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Geochemistry of CI chondrites: Major and trace elements, and Cu and Zn Isotopes

    NASA Astrophysics Data System (ADS)

    Barrat, J. A.; Zanda, B.; Moynier, F.; Bollinger, C.; Liorzou, C.; Bayon, G.

    2012-04-01

    In order to check the heterogeneity of the CI chondrites and determine the average composition of this group of meteorites, we analyzed a series of six large chips (weighing between 0.6 and 1.2 g) of Orgueil prepared from five different stones. In addition, one sample from each of Ivuna and Alais was analyzed. Although the sizes of the chips used in this study were “large”, our results show evidence for minor chemical heterogeneity in Orgueil, particularly for alkali elements and U. After removal of one outlier sample, the spread of the results is considerably reduced. For most of the 46 elements analyzed in this study, the average composition calculated for Orgueil is in very good agreement with previous CI estimates. This average, obtained with a “large” mass of samples, is analytically homogeneous and is suitable for normalization purposes. Finally, the Cu and Zn isotopic ratios are homogeneously distributed within the CI parent body with a spread of less than 100 ppm per atomic mass unit (amu).

  11. Quality of Dying in Nursing Home Residents Dying with Dementia: Does Advanced Care Planning Matter? A Nationwide Postmortem Study

    PubMed Central

    Vandervoort, An; Houttekier, Dirk; Vander Stichele, Robert; van der Steen, Jenny T.; Van den Block, Lieve

    2014-01-01

    Background Advance care planning is considered a central component of good quality palliative care and especially relevant for people who lose the capacity to make decisions at the end of life, which is the case for many nursing home residents with dementia. We set out to investigate to what extent (1) advance care planning in the form of written advance patient directives and verbal communication with patient and/or relatives about future care and (2) the existence of written advance general practitioner orders are related to the quality of dying of nursing home residents with dementia. Methods Cross-sectional study of deaths (2010) using random cluster-sampling. Representative sample of nursing homes in Flanders, Belgium. Deaths of residents with dementia in a three-month period were reported; for each the nurse most involved in care, GP and closest relative completed structured questionnaires. Findings We identified 101 deaths of residents with dementia in 69 nursing homes (58% response rate). A written advance patient directive was present for 17.5%, GP-orders for 56.7%. Controlling for socio-demographic/clinical characteristics in multivariate regression analyses, chances of having a higher mean rating of emotional well-being (less fear and anxiety) on the Comfort Assessment in Dying with Dementia scale were three times higher with a written advance patient directive and more specifically when having a do-not-resuscitate order (AOR 3.45; CI,1.1–11) than for those without either (AOR 2.99; CI,1.1–8.3). We found no association between verbal communication or having a GP order and quality of dying. Conclusion For nursing home residents with dementia there is a strong association between having a written advance directive and quality of dying. Where wishes are written, relatives report lower levels of emotional distress at the end of life. These results underpin the importance of advance care planning for people with dementia and beginning this process as

  12. Clinical and radiographic evaluation of maxillary central incisors exposure in patients undergoing maxillary advancement

    PubMed Central

    Trento, Guilherme dos Santos; Bernabé, Felipe Bueno Rosettti; da Costa, Delson João; Rebellato, Nelson Luis Barbosa; Klüppel, Leandro Eduardo; Scariot, Rafaela

    2015-01-01

    Abstract Introduction: Patients with dentofacial deformities may undergo orthodontic or orthodontic-surgical treatment. Both modalities can affect esthetics. Objective: This study aims to evaluate clinical and radiographic changes in exposure of maxillary central incisors occurring after orthognathic surgery for maxillary advancement. Methods: A total of 17 patients who underwent orthognathic surgery for maxillary advancement between September, 2010 and July, 2011 were selected. Exposure of maxillary central incisors was evaluated clinically and by lateral cephalograms. Measurements were taken one week before and three months after surgery. Data were paired in terms of sex, age, nasolabial angle, height and thickness of the upper lip, the amount of maxillary advancement, clinical exposure and inclination of maxillary central incisor by statistical tests (CI 95%). Results: After maxillary advancement, incisor clinical exposure had increased even with relaxed lips and under forced smile. Moreover, there was a mean increase of 23.33% revealed by lateral cephalograms. There was an inverse correlation between upper lip thickness and incisors postsurgical exposure revealed by radiographic images (p = 0.002). Conclusions: Significant changes in the exposure of maxillary central incisors occur after maxillary advancement, under the influence of some factors, especially lip thickness. PMID:26691970

  13. Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury

    PubMed Central

    Pannu, Neesh; Hemmelgarn, Brenda R.; Austin, Peter C.; Tan, Zhi; McArthur, Eric; Manns, Braden J.; Tonelli, Marcello; Wald, Ron; Quinn, Robert R.; Ravani, Pietro; Garg, Amit X.

    2017-01-01

    baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%). Conclusions and Relevance A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research. PMID:29136443

  14. A phase II and biomarker study of ramucirumab, a human monoclonal antibody targeting the VEGF receptor-2, as first-line monotherapy in patients with advanced hepatocellular cancer.

    PubMed

    Zhu, Andrew X; Finn, Richard S; Mulcahy, Mary; Gurtler, Jayne; Sun, Weijing; Schwartz, Jonathan D; Dalal, Rita P; Joshi, Adarsh; Hozak, Rebecca R; Xu, Yihuan; Ancukiewicz, Marek; Jain, Rakesh K; Nugent, Francis W; Duda, Dan G; Stuart, Keith

    2013-12-01

    To assess the efficacy and safety of the anti-VEGF receptor-2 (VEGFR-2) antibody ramucirumab as first-line therapy in patients with advanced hepatocellular carcinoma and explore potential circulating biomarkers. Adults with advanced hepatocellular carcinoma and no prior systemic treatment received ramucirumab 8 mg/kg every two weeks until disease progression or limiting toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR) and overall survival (OS). Circulating biomarkers were evaluated before and after ramucirumab treatment in a subset of patients. Forty-two patients received ramucirumab. Median PFS was 4.0 months [95% confidence interval (CI), 2.6-5.7], ORR was 9.5% (95% CI, 2.7-22.6; 4/42 patients had a partial response), and median OS was 12.0 months (95% CI, 6.1-19.7). For patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease, median OS was 4.4 months (95% CI, 0.5-9.0) for patients with Child-Pugh B cirrhosis versus 18.0 months (95% CI, 6.1-23.5) for patients with Child-Pugh A cirrhosis. Treatment-related grade ≥ 3 toxicities included hypertension (14%), gastrointestinal hemorrhage and infusion-related reactions (7% each), and fatigue (5%). There was one treatment-related death (gastrointestinal hemorrhage). After treatment with ramucirumab, there was an increase in serum VEGF and placental growth factor (PlGF) and a transient decrease in soluble VEGFR-2. Ramucirumab monotherapy may confer anticancer activity in advanced hepatocellular carcinoma with an acceptable safety profile. Exploratory biomarker studies showed changes in circulating VEGF, PlGF, and sVEGFR-2 that are consistent with those seen with other anti-VEGF agents. ©2013 AACR.

  15. Spacecraft COst REduction Team (SCORE): TQM/CI on a massive scale

    NASA Technical Reports Server (NTRS)

    Bullard, Jerry D.

    1992-01-01

    The business of building satellites and space systems has matured. Few missions require, or can afford, excellent performance at any price. The new paradigm is doing more with less, providing quality systems at lower cost--in other words, doing our job 'Faster-Better-Cheaper.' The TRW Spacecraft COst REduction (SCORE) initiative was launched in 1990 by Daniel S. Goldin, then general manager of TRW's Space & Technology Group. The SCORE mission is to apply continuous improvement (CI) techniques to effect major reductions in the cost (our primary goal) and span time (as a corollary) required for the production of spacecraft. SCORE is a multi-year initiative that is having a profound effect on both the procedural and the cultural aspects of how we do business. The objectives of this initiative are being realized. The focus of this paper is not on the results of SCORE per se, but rather on the things we have leaned about how to do continuous improvement on a massive scale, with multilevel (hierarchical) CI teams. The following sections summarize the chronology of the SCORE initiative, from team formation to development of the year-end report for 1991. Lessons learned, the core of this presentation, are discussed--with particular focus on the unique aspects of SCORE. The SCORE initiative is continuing and, as a part of our evolving culture, will never end. It has resulted in profound insights into the way we do work and (the topic at hand) how to do CI for large and complex multidisciplinary development activities.

  16. School performance and wellbeing of children with CI in different communicative-educational environments.

    PubMed

    Langereis, Margreet; Vermeulen, Anneke

    2015-06-01

    This study aimed to evaluate the long term effects of CI on auditory, language, educational and social-emotional development of deaf children in different educational-communicative settings. The outcomes of 58 children with profound hearing loss and normal non-verbal cognition, after 60 months of CI use have been analyzed. At testing the children were enrolled in three different educational settings; in mainstream education, where spoken language is used or in hard-of-hearing education where sign supported spoken language is used and in bilingual deaf education, with Sign Language of the Netherlands and Sign Supported Dutch. Children were assessed on auditory speech perception, receptive language, educational attainment and wellbeing. Auditory speech perception of children with CI in mainstream education enable them to acquire language and educational levels that are comparable to those of their normal hearing peers. Although the children in mainstream and hard-of-hearing settings show similar speech perception abilities, language development in children in hard-of-hearing settings lags significantly behind. Speech perception, language and educational attainments of children in deaf education remained extremely poor. Furthermore more children in mainstream and hard-of-hearing environments are resilient than in deaf educational settings. Regression analyses showed an important influence of educational setting. Children with CI who are placed in early intervention environments that facilitate auditory development are able to achieve good auditory speech perception, language and educational levels on the long term. Most parents of these children report no social-emotional concerns. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Understanding chemotherapy treatment pathways of advanced colorectal cancer patients to inform an economic evaluation in the United Kingdom

    PubMed Central

    Shabaruddin, F H; Elliott, R A; Valle, J W; Newman, W G; Payne, K

    2010-01-01

    Background: Accurate description of current practice within advanced colorectal cancer (CRC) specialties were needed to inform an economic evaluation of the UGT1A1 pharmacogenetic test for irinotecan in the United Kingdom. Methods: The study was based on a literature review and elicitation of expert opinion. The expert panel comprised 44 consultant oncologists in NHS Hospital Trusts across England. Results: Ten first-line, 10 second-line and 12 third-line chemotherapy regimens were reported, reflecting wide variations in treatment pathways. Predominant pathways emerged with: first-line treatment with oxaliplatin-based regimens, second-line treatment with irinotecan-based regimens and third-line treatment with mitomycin-based regimens. Experts estimated the frequency of febrile neutropaenia 8.4% (95% CI: 6.7–10.0), septic neutropaenia 4.7% (95% CI: 3.4–6.0) and severe diarrhoea 13.1% (95% CI: 10.8–15.5). Approaches for the clinical management of neutropaenia within the NHS were described. Conclusions: This study identified wide variations in the clinical management of advanced CRC patients. Descriptions of current treatment pathways are necessary for economic evaluations. Variations in clinical practice must be reflected in the model to ensure the findings from an economic evaluation of UGT1A1 testing are sufficient to inform policy regarding the cost-effective use of NHS resources. PMID:20661248

  18. On the extension of the MCSCF/CI method

    NASA Technical Reports Server (NTRS)

    Bauschlicher, C., Jr.; Nelin, C. J.; Komornicki, A.

    1984-01-01

    Research conducted during this period was focused on two main areas: (1) bonding in transition metal oxides; and (2) adsorption of CO on Al and Ni. In both of these theoretical studies a major interest was to obtain a better understanding of the nature of the bonding in transition metal containing systems. The studies used self consistent field (SCF), multi-configuration self cosistent field (MCSCF) and configuration interaction (CI) methods in the treatment of the transition metal oxides and only the SCF method in the adsorption studies. The reports of three principle investigators who contributed to this work during the tenure of the project are presented along with associated published papers.

  19. Advanced Understanding of Convection Initiation and Optimizing Cloud Seeding by Advanced Remote Sensing and Land Cover Modification over the United Arab Emirates

    NASA Astrophysics Data System (ADS)

    Wulfmeyer, V.; Behrendt, A.; Branch, O.; Schwitalla, T.

    2016-12-01

    A prerequisite for significant precipitation amounts is the presence of convergence zones. These are due to land surface heterogeneity, orography as well as mesoscale and synoptic scale circulations. Only, if these convergence zones are strong enough and interact with an upper level instability, deep convection can be initiated. For the understanding of convection initiation (CI) and optimal cloud seeding deployment, it is essential that these convergence zones are detected before clouds are developing in order to preempt the decisive microphysical processes for liquid water and ice formation. In this presentation, a new project on Optimizing Cloud Seeding by Advanced Remote Sensing and Land Cover Modification (OCAL) is introduced, which is funded by the United Arab Emirates Rain Enhancement Program (UAEREP). This project has two research components. The first component focuses on an improved detection and forecasting of convergence zones and CI by a) operation of scanning Doppler lidar and cloud radar systems during two seasonal field campaigns in orographic terrain and over the desert in the UAE, and b) advanced forecasting of convergence zones and CI with the WRF-NOAHMP model system. Nowcasting to short-range forecasting of convection will be improved by the assimilation of Doppler lidar and the UAE radar network data. For the latter, we will apply a new model forward operator developed at our institute. Forecast uncertainties will be assessed by ensemble simulations driven by ECMWF boundaries. The second research component of OCAL will study whether artificial modifications of land surface heterogeneity are possible through plantations or changes of terrain, leading to an amplification of convergence zones. This is based on our pioneering work on high-resolution modeling of the impact of plantations on weather and climate in arid regions. A specific design of the shape and location of plantations can lead to the formation of convergence zones, which can

  20. Combustion Characteristics of CI Diesel Engine Fuelled With Blends of Jatropha Oil Biodiesel

    NASA Astrophysics Data System (ADS)

    Singh, Manpreet; Yunus Sheikh, Mohd.; Singh, Dharmendra; Nageswara rao, P.

    2018-03-01

    Jatropha Curcas oil is a non-edible oil which is used for Jatropha biodiesel (JBD) production. Jatropha biodiesel is produced using transesterification technique and it is used as an alternative fuel in CI diesel engine without any hardware modification. Jatropha biodiesel is used in CI diesel engine with various volumetric concentrations (blends) such as JBD5, JBD15, JBD25, JBD35 and JBD45. The combustion parameters such as in-cylinder pressure, rate of pressure rise, net heat release, cumulative heat release, mass fraction burned are analyzed and compared for all blends combustion data with mineral diesel fuel (D100).

  1. The circular RNA ciRS-7 promotes APP and BACE1 degradation in an NF-κB-dependent manner.

    PubMed

    Shi, Zhemin; Chen, Ting; Yao, Qingbin; Zheng, Lina; Zhang, Zhen; Wang, Jingzhao; Hu, Zhimei; Cui, Hongmei; Han, Yawei; Han, Xiaohui; Zhang, Kun; Hong, Wei

    2017-04-01

    The aberrant accumulation of β-amyloid peptide (Aβ) in the brain is a key feature of Alzheimer's disease (AD), and enhanced cleavage of β-amyloid precursor protein (APP) by β-site APP-cleaving enzyme 1 (BACE1) has a major causative role in AD. Despite their prominence in AD pathogenesis, the regulation of BACE1 and APP is incompletely understood. In this study, we report that the circular RNA circular RNA sponge for miR-7 (ciRS-7) has an important role in regulating BACE1 and APP protein levels. Previous studies have shown that ciRS-7, which is highly expressed in the human brain, is down-regulated in the brain of people with AD but the relevance of this finding was not clear. We have found that ciRS-7 is not involved in the regulation of APP and BACE1 gene expression, but instead reduces the protein levels of APP and BACE1 by promoting their degradation via the proteasome and lysosome. Consequently, overexpression of ciRS-7 reduces the generation of Aβ, indicating a potential neuroprotective role of ciRS-7. Our data also suggest that ciRS-7 modulates APP and BACE1 levels in a nuclear factor-κB (NF-κB)-dependent manner: ciRS-7 expression inhibits translation of NF-κB and induces its cytoplasmic localization, thus derepressing expression of UCHL1, which promotes APP and BACE1 degradation. Additionally, we demonstrated that APP reduces the level of ciRS-7, revealing a mutual regulation of ciRS-7 and APP. Taken together, our data provide a molecular mechanism implicating reduced ciRS-7 expression in AD, suggesting that ciRS-7 may represent a useful target in the development of therapeutic strategies for AD. © 2017 Federation of European Biochemical Societies.

  2. Genial tubercle advancement and genioplasty for obstructive sleep apnea: A systematic review and meta-analysis.

    PubMed

    Song, Sungjin A; Chang, Edward T; Certal, Victor; Del Do, Michael; Zaghi, Soroush; Liu, Stanley Yung; Capasso, Robson; Camacho, Macario

    2017-04-01

    To perform a systematic review and meta-analysis for studies evaluating genioplasty alone, genial tubercle advancement (GTA) alone, and GTA with hyoid surgery (GTA-HS) to treat obstructive sleep apnea (OSA). Ten databases. Three authors searched through November 15, 2015. 1,207 studies were screened; 69 were downloaded; and 13 studies met inclusion criteria. A total of 111 patients were included, with 27 standard genioplasty, 10 modified genioplasty, 24 GTA, and 50 GTA-HS patients. For standard genioplasty, the apnea-hypopnea index (AHI) reduced from a mean ± standard deviation (M ± SD) of 18.8 ± 3.8 (95% confidence interval [CI] 17.6, 20.0) to 10.8 ± 4.0 (95% CI 9.5, 12.1) events/hour (relative reduction 43.8%), P value = 0.0001. Genioplasty improved lowest oxygen saturation (LSAT) from 82.3 ± 7.3% (95% CI 80.0, 84.7) to 86.8 ± 5.2% (95% CI 85.1, 88.5), P value = 0.0032. For modified genioplasty AHI increased by 37.3%. For GTA, the AHI reduced from an M ± SD of 37.6 ± 24.2 (95% CI 27.9, 47.3) to 20.4 ± 15.1 (95% CI 14.4, 26.4) events/hour (relative reduction 45.7%), P value = 0.0049. GTA improved LSAT from 83.1 ± 8.3% (95% CI 79.8, 86.4) to 85.5 ± 6.8% (95% CI 82.8, 88.2), P value = 0.2789. For GTA-HS, the AHI reduced from an M ± SD of 34.5 ± 22.1 (95% CI 28.4, 40.6) to 15.3 ± 17.6 (95% CI 10.4, 20.2) events/hour (relative reduction 55.7%), P value < 0.0001; GTA-HS improved LSAT from 80.1 ± 16.6% (95% CI 75.5, 84.7) to 88.3 ± 6.9% (95% CI 86.4, 90.2), P value = 0.0017. Standard genioplasty, GTA and GTA-HS can improve OSA outcomes such as AHI and LSAT. Given the low number of studies, these procedures remain as an area for additional OSA research. Laryngoscope, 127:984-992, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  3. Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study

    PubMed Central

    GADALETA-CALDAROLA, GENNARO; INFUSINO, STEFANIA; GALISE, IDA; RANIERI, GIROLAMO; VINCIARELLI, GIANLUCA; FAZIO, VITO; DIVELLA, ROSA; DANIELE, ANTONELLA; FILIPPELLI, GIANFRANCO; GADALETA, COSMO DAMIANO

    2014-01-01

    The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55–73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2–6.2) and 10.4 (95% CI, 10–11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC. PMID:25202410

  4. Determining the Optimum Cut-Off Grades in Sulfide Copper Deposits / Określanie Optymalnej Wartości Odcięcia Zawartości Procentowej Pierwiastka Użytecznego W Złożach Siarczku Miedzi

    NASA Astrophysics Data System (ADS)

    Rahimi, Esmaeil; Oraee, Kazem; Shafahi, Zia Aldin; Ghasemzadeh, Hasan

    2015-03-01

    Optimum cut-off grades determination in mining life affects production planning and ultimate pit limit and it is also important from social, economical and environmental aspects. Calculation of optimum cut-off grades has been less considered for mines containing various mineral processing methods. In this paper, an optimization technique is applied to obtain optimum cut-off grades for both concentration and heap leaching processes. In this technique, production costs and different recoveries of heap leaching method directed into modeling different annual cash flows in copper mines. Considering the governing constraints, the Lagrange multiplier method is practiced to optimize the cut-off grades in which the objective function is supposed to maximize Net Present Value. The results indicate the effect of heap leaching process on the optimum cut-off grades of primary and secondary sulfide deposits. Określanie optymalnego poziomu odcięcia dla zawartości procentowej pierwiastka użytecznego ma poważny wpływ na planowanie produkcji, określanie ostatecznych limitów zasobów złoża; jest to także ważna kwestia z punktu widzenia kwestii społecznych, ekonomicznych i środowiskowych. Obliczanie optymalnego poziomu odcięcia dla zawartości procentowej pierwiastka użytecznego nie było zwykle szeroko rozważane w przypadku kopalni prowadzących ciągły system przeróbki. W pracy tej przedstawiono technikę optymalizacji określania poziomu zawartości procentowej pierwiastka użytecznego z uwzględnieniem zarówno procesów koncentracji jak i ługowania. W metodzie uwzględniono koszty produkcji i różne wskaźniki odzysku rudy, wielkości te wykorzystane zostały do modelowania rocznych przepływów gotówki w kopalniach miedzi. Uwzględniając narzucone ograniczenia, zastosowano metodę mnożników Lagrange'a w celu optymalizacji określania poziomu zawartości procentowej pierwiastka użytecznego, gdzie przyjętą funkcją celu jest

  5. Spectral characteristics of iron-bearing phyllosilicates: Comparison to Orgueil (CI1), Murchison and Murray (CM2)

    USGS Publications Warehouse

    Calvin, W.M.; King, T.V.V.

    1997-01-01

    Phyllosilicate alteration minerals are commonly found in low petrologic types of carbonaceous chondrites. Previous spectral studies have examined Mg-bearing phyllosilicates with limited success in matching the spectral properties of CM and CI chondrites. Transmission electron microscope and other analytical techniques suggest that Fe-bearing clays are more abundant in CI and CM chondrites than magnesian varieties. Here, we present the results of an examination of the reflectance spectra of Fe-phyllosilicates, including serpentines and berthierines, of which the latter were formerly known as septechlorites. We have measured the diffuse reflectance spectra of powdered samples from 0.3 to 25 ??m. We find that these minerals provide a better spectral match to many of the features seen in CI and CM chondrites, and simple linear combinations of the spectra of both Fe- and Mg-phyllosilicates closely approximate the spectra of CM and CI chondrites.

  6. Progress in the clinical development and utilization of vision prostheses: an update

    PubMed Central

    Brandli, Alice; Luu, Chi D; Guymer, Robyn H; Ayton, Lauren N

    2016-01-01

    Vision prostheses, or “bionic eyes”, are implantable medical bionic devices with the potential to restore rudimentary sight to people with profound vision loss or blindness. In the past two decades, this field has rapidly progressed, and there are now two commercially available retinal prostheses in the US and Europe, and a number of next-generation devices in development. This review provides an update on the development of these devices and a discussion on the future directions for the field. PMID:28539798

  7. HIV-infection has no prognostic impact on advanced-stage Hodgkin lymphoma.

    PubMed

    Sorigué, Marc; García, Olga; Tapia, Gustavo; Baptista, Maria-Joao; Moreno, Miriam; Mate, José-Luis; Sancho, Juan M; Feliu, Evarist; Ribera, Josep-Maria; Navarro, José-Tomás

    2017-06-19

    Classical Hodgkin lymphoma (cHL) is a non-AIDS-defining cancer with a good response to chemotherapy in the combined antiretroviral therapy (cART) era. The aim of the present study was to compare the characteristics, the response to treatment and the survival of advanced-stage cHL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) between cART-treated HIV-positive and HIV-negative patients. We retrospectively analyzed advanced-stage cHL patients from a single institution, uniformly treated with ABVD. All HIV-positive patients received cART concomitantly with ABVD. A total of 69 patients were included in the study: 21 were HIV-positive and 48 were HIV-negative. HIV-positive patients had more aggressive features at cHL diagnosis, such as worse performance status, more frequent bone marrow involvement and mixed cellularity histologic subtype. There were no differences in complete response rate (89% in HIV-positive vs. 91% in HIV-negative), P = 1; disease-free survival (DFS) [10-year DFS probability (95% CI) 70% (41-99%) vs. 74% (57-91%)], P = 0.907 and overall survival (OS) [10-year OS probability (95% CI) 73% (52-94%) vs. 68% (51-85%)], P = 0.904. On multivariate analysis, HIV infection did not correlate with worse OS. Although HIV-positive patients with cHL had more aggressive baseline features in this series, there were no differences in response rate or survival between HIV-positive and HIV-negative patients.

  8. Early Sign Language Experience Goes Along with an Increased Cross-modal Gain for Affective Prosodic Recognition in Congenitally Deaf CI Users.

    PubMed

    Fengler, Ineke; Delfau, Pia-Céline; Röder, Brigitte

    2018-04-01

    It is yet unclear whether congenitally deaf cochlear implant (CD CI) users' visual and multisensory emotion perception is influenced by their history in sign language acquisition. We hypothesized that early-signing CD CI users, relative to late-signing CD CI users and hearing, non-signing controls, show better facial expression recognition and rely more on the facial cues of audio-visual emotional stimuli. Two groups of young adult CD CI users-early signers (ES CI users; n = 11) and late signers (LS CI users; n = 10)-and a group of hearing, non-signing, age-matched controls (n = 12) performed an emotion recognition task with auditory, visual, and cross-modal emotionally congruent and incongruent speech stimuli. On different trials, participants categorized either the facial or the vocal expressions. The ES CI users more accurately recognized affective prosody than the LS CI users in the presence of congruent facial information. Furthermore, the ES CI users, but not the LS CI users, gained more than the controls from congruent visual stimuli when recognizing affective prosody. Both CI groups performed overall worse than the controls in recognizing affective prosody. These results suggest that early sign language experience affects multisensory emotion perception in CD CI users.

  9. Efficacy and safety of sorafenib in combination with gemcitabine in patients with advanced hepatocellular carcinoma: a multicenter, open-label, single-arm phase II study.

    PubMed

    Srimuninnimit, Vichien; Sriuranpong, Virote; Suwanvecho, Suthida

    2014-09-01

    Currently, the only standard systemic treatment for advanced hepatocellular carcinoma is sorafenib monotherapy. The study was conducted to assess the efficacy and safety of the novel combination of sorafenib and gemcitabine in the treatment of advanced hepatocellular carcinoma. Between March 2008 and October 2010, patients with advanced pathologically proven hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A or B received sorafenib plus gemcitabine. Treatment included 4-week cycle of gemcitabine (1000 mg/m(2) days 1, 8, 15) to the maximum of six cycles together with sorafenib (400 mg twice daily). Patient continued sorafenib until disease progression or withdrawal from other reasons. The primary end point is progression-free survival. Forty-five patients were enrolled in this study. The median progression-free survival was 3.7 months (95% CI 3.5-3.8). The overall response rate was 4% with no complete responses and the disease control rate was 66%. The median overall survival (OS) was 11.6 months (95% CI 7.4-15.9). The median time to progression was 3.6 months (95% CI 3.4-3.7). The most frequently reported grade 3/4 treatment-related adverse events included thrombocytopenia 33%, neutropenia 16% and hand-foot skin reaction 13%. The study regimen was well tolerated. The combination of sorafenib and gemcitabine in advanced hepatocellular carcinoma is generally well tolerated and has modest clinical efficacy. The median OS is up to 1 year. However, well-designed randomized controlled trials with a sorafenib alone comparator arm are needed to confirm this finding. © 2014 Wiley Publishing Asia Pty Ltd.

  10. Determination of Spatially Resolved Tablet Density and Hardness Using Near-Infrared Chemical Imaging (NIR-CI).

    PubMed

    Talwar, Sameer; Roopwani, Rahul; Anderson, Carl A; Buckner, Ira S; Drennen, James K

    2017-08-01

    Near-infrared chemical imaging (NIR-CI) combines spectroscopy with digital imaging, enabling spatially resolved analysis and characterization of pharmaceutical samples. Hardness and relative density are critical quality attributes (CQA) that affect tablet performance. Intra-sample density or hardness variability can reveal deficiencies in formulation design or the tableting process. This study was designed to develop NIR-CI methods to predict spatially resolved tablet density and hardness. The method was implemented using a two-step procedure. First, NIR-CI was used to develop a relative density/solid fraction (SF) prediction method for pure microcrystalline cellulose (MCC) compacts only. A partial least squares (PLS) model for predicting SF was generated by regressing the spectra of certain representative pixels selected from each image against the compact SF. Pixel selection was accomplished with a threshold based on the Euclidean distance from the median tablet spectrum. Second, micro-indentation was performed on the calibration compacts to obtain hardness values. A univariate model was developed by relating the empirical hardness values to the NIR-CI predicted SF at the micro-indented pixel locations: this model generated spatially resolved hardness predictions for the entire tablet surface.

  11. Echocardiographic evaluation of right ventricular stroke work index in advanced heart failure: a new index?

    PubMed

    Frea, Simone; Bovolo, Virginia; Bergerone, Serena; D'Ascenzo, Fabrizio; Antolini, Marina; Capriolo, Michele; Canavosio, Federico Giovanni; Morello, Mara; Gaita, Fiorenzo

    2012-12-01

    Right ventricular (RV) function plays a pivotal role in advanced heart failure patients, especially for screening those who may benefit from left ventricular assist device (LVAD) implantation. We introduce RV contraction pressure index (RVCPI) as a new echo-Doppler parameter of RV function. The accuracy of RVCPI in detecting RV failure was compared with the criterion standard, the RV stroke work index (RVSWI) obtained through right heart catheterization in advanced heart failure patients referred for heart transplantation or LVAD implantation. Right heart catheterization and echo-Doppler were simultaneously performed in 94 consecutive patients referred to our center for advanced heart failure (ejection fraction (EF) 24 ± 8.8%, 40% NYHA functional class IV). RV stroke volume and invasive pulmonary pressures were used to obtain RVSWI. Simplified RVCPI (sRVCPI) was derived as TAPSE × (RV - right atrial pressure gradient). Close positive correlation between sRVCPI and RVSWI was found (r = 0.68; P < .001). With logistic regression, we found that increased sRVCPI showed an independent reduced risk (odds ratio 0.98, 95% confidence interval [CI] 0.97-0.99; P = .016) for patients to present a depressed RVSWI (<0.25 mm Hg/L·m(2)). Simplified RVCPI showed high diagnostic accuracy (area under the receiver operating characteristic curve 0.94, 95% CI 0.89-0.99) and good sensitivity and specificity (92% and 85%, respectively) to predict depressed RVSWI with the use of a cutoff value of <400 mm·mm Hg. In patients with advanced heart failure, the new simple bedside sRVCPI closely correlated with RVSWI, providing an independent, noninvasive, and easy tool for the evaluation of RV function. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Advance Care Planning and the Quality of End-of-Life Care among Older Adults

    PubMed Central

    Bischoff, Kara E.; Sudore, Rebecca; Miao, Yinghui; Boscardin, W. John; Smith, Alexander K.

    2013-01-01

    Background Advance care planning is increasingly common, but whether it influences end-of-life quality of care remains controversial. Design Medicare data and survey data from the Health and Retirement Study were combined to determine whether advance care planning was associated with quality metrics. Setting The nationally representative Health and Retirement Study. Participants 4394 decedent subjects (mean age 82.6 years at death, 55% women). Measurements Advance care planning was defined as having an advance directive, durable power of attorney or having discussed preferences for end-of-life care with a next-of-kin. Outcomes included previously reported quality metrics observed during the last month of life (rates of hospital admission, in-hospital death, >14 days in the hospital, intensive care unit admission, >1 emergency department visit, hospice admission, and length of hospice ≤3 days). Results Seventy-six percent of subjects engaged in advance care planning. Ninety-two percent of advance directives stated a preference to prioritize comfort. After adjustment, subjects who engaged in advance care planning were less likely to die in a hospital (adjusted RR 0.87, 95% CI 0.80-0.94), more likely to be enrolled in hospice (aRR 1.68, 1.43-1.97), and less likely to receive hospice for ≤3 days before death (aRR 0.88, 0.85-0.91). Having an advance directive, a durable-power-of-attorney or an advance care planning discussion were each independently associated with a significant increase in hospice use (p<0.01 for all). Conclusion Advance care planning was associated with improved quality of care at the end of life, including less in-hospital death and increased use of hospice. Having an advance directive, assigning a durable power of attorney and conducting advance care planning discussions are all important elements of advance care planning. PMID:23350921

  13. Low-lying π∗ resonances associated with cyano groups: A CAP/SAC-CI study

    NASA Astrophysics Data System (ADS)

    Ehara, Masahiro; Kanazawa, Yuki; Sommerfeld, Thomas

    2017-01-01

    The complex absorbing potential (CAP)/symmetry-adapted cluster-configuration interaction (SAC-CI) method is applied to low-lying π∗ resonance states of molecules containing one or two cyano (CN) groups. Benchmark calculations are carried out comparing the non-variational and approximate variational approach of SAC-CI and studying the selection threshold of operators. Experimental resonance positions from electron transmission spectroscopy (ETS) are reproduced provided the anticipated deviations due to vibronic effects are taken into account. Moreover, the calculated positions and widths agree well with those obtained in previous electron scattering calculations for HCN, CH3CN and their isonitriles. Based on our results, we suggest a reassignment of the experimental ETS of fumaronitrile and malononitrile. Our present results demonstrate again that the CAP/SAC-CI method reliably predicts low-lying π∗ resonances, and regarding the total numbers of molecules and resonances investigated, it is fair to say that it is presently the most extensively used high-level method in the temporary anion field.

  14. Psychiatric Disorders and Mental Health Service Use in Patients with Advanced Cancer

    PubMed Central

    Kadan-Lottick, Nina S.; Vanderwerker, Lauren C.; Block, Susan D.; Zhang, Baohui; Prigerson, Holly G.

    2006-01-01

    BACKGROUND. Psychological morbidity has been proposed as a source of distress in cancer patients. This study aimed to: 1) determine the prevalence of diagnosable psychiatric illnesses, and 2) describe the mental health services received and predictors of service utilization in patients with advanced cancer. METHODS. This was a cross-sectional, multi-institutional study of 251 eligible patients with advanced cancer. Eligibility included: distant metastases, primary therapy failure, nonpaid caregiver, age ≥20 years, stamina for the interview, English or Spanish-speaking, and adequate cognitive ability. Trained interviewers administered the Structured Clinical Interview for the Diagnostic Statistical Manual IV (DSM-IV) modules for Major Depressive Disorder, Generalized Anxiety Disorder, Panic Disorder, Post-Traumatic Stress Disorder, and a detailed questionnaire regarding mental health service utilization. RESULTS. Overall, 12% met criteria for a major psychiatric condition and 28% had accessed a mental health intervention for a psychiatric illness since the cancer diagnosis. Seventeen percent had discussions with a mental health professional; 90% were willing to receive treatment for emotional problems. Mental health services were not accessed by 55% of patients with major psychiatric disorders. Cancer patients who had discussed psychological concerns with mental health staff (odds ratio [OR] = 19.2; 95% confidence interval [95% CI], 8.90-41.50) and non-Hispanic white patients (OR = 2.7; 95% CI, 1.01-7.43) were more likely to receive mental health services in adjusted analysis. CONCLUSIONS. Advanced cancer patients experience major psychiatric disorders at a prevalence similar to the general population, but affected individuals have a low rate of utilizing mental health services. Oncology providers can enhance utilization of mental health services, and potentially improve clinical outcomes, by discussing mental health concerns with their patients. PMID:16284994

  15. On-road Driving Performance of Patients with Bilateral Moderate and Advanced Glaucoma

    PubMed Central

    Bhorade, Anjali M.; Yom, Victoria H.; Barco, Peggy; Wilson, Bradley; Gordon, Mae; Carr, David

    2017-01-01

    Purpose To compare on-road driving performance of patients with moderate or advanced glaucoma to controls and evaluate factors associated with unsafe driving. Design Case-control pilot study. Methods A consecutive sample of 21 patients with bilateral moderate or advanced glaucoma from Washington University, St. Louis, MO and 38 community-dwelling controls were enrolled. Participants, ages 55–90 years, underwent a comprehensive clinical evaluation by a trained occupational therapist and an on-road driving evaluation by a masked driver rehabilitation specialist. Overall driving performance of pass vs. marginal/fail and number of wheel and/or brake interventions were recorded. Results Fifty-two percent of glaucoma participants scored a marginal/fail compared to 21% of controls (odds ratio [OR], 4.1; 95% CI, 1.30–13.14;p=.02). Glaucoma participants had a higher risk of wheel interventions than controls (OR, 4.67; 95% CI, 1.03–21.17;p=.046). There were no differences detected between glaucoma participants who scored a pass vs. marginal/fail for visual field mean deviation of the better (p=.62) or worse (p=.88) eye, binocular distance (p=.15) or near (p=.23) visual acuity, contrast sensitivity (p=.28) or glare (p=.88). However, glaucoma participants with a marginal/fail score performed worse on Trail Making Tests A (p=.03) and B (p=.05), right-sided Jamar grip strength (p=.02), Rapid Pace Walk (p=.03), Braking Response Time (p=.03), and identifying traffic signs (p=.05). Conclusions and Relevance Patients with bilateral moderate or advanced glaucoma are at risk for unsafe driving – particularly those with impairments on psychometric and mobility tests. A comprehensive clinical assessment and on-road driving evaluation is recommended to effectively evaluate driving safety of these patients. PMID:26949136

  16. Hematopoietic cell transplantation comorbidity index (HCT-CI) is predictive of adverse events and overall survival in older allogeneic transplant recipients.

    PubMed

    Keller, Jesse W; Andreadis, Charalambos; Damon, Lloyd E; Kaplan, Lawrence D; Martin, Thomas G; Wolf, Jeffrey L; Ai, Weiyun Z; Venstrom, Jeffrey M; Smith, Catherine C; Gaensler, Karin M L; Hwang, Jimmy; Olin, Rebecca L

    2014-07-01

    Our goal was to evaluate the ability of the hematopoietic cell transplantation comorbidity index (HCT-CI) to predict outcomes after allogeneic stem cell transplant (SCT) within the context of an older patient population, where multiple comorbidities are common. We performed a retrospective cohort study of SCT patients ≥50years of age at our institution, identifying 59 patients with complete HCT-CI data collected prospectively. HCT-CI category distribution in our sample was disproportionate, with almost half of patients having scores ≥3. High HCT-CI score (≥3 vs <3) was associated with significantly inferior OS (median OS not reached for HCT-CI <3 vs 14months for HCT-CI ≥3; hazard ratio (HR) 2.2, p=0.02). HCT-CI score was a better predictor of OS than age, performance status or conditioning intensity. When adjusted for disease relapse risk, HCT-CI score conferred a worse prognosis in the low risk group (HR 1.43, p=0.03) but not in the intermediate/high risk group (HR 1.08, p=0.65). NRM was low in the total sample (6% at one year) and was not associated with HCT-CI score. Grade 3-4 non-hematologic adverse events within the first 100days after SCT were significantly more common in the higher HCT-CI groups (p=0.02). In our older patient cohort with a high incidence of multiple comorbidities, HCT-CI score ≥3 was significantly associated with OS, particularly in the subset of patients with a low disease relapse risk. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD.

    PubMed

    Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A; Kleiner, David; Brunt, Elizabeth M; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James; Loomba, Rohit

    2015-07-01

    Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m(2), respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with

  18. Prospective Validation of Objective Prognostic Score for Advanced Cancer Inpatients in South Korea: A Multicenter Study.

    PubMed

    Yoon, Seok Joon; Suh, Sang-Yeon; Lee, Yong Joo; Park, Jeanno; Hwang, Sunwook; Lee, Sanghee Shiny; Ahn, Hong Yup; Koh, Su-Jin; Park, Keon Uk

    2017-01-01

    Objective Prognostic Score (OPS) was developed as an easy and simple prognosticating tool in South Korea. It has been validated retrospectively in a single center in South Korea. We aimed to validate the OPS prospectively for advanced cancer inpatients in South Korea using a multicenter study. This was a prospective cohort study. We enrolled 243 advanced cancer patients admitted in five palliative care units in South Korea from May 2013 till March 2015. Seven members of the Korean Palliative Medicine Research Network who are experts of palliative care led the study. Clinical variables (dyspnea/anorexia/performance status) and laboratory variables (total leukocyte counts/serum total bilirubin/serum creatinine/lactate dehydrogenase) were collected at the enrollment. Survival time was calculated as days from enrollment to death during admission. A total of 217 patients were included in the final analysis (feasibility: 89.3%). Survival time of the higher OPS group (OPS ≥3) and the lower OPS group (OPS <3) was 10.0 (95% confidence interval (CI) 7.72-12.28) days and 32.0 (95% CI 25.44-38.56) days, respectively. There were significant differences between the 2 groups (p < 0.001). Overall accuracy of OPS ≥3 for predicting survival less than three weeks was 71.0%. OPS was successfully validated using a prospective multicenter study in South Korea. It is a useful method to predict three-week survival of Korean inpatients with advanced cancer.

  19. The Impact of Advanced Age on Driving Safety in Adults with Medical Conditions.

    PubMed

    Moon, Sanghee; Ranchet, Maud; Akinwuntan, Abiodun Emmanuel; Tant, Mark; Carr, David Brian; Raji, Mukaila Ajiboye; Devos, Hannes

    2018-01-01

    Adults aged 85 and older, often referred to as the oldest-old, are the fastest-growing segment of the population. The rapidly increasing number of older adults with chronic and multiple medical conditions poses challenges regarding their driving safety. To investigate the effect of advanced age on driving safety in drivers with medical conditions. We categorized 3,425 drivers with preexisting medical conditions into four age groups: middle-aged (55-64 years, n = 1,386), young-old (65-74 years, n = 1,013), old-old (75-84 years, n = 803), or oldest-old (85 years and older, n = 223). All underwent a formal driving evaluation. The outcome measures included fitness to drive recommendation by the referring physician, comprehensive fitness to drive decision from an official driving evaluation center, history of motor vehicle crashes (MVCs), and history of traffic violations. The oldest-old reported more cardiopulmonary and visual conditions, but less neurological conditions than the old-old. Compared to the middle-aged, the oldest-old were more likely to be considered unfit to drive by the referring physicians (odds ratio [OR] = 4.47, 95% confidence interval [CI] 2.20-9.10) and by the official driving evaluation center (OR = 2.74, 95% CI 1.87-4.03). The oldest-old reported more MVCs (OR = 2.79, 95% CI 1.88-4.12) compared to the middle-aged. Advanced age adversely affected driving safety outcomes. The oldest-old are a unique age group with medical conditions known to interfere with safe driving. Driving safety strategies should particularly target the oldest-old since they are the fastest-growing group and their increased frailty is associated with severe or fatal injuries due to MVCs. © 2018 S. Karger AG, Basel.

  20. The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib: A Prisma-Compliant Systematic Review and Meta-Analysis.

    PubMed

    Zhou, Jian-Guo; Tian, Xu; Cheng, Long; Zhou, Quan; Liu, Yuan; Zhang, Yu; Bai, Yu-ju; Ma, Hu

    2015-10-01

    Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a critical member of systemic therapy for advanced non-small-cell lung cancer (NSCLC). Erlotinib is the first-generation EGFR-TKIs, the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations. However, the safety of erlotinib plus chemotherapy (CT) or erlotinib alone for advanced NSCLC remains controversial. We carried out a systematic meta-analysis to determine the overall risk of neutropenia and leukopenia associated with erlotinib. PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. RR with 95% CIs for neutropenia and leukopenia were all extracted. The random-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were conducted. We identified 12 eligible studies involving 3932 patients. Erlotinib plus CT or alone relative to CT is associated with significantly decreased risks of neutropenia and leukopenia in patients with advanced NSCLC (RR, 0.38; 95% CI, 0.21-0.71; P = 0.00; incidence: 9.9 vs. 35.2%) and (RR, 0.32; 95% CI, 0.11-0.93; P = 0.04; incidence: 3.5 vs. 11.6%), respectively. The subgroup analysis by erlotinib with or without CT showed that erlotinib combine with CT have no significance decrease the relative risks of neutropenia or leukopenia (RR, 0.98; 95% CI, 0.78-1.23; P = 0.87; incidence: 26.2 vs. 30.5%) and (RR, 0.81; 95% CI, 0.34-1.95; P = 0.64; incidence: 6.5 vs. 9.3%), respectively. However, erlotinib alone could decrease incidence of neutropenia (RR, 0.14; 95% CI, 0.07-0.27; P = 0.00; incidence: 3.7 vs. 40.8%) or leukopenia (RR, 0.07; 95% CI, 0.01-0.45; P = 0.01; incidence: 0.8 vs. 15.7%). The power analysis suggests that a power of 61.31% was determined

  1. Red blood cell transfusion, hyperkalemia, and heart failure in advanced chronic kidney disease.

    PubMed

    Gill, Karminder; Fink, Jeffrey C; Gilbertson, David T; Monda, Keri L; Muntner, Paul; Lafayette, Richard A; Petersen, Jeffrey; Chertow, Glenn M; Bradbury, Brian D

    2015-06-01

    In recent years, the use of red blood cell (RBC) transfusion for the treatment of chronic kidney disease (CKD)-related anemia has increased. We used the OptumInsight medical claims database to study the association between receiving a transfusion and hyperkalemia and heart failure events. Persons 18-64 years of age with diagnosed stage 4 or 5 CKD (not requiring dialysis) between 2006 and 2010 were followed until their first hospitalization or emergency room visit with a diagnosis of hyperkalemia or heart failure, termination of insurance coverage, or death. We used a case-only design and conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CIs) describing associations between RBC transfusion and the risks of hyperkalemia or heart failure. We used single (1:1) and variable (1:m) self-control matching intervals, with adjustment for time-varying confounders. Seven thousand eight hundred twenty-nine individuals met our inclusion criteria; two-thirds were age 50 years or older; 43% were women and 51% had diabetes. Rates of hyperkalemia and heart failure were 7.9/100 person-years (95%CI: 7.3, 8.5) and 16.3/100 person-years (95%CI: 15.5, 17.2), respectively. RBC transfusion was associated with an increased risk of both hyperkalemia (single interval matched RR = 12.0, 95%CI: 1.3, 109; multiple interval matched RR = 6.1, 95%CI: 2.5, 15.1) and heart failure (single interval matched RR = 1.7, 95%CI: 0.3, 9.2; multiple interval matched RR = 3.8, 95%CI: 1.4, 10.3). In patients with advanced CKD, RBC transfusion appears to be associated with an elevated risk of hyperkalemia and heart failure; further investigation into these risks is warranted. Copyright © 2015 John Wiley & Sons, Ltd.

  2. 40 CFR 60.4210 - What are my compliance requirements if I am a stationary CI internal combustion engine manufacturer?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... I am a stationary CI internal combustion engine manufacturer? 60.4210 Section 60.4210 Protection of... Combustion Engines Compliance Requirements § 60.4210 What are my compliance requirements if I am a stationary CI internal combustion engine manufacturer? (a) Stationary CI internal combustion engine...

  3. 40 CFR 60.4210 - What are my compliance requirements if I am a stationary CI internal combustion engine manufacturer?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... I am a stationary CI internal combustion engine manufacturer? 60.4210 Section 60.4210 Protection of... Combustion Engines Compliance Requirements § 60.4210 What are my compliance requirements if I am a stationary CI internal combustion engine manufacturer? (a) Stationary CI internal combustion engine...

  4. 40 CFR 60.4210 - What are my compliance requirements if I am a stationary CI internal combustion engine manufacturer?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... I am a stationary CI internal combustion engine manufacturer? 60.4210 Section 60.4210 Protection of... Combustion Engines Compliance Requirements § 60.4210 What are my compliance requirements if I am a stationary CI internal combustion engine manufacturer? (a) Stationary CI internal combustion engine...

  5. 40 CFR 60.4210 - What are my compliance requirements if I am a stationary CI internal combustion engine manufacturer?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... I am a stationary CI internal combustion engine manufacturer? 60.4210 Section 60.4210 Protection of... Combustion Engines Compliance Requirements § 60.4210 What are my compliance requirements if I am a stationary CI internal combustion engine manufacturer? (a) Stationary CI internal combustion engine...

  6. 40 CFR 60.4210 - What are my compliance requirements if I am a stationary CI internal combustion engine manufacturer?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... I am a stationary CI internal combustion engine manufacturer? 60.4210 Section 60.4210 Protection of... Combustion Engines Compliance Requirements § 60.4210 What are my compliance requirements if I am a stationary CI internal combustion engine manufacturer? (a) Stationary CI internal combustion engine...

  7. Magnetorheological properties of sodium sulphonate capped electrolytic iron based MR fluid: a comparison with CI based MR fluid

    NASA Astrophysics Data System (ADS)

    Vinod, Sithara; John, Reji; Philip, John

    2017-02-01

    Magnetorheological fluids have numerous engineering applications due to their interesting field assisted rheological behavior. Most commonly used dispersed phase in MR fluids is carbonyl iron (CI). The relatively high cost of CI warrants the need to develop cheaper alternatives to CI, without compromising rheological properties. With the above goal in mind, we have synthesized sodium sulphonate capped electrolytic iron based MR fluid and studied their magnetorheological properties. The results are compared with that of CI based MR fluid. EI and CI particles of average particle size of ∼10 μm with fumed silica particles additives are used in the present study. The dynamic yield stress for EI and CI based MR fluid were found to vary with field strength with an exponent of roughly 1.2 and 1.24, respectively. The slightly lower static and dynamic yield stress values of EI based MR fluid is attributed to the lower magnetization and polydispersity values. The dynamic yield stress showed a decrease of 18.73% and 61.8% for field strengths of 177 mT and 531 mT, respectively as the temperature was increased from 293 to 323 K. The optorheological studies showed a peak in the loss moduli, close to the crossover point of the storage and loss moduli, due to freely moving large sized aggregates along the shear direction that are dislodged from the rheometer plates at higher strains. Our results suggests that EI based MR fluids have magnetorheological behavior comparable to that of CI based MR fluids. As EI is much cheaper than CI, our findings will have important commercial implications in producing cost effective EI based MR fluids.

  8. Phase 2 study of bevacizumab plus erlotinib in patients with advanced hepatocellular cancer.

    PubMed

    Philip, Philip A; Mahoney, Michelle R; Holen, Kyle D; Northfelt, Donald W; Pitot, Henry C; Picus, Joel; Flynn, Patrick J; Erlichman, Charles

    2012-05-01

    Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC). Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2-stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child's Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point. Twenty-seven patients with advanced HCC (median age, 60 years) were enrolled in this multi-institutional study. The proportion of patients with Child's A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8-7.1). Median survival time was 9.5 months (95% CI, 7.1-17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea. In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression-free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients. Copyright © 2011 American Cancer Society.

  9. Phase 2 Study of Bevacizumab Plus Erlotinib in Patients With Advanced Hepatocellular Cancer

    PubMed Central

    Philip, Philip A.; Mahoney, Michelle R.; Holen, Kyle D.; Northfelt, Donald W.; Pitot, Henry C.; Picus, Joel; Flynn, Patrick J.; Erlichman, Charles

    2013-01-01

    BACKGROUND Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC). METHODS Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2-stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child’s Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point. RESULTS Twenty-seven patients with advanced HCC (median age, 60 years) were enrolled in this multi-institutional study. The proportion of patients with Child’s A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8-7.1). Median survival time was 9.5 months (95% CI, 7.1-17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea. CONCLUSIONS In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression-free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients. PMID:21953248

  10. Molecular profiling in Italian patients with advanced non-small-cell lung cancer: An observational prospective study.

    PubMed

    Gobbini, Elisa; Galetta, Domenico; Tiseo, Marcello; Graziano, Paolo; Rossi, Antonio; Bria, Emilio; Di Maio, Massimo; Rossi, Giulio; Gregorc, Vanesa; Riccardi, Ferdinando; Scotti, Vieri; Ceribelli, Anna; Buffoni, Lucio; Delmonte, Angelo; Franchina, Tindara; Migliorino, Maria Rita; Cortinovis, Diego; Pisconti, Salvatore; Bordi, Paola; Catino, Annamaria; Maiello, Evaristo; Arizio, Francesca; Novello, Silvia

    2017-09-01

    Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to European and Italian guidelines. However, molecular routine assessment remains still heterogeneous. This observational study aimed to take a picture of the real clinical practice in molecular testing and therapeutic choices in advanced Italian NSCLCs. This study prospectively enrolled newly diagnosed advanced or recurrent NSCLCs referred to 38 Italian centres, from November 2014 to November 2015. Information regarding molecular profiling and treatment choices were collected. Description of patients' outcome included overall survival (OS), progression-free survival in first (PFS1) and second-line (PFS2). Among 1787 patients enrolled, 1388 (78%) performed at least one molecular analysis during the history of disease: 76% were tested for EGFR, 53% for ALK, 27% for KRAS, 16% for ROS1, 14% for BRAF, 5% for HER2, 4% for MET and 1% for FGFR. The remaining 399 patients (22.3%) did not receive any molecular test. Among patients receiving at least one molecular analysis, 583 (42%) presented a molecular alteration. Considering EGFR mutated and/or ALK rearranged patients (402), for which target agents were routinely reimbursed at time of study in Italy, the 86% received a personalized treatment as first and/or second line: the 90% (286) of EGFR mutants received an EGFR tyrosine kinase inhibitor, mostly gefitinib (41.1%) or afatinib (36.4%) while 74% (62) of ALK translocated patients received an ALK inhibitor, mostly crizotinib (64%). Median OS was 9.34 months (95% CI 8.62-10.0), median PFS1 was 4.61 months (95%CI 4.31-4.84) and median PFS2 was 2.76 months (95%CI 2.57-3.19). In the Italian clinical practice, routine molecular assessment was largely applied in NSCLC patients, according to national guidelines, but a low level of ALK test was reached. Most of EGFR mutants an ALK rearranged patients received a personalized treatment as first and/or second line. Copyright © 2017 Elsevier

  11. Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution.

    PubMed

    Han, Kun; Sun, Yuanjue; Zhang, Jianjun; He, Aina; Zheng, Shui'er; Shen, Zan; Yao, Yang

    2014-06-01

    To investigate the feasibility and efficacy of cyclophosphamide (CTX)-hydroxycamptothecin (HCPT) as second-line chemotherapy on advanced Ewing's sarcoma. From April 2009 to November 2010, 27 patients with advanced Ewing's sarcoma who had progressive disease after the first-line chemotherapy regimen of vincristine, dactinomycin and cyclophosphamide and ifosfamide and etoposide were retrospectively reviewed in this analysis. CTX was given (0.6 g/m(2), i.v. push day 1) and HCPT (6 mg/m(2), i.v. drip days 1-5) as second-line chemotherapy every 3 weeks. The primary end-point was overall response rate, the secondary end-point included progression-free, overall survival, disease control rate and toxicities. A total of 134 cycles were given, median four cycles per patient (range 2-6). Overall response rate was 30% and disease control rate was 82%, with two complete response (8%), six partial remission (22%) and 14 stable disease (52%). The median time to progression and overall survival time were 7 months (95% CI 3-10) and 11 months (95% CI 5-18), respectively. Major severe toxicities (grade 3 and 4) were: nausea/vomiting (17%), alopecia (17%); leukopenia (27%) in total cycles. Mild toxicities (grade 1 or 2) were leukopenia (73%), nausea/vomiting (83%), hepatic lesion (14%) and anemia (44%). A CTX-HCPT regimen can control disease progression effectively and the side effects can be tolerable for Chinese advanced Ewing's sarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment. © 2012 Wiley Publishing Asia Pty Ltd.

  12. The Histone Deacetylase Inhibitor, CI994, Improves Nuclear Reprogramming and In Vitro Developmental Potential of Cloned Pig Embryos.

    PubMed

    Jin, Long; Guo, Qing; Zhang, Guang-Lei; Xing, Xiao-Xu; Xuan, Mei-Fu; Luo, Qi-Rong; Luo, Zhao-Bo; Wang, Jun-Xia; Yin, Xi-Jun; Kang, Jin-Dan

    2018-06-01

    Epigenetic reprogramming and somatic cell nuclear transfer (SCNT) cloning efficiency were recently enhanced using histone deacetylase inhibitors (HDACis). In this study, we investigated the time effect of CI994, an HDACi, on the blastocyst formation rate, acetylation levels of H3K9 and H4K12, DNA methylation levels of anti-5-methylcytosine (5mC), and some mRNA expression of pluripotency-related genes in pig SCNT embryos. Treatment with 10 μM CI994 for 24 hours significantly improved the blastocyst formation rate of SCNT embryos in comparison with the untreated group (p < 0.05). Moreover, average fluorescence intensities of H3K9 and H4K12 in CI994-treated embryos were remarkably increased at the pseudo-pronuclear stage, but not at the blastocyst stage. The intensity of POU5F1 was higher in CI994-treated blastocysts than in control blastocysts, whereas that of 5mC did not differ between the two groups. The percentage of apoptotic cells in blastocysts was significantly higher in the untreated group than in the CI994-treated group. mRNA levels of POU5F1 and SOX2 were significantly increased in the CI994-treated group. These observations suggest that optimum exposure (10 μM for 24 hours) to CI994 after activation elevates the level of histone acetylation and subsequently improves the in vitro development of pig SCNT embryos.

  13. Computer-assisted CI fitting: Is the learning capacity of the intelligent agent FOX beneficial for speech understanding?

    PubMed

    Meeuws, Matthias; Pascoal, David; Bermejo, Iñigo; Artaso, Miguel; De Ceulaer, Geert; Govaerts, Paul J

    2017-07-01

    The software application FOX ('Fitting to Outcome eXpert') is an intelligent agent to assist in the programing of cochlear implant (CI) processors. The current version utilizes a mixture of deterministic and probabilistic logic which is able to improve over time through a learning effect. This study aimed at assessing whether this learning capacity yields measurable improvements in speech understanding. A retrospective study was performed on 25 consecutive CI recipients with a median CI use experience of 10 years who came for their annual CI follow-up fitting session. All subjects were assessed by means of speech audiometry with open set monosyllables at 40, 55, 70, and 85 dB SPL in quiet with their home MAP. Other psychoacoustic tests were executed depending on the audiologist's clinical judgment. The home MAP and the corresponding test results were entered into FOX. If FOX suggested to make MAP changes, they were implemented and another speech audiometry was performed with the new MAP. FOX suggested MAP changes in 21 subjects (84%). The within-subject comparison showed a significant median improvement of 10, 3, 1, and 7% at 40, 55, 70, and 85 dB SPL, respectively. All but two subjects showed an instantaneous improvement in their mean speech audiometric score. Persons with long-term CI use, who received a FOX-assisted CI fitting at least 6 months ago, display improved speech understanding after MAP modifications, as recommended by the current version of FOX. This can be explained only by intrinsic improvements in FOX's algorithms, as they have resulted from learning. This learning is an inherent feature of artificial intelligence and it may yield measurable benefit in speech understanding even in long-term CI recipients.

  14. Short versus long duration infusions of paclitaxel for any advanced adenocarcinoma

    PubMed Central

    Williams, Chris; Bryant, Andrew

    2014-01-01

    cases a greater proportion of adverse events and severe toxicity occurred in the 24 hour infusion group compared to the 3 hour group with many of the analyses being highly statistically significant (RR = 0.32, 95% CI 0.22, 0.47, RR = 0.06, 95% CI 0.02, 0.17, RR = 0.59, 95% CI 0.40, 0.88, RR = 0.52, 95% CI 0.28, 0.97 for severe hypersensitivity, febrile neutropenia, sore mouth and diarrhoea outcomes respectively). Although a meta analysis of three trials found that 3 hour infusions were associated with a statistically significant increase in the risk of neurosensory changes compared with 24 hour infusions (RR = 1.26, 95% CI 1.09 to 1.46). Adverses events were not comprehensively reported for any of the other comparisons. Outcomes were incompletely documented and QoL outcomes were not reported in any of the trials. The strength of the evidence is weak in this review as it is based on meta analyses of very few trials or single trial analyses and all trials were at moderate risk of bias and two were published in abstract form only. Authors’ conclusions Ideally, large, multi-centre supporting trials are needed as outcomes were incompletely reported in included trials in this review. It may be beneficial to design a multi-arm trial comparing 3, 24 and 96 hour infusions or maybe looking at different schedules. In the absence of such trials, the decision to offer short or long infusions in advanced adenocarcinoma may need to be individualised, although it certainly appears that women have less toxicity, apart from sensory nerve damage, with a shorter infusion. Efficacy appearing similar regardless of infusion duration. PMID:21563139

  15. Differentiation of early from advanced coronary atherosclerotic lesions: systematic comparison of CT, intravascular US, and optical frequency domain imaging with histopathologic examination in ex vivo human hearts.

    PubMed

    Maurovich-Horvat, Pál; Schlett, Christopher L; Alkadhi, Hatem; Nakano, Masataka; Stolzmann, Paul; Vorpahl, Marc; Scheffel, Hans; Tanaka, Atsushi; Warger, William C; Maehara, Akiko; Ma, Shixin; Kriegel, Matthias F; Kaple, Ryan K; Seifarth, Harald; Bamberg, Fabian; Mintz, Gary S; Tearney, Guillermo J; Virmani, Renu; Hoffmann, Udo

    2012-11-01

    To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic. Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both P<.0001), while mixed plaque at coronary CT angiography, calcified plaque at intravascular US, and lipid-rich plaque at OFDI were associated with advanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, P<.0001, respectively). OFDI had higher accuracy for discriminating early from advanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, P<.0001). Interobserver agreement was excellent for OFDI and coronary CT angiography (κ=0.87 and 0.85, respectively) and was good for intravascular US (κ=0.66). Systematic and standardized comparison between invasive and noninvasive modalities for coronary plaque characterization in ex vivo specimens demonstrated that coronary CT angiography and intravascular US are

  16. Engineering of a genetically encodable fluorescent voltage sensor exploiting fast Ci-VSP voltage-sensing movements.

    PubMed

    Lundby, Alicia; Mutoh, Hiroki; Dimitrov, Dimitar; Akemann, Walther; Knöpfel, Thomas

    2008-06-25

    Ci-VSP contains a voltage-sensing domain (VSD) homologous to that of voltage-gated potassium channels. Using charge displacement ('gating' current) measurements we show that voltage-sensing movements of this VSD can occur within 1 ms in mammalian membranes. Our analysis lead to development of a genetically encodable fluorescent protein voltage sensor (VSFP) in which the fast, voltage-dependent conformational changes of the Ci-VSP voltage sensor are transduced to similarly fast fluorescence read-outs.

  17. Very advanced maternal age and morbidity in Victoria, Australia: a population based study

    PubMed Central

    2013-01-01

    Background In Australia, approximately 0.1% of births occur to women 45 years or older and this rate has been increasing in recent years. There are however, few population based studies examining perinatal outcomes among this age group. The aim of this study was to determine the maternal and perinatal outcomes of pregnancies in women aged 45 years or older compared to women aged 30–34 years. Methods Data on births at 20 or more weeks’ gestation were obtained from the Victorian Perinatal Data Collection for the years 2005 and 2006. We examined selected maternal and perinatal outcomes for women of very advanced maternal age (VAMA) aged 45 years or older (n = 217) and compared them to women aged 30–34 years (n = 48,909). Data were summarised using numbers and percentages. Categorical data were analysed by Chi-square tests and Fisher’s exact test. Comparisons are presented using unadjusted odds ratios, 95 percent confidence intervals (CIs) and p-values. Results Women aged 45 years and older had higher odds of gestational diabetes (OR 2.05; 95% CI 1.3–3.3); antepartum haemorrhage (OR 1.89; 95% CI 1.01–3.5), and placenta praevia (OR 4.88; 95% CI 2.4–9.5). The older age-group also had higher odds of preterm birth between 32–36 weeks (OR 2.61; 95% CI 1.8–3.8); low birth-weight (<2,500 gr) (OR 2.22; 95% CI 1.5–3.3) and small for gestational age (OR 1.53; 95% CI 1.0–2.3). Stratified analysis revealed that VAMA was most strongly associated with caesarean section in primiparous women (OR 8.24; 95% CI 4.5, 15.4) and those using ART (OR 5.75; 95% CI 2.5, 13.3), but the relationship persisted regardless of parity, ART use and plurality. Low birthweight was associated with VAMA only in first births (OR 3.90; 95% CI 2.3, 6.6), while preterm birth was more common in older women for both first (OR 3.13; 95% CI 1.8, 5.3) and subsequent (OR 2.08; 95% CI 1.2, 3.5) births, and for those having singleton births (OR 2.11; 95% CI 1.3, 3.4), and those who

  18. Final results of sequential doxorubicin plus gemcitabine and ifosfamide, paclitaxel, and cisplatin chemotherapy in patients with metastatic or locally advanced transitional cell carcinoma of the urothelium.

    PubMed

    Milowsky, Matthew I; Nanus, David M; Maluf, Fernando C; Mironov, Svetlana; Shi, Weiji; Iasonos, Alexia; Riches, Jamie; Regazzi, Ashley; Bajorin, Dean F

    2009-09-01

    Sequential chemotherapy with doxorubicin and gemcitabine (AG) followed by ifosfamide, paclitaxel, and cisplatin (ITP) was previously demonstrated to be well tolerated in patients with advanced transitional cell carcinoma (TCC). This study sought to evaluate the efficacy and to additionally define toxicity. Sixty patients with advanced TCC received AG every 2 weeks for five or six cycles followed by ITP every 21 days for four cycles. Granulocyte colony-stimulating factor was given between cycles. Myelosuppression was seen with 68% of patients who experienced grades 3 to 4 neutropenia and with 25% who experienced febrile neutropenia. Grade 3 or greater nonhematologic toxicities were infrequent. Forty (73%) of 55 evaluable patients (95% CI, 59% to 84%) demonstrated a major response (complete, n = 19; partial, n = 21) and had a median response duration of 11.3 months (range, 1.7 to >or= 105.6 months). Twenty-seven (79%) of 34 patients with locally advanced disease (ie, T4, N0, M0) or with regional lymph node involvement (ie, T3-4, N1, M0) and 10 (56%) of 18 patients with distant metastases achieved a major response. The median progression-free survival was 12.1 months (95% CI, 9.0 to 14.8 months), and the median overall survival was 16.4 months (95% CI, 14.0 to 22.5 months). At a median follow-up of 76.4 months, seven (11.7%) patients remain alive, and all were disease free. AG plus ITP is an active regimen in previously untreated patients with advanced TCC; however, it is associated with toxicity and does not clearly offer a benefit compared with other nonsequential, cisplatin-based regimens.

  19. Plasma D-dimer Can Effectively Predict the Prospective Occurrence of Ascites in Advanced Schistosomiasis Japonica Patients.

    PubMed

    Wu, Xiaoying; Ren, Jianwei; Gao, Zulu; Xu, Yun; Xie, Huiqun; Li, Tingfang; Cheng, Yanhua; Hu, Fei; Liu, Hongyun; Gong, Zhihong; Liang, Jinyi; Shen, Jia; Liu, Zhen; Wu, Feng; Sun, Xi; Niu, Zhongzheng; Ning, An

    2017-04-01

    China still has more than 30,000 patients of advanced schistosomiasis while new cases being reported consistently. D-dimer is a fibrin degradation product. As ascites being the dominating symptom in advanced schistosomiasis, the present study aimed to explore a prediction model of ascites with D-dimer and other clinical easy-achievable indicators. A case-control study nested in a prospective cohort was conducted in schistosomiasis-endemic area of southern China. A total of 291 patients of advanced schistosomiasis were first investigated in 2013 and further followed in 2014. Information on clinical history, physical examination, and abdominal ultrasonography, including the symptom of ascites was repeatedly collected. Result showed 44 patients having ascites. Most of the patients' ascites were confined in the kidney area with median area of 20 mm 2 . The level of plasma D-dimer and pertinent liver function indicators were measured at the initial investigation in 2013. Compared with those without ascites, cases with ascites had significantly higher levels of D-dimer (0.71±2.44 μg/L vs 0.48±2.12 μg/L, P =0.005), as well ALB (44.5 vs 46.2, g/L) and Type IV collagen (50.04 vs 44.50 μg/L). Receiver operating characteristic curve analyses indicated a moderate predictive value of D-dimer by its own area under curve (AUC) of 0.64 (95% CI: 0.54-0.73) and the cutoff value as 0.81 μg/L. Dichotomized by the cutoff level, D-dimer along with other categorical variables generated a prediction model with AUC of 0.76 (95% CI: 0.68-0.89). Risks of patients with specific characteristics in the prediction model were summarized. Our study suggests that the plasma D-dimer level is a reliable predictor for incident ascites in advanced schistosomiasis japonica patients.

  20. Plasma D-dimer Can Effectively Predict the Prospective Occurrence of Ascites in Advanced Schistosomiasis Japonica Patients

    PubMed Central

    Wu, Xiaoying; Ren, Jianwei; Gao, Zulu; Xu, Yun; Xie, Huiqun; Li, Tingfang; Cheng, Yanhua; Hu, Fei; Liu, Hongyun; Gong, Zhihong; Liang, Jinyi; Shen, Jia; Liu, Zhen; Wu, Feng; Sun, Xi; Niu, Zhongzheng; Ning, An

    2017-01-01

    China still has more than 30,000 patients of advanced schistosomiasis while new cases being reported consistently. D-dimer is a fibrin degradation product. As ascites being the dominating symptom in advanced schistosomiasis, the present study aimed to explore a prediction model of ascites with D-dimer and other clinical easy-achievable indicators. A case-control study nested in a prospective cohort was conducted in schistosomiasis-endemic area of southern China. A total of 291 patients of advanced schistosomiasis were first investigated in 2013 and further followed in 2014. Information on clinical history, physical examination, and abdominal ultrasonography, including the symptom of ascites was repeatedly collected. Result showed 44 patients having ascites. Most of the patients’ ascites were confined in the kidney area with median area of 20 mm2. The level of plasma D-dimer and pertinent liver function indicators were measured at the initial investigation in 2013. Compared with those without ascites, cases with ascites had significantly higher levels of D-dimer (0.71±2.44 μg/L vs 0.48±2.12 μg/L, P=0.005), as well ALB (44.5 vs 46.2, g/L) and Type IV collagen (50.04 vs 44.50 μg/L). Receiver operating characteristic curve analyses indicated a moderate predictive value of D-dimer by its own area under curve (AUC) of 0.64 (95% CI: 0.54–0.73) and the cutoff value as 0.81 μg/L. Dichotomized by the cutoff level, D-dimer along with other categorical variables generated a prediction model with AUC of 0.76 (95% CI: 0.68–0.89). Risks of patients with specific characteristics in the prediction model were summarized. Our study suggests that the plasma D-dimer level is a reliable predictor for incident ascites in advanced schistosomiasis japonica patients. PMID:28506039

  1. A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy

    PubMed Central

    Kaminski, Michal F; Polkowski, Marcin; Kraszewska, Ewa; Rupinski, Maciej; Butruk, Eugeniusz; Regula, Jaroslaw

    2014-01-01

    Objective This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. Design We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Results Advanced colorectal neoplasia was detected in 2544 of the 35 918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7–8. Conclusions Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies. PMID:24385598

  2. Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer.

    PubMed

    Tangjitgamol, Siriwan; Katanyoo, Kanyarat; Laopaiboon, Malinee; Lumbiganon, Pisake; Manusirivithaya, Sumonmal; Supawattanabodee, Busaba

    2014-12-03

    Current standard treatment for patients with cervical cancer who have locally advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IVA) is concurrent chemoradiation therapy (CCRT). However, less than two-thirds of patients in this group survive for longer than five years post treatment. Adjuvant chemotherapy (ACT) can be given in an attempt to improve survival by eradicating residual disease in the pelvis and treating occult disease outside the pelvic radiation field. However, inconsistency in trial design, inclusion criteria for participants, interventions and survival benefit has been noted among trials of ACT after CCRT for locally advanced cervical cancer (LACC). To evaluate the effect of adjuvant chemotherapy (ACT) after concurrent chemoradiation (CCRT) on survival of women with locally advanced cervical cancer compared with CCRT alone. We searched the Cochrane Gynaecological Review Group Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and conference proceedings to March 2014. We handsearched citation lists of relevant studies. Randomised controlled trials (RCTs) comparing CCRT alone versus CCRT plus ACT were included. Patients were diagnosed with cervical cancer FIGO stage IIB to IVA with a histopathology of squamous cell carcinoma, adenosquamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma. Two review authors (ST, KK) selected relevant trials, extracted data, assessed risk of bias independently, compared results and resolved disagreements by discussion. We identified two RCTs involving 978 women with cervical cancer stage IIB to IVA. As the trials were significantly different clinically, we did not perform meta-analyses. One industry-funded trial involving 515 women compared CCRT (cisplatin) versus CCRT (cisplatin and gemcitabine) plus ACT (two additional cycles). This trial reported significant improvement in progression-free survival (PFS) and overall

  3. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial.

    PubMed

    Banikazemi, Maryam; Bultas, Jan; Waldek, Stephen; Wilcox, William R; Whitley, Chester B; McDonald, Marie; Finkel, Richard; Packman, Seymour; Bichet, Daniel G; Warnock, David G; Desnick, Robert J

    2007-01-16

    Fabry disease (alpha-galactosidase A deficiency) is a rare, X-linked lysosomal storage disorder that can cause early death from renal, cardiac, and cerebrovascular involvement. To see whether agalsidase beta delays the onset of a composite clinical outcome of renal, cardiovascular, and cerebrovascular events and death in patients with advanced Fabry disease. Randomized (2:1 treatment-to-placebo randomization), double-blind, placebo-controlled trial. 41 referral centers in 9 countries. 82 adults with mild to moderate kidney disease; 74 of whom were protocol-adherent. Intravenous infusion of agalsidase beta (1 mg per kg of body weight) or placebo every 2 weeks for up to 35 months (median, 18.5 months). The primary end point was the time to first clinical event (renal, cardiac, or cerebrovascular event or death). Six patients withdrew before reaching an end point: 3 to receive commercial therapy and 3 due to positive or inconclusive serum IgE or skin test results. Three patients assigned to agalsidase beta elected to transition to open-label treatment before reaching an end point. Thirteen (42%) of the 31 patients in the placebo group and 14 (27%) of the 51 patients in the agalsidase-beta group experienced clinical events. Primary intention-to-treat analysis that adjusted for an imbalance in baseline proteinuria showed that, compared with placebo, agalsidase beta delayed the time to first clinical event (hazard ratio, 0.47 [95% CI, 0.21 to 1.03]; P = 0.06). Secondary analyses of protocol-adherent patients showed similar results (hazard ratio, 0.39 [CI, 0.16 to 0.93]; P = 0.034). Ancillary subgroup analyses found larger treatment effects in patients with baseline estimated glomerular filtration rates greater than 55 mL/min per 1.73 m2 (hazard ratio, 0.19 [CI, 0.05 to 0.82]; P = 0.025) compared with 55 mL/min per 1.73 m2 or less (hazard ratio, 0.85 [CI, 0.32 to 2.3]; P = 0.75) (formal test for interaction, P = 0.09). Most treatment-related adverse events were mild or

  4. Feeding tubes and health costs postinsertion in nursing home residents with advanced dementia.

    PubMed

    Hwang, Deborah; Teno, Joan M; Gozalo, Pedro; Mitchell, Susan

    2014-06-01

    The best evidence suggests that feeding tubes are ineffective in persons with advanced dementia. Little is known about their health care costs. To estimate Medicare costs attributable to inpatient care among nursing home (NH) residents with advanced dementia during the year following the placement of a percutaneous endoscopic gastrostomy (PEG) tube during an index hospitalization. Medicare claims (1999-2009) and Minimum Data Set data (1999-2009) were used to estimate Medicare costs attributable to inpatient care among NH residents with advanced dementia during the year following the placement of a PEG tube and compared with those who did not get a PEG tube. The study used a 3:1 propensity-matched cohort design. Matched residents with (n=1924, 68.9% female, 28.8% African American, average age 83.1 years) and without (weighted n=1924, unique n=4337) PEG insertion showed comparable sociodemographic characteristics, similar rates of feeding tube risk factors, and similar mortality (51.9% 180 day mortality among those with a feeding tube vs. 49.8% among those without a feeding tube, P=0.11). One year hospital costs were $2224 higher in NH residents with a feeding tube ($10,191 vs. $7967, 95% CI of difference=$1514, $2933), with those with a feeding tube likely to spend more time in an intensive care unit (1.92 vs. 1.29 days, 95% CI of difference=0.34, 0.92 days). In an analysis controlling for selection bias, PEG tube insertion is associated with a small but significant increase in annual inpatient health care costs, as well as in hospital and intensive care unit days, postinsertion. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  5. Advances in Valveless Piezoelectric Pump with Cone-shaped Tubes

    NASA Astrophysics Data System (ADS)

    Zhang, Jian-Hui; Wang, Ying; Huang, Jun

    2017-07-01

    This paper reviews the development of valveless piezoelectric pump with cone-shaped tube chronologically, which have widely potential application in biomedicine and micro-electro-mechanical systems because of its novel principles and deduces the research direction in the future. Firstly, the history of valveless piezoelectric pumps with cone-shaped tubes is reviewed and these pumps are classified into the following types: single pump with solid structure or plane structure, and combined pump with parallel structure or series structure. Furthermore, the function of each type of cone-shaped tubes and pump structures are analyzed, and new directions of potential expansion of valveless piezoelectric pumps with cone-shaped tubes are summarized and deduced. The historical argument, which is provided by the literatures, that for a valveless piezoelectric pump with cone-shaped tubes, cone angle determines the flow resistance and the flow resistance determines the flow direction. The argument is discussed in the reviewed pumps one by one, and proved to be convincing. Finally, it is deduced that bionics is pivotal in the development of valveless piezoelectric pump with cone-shaped tubes from the perspective of evolution of biological structure. This paper summarizes the current valveless piezoelectric pumps with cone-shaped tubes and points out the future development, which may provide guidance for the research of piezoelectric actuators.

  6. Biophysics of cochlear implant/MRI interactions emphasizing bone biomechanical properties.

    PubMed

    Sonnenburg, Robert E; Wackym, Phillip A; Yoganandan, Narayan; Firszt, Jill B; Prost, Robert W; Pintar, Frank A

    2002-10-01

    The forces exerted during a 1.5-Tesla MRI evaluation on the internal magnet of a cochlear implant (CI) raise concern about the safety for CI recipients. This study determines the magnitude of force required to fracture the floor of a CI receiver bed. Recessed CI beds were drilled to maximum uniform thinness into formalin-fixed and fresh-frozen human calvaria specimens. A Med-El stainless steel CI template mounted to the piston of an electrohydraulic testing device was used to fracture the floor of the implant beds. Force and displacement were measured as a function of time using a digital data acquisition system. Mean force to first failure, displacement to first failure, and minimum thickness, respectively, were: group 1 (formalin-fixed, 0.3-0.4-mm thick [n = 22]), 34.08 N (8.21-59.64 N, standard deviation [SD] 15.41 N), 1.09 mm (0.40-2.16 mm, SD 0.51 mm), 0.36 mm (0.3-0.4 mm, SD 0.05 mm); group 2 (formalin-fixed, 0.5-0.9 mm thick [n = 21]), 52.82 N (20.28-135.53 N, SD 25.29 N), 1.08 mm (0.50-2.28 mm, SD 0.47 mm), 0.58 mm (0.5-0.9 mm, SD 0.12 mm); group 3 (fresh-frozen [n = 9]), 134.13 N (86.44-190.70 N, SD 34.92 N), 1.96 mm (1.47-2.46 mm, SD 0.35 mm), 0.42 mm (0.3-0.6 mm, SD 0.11 mm). The mean magnitude of force required to fracture the floor of a CI bed is significantly greater than those that are generated when a Med-El Combi 40+, CII Bionic Ear CI, or Nucleus Contour CI is placed into a 1.5-Tesla MRI unit.

  7. Real world study of regimen containing bevacizumab as first-line therapy in Chinese patients with advanced non-small cell lung cancer.

    PubMed

    Xing, Puyuan; Mu, Yuxin; Wang, Yan; Hao, Xuezhi; Zhu, Yixiang; Hu, Xingsheng; Wang, Hongyu; Liu, Peng; Lin, Lin; Wang, Zhijie; Li, Junling

    2018-05-16

    Large scale randomized controlled trials have demonstrated that the use of bevacizumab in addition to chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) conveys significant survival benefits. We explored the clinical impact of a first-line regimen containing bevacizumab (B+) versus a non-bevacizumab regimen (non-B) in advanced non-squamous NSCLC (NS-NSCLC) patients in a real world setting. The medical records of patients with advanced NS-NSCLC who received first-line therapy with or without bevacizumab were retrospectively collected. The primary outcome was progression-free survival (PFS), with secondary objectives of objective response rate (ORR), disease control rate (DCR), and safety. Exploratory analysis of EGFR and ALK status was conducted in subgroup. One hundred and forty-nine patients met the selection criteria: 62 in the B+ and 87 in the non-B group. The baseline characteristics were well balanced. In the overall population, the median PFS was significantly longer in the B+ than in the non-B group (9.7 vs. 7.0 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.30-0.91; P = 0.0184). Improved trends in both ORR and DCR were observed in the B+ group. In wild-type patients, the median PFS of the B+ was 11.3 compared to 5.5 months in the non-B group (HR 0.43, 95% CI 0.20-0.91; P = 0.0234). In wild type and unknown populations, the median PFS was 11.3 (B+) compared to 6.0 months (non-B) (HR 0.53; 95% CI 0.28-1.02; P = 0.0520). The safety profile was acceptable in both groups and no unexpected findings were observed. Our analysis confirmed that a first-line regimen containing bevacizumab showed superior clinical benefits over a non-bevacizumab regimen in Chinese patients with advanced NS-NSCLC in a real world setting. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  8. Comment on Mars as the Parent Body of the CI Carbonaceous Chondrites by J. E. Brandenburg

    NASA Technical Reports Server (NTRS)

    Treiman, Allan H.

    1996-01-01

    Geological and chemical data refute a martian origin for the CI carbonaceous chondrites. Here, I will first consider Brandenburg's [1996] proposal that the CI's formed as water-deposited sediments on Mars, and that these sediments had limited chemical interactions with their martian environment. Finally, I will address oxygen isotope ratios, the strongest link between the CIs and the martian meteorites.

  9. Palbociclib: A Novel Cyclin-Dependent Kinase Inhibitor for Hormone Receptor-Positive Advanced Breast Cancer.

    PubMed

    Mangini, Neha S; Wesolowski, Robert; Ramaswamy, Bhuvaneswari; Lustberg, Maryam B; Berger, Michael J

    2015-11-01

    To review palbociclib, a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6, and its current place in therapy for the treatment of hormone receptor (HMR)-positive, human epidermal growth factor receptor 2 (Her2)-negative advanced breast cancer. Four phase I trials, 2 phase II trials, and 1 phase III trial were identified from May 2004 to May 2015 using PubMed, American Society of Clinical Oncology (ASCO) abstracts, and European Society of Medical Oncology (ESMO) abstracts. In the first-line setting, the phase II PALbociclib: Ongoing trials in the Management of breast cAncer (PALOMA)-1 trial randomized patients to receive letrozole alone or letrozole plus palbociclib 125 mg daily for 3 weeks, followed by 1 week off, as initial therapy for advanced breast cancer. The investigator-assessed median progression-free survival (PFS) was 20. 2 months for the combination versus 10.2 months for letrozole alone (hazard ratio [HR] = 0.488; 95% CI = 0.319-0.748; 1-sided P = 0.0004). The ensuing Food and Drug Administration approval of palbociclib was given a "breakthrough therapy" designation, where preliminary evidence suggests substantial improvement over existing therapies for a serious or life-threatening disease. A confirmatory phase III trial, PALOMA-2, is under way. In patients who were previously treated with endocrine therapy for advanced breast cancer, the phase III PALOMA-3 trial randomized patients to fulvestrant plus palbociclib versus fulvestrant plus placebo. The investigator-assessed median PFS at the time of a preplanned analysis was 9.2 months with palbociclib-fulvestrant compared with 3.8 months with placebo-fulvestrant (HR = 0.42; 95% CI = 0.32-0.56; P < 0.001). Palbociclib, the first-in-class CDK4/6 inhibitor, significantly extended PFS in combination with endocrine therapy in the first and subsequent lines of treatment for HMR-positive, Her2-negative advanced breast cancer. © The Author(s) 2015.

  10. AEROBIC AND ANAEROBIC TREATMENT OF C.I. DISPERSE BLUE 79 - VOLUME I

    EPA Science Inventory

    This study was conducted to determine the fate of C.I. Disperse Blue 79, one of the largest production volume dyes, and select biodegradation products in a conventionally operated activated sludge process and an anaerobic sludge digestion system. To achieve this objective, a pilo...

  11. 10 CFR 709.17 - Final disposition of CI evaluation findings and recommendations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... recommendations. 709.17 Section 709.17 Energy DEPARTMENT OF ENERGY COUNTERINTELLIGENCE EVALUATION PROGRAM CI... Intelligence and Counterintelligence must recommend, in writing, to the appropriate Program Manager that the covered person's access be approved or retained, or denied or revoked. (b) If the Program Manager agrees...

  12. Comparison of EGFR signaling pathway somatic DNA mutations derived from peripheral blood and corresponding tumor tissue of patients with advanced non-small-cell lung cancer using liquidchip technology.

    PubMed

    Zhang, Hui; Liu, Deruo; Li, Shanqing; Zheng, Yongqing; Yang, Xinjie; Li, Xi; Zhang, Quan; Qin, Na; Lu, Jialin; Ren-Heidenreich, Lifen; Yang, Huiyi; Wu, Yuhua; Zhang, Xinyong; Nong, Jingying; Sun, Yifen; Zhang, Shucai

    2013-11-01

    Somatic DNA mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway are known to predict responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers. We evaluated a sensitive liquidchip platform for detecting EGFR, KRAS (alias Ki-ras), proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations in plasma samples, which were highly correlated with matched tumor tissues from 86 patients with advanced non-small-cell lung cancers. Either EGFR exon 19 or 21 mutations were detected in 36 patients: 23 of whom had identical mutations in both their blood and tissue samples; whereas mutations in the remaining 13 were found only in their tumor samples. These EGFR mutations occurred at a significantly higher frequency in females, never-smokers, and in patients with adenocarcinomas (P ≤ 0.001). The EGFR exon 20 T790M mutation was detected in only one of the paired samples [100% (95% CI, 96% to 100%) agreement]. For KRAS, proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations, the overall agreements were 97% (95% CI, 90% to 99%), 98% (95% CI, 92% to 99%), and 97% (95% CI, 90% to 99%), respectively, and these were not associated with age, sex, smoking history, or histopathologic type. In conclusion, mutations detected in plasma correlated strongly with mutation profiles in each respective tumor sample, suggesting that this liquidchip platform may offer a rapid and noninvasive method for predicting tumor responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  13. A prospective, observational grouped analysis to evaluate the effect of triptorelin on lower urinary tract symptoms in patients with advanced prostate cancer

    PubMed Central

    Gil, Thierry; Aoun, Fouad; Cabri, Patrick; Maisonobe, Pascal

    2015-01-01

    Objectives: Few studies have assessed the effect of gonadotropin-releasing hormone (GnRH) agonists, such as triptorelin, on lower urinary tract symptoms (LUTS) in patients with advanced prostate cancer. Therefore, multiple, national observational, noninterventional studies were initiated to assess the effectiveness of triptorelin in reducing moderate or severe LUTS [International Prostate Symptom Score (IPSS) >7] in men with prostate cancer starting triptorelin therapy in clinical practice. Methods: Prospective, noninterventional, multicentre studies of LUTS located in Algeria, Belgium, China, Hungary, Romania and South Korea, in patients who were scheduled to receive triptorelin (3-month extended release or 1-month formulation) in clinical practice. The primary effectiveness endpoint was the proportion of patients with moderate or severe LUTS after 48 weeks as assessed by IPSS. Secondary endpoints included the distribution of IPSS categories, total IPSS and prostate-specific antigen (PSA) levels at baseline, 24 and 48 weeks. Results: In total, 2461 patients were recruited in the studies; 1282 patients had moderate or severe LUTS at baseline (IPSS > 7), received triptorelin and had follow-up IPSS. Mean total IPSS was reduced from 18.2 [95% confidence interval (CI) 17.8–18.5] at baseline to 11.9 (95% CI 11.5–12.3; p < 0.001) and 10.6 (95% CI 10.2–11.0; p < 0.001) at weeks 24 and 48, respectively. Mean PSA levels were reduced from 117.9 ng/ml (95% CI 93.8–141.9) at baseline to 8.5 ng/ml (95% CI 5.2–11.7) and 16.6 ng/ml (95% CI 7.4–25.8) at weeks 24 and 48, respectively. There was a significant correlation between total IPSS change from baseline and PSA change from baseline at weeks 24 and 48 (ρ = 0.3 and 0.2, p < 0.001). Conclusions: The improvement in LUTS in men with locally advanced or metastatic prostate cancer after 24–48 weeks suggests that triptorelin is effective in improving LUTS in this subgroup of patients. PMID:26161142

  14. Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

    PubMed Central

    Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

    2013-01-01

    Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

  15. Blood pressure and risk of all-cause mortality in advanced chronic kidney disease and hemodialysis: the CRIC study

    PubMed Central

    Bansal, Nisha; McCulloch, Charles E.; Rahman, Mahboob; Kusek, John W.; Anderson, Amanda H.; Xie, Dawei; Townsend, Raymond R.; Lora, Claudia M.; Wright, Jackson; Go, Alan S.; Ojo, Akinlolu; Alper, Arnold; Lustigova, Eva; Cuevas, Magda; Kallem, Radhakrishna; Hsu, Chi-yuan

    2014-01-01

    Studies of hemodialysis patients have shown a U-shaped association between systolic blood pressure (SBP) and mortality. These studies have largely relied on dialysis-unit SBP measures and have not evaluated whether this U-shape also exists in advanced chronic kidney disease (CKD), prior to starting hemodialysis. We determined the association between SBP and mortality at advanced CKD and again after initiation of hemodialysis. This was a prospective study of Chronic Renal Insufficiency Cohort (CRIC) participants with advanced CKD followed through initiation of hemodialysis. We studied the association between SBP and mortality when participants: 1) had an estimated glomerular filtration rate <30 ml/min/1.73m2 (N=1,705); 2) initiated hemodialysis and had dialysis-unit SBP measures (N=403) and; 3) initiated hemodialysis and had out-of-dialysis-unit SBP measured at a CRIC study visit (N=326). Cox models adjusted for demographics, cardiovascular risk factors and dialysis parameters. A quadratic term for SBP was included to test for a U-shaped association. At advanced CKD, there was no association between SBP and mortality (HR 1.02 [95% CI: 0.98–1.07] per every 10 mm Hg increase). Among participants who started hemodialysis, a U-shaped association between dialysis-unit SBP and mortality was observed. In contrast, there was a linear association between out-of-dialysis-unit SBP and mortality (HR 1.26 [95% CI: 1.14–1.40] per every 10 mm Hg increase). In conclusion, more efforts should be made to obtain out-of-dialysis-unit SBP which may merit more consideration as a target for clinical management and in interventional trials. PMID:25287404

  16. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.

    PubMed

    Hortobagyi, Gabriel N; Stemmer, Salomon M; Burris, Howard A; Yap, Yoon-Sim; Sonke, Gabe S; Paluch-Shimon, Shani; Campone, Mario; Blackwell, Kimberly L; André, Fabrice; Winer, Eric P; Janni, Wolfgang; Verma, Sunil; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Petrakova, Katarina; Hart, Lowell L; Villanueva, Cristian; Chan, Arlene; Jakobsen, Erik; Nusch, Arnd; Burdaeva, Olga; Grischke, Eva-Maria; Alba, Emilio; Wist, Erik; Marschner, Norbert; Favret, Anne M; Yardley, Denise; Bachelot, Thomas; Tseng, Ling-Ming; Blau, Sibel; Xuan, Fengjuan; Souami, Farida; Miller, Michelle; Germa, Caroline; Hirawat, Samit; O'Shaughnessy, Joyce

    2016-11-03

    The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10 -5 . The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10 -6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2

  17. 75 FR 5566 - NOAA Cooperative Institutes (CIs): (1) A CI To Support NOAA Research Facilities in the Pacific...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... Northwest, (2) A CI for Southwestern U.S. Marine Ecosystems, Climate and Ocean Studies, and (3) A... Southwestern U.S. Marine Ecosystems, Climate and Ocean Studies, and (3) A Southeastern Regional CI for...

  18. Factors associated with presenting late or with advanced HIV disease in the Netherlands, 1996–2014: results from a national observational cohort

    PubMed Central

    Op de Coul, Eline L M; van Sighem, Ard; Brinkman, Kees; van Benthem, Birgit H; van der Ende, Marchina E; Geerlings, Suzanne; Reiss, Peter

    2016-01-01

    Objectives Early testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with late or advanced disease in HIV-infected patients in the Netherlands. Methods HIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort. Risk factors for late presentation and advanced disease were analysed by multivariable logistic regression. Furthermore, geographical differences and time trends were examined. Results Of 20 965 patients, 53% presented with late-stage HIV infection, and 35% had advanced disease. Late presentation decreased from 62% (1996) to 42% (2013), while advanced disease decreased from 46% to 26%. Late presentation only declined significantly among men having sex with men (MSM; p <0.001), but not among heterosexual males (p=0.08) and females (p=0.73). Factors associated with late presentation were: heterosexual male (adjusted OR (aOR), 1.59; 95% CI 1.44 to 1.75 vs MSM), injecting drug use (2.00; CI 1.69 to 2.38), age ≥50 years (1.46; CI 1.33 to 1.60 vs 30–49 years), region of origin (South-East Asia 2.14; 1.80 to 2.54, sub-Saharan Africa 2.11; 1.88 to 2.36, Surinam 1.59; 1.37 to 1.84, Caribbean 1.31; 1.13 to 1.53, Latin America 1.23; 1.04 to 1.46 vs the Netherlands), and location of HIV diagnosis (hospital 3.27; 2.94 to 3.63, general practitioner 1.66; 1.50 to 1.83, antenatal screening 1.76; 1.38 to 2.34 vs sexually transmitted infection clinic). No association was found for socioeconomic status or level of urbanisation. Compared with Amsterdam, 2 regions had higher adjusted odds and 2 regions had lower odds of late presentation. Results were highly similar for advanced disease. Conclusions Although the overall rate of late presentation is declining in the Netherlands, targeted programmes to reduce late HIV diagnoses remain needed for all risk groups, but

  19. 10 CFR 709.14 - Consequences of a refusal to complete a CI evaluation including a polygraph examination.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Consequences of a refusal to complete a CI evaluation including a polygraph examination. 709.14 Section 709.14 Energy DEPARTMENT OF ENERGY COUNTERINTELLIGENCE EVALUATION PROGRAM CI Evaluation Protocols and Protection of National Security § 709.14 Consequences of a...

  20. 10 CFR 709.17 - Final disposition of CI evaluation findings and recommendations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... and recommendations. (a) Following completion of a CI evaluation, the Director of the Office of Intelligence and Counterintelligence must recommend, in writing, to the appropriate Program Manager that the covered person's access be approved or retained, or denied or revoked. (b) If the Program Manager agrees...

  1. Identification of Apolipoprotein C-I as a Potential Wilms’ Tumor Marker after Excluding Inflammatory Factors

    PubMed Central

    Zhang, Junjie; Guo, Fei; Wang, Lei; Zhao, Wei; Zhang, Da; Yang, Heying; Yu, Jiekai; Niu, Lili; Yang, Fuquan; Zheng, Shu; Wang, Jiaxiang

    2014-01-01

    Wilms’ tumor is one of the most common malignant tumors observed in children, and its early diagnosis is important for late-stage treatment and prognosis. We previously screened and identified protein markers for Wilms’ tumor; however, these markers lacked specificity, and some were associated with inflammation. In the current study, serum samples from children with Wilms’ tumors were compared with those of healthy controls and patients with systemic inflammatory response syndrome (SIRS). After exclusion of factors associated with inflammation, specific protein markers for Wilms’ tumors were identified. After comparing the protein peak values obtained from all three groups, a protein with a m/z of 6438 Da was specified. Purification and identification of the target protein using high-pressure liquid chromatography (HPLC) and two-dimensional liquid chromatography-linearion trap mass spectrometry(2D-LC-LTQ-MS) mass spectrometry, respectively, revealed that it was apolipoprotein C-I (APO C-I). Thus, APO C-I is a specific protein marker for Wilms’ tumor. PMID:25222555

  2. The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI): Revision for Clinical Use, Content Validation, and Inter-rater Reliability.

    PubMed

    Rosenson, Robert S; Miller, Kate; Bayliss, Martha; Sanchez, Robert J; Baccara-Dinet, Marie T; Chibedi-De-Roche, Daniela; Taylor, Beth; Khan, Irfan; Manvelian, Garen; White, Michelle; Jacobson, Terry A

    2017-04-01

    The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) is a method for assessing the likelihood that a patient's muscle symptoms (e.g., myalgia or myopathy) were caused or worsened by statin use. The objectives of this study were to prepare the SAMS-CI for clinical use, estimate its inter-rater reliability, and collect feedback from physicians on its practical application. For content validity, we conducted structured in-depth interviews with its original authors as well as with a panel of independent physicians. Estimation of inter-rater reliability involved an analysis of 30 written clinical cases which were scored by a sample of physicians. A separate group of physicians provided feedback on the clinical use of the SAMS-CI and its potential utility in practice. Qualitative interviews with providers supported the content validity of the SAMS-CI. Feedback on the clinical use of the SAMS-CI included several perceived benefits (such as brevity, clear wording, and simple scoring process) and some possible concerns (workflow issues and applicability in primary care). The inter-rater reliability of the SAMS-CI was estimated to be 0.77 (confidence interval 0.66-0.85), indicating high concordance between raters. With additional provider feedback, a revised SAMS-CI instrument was created suitable for further testing, both in the clinical setting and in prospective validation studies. With standardized questions, vetted language, easily interpreted scores, and demonstrated reliability, the SAMS aims to estimate the likelihood that a patient's muscle symptoms were attributable to statins. The SAMS-CI may support better detection of statin-associated muscle symptoms in clinical practice, optimize treatment for patients experiencing muscle symptoms, and provide a useful tool for further clinical research.

  3. 40 CFR 721.9662 - Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro... Specific Chemical Substances § 721.9662 Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI). (a) Chemical...-b]-1,4-dioxin, 2,3-dihydro- (9CI) (PMN P-95-1825; CAS No. 126213-50-1) is subject to reporting under...

  4. The origin of the eccentricity of the hot Jupiter in CI Tau

    NASA Astrophysics Data System (ADS)

    Rosotti, G. P.; Booth, R. A.; Clarke, C. J.; Teyssandier, J.; Facchini, S.; Mustill, A. J.

    2017-01-01

    Following the recent discovery of the first radial velocity planet in a star still possessing a protoplanetary disc (CI Tau), we examine the origin of the planet's eccentricity (e ˜0.3). We show through long time-scale (105 orbits) simulations that the planetary eccentricity can be pumped by the disc, even when its local surface density is well below the threshold previously derived from short time-scale integrations. We show that the disc may be able to excite the planet's orbital eccentricity in <1 Myr for the system parameters of CI Tau. We also perform two-planet scattering experiments and show that alternatively the observed planet may plausibly have acquired its eccentricity through dynamical scattering of a migrating lower mass planet, which has either been ejected from the system or swallowed by the central star. In the latter case the present location and eccentricity of the observed planet can be recovered if it was previously stalled within the disc's magnetospheric cavity.

  5. IOTA interferometer observations of the B[e] star/X-ray transient object CI Cam.

    NASA Astrophysics Data System (ADS)

    Thureau, N. D.; Traub, W.; Millan-Gabet, R.; Monnier, J. D.; Pedretti, E.; Berger, J.-P.; Schloerb, P.

    2005-12-01

    We present the results from an observing campaign on the star CI Cam carried out at the IOTA interferometer in November-December 2004 using the IONIC 3 telescope beam combiner in the H spectral band with projected baselines in the range 10-36m. CI Cam is a known B[e] star and X-ray transient source and has been intensively observed since its powerful X-ray, radio and optical outburst occurred in April 1998. Our visibility measurements put strong constraints on the nature of the source and we can rule out all existing SED models available in the literature. Our new results are in agreement with previous observations of CI Cam obtained with IOTA2 in the H and K' spectral bands in September-November 1998, indicating the infrared excess is long-lived and not directly associated with the outburst. We have explored new models that can better fit our observations. Additionally, we have measured small non-zero closure phases which are the signature of asymmetries in the brightness distribution function. Financial support for NDT is provided by the European Commission through a Marie Curie Outgoing International Fellowships MOIF-CT-2004-002990.

  6. K2 Reveals Pulsed Accretion Driven by the 2 Myr Old Hot Jupiter CI Tau b

    NASA Astrophysics Data System (ADS)

    Biddle, Lauren I.; Johns-Krull, Christopher M.; Llama, Joe; Prato, Lisa; Skiff, Brian A.

    2018-02-01

    CI Tau is a young (∼2 Myr) classical T Tauri star located in the Taurus star-forming region. Radial velocity observations indicate it hosts a Jupiter-sized planet with an orbital period of approximately 9 days. In this work, we analyze time series of CI Tau’s photometric variability as seen by K2. The light curve reveals the stellar rotation period to be ∼6.6 days. Although there is no evidence that CI Tau b transits the host star, a ∼9 day signature is also present in the light curve. We believe this is most likely caused by planet–disk interactions that perturb the accretion flow onto the star, resulting in a periodic modulation of the brightness with the ∼9 day period of the planet’s orbit.

  7. Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial.

    PubMed

    Basset-Séguin, N; Hauschild, A; Kunstfeld, R; Grob, J; Dréno, B; Mortier, L; Ascierto, P A; Licitra, L; Dutriaux, C; Thomas, L; Meyer, N; Guillot, B; Dummer, R; Arenberger, P; Fife, K; Raimundo, A; Dika, E; Dimier, N; Fittipaldo, A; Xynos, I; Hansson, J

    2017-11-01

    The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665), assessed safety and efficacy of vismodegib-a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell carcinoma (BCC)-in a patient population representative of clinical practice. Primary analysis data are presented. Patients with locally advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive disease, unacceptable toxicity, or withdrawal. Primary objective was safety. Efficacy variables were assessed as secondary end-points. Evaluable adult patients (N = 1215, 1119 locally advanced; 96 metastatic BCC) from 36 countries were treated; 147 patients (12%) remained on study at time of reporting. Median (range) treatment duration was 8.6 (0-44) months. Most patients (98%) had ≥1 treatment-emergent adverse event (TEAE). The incidence of the most common TEAEs was consistent with reports in previous analyses. No association between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed. Serious TEAEs occurred in 289 patients (23.8%). Exposure ≥12 months did not lead to increased incidence or severity of new TEAEs. The majority of the most common TEAEs ongoing at time of treatment discontinuation resolved by 12 months afterwards, regardless of Gorlin syndrome status. Response rates (investigator-assessed) in patients with histologically confirmed measurable baseline disease were 68.5% (95% confidence interval (CI) 65.7-71.3) in patients with locally advanced BCC and 36.9% (95% CI 26.6-48.1) in patients with metastatic BCC. The primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. CLINICALTRIALS.GOV: NCT01367665. Copyright © 2017 The Authors

  8. Does quality of life impact the decision to pursue stem cell transplantation for elderly patients with advanced MDS?

    PubMed

    El-Jawahri, A; Kim, H T; Steensma, D P; Cronin, A M; Stone, R M; Watts, C D; Chen, Y-B; Cutler, C S; Soiffer, R J; Abel, G A

    2016-08-01

    The factors that influence utilization of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HCT) among medically fit older patients with advanced myelodysplastic syndromes (MDS) are largely unknown. The MDS Transplant-Associated Outcomes (MDS-TAO) study is an ongoing prospective observational study at the Dana-Farber Cancer Institute and Massachusetts General Hospital that enrolls transplant-eligible fit patients aged 60-75 years with advanced MDS and follows them through RIC HCT vs non-HCT treatment. In this analysis of 127 patients enrolled from May 2011 to June 2014, we examined the influence of age, gender, cytogenetics, International Prognostic Scoring System (IPSS) category, performance status, distance from HCT center and baseline patient-reported quality of life (QOL) from the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) on the likelihood of receiving RIC HCT using competing risk regression modeling. With a median follow-up of 16 months, 44 patients (35%) had undergone RIC HCT. In multivariable analyses, age (hazard ratio (HR) 0.87 per year, 95% confidence interval (CI): 0.81-0.92, P<0.001) and higher IPSS (intermediate-2/high; HR 2.29, 95% CI: 1.25-4.19, P=0.007) were significantly predictive of receipt of RIC HCT; neither global QOL score nor any QOL subscales scores were predictive. These data suggest that baseline patient-reported QOL has little influence on the decision to undergo RIC HCT for older patients with advanced MDS.

  9. Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer.

    PubMed

    Fribbens, Charlotte; O'Leary, Ben; Kilburn, Lucy; Hrebien, Sarah; Garcia-Murillas, Isaac; Beaney, Matthew; Cristofanilli, Massimo; Andre, Fabrice; Loi, Sherene; Loibl, Sibylle; Jiang, John; Bartlett, Cynthia Huang; Koehler, Maria; Dowsett, Mitch; Bliss, Judith M; Johnston, Stephen R D; Turner, Nicholas C

    2016-09-01

    ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor-positive advanced breast cancer. In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). ESR1 mutation analysis in

  10. Concurrent Chemoradiation with Concomitant Boost in Locally Advanced Rectal Cancer: A Phase II Study.

    PubMed

    Picardi, Vincenzo; Deodato, Francesco; Guido, Alessandra; Giaccherini, Lucia; Macchia, Gabriella; Gambacorta, Maria A; Arcelli, Alessandra; Farioli, Andrea; Cellini, Francesco; Cuicchi, Dajana; DI Fabio, Francesca; Poggioli, Gilberto; Ardizzoni, Andrea; Frezza, Giovanni; Cilla, Savino; Caravatta, Luciana; Valentini, Vincenzo; Fuccio, Lorenzo; Morganti, Alessio G

    2016-08-01

    The aim of this study was to evaluate the pathological response of locally advanced rectal cancer after preoperative concurrent two-drug chemotherapy and intensified radiation therapy (RT) with concomitant boost. Patients with T4 tumor or local recurrence were included. A trial based on two-stage Simon's design was planned. RT was performed with 3D-conformal technique. The dose to the mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered to Gross Tumor Volume (GTV) 2 cm margin to a total dose of 55 Gy (2.2 Gy/fraction). The following concurrent chemotherapy was administered: Raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) on days 1, 17, and 35 of RT. Pathological response was evaluated according to the Mandard classification. Toxicities were scored according to the Common Terminology Criteria for Adverse Events v3.0 scale. Eighteen patients (median age=64.5 years) were enrolled. The median follow-up was 22 months (range=2-36 months). After chemoradiation treatment, 16 patients underwent surgical resection (seven anterior resections and nine abdominal-perineal amputation); two patients did not undergo surgery due to early metastatic progression or refusal. R0 resection was achieved in all patients who underwent surgery. Five patients had pathological complete response [27.7%; 95% confidence interval (CI)=9.7-53.5%] and two patients showed only microscopic residual disease (11.1%; 95% CI=0.1-34.7%). Mandard grades 1 and 2 were detected in seven patients (38.9%; 95% CI=17.3-64.3%). Acute grade 3 or more toxicity was found in eight patients (44.4%; 95% CI=21.5-69.2%): one leucopenia-neutropenia, one liver, one skin and five cases of gastrointestinal toxicities. No patient had local tumor recurrence. One-, 2- and 3-year cumulative disease-free survival were 93.8%. One-, 2- and 3-year cumulative overall survival were 92.3%. Concurrent chemoradiation with concomitant boost in patients with advanced rectal cancer allows

  11. 40 CFR 60.4202 - What emission standards must I meet for emergency engines if I am a stationary CI internal...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... emergency engines if I am a stationary CI internal combustion engine manufacturer? 60.4202 Section 60.4202... Combustion Engines Emission Standards for Manufacturers § 60.4202 What emission standards must I meet for emergency engines if I am a stationary CI internal combustion engine manufacturer? (a) Stationary CI...

  12. 40 CFR 60.4208 - What is the deadline for importing or installing stationary CI ICE produced in previous model years?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... installing stationary CI ICE produced in previous model years? 60.4208 Section 60.4208 Protection of... or installing stationary CI ICE produced in previous model years? (a) After December 31, 2008, owners and operators may not install stationary CI ICE (excluding fire pump engines) that do not meet the...

  13. 40 CFR 60.4208 - What is the deadline for importing or installing stationary CI ICE produced in previous model years?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... installing stationary CI ICE produced in previous model years? 60.4208 Section 60.4208 Protection of... or installing stationary CI ICE produced in previous model years? (a) After December 31, 2008, owners and operators may not install stationary CI ICE (excluding fire pump engines) that do not meet the...

  14. 40 CFR 60.4208 - What is the deadline for importing or installing stationary CI ICE produced in previous model years?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... installing stationary CI ICE produced in previous model years? 60.4208 Section 60.4208 Protection of... or installing stationary CI ICE produced in previous model years? (a) After December 31, 2008, owners and operators may not install stationary CI ICE (excluding fire pump engines) that do not meet the...

  15. Nanoindentation investigation of the stress exponent for the creep of dung beetle (Copris ochus Motschulsky) cuticle

    PubMed Central

    Zhang, Zhijun; Jia, Honglei; Sun, Jiyu; Tong, Jin

    2016-01-01

    ABSTACT With the rapid development of bionic science, especially the progress that has been made in the fields of biomaterials and biomimetics, there is now great interest in the surface and internal mechanical properties of biological materials at the micro- and nanoscale. The study of micro- and nanoscale biomaterial mechanical properties could enable interdisciplinary applications in materials science, biological science and bionic science. Dung beetle (Copris ochus Motschulsky) cuticle is a viscoelastic material that is both viscous and flexible via elastic deformation under external forces; where stress σ, strain ε and elastic modulus E are related in the following way: σ = Eε. In addition, as σ is related to the rate of strain, time is also a factor. The stress-strain relationships of various parts of dung beetle cuticle were investigated in this paper. As time increased, the stress and strain of the material were found to decrease and increase, respectively, indicating that when the material was indented for a certain period, the interaction force between the indenter and the material gradually achieved a state of dynamic equilibrium. However, strain continued to occur until reaching a point of equilibrium because of the creep phenomenon. The stress-strain curves showed a strong character in each holding time condition: the longer the holding time, the more flattened the stress-strain curve. These findings will be useful in the advanced design of strong, lightweight, and biomimetic composites. PMID:27710435

  16. Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial.

    PubMed

    Hecht, J Randolph; Bang, Yung-Jue; Qin, Shukui K; Chung, Hyun C; Xu, Jianming M; Park, Joon O; Jeziorski, Krzysztof; Shparyk, Yaroslav; Hoff, Paulo M; Sobrero, Alberto; Salman, Pamela; Li, Jin; Protsenko, Svetlana A; Wainberg, Zev A; Buyse, Marc; Afenjar, Karen; Houé, Vincent; Garcia, Agathe; Kaneko, Tomomi; Huang, Yingjie; Khan-Wasti, Saba; Santillana, Sergio; Press, Michael F; Slamon, Dennis

    2016-02-10

    To evaluate the efficacy of adding lapatinib to capecitabine and oxaliplatin (CapeOx) in patients with previously untreated human epidermal growth factor receptor 2 (HER2) -amplified advanced gastroesophageal adenocarcinoma. Patients with HER2-positive advanced gastroesophageal adenocarcinoma were randomly assigned at a one-to-one ratio to CapeOx plus lapatinib 1,250 mg or placebo daily. Primary end point was overall survival (OS) in patients with centrally confirmed HER2 amplification in the primary efficacy population. A total of 545 patients were randomly assigned, and 487 patients comprised the primary efficacy population. Median OS in the lapatinib and placebo arms was 12.2 (95% CI, 10.6 to 14.2) and 10.5 months (95% CI, 9.0 to 11.3), respectively, which was not significantly different (hazard ratio, 0.91; 95% CI, 0.73 to 1.12). Median progression-free survival in the lapatinib and placebo arms was 6.0 (95% CI, 5.6 to 7.0) and 5.4 months (95% CI, 4.4 to 5.7), respectively (hazard ratio, 0.82; 95% CI, 0.68 to 1.00; P = .0381). Response rate was significantly higher in the lapatinib arm: 53% (95% CI, 46.4 to 58.8) compared with 39% (95% CI, 32.9 to 45.3) in the placebo arm (P = .0031). Preplanned exploratory subgroup analyses showed OS in the lapatinib arm was prolonged in Asian and younger patients. No correlation was observed between HER2 immunohistochemistry status and survival. There were increased toxicities in the lapatinib arm, particularly diarrhea. Addition of lapatinib to CapeOx did not increase OS in patients with HER2-amplified gastroesophageal adenocarcinoma. There were clear differences in the effect of lapatinib depending on region and age. Future studies could examine this correlation. © 2015 by American Society of Clinical Oncology.

  17. Chemoradiotherapy versus chemotherapy for locally advanced unresectable pancreatic cancer: A systematic review and meta-analysis.

    PubMed

    Ng, Ivy Weishan; Soon, Yu Yang; Chen, Desiree; Tey, Jeremy Chee Seong

    2018-06-22

    To determine the benefit of adding radiotherapy (RT) to chemotherapy for patients with locally advanced unresectable pancreatic cancer (LAUPC). We searched MEDLINE for comparative studies comparing chemoradiotherapy with chemotherapy for patients with LAUPC. We performed the meta-analysis with random effects model. The primary outcome was overall survival (OS); secondary outcomes include progression-free survival (PFS) and adverse events (AE). We found five randomized (RCT) and three observational studies (OBS) including 830 patients. For RCTs, the addition of radiotherapy did not improve PFS (hazard ratio [HR] 0.90; 95% confidence interval [CI], 0.74-1.10; P = 0.30; I 2   =  11%,) or OS (HR 0.87; 95% CI, 0.63-1.21; P = 0.41; I 2 = 67%,) and was associated with increased grade 3 or 4 gastrointestinal AE. In contrast, OBS reported an improvement in PFS (HR 0.58; 95% CI, 0.37-0.92; P = 0.02; I 2 = 32%) and OS (HR 0.48; 95% CI, 0.35-0.60; P < 0.0001; I 2 = 6%). The addition of radiotherapy did not improve the OS and PFS in RCTs. The divergence in results seen in OBS may be due to imbalance in baseline characteristics. Further research incorporating biomarkers may help to better select patients who will benefit from RT. © 2018 John Wiley & Sons Australia, Ltd.

  18. Distal Pancreatectomy With En Bloc Celiac Axis Resection for Locally Advanced Pancreatic Cancer

    PubMed Central

    Gong, Haibing; Ma, Ruirui; Gong, Jian; Cai, Chengzong; Song, Zhenshun; Xu, Bin

    2016-01-01

    Abstract Although distal pancreatectomy with en bloc celiac resection (DP-CAR) is used to treat locally advanced pancreatic cancer, the advantages and disadvantages of this surgical procedure remain unclear. The purpose of this study was to evaluate its clinical safety and efficacy. Studies regarding DP-CAR were retrieved from the following databases: PubMed, EMBASE, Web of Science, Cochrane Library, and Chinese electronic databases. Articles were selected according to predesigned inclusion criteria, and data were extracted according to predesigned sheets. Clinical, oncologic, and survival outcomes of DP-CAR were systematically reviewed by hazard ratios (HRs) or odds ratio (OR) using fixed- or random-effects models. Eighteen studies were included. DP-CAR had a longer operating time and greater intraoperative blood loss compared to distal pancreatectomy (DP). A high incidence of vascular reconstruction occurred in DP-CAR: 11.53% (95%CI: 6.88–18.68%) for artery and 33.28% (95%CI: 20.45–49.19%) for vein. The pooled R0 resection rate of DP-CAR was 72.79% (95% CI, 46.19–89.29%). Higher mortality and morbidity rates were seen in DP-CAR, but no significant differences were detected compared to DP; the pooled OR was 1.798 for mortality (95% CI, 0.360–8.989) and 2.106 for morbidity (95% CI, 0.828–5.353). The pooled incidence of postoperative pancreatic fistula (POPF) was 31.31% (95%CI, 23.69–40.12%) in DP-CAR, similar to that of DP (OR = 1.07; 95%CI, 0.52–2.20). The pooled HR against DP-CAR was 5.67 (95%CI, 1.48–21.75) for delayed gastric emptying. The pooled rate of reoperation was 9.74% (95%CI, 4.56–19.59%) in DP-CAR. The combined 1-, 2-, and 3-year survival rates in DP-CAR were 65.22% (49.32–78.34%), 30.20% (21.50–40. 60%), and 18.70% (10.89–30.13%), respectively. The estimated means and medians for survival time in DP-CAR patients were 24.12 (95%CI, 18.26–29.98) months and 17.00 (95%CI, 13.52–20.48) months, respectively. There were no

  19. Sugary interfaces mitigate contact damage where stiff meets soft

    PubMed Central

    Yoo, Hee Young; Iordachescu, Mihaela; Huang, Jun; Hennebert, Elise; Kim, Sangsik; Rho, Sangchul; Foo, Mathias; Flammang, Patrick; Zeng, Hongbo; Hwang, Daehee; Waite, J. Herbert; Hwang, Dong Soo

    2016-01-01

    The byssal threads of the fan shell Atrina pectinata are non-living functional materials intimately associated with living tissue, which provide an intriguing paradigm of bionic interface for robust load-bearing device. An interfacial load-bearing protein (A. pectinata foot protein-1, apfp-1) with L-3,4-dihydroxyphenylalanine (DOPA)-containing and mannose-binding domains has been characterized from Atrina's foot. apfp-1 was localized at the interface between stiff byssus and the soft tissue by immunochemical staining and confocal Raman imaging, implying that apfp-1 is an interfacial linker between the byssus and soft tissue, that is, the DOPA-containing domain interacts with itself and other byssal proteins via Fe3+–DOPA complexes, and the mannose-binding domain interacts with the soft tissue and cell membranes. Both DOPA- and sugar-mediated bindings are reversible and robust under wet conditions. This work shows the combination of DOPA and sugar chemistry at asymmetric interfaces is unprecedented and highly relevant to bionic interface design for tissue engineering and bionic devices. PMID:27305949

  20. Adaptive algorithm of selecting optimal variant of errors detection system for digital means of automation facility of oil and gas complex

    NASA Astrophysics Data System (ADS)

    Poluyan, A. Y.; Fugarov, D. D.; Purchina, O. A.; Nesterchuk, V. V.; Smirnova, O. V.; Petrenkova, S. B.

    2018-05-01

    To date, the problems associated with the detection of errors in digital equipment (DE) systems for the automation of explosive objects of the oil and gas complex are extremely actual. Especially this problem is actual for facilities where a violation of the accuracy of the DE will inevitably lead to man-made disasters and essential material damage, at such facilities, the diagnostics of the accuracy of the DE operation is one of the main elements of the industrial safety management system. In the work, the solution of the problem of selecting the optimal variant of the errors detection system of errors detection by a validation criterion. Known methods for solving these problems have an exponential valuation of labor intensity. Thus, with a view to reduce time for solving the problem, a validation criterion is compiled as an adaptive bionic algorithm. Bionic algorithms (BA) have proven effective in solving optimization problems. The advantages of bionic search include adaptability, learning ability, parallelism, the ability to build hybrid systems based on combining. [1].

  1. Sugary interfaces mitigate contact damage where stiff meets soft

    NASA Astrophysics Data System (ADS)

    Yoo, Hee Young; Iordachescu, Mihaela; Huang, Jun; Hennebert, Elise; Kim, Sangsik; Rho, Sangchul; Foo, Mathias; Flammang, Patrick; Zeng, Hongbo; Hwang, Daehee; Waite, J. Herbert; Hwang, Dong Soo

    2016-06-01

    The byssal threads of the fan shell Atrina pectinata are non-living functional materials intimately associated with living tissue, which provide an intriguing paradigm of bionic interface for robust load-bearing device. An interfacial load-bearing protein (A. pectinata foot protein-1, apfp-1) with L-3,4-dihydroxyphenylalanine (DOPA)-containing and mannose-binding domains has been characterized from Atrina's foot. apfp-1 was localized at the interface between stiff byssus and the soft tissue by immunochemical staining and confocal Raman imaging, implying that apfp-1 is an interfacial linker between the byssus and soft tissue, that is, the DOPA-containing domain interacts with itself and other byssal proteins via Fe3+-DOPA complexes, and the mannose-binding domain interacts with the soft tissue and cell membranes. Both DOPA- and sugar-mediated bindings are reversible and robust under wet conditions. This work shows the combination of DOPA and sugar chemistry at asymmetric interfaces is unprecedented and highly relevant to bionic interface design for tissue engineering and bionic devices.

  2. Electronic and vibrational spectroscopic studies of jet-cooled 5-cyanoindole and its water clusters, 5CI-(H2O)n, (n = 0-2)

    NASA Astrophysics Data System (ADS)

    Min, Ahreum; Moon, Cheol Joo; Ahn, Ahreum; Lee, Ji Hoon; Kim, Seong Keun; Choi, Myong Yong

    2016-08-01

    Mass-selected resonant two-photon ionization (R2PI) and UV-UV hole-burning, and infrared-dip spectra of 5-cyanoindole (5CI) and its water clusters, 5CI-(H2O)n (n = 1 and 2) were measured. Although, the structures of 5CI-(H2O)1-2 are similar to those of 3CI-(H2O)1-2, the photofragmentation behaviors of the two systems are quite different due to the La-Lb state energy lowering and higher binding energies of 5CI-(H2O)1-2 compared to those of 3CI-(H2O)1-2. Especially for the case of 5CI-(H2O)2 cluster, shortening excited-state lifetime of 5CI-(H2O)2 causes the broad background in the R2PI spectrum of 5CI-(H2O)2.

  3. A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy.

    PubMed

    Kaminski, Michal F; Polkowski, Marcin; Kraszewska, Ewa; Rupinski, Maciej; Butruk, Eugeniusz; Regula, Jaroslaw

    2014-07-01

    This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Advanced colorectal neoplasia was detected in 2544 of the 35,918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7-8. Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. 40 CFR 60.4208 - What is the deadline for importing or installing stationary CI ICE produced in the previous model...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... installing stationary CI ICE produced in the previous model year? 60.4208 Section 60.4208 Protection of... or installing stationary CI ICE produced in the previous model year? (a) After December 31, 2008, owners and operators may not install stationary CI ICE (excluding fire pump engines) that do not meet the...

  5. 40 CFR 60.4208 - What is the deadline for importing or installing stationary CI ICE produced in the previous model...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... installing stationary CI ICE produced in the previous model year? 60.4208 Section 60.4208 Protection of... or installing stationary CI ICE produced in the previous model year? (a) After December 31, 2008, owners and operators may not install stationary CI ICE (excluding fire pump engines) that do not meet the...

  6. Development of Xi'an-CI package – applying the hole–particle symmetry in multi-reference electronic correlation calculations

    NASA Astrophysics Data System (ADS)

    Suo, Bingbing; Lei, Yibo; Han, Huixian; Wang, Yubin

    2018-04-01

    This mini-review introduces our works on the Xi'an-CI (configuration interaction) package using graphical unitary group approach (GUGA). Taking advantage of the hole-particle symmetry in GUGA, the Galfand states used to span the CI space are classified into CI subspaces according to the number of holes and particles, and the coupling coefficients used to calculate Hamiltonian matrix elements could be factorised into the segment factors in the hole, active and external spaces. An efficient multi-reference CI with single and double excitations (MRCISD) algorithm is thus developed that reduces the storage requirement and increases the number of correlated electrons significantly. The hole-particle symmetry also gives rise to a doubly contracted MRCISD approach. Moreover, the internally contracted Gelfand states are defined within the CI subspace arising from the hole-particle symmetry, which makes the implementation of internally contracted MRCISD in the framework of GUGA possible. In addition to MRCISD, the development of multi-reference second-order perturbation theory (MRPT2) also benefits from the hole-particle symmetry. A configuration-based MRPT2 algorithm is proposed and extended to the multi-state n-electron valence-state second-order perturbation theory.

  7. Development of the radical-stable Coprinus cinereus peroxidase (CiP) by blocking the radical attack.

    PubMed

    Kim, Su Jin; Joo, Jeong Chan; Kim, Han Sang; Kwon, Inchan; Song, Bong Keun; Yoo, Young Je; Kim, Yong Hwan

    2014-11-10

    Despite the potential use of peroxidases as industrial biocatalysts, their practical application is often impeded due to suicide inactivation by radicals generated in oxidative reactions. Using a peroxidase from Coprinus cinereus (CiP) as a model enzyme, we revealed a dominant factor for peroxidase inactivation during phenol oxidation, and we engineered radical-stable mutants by site-directed mutagenesis of an amino acid residue susceptible to modification by phenoxyl radical. Mass spectrometry analysis of inactivated CiP identified an adduct between F230 and a phenoxyl radical, and subsequently, the F230 residue was mutated to amino acids that resisted radical coupling. Of the F230 mutants, the F230A mutant showed the highest stability against radical inactivation, retaining 80% of its initial activity, while the wild-type protein was almost completely inactivated. The F230A mutant also exhibited a 16-fold higher turnover of the phenol substrate compared with the wild-type enzyme. Furthermore, the F230A mutant was stable during the oxidation of other phenolic compounds, including m-cresol and 3-methoxyphenol. No structural changes were observed by UV-vis and CD spectra of CiP after radical coupling, implying that the F230-phenol radical adduct inactivated CiP by blocking substrate access to the active site. Our novel strategy can be used to improve the stability of other peroxidases inactivated by radicals. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Recent advances in electronic structure theory and their influence on the accuracy of ab initio potential energy surfaces

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.; Taylor, Peter R.

    1989-01-01

    Recent advances in electronic structure theory and the availability of high speed vector processors have substantially increased the accuracy of ab initio potential energy surfaces. The recently developed atomic natural orbital approach for basis set contraction has reduced both the basis set incompleteness and superposition errors in molecular calculations. Furthermore, full CI calculations can often be used to calibrate a CASSCF/MRCI approach that quantitatively accounts for the valence correlation energy. These computational advances also provide a vehicle for systematically improving the calculations and for estimating the residual error in the calculations. Calculations on selected diatomic and triatomic systems will be used to illustrate the accuracy that currently can be achieved for molecular systems. In particular, the F + H2 yields HF + H potential energy hypersurface is used to illustrate the impact of these computational advances on the calculation of potential energy surfaces.

  9. Recent advances in electronic structure theory and their influence on the accuracy of ab initio potential energy surfaces

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.; Taylor, Peter R.

    1988-01-01

    Recent advances in electronic structure theory and the availability of high speed vector processors have substantially increased the accuracy of ab initio potential energy surfaces. The recently developed atomic natural orbital approach for basis set contraction has reduced both the basis set incompleteness and superposition errors in molecular calculations. Furthermore, full CI calculations can often be used to calibrate a CASSCF/MRCI approach that quantitatively accounts for the valence correlation energy. These computational advances also provide a vehicle for systematically improving the calculations and for estimating the residual error in the calculations. Calculations on selected diatomic and triatomic systems will be used to illustrate the accuracy that currently can be achieved for molecular systems. In particular, the F+H2 yields HF+H potential energy hypersurface is used to illustrate the impact of these computational advances on the calculation of potential energy surfaces.

  10. Verification of a Proposed Clinical Electroacoustic Test Protocol for Personal Digital Modulation Receivers Coupled to Cochlear Implant Sound Processors.

    PubMed

    Nair, Erika L; Sousa, Rhonda; Wannagot, Shannon

    Guidelines established by the AAA currently recommend behavioral testing when fitting frequency modulated (FM) systems to individuals with cochlear implants (CIs). A protocol for completing electroacoustic measures has not yet been validated for personal FM systems or digital modulation (DM) systems coupled to CI sound processors. In response, some professionals have used or altered the AAA electroacoustic verification steps for fitting FM systems to hearing aids when fitting FM systems to CI sound processors. More recently steps were outlined in a proposed protocol. The purpose of this research is to review and compare the electroacoustic test measures outlined in a 2013 article by Schafer and colleagues in the Journal of the American Academy of Audiology titled "A Proposed Electroacoustic Test Protocol for Personal FM Receivers Coupled to Cochlear Implant Sound Processors" to the AAA electroacoustic verification steps for fitting FM systems to hearing aids when fitting DM systems to CI users. Electroacoustic measures were conducted on 71 CI sound processors and Phonak Roger DM systems using a proposed protocol and an adapted AAA protocol. Phonak's recommended default receiver gain setting was used for each CI sound processor manufacturer and adjusted if necessary to achieve transparency. Electroacoustic measures were conducted on Cochlear and Advanced Bionics (AB) sound processors. In this study, 28 Cochlear Nucleus 5/CP810 sound processors, 26 Cochlear Nucleus 6/CP910 sound processors, and 17 AB Naida CI Q70 sound processors were coupled in various combinations to Phonak Roger DM dedicated receivers (25 Phonak Roger 14 receivers-Cochlear dedicated receiver-and 9 Phonak Roger 17 receivers-AB dedicated receiver) and 20 Phonak Roger Inspiro transmitters. Employing both the AAA and the Schafer et al protocols, electroacoustic measurements were conducted with the Audioscan Verifit in a clinical setting on 71 CI sound processors and Phonak Roger DM systems to

  11. 3D Printed Stretchable Tactile Sensors.

    PubMed

    Guo, Shuang-Zhuang; Qiu, Kaiyan; Meng, Fanben; Park, Sung Hyun; McAlpine, Michael C

    2017-07-01

    The development of methods for the 3D printing of multifunctional devices could impact areas ranging from wearable electronics and energy harvesting devices to smart prosthetics and human-machine interfaces. Recently, the development of stretchable electronic devices has accelerated, concomitant with advances in functional materials and fabrication processes. In particular, novel strategies have been developed to enable the intimate biointegration of wearable electronic devices with human skin in ways that bypass the mechanical and thermal restrictions of traditional microfabrication technologies. Here, a multimaterial, multiscale, and multifunctional 3D printing approach is employed to fabricate 3D tactile sensors under ambient conditions conformally onto freeform surfaces. The customized sensor is demonstrated with the capabilities of detecting and differentiating human movements, including pulse monitoring and finger motions. The custom 3D printing of functional materials and devices opens new routes for the biointegration of various sensors in wearable electronics systems, and toward advanced bionic skin applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Plasticity in the Oxidative Folding Pathway of the High Affinity Nerita Versicolor Carboxypeptidase Inhibitor (NvCI).

    PubMed

    Esperante, Sebastián A; Covaleda, Giovanni; Trejo, Sebastián A; Bronsoms, Sílvia; Aviles, Francesc X; Ventura, Salvador

    2017-07-14

    Nerita Versicolor carboxypeptidase inhibitor (NvCI) is the strongest inhibitor reported so far for the M14A subfamily of carboxypeptidases. It comprises 53 residues and a protein fold composed of a two-stranded antiparallel β sheet connected by three loops and stabilized by three disulfide bridges. Here we report the oxidative folding and reductive unfolding pathways of NvCI. Much debate has gone on whether protein conformational folding guides disulfide bond formation or instead they are disulfide bonds that favour the arrangement of local or global structural elements. We show here that for NvCI both possibilities apply. Under physiological conditions, this protein folds trough a funnelled pathway involving a network of kinetically connected native-like intermediates, all sharing the disulfide bond connecting the two β-strands. In contrast, under denaturing conditions, the folding of NvCI is under thermodynamic control and follows a "trial and error" mechanism, in which an initial quasi-stochastic population of intermediates rearrange their disulfide bonds to attain the stable native topology. Despite their striking mechanistic differences, the efficiency of both folding routes is similar. The present study illustrates thus a surprising plasticity in the folding of this extremely stable small disulfide-rich inhibitor and provides the basis for its redesign for biomedical applications.

  13. Discussions of Life Expectancy and Changes in Illness Understanding in Patients With Advanced Cancer.

    PubMed

    Epstein, Andrew S; Prigerson, Holly G; O'Reilly, Eileen M; Maciejewski, Paul K

    2016-07-10

    Accurate illness understanding enables patients to make informed decisions. Evidence of the influence of prognostic discussions on the accuracy of illness understanding by patients would demonstrate the value of discussions. Recent and past oncology provider-patient discussions about prognosis/life expectancy were examined for their association with changes in illness understanding by patients. Patients (N = 178) with advanced cancers refractory to prior chemotherapy whom oncologists expected to die within 6 months were interviewed before and after a visit in which cancer restaging scan results were discussed. Illness understanding scores were the sum of four indicator variables: patient terminal illness acknowledgment, recognition of incurable disease status, knowledge of the advanced stage of the disease, and expectation to live months as opposed to years. Before the restaging scan visit, nine (5%) of 178 patients had completely accurate illness understanding (ie, correctly answered each of the four illness understanding questions). Eighteen patients (10%) reported only recent discussions of prognosis/life expectancy with their oncologists; 68 (38%) reported only past discussions; 24 (13%) reported both recent and past discussions; and 68 (38%) reported that they never had discussions of prognosis/life expectancy with their oncologists. After adjustment for potential confounders (ie, education and race/ethnicity), analysis identified significant, positive changes in illness understanding scores for patients in groups that reported recent only (least-squares mean change score, 0.62; 95% CI, 0.23 to 1.01; P = .002) and both recent and past (least-squares mean change score, 0.37; 95% CI, 0.04 to 0.70; P = 0.028) discussions of prognosis/life expectancy with their oncologists. Patients with advanced cancer who report recent discussions of prognosis/life expectancy with their oncologists come to have a better understanding of the terminal nature of their illnesses.

  14. Discussions of Life Expectancy and Changes in Illness Understanding in Patients With Advanced Cancer

    PubMed Central

    Epstein, Andrew S.; O’Reilly, Eileen M.; Maciejewski, Paul K.

    2016-01-01

    Purpose Accurate illness understanding enables patients to make informed decisions. Evidence of the influence of prognostic discussions on the accuracy of illness understanding by patients would demonstrate the value of discussions. Methods Recent and past oncology provider-patient discussions about prognosis/life expectancy were examined for their association with changes in illness understanding by patients. Patients (N = 178) with advanced cancers refractory to prior chemotherapy whom oncologists expected to die within 6 months were interviewed before and after a visit in which cancer restaging scan results were discussed. Illness understanding scores were the sum of four indicator variables: patient terminal illness acknowledgment, recognition of incurable disease status, knowledge of the advanced stage of the disease, and expectation to live months as opposed to years. Results Before the restaging scan visit, nine (5%) of 178 patients had completely accurate illness understanding (ie, correctly answered each of the four illness understanding questions). Eighteen patients (10%) reported only recent discussions of prognosis/life expectancy with their oncologists; 68 (38%) reported only past discussions; 24 (13%) reported both recent and past discussions; and 68 (38%) reported that they never had discussions of prognosis/life expectancy with their oncologists. After adjustment for potential confounders (ie, education and race/ethnicity), analysis identified significant, positive changes in illness understanding scores for patients in groups that reported recent only (least-squares mean change score, 0.62; 95% CI, 0.23 to 1.01; P = .002) and both recent and past (least-squares mean change score, 0.37; 95% CI, 0.04 to 0.70; P = 0.028) discussions of prognosis/life expectancy with their oncologists. Conclusion Patients with advanced cancer who report recent discussions of prognosis/life expectancy with their oncologists come to have a better understanding of the

  15. Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy.

    PubMed

    Nogué-Aliguer, Miquel; Carles, Joan; Arrivi, Antonio; Juan, Oscar; Alonso, Lorenzo; Font, Albert; Mellado, Begoña; Garrido, Pilar; Sáenz, Alberto

    2003-05-01

    Cisplatin-based combinations are considered to be the standard treatment for advanced transitional cell carcinoma (TCC) of the urothelium. Many of the patients are elderly with concomitant diseases or impaired renal function. We studied the tolerance and activity of the gemcitabine/carboplatin combination as a therapeutic alternative. Patients with locally advanced or metastatic TCC of the urothelium were treated with gemcitabine 1000 mg/m(2) on Days 1 and 8 and carboplatin area under the concentration-time curve 5 on Day 1 every 21 days. Patients with creatinine clearance of 30 mL/min or above and Karnofsky performance status (KPS) scores 60 or above were enrolled. A total of 227 cycles were administered to 41 patients, with an average of 5.5 cycles per patient (range, 1-8 cycles). Creatinine clearance was below 60 mL/min in 54% of patients, KPS was 70 or below in 37% of patients, and 37% of patients were 70 years old or older. Hematologic toxicity was mainly Grade 3/4 neutropenia in 63%, Grade 3/4 thrombocytopenia in 32%, and Grade 3/4 anemia in 54% of patients. There were only three episodes of febrile neutropenia and one death from neutropenic sepsis. Nonhematologic toxicity was mild, with asthenia as the most frequently reported event. We obtained 6 complete and 17 partial responses, for an overall response rate of 56.1% (95% confidence interval [CI], 40.6-71.6%). Progression-free survival was 7.2 months (95% CI, 5.7-8.5) and median survival was 10.1 months (95% CI, 8.8-12.2). The combination of gemcitabine plus carboplatin achieves a similar result to doublets using cisplatin. It has an acceptable toxicity profile and enables patients with impaired renal function and/or poor performance status and elderly patients to be treated. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.10990

  16. Carboxymethyl lysine, an advanced glycation end product, and incident diabetes: a case-cohort analysis of the ARIC Study.

    PubMed

    Luft, V C; Duncan, B B; Schmidt, M I; Chambless, L E; Pankow, J S; Hoogeveen, R C; Couper, D J; Heiss, G

    2016-10-01

    To verify whether elevated fasting levels of circulating carboxymethyl lysine (CML), an advanced glycation end product, predict the development of diabetes in middle-age adults. Using a stratified case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 514 who did not over a median 9 years in the Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses were used to account for the design. In weighted analyses, correlation between CML levels and anthropometric, inflammatory or metabolic variables was minimal (Pearson correlations usually < 0.10). CML, when modelled as a continuous variable and after adjustment for age, sex, race, centre, parental history of diabetes, BMI, waist-to-hip ratio, non-esterified fatty acids, oxidized LDL-cholesterol, GFR, smoking, an inflammation score, adiponectin, leptin, insulin and glucose levels, was associated with an increased risk of diabetes [Hazard ratio (HR) = 1.35; 95% confidence interval (CI) 1.09-1.67, for each 100 ng/ml CML increment]. Baseline glucose level and race each modified the association (P < 0.05 for interaction), which was present only among those with impaired fasting glucose (≥ 5.6 mmol/l, HR = 1.61, 95% CI 1.26-2.05) and among white participants (HR = 1.50, 95% CI 1.13-1.99). Elevated fasting CML, after adjustment for multiple risk factors for diabetes, predicts the development of incident diabetes, the association being present among those with impaired fasting glucose and in white participants. These prospective findings suggest that advanced glycation end products might play a role in the development of diabetes. © 2015 Diabetes UK.

  17. 40 CFR 63.6604 - What fuel requirements must I meet if I own or operate an existing stationary CI RICE?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... I own or operate an existing stationary CI RICE? 63.6604 Section 63.6604 Protection of Environment....6604 What fuel requirements must I meet if I own or operate an existing stationary CI RICE? If you own or operate an existing non-emergency, non-black start CI stationary RICE with a site rating of more...

  18. Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium

    PubMed Central

    Wroblewski, Kristen; Wallace, James A.; Hall, Michael J.; Locker, Gershon; Nattam, Sreenivasa; Agamah, Edem; Stadler, Walter M.; Vokes, Everett E.

    2015-01-01

    Summary Background Sorafenib, an inhibitor of B-raf, VEGFR2, and PDGFR-β, has activity against pancreatic cancer in preclinical models. In a phase I trial of gemcitabine plus sorafenib, 57% of pancreatic cancer patients achieved stable disease. Patients and methods We conducted a multi-center phase II trial of sorafenib plus gemcitabine in chemo-naïve patients with histologicallyconfirmed, advanced pancreatic cancer. Patients received sorafenib 400 mg twice daily and gemcitabine 1,000 mg/m2 on days 1, 8 and 15 of a 28 day cycle. Results Seventeen patients enrolled at 4 centers; 13 were evaluable for response. There were no objective responses; 18% had stable disease. Median overall survival was 4.0 months (95% CI: 3.4, 5.9); median progression-free survival was 3.2 months (95% CI: 1.6, 3.6). Grade 3/4 toxicities included thrombosis in 18% of patients, dehydration or hand-foot syndrome in 12%, and hypertension or gastrointestinal bleeding in 6%. Conclusion Gemcitabine plus sorafenib is inactive in advanced pancreatic cancer. PMID:20803052

  19. Concurrent chemoradiotherapy versus radiotherapy alone for locoregionally advanced nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy: a meta-analysis.

    PubMed

    He, Yan; Guo, Tao; Guan, Hui; Wang, Jingjing; Sun, Yu; Peng, Xingchen

    2018-01-01

    In this study, we attempted to compare the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with radiotherapy alone (RT) for locoregionally advanced nasopharyngeal carcinoma (LANPC) in the era of intensity-modulated radiotherapy (IMRT) by meta-analysis. We searched databases, and all randomized controlled trials meeting the inclusion criteria were utilized for a meta-analysis with RevMan 5.3 based on the Cochrane methodology. Fifteen studies were found suitable based on the inclusion criteria. CCRT not only significantly improved the overall response rate (risk ratio [RR]=0.53, 95% CI 0.43-0.66) and the complete response rate (RR=0.60, 95% CI 0.51-0.71) but also contributed to longer overall survival. The incidence of grade 3-4 adverse events from CCRT group increased in hematologic toxicity (RR 2.25, 95% CI 1.54-3.29), radiation-induced oral mucositis (RR 1.64, 95% CI 1.14-2.35), and radiodermatitis (RR 1.80, 95% CI 1.13-2.88). Compared with IMRT alone, CCRT provided survival benefit with acceptable toxicity in patients with LANPC. However, we need multicenter randomized controlled trials and long-term follow-up to evaluate the eventual efficacy and toxicity of concurrent chemotherapy plus IMRT.

  20. Increased risk of adverse drug events secondary to bevacizumab treatment in patients with advanced or metastatic breast cancer: a meta-analysis of randomized controlled trials.

    PubMed

    Shin, Sooyoung; Noh, Yoojin

    2018-01-01

    Several clinical trials have shown an increased risk of hypertension with bevacizumab when added to chemotherapy in different types of malignancy; however, the risks of other significant adverse events besides hypertension, specifically in breast cancer, have not been completely elucidated. This study was conducted with the aim, primarily, to assess the overall incidence and risk of common toxicities associated with bevacizumab in patients with advanced or metastatic breast cancer and, secondarily, to descriptively review study results concerning a potential correlation between bevacizumab-induced hypertension and its efficacy for breast cancer treatment. We carried out a meta-analysis of relevant randomized controlled trials (RCTs) identified from a database search (Cochrane Library and PubMed) and, additionally, by reviewing previous reviews and meta-analyses. Overall incidence rates, odds ratios (ORs), and 95% confidence intervals (CIs) were assessed with the random- or fixed-effect models, depending on the level of heterogeneity across the included trials. The primary clinical outcomes were high-grade adverse events commonly reported with bevacizumab therapy. We included 6,260 patients with advanced-stage breast cancer from 12 RCTs in the meta-analysis. Five types of high-grade (Grade 3 or 4) adverse drug events were identified as being correlated with bevacizumab treatment versus alternative treatment with statistical significance: hypertension (OR 5.67, 95% CI 3.02-10.65), proteinuria (OR 10.09, 95% CI 4.79-21.27), bleeding (OR 3.45, 95% CI 2.25-5.30), cardiac toxicity (OR 2.15, 95% CI 1.29-3.59), and neutropenic fever (OR 1.51, 95% CI 1.15-2.00). The prognostic value of bevacizumab-induced hypertension for its antitumor efficacy among patients with breast cancer remains controversial, with mixed results presented in the five retrospective studies that were identified from our additional literature search. The addition of bevacizumab to anticancer therapy was