Do infants perceive the social robot Keepon as a communicative partner?

PubMed

Peca, Andreea; Simut, Ramona; Cao, Hoang-Long; Vanderborght, Bram

2016-02-01

This study investigates if infants perceive an unfamiliar agent, such as the robot Keepon, as a social agent after observing an interaction between the robot and a human adult. 23 infants, aged 9-17 month, were exposed, in a first phase, to either a contingent interaction between the active robot and an active human adult, or to an interaction between an active human adult and the non-active robot, followed by a second phase, in which infants were offered the opportunity to initiate a turn-taking interaction with Keepon. The measured variables were: (1) the number of social initiations the infant directed toward the robot, and (2) the number of anticipatory orientations of attention to the agent that follows in the conversation. The results indicate a significant higher level of initiations in the interactive robot condition compared to the non-active robot condition, while the difference between the frequencies of anticipations of turn-taking behaviors was not significant. Copyright © 2015 Elsevier Inc. All rights reserved.

Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

PubMed

Worek, Franz; Seeger, Thomas; Neumaier, Katharina; Wille, Timo; Thiermann, Horst

2016-11-16

The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals. To overcome disadvantages of vertebrates the present pilot study was initiated to investigate the suitability of South American cockroaches (Blaptica dubia) as warning system for exposure to chemical warfare nerve and blister agents. Initial in vitro experiments with nerve agents showed an increasing inhibitory potency in the order tabun - cyclosarin - sarin - soman - VX of cockroach cholinesterase. Exposure of cockroaches to chemical warfare agents resulted in clearly visible and reproducible reactions, the onset being dependent on the agent and dose. With nerve agents the onset was related to the volatility of the agents. The blister agent lewisite induced signs largely comparable to those of nerve agents while sulfur mustard exposed animals exhibited a different sequence of events. In conclusion, this first pilot study indicates that Blaptica dubia could serve as a warning system to exposure of chemical warfare agents. A cockroach-based system will not detect or identify a particular chemical warfare agent but could trigger further actions, e.g. specific detection and increased protective status. By designing appropriate boxes with (IR) motion sensors and remote control (IR) camera automated off-site warning systems could be realized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reach a nonlinear consensus for MAS via doubly stochastic quadratic operators

NASA Astrophysics Data System (ADS)

Abdulghafor, Rawad; Turaev, Sherzod; Zeki, Akram; Al-Shaikhli, Imad

2018-06-01

This technical note addresses the new nonlinear protocol class of doubly stochastic quadratic operators (DSQOs) for coordination of consensus problem in multi-agent systems (MAS). We derive the conditions for ensuring that every agent reaches consensus on a desired rate of the group's decision where the group decision value in its agent's initial statuses varies. Besides that, we investigate a nonlinear protocol sub-class of extreme DSQO (EDSQO) to reach a consensus for MAS to a common value with nonlinear low-complexity rules and fast time convergence if the interactions for each agent are not selfish. In addition, to extend the results to reach a consensus and to avoid the selfish case we specify a general class of DSQO for reaching a consensus under any given case of initial states. The case that MAS reach a consensus by DSQO is if each member of the agent group has positive interactions of DSQO (PDSQO) with the others. The convergence of both EDSQO and PDSQO classes is found to be directed towards the centre point. Finally, experimental simulations are given to support the analysis from theoretical aspect.

Modeling the Information Age Combat Model: An Agent-Based Simulation of Network Centric Operations

NASA Technical Reports Server (NTRS)

Deller, Sean; Rabadi, Ghaith A.; Bell, Michael I.; Bowling, Shannon R.; Tolk, Andreas

2010-01-01

The Information Age Combat Model (IACM) was introduced by Cares in 2005 to contribute to the development of an understanding of the influence of connectivity on force effectiveness that can eventually lead to quantitative prediction and guidelines for design and employment. The structure of the IACM makes it clear that the Perron-Frobenius Eigenvalue is a quantifiable metric with which to measure the organization of a networked force. The results of recent experiments presented in Deller, et aI., (2009) indicate that the value of the Perron-Frobenius Eigenvalue is a significant measurement of the performance of an Information Age combat force. This was accomplished through the innovative use of an agent-based simulation to model the IACM and represents an initial contribution towards a new generation of combat models that are net-centric instead of using the current platform-centric approach. This paper describes the intent, challenges, design, and initial results of this agent-based simulation model.

Survival of multiple myeloma patients aged 65-70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network.

PubMed

Ozaki, Shuji; Harada, Takeshi; Saitoh, Takayuki; Shimazaki, Chihiro; Itagaki, Mitsuhiro; Asaoku, Hideki; Kuroda, Yoshiaki; Chou, Takaaki; Yoshiki, Yumiko; Suzuki, Kenshi; Murakami, Hirokazu; Hayashi, Kunihiko; Mina, Roberto; Palumbo, Antonio; Shimizu, Kazuyuki

2014-01-01

Novel agents such as thalidomide, lenalidomide and bortezomib have dramatically changed the treatment paradigm of multiple myeloma (MM). However, it is not clear whether these agents improve the prognosis of elderly patients who have undergone autologous stem cell transplantation (auto-SCT). We retrospectively analyzed the outcome of 318 newly diagnosed patients aged 65–70 years who were treated between January 1, 2004, and December 31, 2009. As initial therapy, 192 patients were treated with conventional chemotherapy,88 with novel agent-containing regimens, 21 with conventional chemotherapy plus auto-SCT and the remaining 17 with novel agents plus auto-SCT. The median progression-free survival was 19.1, 24.5, 26.8 and 35.2 months, respectively, and the 5-year overall survival (OS) was 40, 62, 63 and 87%, respectively. Initial therapy with novel agents (p < 0.001) or auto-SCT (p < 0.02) significantly improved OS compared with the group without these treatment modalities. Salvage therapy with novel agents also significantly improved survival after relapse compared with conventional chemotherapy alone (p < 0.04). In a multivariate analysis, the use of novel agents was an independent prognostic factor significantly associated with extended OS(p < 0.003). These results indicate that novel agents and auto-SCT had a major impact on OS in eligible patients in this subgroup of MM. © 2014 S. Karger AG, Basel

Ozone-initiated terpene reaction products in five European offices: replacement of a floor cleaning agent.

PubMed

Nørgaard, A W; Kofoed-Sørensen, V; Mandin, C; Ventura, G; Mabilia, R; Perreca, E; Cattaneo, A; Spinazzè, A; Mihucz, V G; Szigeti, T; de Kluizenaar, Y; Cornelissen, H J M; Trantallidi, M; Carrer, P; Sakellaris, I; Bartzis, J; Wolkoff, P

2014-11-18

Cleaning agents often emit terpenes that react rapidly with ozone. These ozone-initiated reactions, which occur in the gas-phase and on surfaces, produce a host of gaseous and particulate oxygenated compounds with possible adverse health effects in the eyes and airways. Within the European Union (EU) project OFFICAIR, common ozone-initiated reaction products were measured before and after the replacement of the regular floor cleaning agent with a preselected low emitting floor cleaning agent in four offices located in four EU countries. One reference office in a fifth country did not use any floor cleaning agent. Limonene, α-pinene, 3-carene, dihydromyrcenol, geraniol, linalool, and α-terpineol were targeted for measurement together with the common terpene oxidation products formaldehyde, 4-acetyl-1-methylcyclohexene (4-AMCH), 3-isopropenyl-6-oxo-heptanal (IPOH), 6-methyl-5-heptene-2-one, (6-MHO), 4-oxopentanal (4-OPA), and dihydrocarvone (DHC). Two-hour air samples on Tenax TA and DNPH cartridges were taken in the morning, noon, and in the afternoon and analyzed by thermal desorption combined with gas chromatography/mass spectrometry and HPLC/UV analysis, respectively. Ozone was measured in all sites. All the regular cleaning agents emitted terpenes, mainly limonene and linalool. After the replacement of the cleaning agent, substantially lower concentrations of limonene and formaldehyde were observed. Some of the oxidation product concentrations, in particular that of 4-OPA, were also reduced in line with limonene. Maximum 2 h averaged concentrations of formaldehyde, 4-AMCH, 6-MHO, and IPOH would not give rise to acute eye irritation-related symptoms in office workers; similarly, 6-AMCH, DHC and 4-OPA would not result in airflow limitation to the airways.

Effects of pH buffering agents on the anaerobic hydrolysis acidification stage of kitchen waste.

PubMed

Wang, Yaya; Zang, Bing; Gong, Xiaoyan; Liu, Yu; Li, Guoxue

2017-10-01

This study investigated effects of initial pH buffering agents on the lab-scale anaerobic hydrolysis acidification stage of kitchen waste (KW). Different cheap, available and suitable buffering agents (NaOH(s), NaOH(l), CaO(s)-NaOH, KOH(l)-NaOH, K 2 HPO 4 (s)-KOH, Na 2 CO 3 (s)-NaOH) were added under optimal adjusting mode (first two days: per 16h, after: one time per day) which was obtained in previous work. The effects of buffering agents were evaluated according to indexes of pH, VFAs, NH 4 + -N, TS, VS, VS/TS, TS and VS removal rate. The results showed treatment 5 with adding K 2 HPO 4 -KOH buffering agents had the most stable pH (6.7-7.0). Also treatment 5, 2, 4 and 6 provided stable pH ranging in 5-8. Among the treatments, treatment 6 with adding Na 2 CO 3 as initial buffering agents and 10mol/L NaOH as regulator was chosen as the optimal mode for highest VFAs content (44.05g/L) with high acetic acid and butyrate acid proportion (42.64%), TS and VS removal rate (44.84% and 58.67%, respectively), low VS/TS ratio (58.55), fewer adding dosage and low adjusting frequency. The VFAs content of treatment 6 at the end of hydrolysis acidification stage could be used for methanogenic phase of anaerobic two-phase digestion. Thus, treatment 6 (adding Na 2 CO 3 as initial buffering agents and 10mol/L NaOH as regulator) with highest VFAs content and TS and VS removal rate could be considered using in anaerobic hydrolysis acidification stage pH adjustment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pulse sequences for uniform perfluorocarbon droplet vaporization and ultrasound imaging.

PubMed

Puett, C; Sheeran, P S; Rojas, J D; Dayton, P A

2014-09-01

Phase-change contrast agents (PCCAs) consist of liquid perfluorocarbon droplets that can be vaporized into gas-filled microbubbles by pulsed ultrasound waves at diagnostic pressures and frequencies. These activatable contrast agents provide benefits of longer circulating times and smaller sizes relative to conventional microbubble contrast agents. However, optimizing ultrasound-induced activation of these agents requires coordinated pulse sequences not found on current clinical systems, in order to both initiate droplet vaporization and image the resulting microbubble population. Specifically, the activation process must provide a spatially uniform distribution of microbubbles and needs to occur quickly enough to image the vaporized agents before they migrate out of the imaging field of view. The development and evaluation of protocols for PCCA-enhanced ultrasound imaging using a commercial array transducer are described. The developed pulse sequences consist of three states: (1) initial imaging at sub-activation pressures, (2) activating droplets within a selected region of interest, and (3) imaging the resulting microbubbles. Bubble clouds produced by the vaporization of decafluorobutane and octafluoropropane droplets were characterized as a function of focused pulse parameters and acoustic field location. Pulse sequences were designed to manipulate the geometries of discrete microbubble clouds using electronic steering, and cloud spacing was tailored to build a uniform vaporization field. The complete pulse sequence was demonstrated in the water bath and then in vivo in a rodent kidney. The resulting contrast provided a significant increase (>15 dB) in signal intensity. Copyright © 2014 Elsevier B.V. All rights reserved.

Building an adaptive agent to monitor and repair the electrical power system of an orbital satellite

NASA Technical Reports Server (NTRS)

Tecuci, Gheorghe; Hieb, Michael R.; Dybala, Tomasz

1995-01-01

Over several years we have developed a multistrategy apprenticeship learning methodology for building knowledge-based systems. Recently we have developed and applied our methodology to building intelligent agents. This methodology allows a subject matter expert to build an agent in the same way in which the expert would teach a human apprentice. The expert will give the agent specific examples of problems and solutions, explanations of these solutions, or supervise the agent as it solves new problems. During such interactions, the agent learns general rules and concepts, continuously extending and improving its knowledge base. In this paper we present initial results on applying this methodology to build an intelligent adaptive agent for monitoring and repair of the electrical power system of an orbital satellite, stressing the interaction with the expert during apprenticeship learning.

Stochastic Leader Gravitational Search Algorithm for Enhanced Adaptive Beamforming Technique

PubMed Central

Darzi, Soodabeh; Islam, Mohammad Tariqul; Tiong, Sieh Kiong; Kibria, Salehin; Singh, Mandeep

2015-01-01

In this paper, stochastic leader gravitational search algorithm (SL-GSA) based on randomized k is proposed. Standard GSA (SGSA) utilizes the best agents without any randomization, thus it is more prone to converge at suboptimal results. Initially, the new approach randomly choses k agents from the set of all agents to improve the global search ability. Gradually, the set of agents is reduced by eliminating the agents with the poorest performances to allow rapid convergence. The performance of the SL-GSA was analyzed for six well-known benchmark functions, and the results are compared with SGSA and some of its variants. Furthermore, the SL-GSA is applied to minimum variance distortionless response (MVDR) beamforming technique to ensure compatibility with real world optimization problems. The proposed algorithm demonstrates superior convergence rate and quality of solution for both real world problems and benchmark functions compared to original algorithm and other recent variants of SGSA. PMID:26552032

An Exploratory Study of the Butterfly Effect Using Agent-Based Modeling

NASA Technical Reports Server (NTRS)

Khasawneh, Mahmoud T.; Zhang, Jun; Shearer, Nevan E. N.; Rodriquez-Velasquez, Elkin; Bowling, Shannon R.

2010-01-01

This paper provides insights about the behavior of chaotic complex systems, and the sensitive dependence of the system on the initial starting conditions. How much does a small change in the initial conditions of a complex system affect it in the long term? Do complex systems exhibit what is called the "Butterfly Effect"? This paper uses an agent-based modeling approach to address these questions. An existing model from NetLogo library was extended in order to compare chaotic complex systems with near-identical initial conditions. Results show that small changes in initial starting conditions can have a huge impact on the behavior of chaotic complex systems. The term the "butterfly effect" is attributed to the work of Edward Lorenz [1]. It is used to describe the sensitive dependence of the behavior of chaotic complex systems on the initial conditions of these systems. The metaphor refers to the notion that a butterfly flapping its wings somewhere may cause extreme changes in the ecological system's behavior in the future, such as a hurricane.

Programming secure mobile agents in healthcare environments using role-based permissions.

PubMed

Georgiadis, C K; Baltatzis, J; Pangalos, G I

2003-01-01

The healthcare environment consists of vast amounts of dynamic and unstructured information, distributed over a large number of information systems. Mobile agent technology is having an ever-growing impact on the delivery of medical information. It supports acquiring and manipulating information distributed in a large number of information systems. Moreover is suitable for the computer untrained medical stuff. But the introduction of mobile agents generates advanced threads to the sensitive healthcare information, unless the proper countermeasures are taken. By applying the role-based approach to the authorization problem, we ease the sharing of information between hospital information systems and we reduce the administering part. The different initiative of the agent's migration method, results in different methods of assigning roles to the agent.

The Cost of Performance? Students' Learning about Acting as Change Agents in Their Schools

ERIC Educational Resources Information Center

Kehoe, Ian

2015-01-01

This paper explores how performance culture could affect students' learning about, and disposition towards, acting as organisational change agents in schools. This is based on findings from an initiative aimed to enable students to experience acting as change agents on an aspect of the school's culture that concerned them. The initiative was…

Integrating CLIPS applications into heterogeneous distributed systems

NASA Technical Reports Server (NTRS)

Adler, Richard M.

1991-01-01

SOCIAL is an advanced, object-oriented development tool for integrating intelligent and conventional applications across heterogeneous hardware and software platforms. SOCIAL defines a family of 'wrapper' objects called agents, which incorporate predefined capabilities for distributed communication and control. Developers embed applications within agents and establish interactions between distributed agents via non-intrusive message-based interfaces. This paper describes a predefined SOCIAL agent that is specialized for integrating C Language Integrated Production System (CLIPS)-based applications. The agent's high-level Application Programming Interface supports bidirectional flow of data, knowledge, and commands to other agents, enabling CLIPS applications to initiate interactions autonomously, and respond to requests and results from heterogeneous remote systems. The design and operation of CLIPS agents are illustrated with two distributed applications that integrate CLIPS-based expert systems with other intelligent systems for isolating and mapping problems in the Space Shuttle Launch Processing System at the NASA Kennedy Space Center.

Stationary average consensus protocol for a class of heterogeneous high-order multi-agent systems with application for aircraft

NASA Astrophysics Data System (ADS)

Rezaei, Mohammad Hadi; Menhaj, Mohammad Bagher

2018-01-01

This paper investigates the stationary average consensus problem for a class of heterogeneous-order multi-agent systems. The goal is to bring the positions of agents to the average of their initial positions while letting the other states converge to zero. To this end, three different consensus protocols are proposed. First, based on the auxiliary variables information among the agents under switching directed networks and state-feedback control, a protocol is proposed whereby all the agents achieve stationary average consensus. In the second and third protocols, by resorting to only measurements of relative positions of neighbouring agents under fixed balanced directed networks, two control frameworks are presented with two strategies based on state-feedback and output-feedback control. Finally, simulation results are given to illustrate the effectiveness of the proposed protocols.

Evaluating Social Causality and Responsibility Models: An Initial Report

DTIC Science & Technology

2005-01-01

ICT Technical Report ICT-TR-03-2005 Evaluating Social Causality and Responsibility ... social intelligent agents. In this report, we present a general computational model of social causality and responsibility , and empirical results of...2005 to 00-00-2005 4. TITLE AND SUBTITLE Evaluating Social Causality and Responsibility Models: An Initial Report 5a. CONTRACT NUMBER 5b. GRANT

OK-432 sclerotherapy in head and neck lymphangiomas: long-term follow-up result.

PubMed

Yoo, Jae Chul; Ahn, Youngjin; Lim, Yune Syung; Hah, J Hun; Kwon, Tack-Kyun; Sung, Myung-Whun; Kim, Kwang Hyun

2009-01-01

Nonsurgical treatments, such as sclerotherapy have been attempted for head and neck lymphagiomas. Of the available sclerosing agents, picibanil has shown satisfactory short-term treatment results in many studies, but no study has presented long-term treatment results. Accordingly, in the present study, the authors retrospectively reviewed the long-term treatment results of picibanil sclerotherapy. Fifty-five lymphangioma patients who underwent picibanil sclerotherapy were enrolled. Data about initial and long-term response, recurrence, and excision rate were collected. Initial response rates were 83.5 percent and long-term response rates were 76.3 percent. Initial and the long-term response rate were equally good for lymphangioma.

Comparative gastrointestinal safety of weekly oral bisphosphonates

PubMed Central

Katz, J. N.; Brookhart, M. A.; Stürmer, T.; Stedman, M. R.; Levin, R.; Solomon, D. H.

2012-01-01

Summary Weekly bisphosphonates are the primary agents used to treat osteoporosis. Although these agents are generally well tolerated, serious gastrointestinal adverse events, including hospitalization for gastrointestinal bleed, may arise. We compared the gastrointestinal safety between weekly alendronate and weekly risedronate and found no important difference between new users of these agents. Introduction Weekly bisphosphonates are the primary agents prescribed for osteoporosis. We examined the comparative gastrointestinal safety between weekly bisphosphonates. Methods We studied new users of weekly alendronate and weekly risedronate from June 2002 to August 2005 among enrollees in a state-wide pharmaceutical benefit program for seniors. Our primary outcome was hospitalization for upper gastrointestinal bleed. Secondary outcomes included outpatient diagnoses for upper gastrointestinal disease, symptoms, endoscopic procedures, use of gastroprotective agents, and switching between therapies. We used Cox proportional hazard models to compare outcomes between agents within 120 days of treatment initiation, adjusting for propensity score quintiles. We also examined composite safety outcomes and stratified results by age and prior gastrointestinal history. Results A total of 10,420 new users were studied, mean age=79 years (SD, 6.9), and 95% women. We observed 31 hospitalizations for upper gastrointestinal bleed (0.91 per 100 person-years) within 120 days of treatment initiation. Adjusting for covariates, there was no difference in hospitalization for upper gastrointestinal bleed among those treated with risedronate compared with alendronate (HR, 1.12; 95%CI, 0.55 to 2.28). Risedronate switching rates were lower; otherwise, no differences were observed for secondary or composite outcomes. Conclusions We found no important difference in gastrointestinal safety between weekly oral bisphosphonates. PMID:19266138

Activeness as a key to counter democratic balance

NASA Astrophysics Data System (ADS)

Qian, Shen; Liu, Yijun; Galam, Serge

2015-08-01

According to the classic Galam model of opinion dynamics, each agent participates at each update of an opinion interaction. While the scheme gives everyone the same chance to influence others, in reality, social activity and influence vary considerably from one agent to another. To account for such a feature, we introduce a new individual attribute-"activeness"-which makes some agents more inclined than others at engaging in local discussions. To enhance the corresponding effect, opinion updates are shifted from all-out agent interaction cycles to few agent interaction cycles. Using dynamic analysis and simulations the resulting model is found to exhibit a "Minority Counteroffensive" phenomenon, which under some initial conditions makes the minority to win the opinion competition despite a threshold tipping point at fifty percent. The associated probabilistic phenomenon persists in the case "activeness" is held equal for all agents. The effect of "opinion leaders" is also investigated. Indeed, a leader is an inflexible agent, i.e., an agent who does not change opinion. The results reveal that two opinion leaders with moderate social influence may have a stronger effect than one opinion leader with a strong social influence. The model may shed a new light to the understanding of opinion formation and public voting.

Study and Characterization of Subharmonic Emissions by Using Shaped Ultrasonic Driving Pulse

NASA Astrophysics Data System (ADS)

Masotti, L.; Biagi, E.; Breschi, L.; Vannacci, E.

Subharmonic emissions from Ultrasound Contrast Agents (UCAs) were studied by a Pulse Inversion method in order to assess the feasibility of implementation of this technique to subharmonic imaging. Interesting results concerning the dependence of the subharmonic emission with respect to initial pulse shape are presented. The experimentation was performed also by varying the acoustic pressure and concentration of the contrast agent (SonoVue®)

Effect of pregnancy on the pharmacokinetics of paclitaxel: a case report.

PubMed

Lycette, Jennifer L; Dul, Carrie L; Munar, Myrna; Belle, Donna; Chui, Stephen Y; Koop, Dennis R; Nichols, Craig R

2006-10-01

Breast cancer during pregnancy is increasingly common as women delay childbearing until later in life. Safe administration of adjuvant chemotherapy during pregnancy has been reported. Physiologic and metabolic changes during pregnancy could alter the pharmacokinetics of these agents. This is a pilot study to prospectively study the pharmacokinetics of chemotherapeutic agents during pregnancy. Herein, we report the initial results with paclitaxel in the first patient.

Multiplex method for initial complex testing of antibodies to blood transmitted diseases agents.

PubMed

Poltavchenko, Alexander G; Nechitaylo, Oleg V; Filatov, Pavel V; Ersh, Anna V; Gureyev, Vadim N

2016-10-01

Initial screening of donors and population at high risk of infection with blood transmitted diseases involves a number of analyses using monospesific diagnostic systems, and therefore is expensive labor- and time-consuming process. The goal of this work is to construct a multiplex test enabling to carry out rapid initial complex testing at a low price. The paper describes a kit making it possible to detect simultaneously antibodies to six agents of the most significant blood transmitted diseases: HIV virus, hepatitis B and C viruses, cytomegalovirus, T. pallidum and T. gondii in blood products. The kit comprises multiplex dot-immunoassay based on plane protein arrays (immune chips) using colloidal gold conjugates and silver development. It provides an opportunity to carry out complex analysis within 70min at room temperature, and there is no need of well-qualified personnel. We compared laboratory findings of the kit with monospecific kits for ELISA produced by two Russian commercial companies. Dot-assay results correlate well with data obtained using commercial kits for ELISA. Furthermore, multiplex analysis is quicker and cheaper in comparison with ELISA and can be carried out in non-laboratory conditions. The kit for multiplex dot-immunoassay of antibodies to blood transmitted agents can significantly simplify initial complex testing. Copyright © 2016 Elsevier B.V. All rights reserved.

Potential savings of harmonising hospital and community formularies for chronic disease medications initiated in hospital.

PubMed

Lapointe-Shaw, Lauren; Fischer, Hadas D; Newman, Alice; John-Baptiste, Ava; Anderson, Geoffrey M; Rochon, Paula A; Bell, Chaim M

2012-01-01

Hospitals in Canada manage their formularies independently, yet many inpatients are discharged on medications which will be purchased through publicly-funded programs. We sought to determine how much public money could be saved on chronic medications if hospitals promoted the initiation of agents with the lowest outpatient formulary prices. We used administrative databases for the province of Ontario to identify patients initiated on a proton pump inhibitor (PPI), angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) following hospital admission from April 1(st) 2008-March 31(st) 2009. We assessed the cost to the Ontario Drug Benefit Program (ODB) over the year following initiation and determined the cost savings if prescriptions were substituted with the least expensive agent in each class. The cost for filling all PPI, ACE inhibitor and ARB prescriptions was $ 2.48 million, $968 thousand and $325 thousand respectively. Substituting the least expensive agent could have saved $1.16 million (47%) for PPIs, $162 thousand (17%) for ACE inhibitors and $14 thousand (4%) for ARBs over the year following discharge. In a setting where outpatient prescriptions are publicly funded, harmonising outpatient formularies with inpatient therapeutic substitution resulted in modest cost savings and may be one way to control rising pharmaceutical costs.

Distributed robust finite-time nonlinear consensus protocols for multi-agent systems

NASA Astrophysics Data System (ADS)

Zuo, Zongyu; Tie, Lin

2016-04-01

This paper investigates the robust finite-time consensus problem of multi-agent systems in networks with undirected topology. Global nonlinear consensus protocols augmented with a variable structure are constructed with the aid of Lyapunov functions for each single-integrator agent dynamics in the presence of external disturbances. In particular, it is shown that the finite settling time of the proposed general framework for robust consensus design is upper bounded for any initial condition. This makes it possible for network consensus problems to design and estimate the convergence time offline for a multi-agent team with a given undirected information flow. Finally, simulation results are presented to demonstrate the performance and effectiveness of our finite-time protocols.

Adaptation and survivors in a random Boolean network.

PubMed

Nakamura, Ikuo

2002-04-01

We introduce the competitive agent with imitation strategy in a random Boolean network, in which the agent plays a competitive game that rewards those in minority. After a long time interval, the worst performer changes its strategy to the one of the best and the process is repeated. The network, initially in a chaotic state, evolves to an intermittent state and finally reaches a frozen state. Time series of survived species (whose strategies are imitated by other agents) in the system depend on the connectivity of each agent. In a system with various connectivity groups, the low connectivity groups win the minority game over the high connectivity groups. We also compared the result with mutation strategy system.

Carcinogen-induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumor progression.

PubMed Central

Brown, K; Buchmann, A; Balmain, A

1990-01-01

A number of mouse skin tumors initiated by the carcinogens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methylnitrosourea (MNU), 3-methylcholanthrene (MCA), and 7,12-dimethylbenz[a]anthracene (DMBA) have been shown to contain activated Ha-ras genes. In each case, the point mutations responsible for activation have been characterized. Results presented demonstrate the carcinogen-specific nature of these ras mutations. For each initiating agent, a distinct spectrum of mutations is observed. Most importantly, the distribution of ras gene mutations is found to differ between benign papillomas and carcinomas, suggesting that molecular events occurring at the time of initiation influence the probability with which papillomas progress to malignancy. This study provides molecular evidence in support of the existence of subsets of papillomas with differing progression frequencies. Thus, the alkylating agents MNNG and MNU induced exclusively G ---- A transitions at codon 12, with this mutation being found predominantly in papillomas. MCA initiation produced both codon 13 G ---- T and codon 61 A ---- T transversions in papillomas; only the G ---- T mutation, however, was found in carcinomas. These findings provide strong evidence that the mutational activation of Ha-ras occurs as a result of the initiation process and that the nature of the initiating event can affect the probability of progression to malignancy. Images PMID:2105486

Limits on relief through constrained exchange on random graphs

NASA Astrophysics Data System (ADS)

LaViolette, Randall A.; Ellebracht, Lory A.; Gieseler, Charles J.

2007-09-01

Agents are represented by nodes on a random graph (e.g., “small world”). Each agent is endowed with a zero-mean random value that may be either positive or negative. All agents attempt to find relief, i.e., to reduce the magnitude of that initial value, to zero if possible, through exchanges. The exchange occurs only between the agents that are linked, a constraint that turns out to dominate the results. The exchange process continues until Pareto equilibrium is achieved. Only 40-90% of the agents achieved relief on small-world graphs with mean degree between 2 and 40. Even fewer agents achieved relief on scale-free-like graphs with a truncated power-law degree distribution. The rate at which relief grew with increasing degree was slow, only at most logarithmic for all of the graphs considered; viewed in reverse, the fraction of nodes that achieve relief is resilient to the removal of links.

Therapeutic drug monitoring of antitubercular agents for disseminated Mycobacterium tuberculosis during intermittent haemodialysis and continuous venovenous haemofiltration.

PubMed

Sin, J H; Elshaboury, R H; Hurtado, R M; Letourneau, A R; Gandhi, R G

2018-04-01

There is a lack of data regarding therapeutic drug monitoring (TDM) of antitubercular agents in the setting of continuous venovenous haemofiltration (CVVH). We describe TDM results of numerous antitubercular agents in a critically ill patient during CVVH and haemodialysis. A 49-year-old man was initiated on treatment for disseminated Mycobacterium tuberculosis. During hospital admission, the patient developed critical illness and required renal replacement therapy. TDM results and pharmacokinetic calculations showed adequate serum concentrations of rifampin, ethambutol and amikacin during CVVH and of rifampin, pyrazinamide, ethambutol and levofloxacin during intermittent haemodialysis. The presence of critical illness and renal replacement therapy can induce pharmacokinetic changes that may warrant vigilant TDM to ensure optimal therapy. To our knowledge, this is the first report to describe TDM for several antitubercular agents during CVVH in a critically patient with disseminated M. tuberculosis. © 2017 John Wiley & Sons Ltd.

Linking JNK Activity to the DNA Damage Response

PubMed Central

Picco, Vincent

2013-01-01

The activity of c-Jun N-terminal kinase (JNK) was initially described as ultraviolet- and oncogene-induced kinase activity on c-Jun. Shortly after this initial discovery, JNK activation was reported for a wider variety of DNA-damaging agents, including γ-irradiation and chemotherapeutic compounds. As the DNA damage response mechanisms were progressively uncovered, the mechanisms governing the activation of JNK upon genotoxic stresses became better understood. In particular, a recent set of papers links the physical breakage in DNA, the activation of the transcription factor NF-κB, the secretion of TNF-α, and an autocrine activation of the JNK pathway. In this review, we will focus on the pathway that is initiated by a physical break in the DNA helix, leading to JNK activation and the resultant cellular consequences. The implications of these findings will be discussed in the context of cancer therapy with DNA-damaging agents. PMID:24349633

Optimal Reward Functions in Distributed Reinforcement Learning

NASA Technical Reports Server (NTRS)

Wolpert, David H.; Tumer, Kagan

2000-01-01

We consider the design of multi-agent systems so as to optimize an overall world utility function when (1) those systems lack centralized communication and control, and (2) each agents runs a distinct Reinforcement Learning (RL) algorithm. A crucial issue in such design problems is to initialize/update each agent's private utility function, so as to induce best possible world utility. Traditional 'team game' solutions to this problem sidestep this issue and simply assign to each agent the world utility as its private utility function. In previous work we used the 'Collective Intelligence' framework to derive a better choice of private utility functions, one that results in world utility performance up to orders of magnitude superior to that ensuing from use of the team game utility. In this paper we extend these results. We derive the general class of private utility functions that both are easy for the individual agents to learn and that, if learned well, result in high world utility. We demonstrate experimentally that using these new utility functions can result in significantly improved performance over that of our previously proposed utility, over and above that previous utility's superiority to the conventional team game utility.

Study of photo-oxidative reactivity of sunscreening agents based on photo-oxidation of uric acid by kinetic Monte Carlo simulation.

PubMed

Moradmand Jalali, Hamed; Bashiri, Hadis; Rasa, Hossein

2015-05-01

In the present study, the mechanism of free radical production by light-reflective agents in sunscreens (TiO2, ZnO and ZrO2) was obtained by applying kinetic Monte Carlo simulation. The values of the rate constants for each step of the suggested mechanism have been obtained by simulation. The effect of the initial concentration of mineral oxides and uric acid on the rate of uric acid photo-oxidation by irradiation of some sun care agents has been studied. The kinetic Monte Carlo simulation results agree qualitatively with the existing experimental data for the production of free radicals by sun care agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Controlling the optical properties of polyaniline doped by boric acid particles by changing their doping agent and initiator concentration

NASA Astrophysics Data System (ADS)

Cabuk, Mehmet; Gündüz, Bayram

2017-12-01

In this study, polyaniline doped by boric acid (PAni:BA) conducting polymers were chemically synthesized by oxidative polymerization method using (NH4)2S208 (APS) as initiator. Pani:BA conducting polymers were synthesized by using two different APS/aniline molar ratios as 1:1 and 2:1. Their results were compared with PAni doped by HCl (PAni) conducting polymer. Structural properties of the PAni, PAni:BA (1:1) and PAni:BA (2:1) conducting polymers were characterized by using FTIR, SEM, TGA, particle size and apparent density measurements. Effects of doping agents and initiator concentrations on optical properties were investigated in detail. The optoelectronic parameters such as absorption band edge, molar extinction coefficient, direct allowed band gap, refractive index, optical conductance and electrical conductance of the PAni, PAni:BA (1:1) and PAni:BA (2:1) were determined. The absorption band edge and direct allowed band gap of PAni were decreased with doping BA and increasing APS ratio. Also, the refractive index values of the materials were calculated from experimental results and compared with obtained results from Moss, Ravindra, Herve-Vandamme, Reddy and Kumar-Singh relations.

Radiolabelled D2 agonists as prolactinoma imaging agents

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

Otto, C.A.

1991-12-31

Research conducted in this terminal year of support centered on three distinct areas: mAChR ligand localization in pancreas and the effect of Ca{sup +2} on localization, continuation of assessment of quaternized and neutral mAChR ligands for possible use as PET myocardial imaging agents, and initiation of a study to determine the relationship of the nAChR receptor to the cellular receptor for measles virus. Several tables and figures illustrating the results are included.

Using Agent-Based Distillations to Explore Logistics Support to Urban, Humanitarian Assistance/Disaster Relief Operations

DTIC Science & Technology

2003-09-01

environments is warranted. The author’s initial concept was to set up the same scenario in three different PA agent-based programs, MANA, PYTHAGORAS ...of the consolidation as the result for that particular set of runs. This technique also allowed us to invoke the Central Limit Theorem . D...capabilities in the SOCRATES modeling environment. We encourage MANA and PYTHAGORAS to add this functionality to their products as well. We

Encapsulated boron as an osteoinductive agent for bone scaffolds.

PubMed

Gümüşderelioğlu, Menemşe; Tunçay, Ekin Ö; Kaynak, Gökçe; Demirtaş, Tolga T; Aydın, Seda Tığlı; Hakkı, Sema S

2015-01-01

The aim of this study was to develop boron (B)-releasing polymeric scaffold to promote regeneration of bone tissue. Boric acid-doped chitosan nanoparticles with a diameter of approx. 175 nm were produced by tripolyphosphate (TPP)-initiated ionic gelation process. The nanoparticles strongly attached via electrostatic interactions into chitosan scaffolds produced by freeze-drying with approx. 100 μm pore diameter. According to the ICP-OES results, following first 5h initial burst release, fast release of B from scaffolds was observed for 24h incubation period in conditioned medium. Then, slow release of B was performed over 120 h. The results of the cell culture studies proved that the encapsulated boron within the scaffolds can be used as an osteoinductive agent by showing its positive effects on the proliferation and differentiation of MC3T3-E1 preosteoblastic cells. Copyright © 2015 Elsevier GmbH. All rights reserved.

Resveratrol: A potential challenger against gastric cancer

PubMed Central

Zulueta, Aida; Caretti, Anna; Signorelli, Paola; Ghidoni, Riccardo

2015-01-01

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related mortality in the world. Late diagnosis and classical therapeutic approaches such as surgery, chemotherapy and radiotherapy make this disease a still threatening tumor. Genetic asset, environmental stress, dietary habit and infections caused by Helicobacter pylori (H. pylori) are the major causes concurring to GC initiation. A common mechanism is induction of radicals resulting in gastric mucosal injury. A regular food intake of antioxidant and radical scavenging agents has been proposed to exert protection against tumorigenesis. Resveratrol belongs to the polyphenol flavonoids class of antioxidants produced by a restricted number of plants. Resveratrol exerts bactericidal activity against H. pylori and is a powerful antioxidant, thus acting as a tumor preventive agent. Resveratrol intracellular signaling results in growth arrest and apoptosis, so that it can be directed against tumor progression. Resveratrol therapeutic potential against GC initiation and progression are reviewed here. PMID:26457023

Distributed Planning in a Mixed-Initiative Environment

DTIC Science & Technology

2008-06-01

Knowledge Sources Control Remote Blackboard Remote Knowledge Sources Remot e Data Remot e Data Java Distributed Blackboard Figure 3 - Distributed...an interface agent or planning agent and the second type is a critic agent. Agents in the DEEP architecture extend and use the Java Agent...chosen because it is fully implemented in Java , and supports these requirements. 2.3.3 Interface Agents Interface agents are the interfaces through

Fuselets: an agent based architecture for fusion of heterogeneous information and data

NASA Astrophysics Data System (ADS)

Beyerer, Jürgen; Heizmann, Michael; Sander, Jennifer

2006-04-01

A new architecture for fusing information and data from heterogeneous sources is proposed. The approach takes criminalistics as a model. In analogy to the work of detectives, who attempt to investigate crimes, software agents are initiated that pursue clues and try to consolidate or to dismiss hypotheses. Like their human pendants, they can, if questions beyond their competences arise, consult expert agents. Within the context of a certain task, region, and time interval, specialized operations are applied to each relevant information source, e.g. IMINT, SIGINT, ACINT,..., HUMINT, data bases etc. in order to establish hit lists of first clues. Each clue is described by its pertaining facts, uncertainties, and dependencies in form of a local degree-of-belief (DoB) distribution in a Bayesian sense. For each clue an agent is initiated which cooperates with other agents and experts. Expert agents support to make use of different information sources. Consultations of experts, capable to access certain information sources, result in changes of the DoB of the pertaining clue. According to the significance of concentration of their DoB distribution clues are abandoned or pursued further to formulate task specific hypotheses. Communications between the agents serve to find out whether different clues belong to the same cause and thus can be put together. At the end of the investigation process, the different hypotheses are evaluated by a jury and a final report is created that constitutes the fusion result. The approach proposed avoids calculating global DoB distributions by adopting a local Bayesian approximation and thus reduces the complexity of the exact problem essentially. Different information sources are transformed into DoB distributions using the maximum entropy paradigm and considering known facts as constraints. Nominal, ordinal and cardinal quantities can be treated within this framework equally. The architecture is scalable by tailoring the number of agents according to the available computer resources, to the priority of tasks, and to the maximum duration of the fusion process. Furthermore, the architecture allows cooperative work of human and automated agents and experts, as long as not all subtasks can be accomplished automatically.

Study on Heat Transfer Agent Models of Transmission Line and Transformer

NASA Astrophysics Data System (ADS)

Wang, B.; Zhang, P. P.

2018-04-01

When using heat transfer simulation to study the dynamic overload of transmission line and transformer, it needs to establish the mathematical expression of heat transfer. However, the formula is a nonlinear differential equation or equation set and it is not easy to get general solutions. Aiming at this problem, some different temperature change processes caused by different initial conditions are calculated by differential equation and equation set. New agent models are developed according to the characteristics of different temperature change processes. The results show that the agent models have high precision and can solve the problem that the original equation cannot be directly applied in some practical engineers.

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

PubMed Central

Calvo, Jennifer A.; Moroski-Erkul, Catherine A.; Lake, Annabelle; Eichinger, Lindsey W.; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T.; Christiani, David C.; Meira, Lisiane B.; Samson, Leona D.

2013-01-01

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag −/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage. PMID:23593019

Corticosteroids vs corticosteroids plus antiviral agents in the treatment of Bell palsy: a systematic review and meta-analysis.

PubMed

Goudakos, John K; Markou, Konstantinos D

2009-06-01

To review systematically and meta-analyze the results of all randomized controlled trials (RCTs) for the treatment of patients with Bell palsy with corticosteroids vs corticosteroids plus antiviral agents. A MEDLINE, EMBASE, Cochrane Library, and CENTRAL database search, followed by extensive hand-searching for the identification of relevant studies. No time and language limitations were applied. Prospective RCTs on the treatment of patients with Bell palsy. Odds ratios (ORs), 95% confidence intervals (CIs), and tests for heterogeneity were reported. Five studies were eventually identified and systematically reviewed. Meta-analysis was performed for 4 studies. Regarding the complete recovery rate of facial nerve paralysis 3 months after initiation of therapy, the current systematic review and meta-analysis suggests that the addition of an antiviral agent does not provide any benefit (OR, 1.03 [95% CI, 0.74-1.42]; P = .88). The same conclusion emerged at posterior (fourth, sixth, and ninth) months of assessment. Subgroup analysis, conducted on the basis of time point of therapy initiation, type of antiviral agent, and blindness of assessments did not change the results obtained. The occurrence rate of adverse effects attributable to therapy choice was not significantly different between patients receiving corticosteroids and those following combined treatment. The present systematic review and meta-analysis, based on the currently available evidence, suggests that the addition of an antiviral agent to corticosteroids for the treatment of Bell palsy is not associated with an increase in the complete recovery rate of the facial motor function.

A modified commercial ultrasound scanner used for in vivo photoacoustic imaging of nude mice injected with non-targeted contrast agents

NASA Astrophysics Data System (ADS)

Jankovic, Ladislav; Shahzad, Khalid; Wang, Yao; Burcher, Michael; Scholle, Frank-Detlef; Hauff, Peter; Mofina, Sabine; Skobe, Mihaela

2008-02-01

Photoacoustic (PA) experiments were performed using a modified commercial ultrasound scanner equipped with an array transducer and a Nd:YAG pumped OPO laser. The contrast agent SIDAG (Bayer Schering Pharma AG, Germany), used to enhance the optical absorption, demonstrated an expected pharmacokinetic behavior of the dye in the tumor and in the bladder of the nude mice. A typical behavior in the tumor consisted of an initial linear increase in PA signal followed by an exponential decay. PA signal approached the pre-injection level after about one hour following the dye injection, which was consistent with the behavior for such contrast agents when used in other imaging modalities, such as fluorescence imaging. The in-vivo spectral PA data from the mouse bladder, conducted 1.5 hours after the dye injection, clearly demonstrated presence of the dye. The multi-spectral PA data was obtained at 760nm, 784nm and 850nm laser excitations. The PA intensities obtained at these three wavelengths accurately matched the dye absorption spectrum. In addition, in the kidney, a clearance organ for this contrast agent, both in-vivo and ex-vivo results demonstrated a significant increase (~ 40%) in the ratio of PA signal at 760nm (the peak of the dye absorption) relative to the signal at 850nm (<1% absorption), indicating significant amounts of the dye in this organ. Our initial results confirm the desired photoacoustic properties of the contrast agent, indicating its great potential to be used for imaging with a commercial array-based ultrasound scanner.

Adaptive behaviors in multi-agent source localization using passive sensing.

PubMed

Shaukat, Mansoor; Chitre, Mandar

2016-12-01

In this paper, the role of adaptive group cohesion in a cooperative multi-agent source localization problem is investigated. A distributed source localization algorithm is presented for a homogeneous team of simple agents. An agent uses a single sensor to sense the gradient and two sensors to sense its neighbors. The algorithm is a set of individualistic and social behaviors where the individualistic behavior is as simple as an agent keeping its previous heading and is not self-sufficient in localizing the source. Source localization is achieved as an emergent property through agent's adaptive interactions with the neighbors and the environment. Given a single agent is incapable of localizing the source, maintaining team connectivity at all times is crucial. Two simple temporal sampling behaviors, intensity-based-adaptation and connectivity-based-adaptation, ensure an efficient localization strategy with minimal agent breakaways. The agent behaviors are simultaneously optimized using a two phase evolutionary optimization process. The optimized behaviors are estimated with analytical models and the resulting collective behavior is validated against the agent's sensor and actuator noise, strong multi-path interference due to environment variability, initialization distance sensitivity and loss of source signal.

Modelling trading networks and the role of trust

NASA Astrophysics Data System (ADS)

Barrio, Rafael A.; Govezensky, Tzipe; Ruiz-Gutiérrez, Élfego; Kaski, Kimmo K.

2017-04-01

We present a simple dynamical model for describing trading interactions between agents in a social network by considering only two dynamical variables, namely money and goods or services, that are assumed conserved over the whole time span of the agents' trading transactions. A key feature of the model is that agent-to-agent transactions are governed by the price in units of money per goods, which is dynamically changing, and by a trust variable, which is related to the trading history of each agent. All agents are able to sell or buy, and the decision to do either has to do with the level of trust the buyer has in the seller, the price of the goods and the amount of money and goods at the disposal of the buyer. Here we show the results of extensive numerical calculations under various initial conditions in a random network of agents and compare the results with the available related data. In most cases the agreement between the model results and real data turns out to be fairly good, which allow us to draw some general conclusions as how different trading strategies could affect the distribution of wealth in different kinds of societies. Our calculations reveal the striking effects of trust in commercial relations, namely that trust makes trading links more robust and the wealth distribution more even as well as allows for the existence of a healthy middle class.

Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

PubMed

Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Estes, Leita A; Suthipinijtham, Pharnuk

2008-12-01

Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.

99mTc-stannous colloid white cell scintigraphy in childhood inflammatory bowel disease.

PubMed

Peacock, Kenneth; Porn, Ute; Howman-Giles, Robert; O'Loughlin, Edward; Uren, Roger; Gaskin, Kevin; Dorney, Stuart; Kamath, Ramanand

2004-02-01

99mTc-Labeled white cell scintigraphy (WCS) has been used for the investigation of inflammatory bowel disease (IBD) in adults, but data on children are limited. The most common agent used is (99m) Tc-hexamethylpropyleneamine oxime (HMPAO); however, this agent has limitations. In a retrospective study, we assessed the use of (99m)Tc-stannous colloid WCS for the initial evaluation of children with suspected IBD. Diagnostic, endoscopic, and contrast radiography results were retrospectively collected from the medical records. Two experienced nuclear physicians unaware of the patient data interpreted the WCS results, with agreement reached by consensus. Statistical analysis was performed on the ability of WCS to detect active disease and localize it topographically and on a comparison of diagnostic methods, using a combination of clinical features and endoscopy as the reference standard. Between 1996 and 1999, 64 patients (35 male and 29 female; mean age, 12.5 y; age range, 2-19 y) had WCS performed, with IBD subsequently diagnosed in 34 patients. (99m)Tc-Stannous colloid WCS had an 88% sensitivity, 90% specificity, and 8.8 likelihood ratio for initial investigation of IBD. Agreement was poor for topographic localization of disease. Small-bowel series had a 75% sensitivity, 50% specificity, and 1.5 likelihood ratio for detecting endoscopic disease of the terminal ileum and proximal colon. Our results confirm that WCS is a useful imaging technique for the initial evaluation of patients with suspected IBD. (99m)Tc-Stannous colloid had results at least comparable to those of other WCS agents, and in children, (99m)Tc-stannous colloid WCS should be preferred in view of lower cost, shorter preparation time, and the smaller blood volumes required.

Initial Dosing and Taper Complexity of Methadone and Morphine for Treatment of Neonatal Abstinence Syndrome

PubMed Central

Ibach, Bethany W.; Johnson, Peter N.; Ernst, Kimberly D.; Harrison, Donald; Miller, Jamie L.

2016-01-01

Background: Methadone and morphine are commonly used to treat neonatal abstinence syndrome (NAS). Limited data exist to describe the most appropriate initial doses and taper regimens of these agents. Objectives: Describe the median initial dose and frequency of methadone and morphine for NAS. Compare dose adjustments, time to symptom relief, and taper complexity between groups. Methods: Retrospective study of neonates receiving enteral methadone or morphine for NAS over a 4-year period. Data collection included medication regimen, abstinence scores based on the Modified Finnegan Neonatal Abstinence Scoring Tool, and adverse events. Planned home taper complexity was assessed using the Medication Taper Complexity Score–Revised (MTCS-R). The primary outcome was initial opioid dose. Secondary outcomes included number of dose adjustments, time to symptom relief, and MTCS-R score. Results: Fifty neonates were initially treated for NAS with methadone (n = 36) or morphine (n = 14). The median initial dose was 0.09 mg/kg (range = 0.03-0.2) for methadone and 0.04 mg/kg (range = 0.03-0.4) for morphine. The most common initial dosing interval was q8h for methadone versus q3h for morphine. Number of dose adjustments and time to symptom relief were similar between groups. Median MTCS-R scores were similar between groups. There was no difference in adverse events between groups. Limitations included small sample size, preference toward methadone use, and variability of initial opioid dosing and titration. Conclusions: There was significant variability in initial doses of both agents. Neonates receiving methadone required less frequent dosing than morphine, which may result in easier administration and may allow for safer outpatient administration.

Arsenic Removal and Its Chemistry in Batch Electrocoagulation Studies.

PubMed

Sharma, Anshul; Adapureddy, Sri Malini; Goel, Sudha

2014-04-01

The aim of this study was to evaluate the impact of different oxidizing agents like light, aeration (by mixing) and electrocoagulation (EC) on the oxidation of As (III) and its subsequent removal in an EC batch reactor. Arsenic solutions prepared using distilled water and groundwater were evaluated. Optimum pH and the effect of varying initial pH on As removal efficiency were also evaluated. MaximumAs (III) removal efficiency with EC, light and aeration was 97% from distilled water and 71% from groundwater. Other results show that EC alone resulted in 90% As removal efficiency in the absence of light and mixing from distilled water and 53.6% from groundwater. Removal with light and mixing but without EC resulted in only 26% As removal from distilled water and 29% from groundwater proving that electro-oxidation and coagulation were more effective in removing arsenic compared to the other oxidizing agents examined. Initial pH was varied from 5 to 10 in distilled water and from 3 to 12 in groundwater for evaluating arsenic removal efficiency by EC. The optimum initial pH for arsenic removal was 7 for distilled water and groundwater. For all initial pHs tested between 5 and 10 in distilled water, the final pH ranged between 7 and 8 indicating that the EC process tends towards near neutral pH under the conditions examined in this study.

RSDL decontamination of human skin contaminated with the nerve agent VX.

PubMed

Thors, L; Lindberg, S; Johansson, S; Koch, B; Koch, M; Hägglund, L; Bucht, A

2017-03-05

Dermal exposure to low volatile organophosphorus compounds (OPC) may lead to penetration through the skin and uptake in the blood circulation. Skin decontamination of toxic OPCs, such as pesticides and chemical warfare nerve agents, might therefore be crucial for mitigating the systemic toxicity following dermal exposure. Reactive skin decontamination lotion (RSDL) has been shown to reduce toxic effects in animals dermally exposed to the nerve agent VX. In the present study, an in vitro flow-through diffusion cell was utilized to evaluate the efficacy of RSDL for decontamination of VX exposed to human epidermis. In particular, the impact of timing in the initiation of decontamination and agent dilution in water was studied. The impact of the lipophilic properties of VX in the RSDL decontamination was additionally addressed by comparing chemical degradation in RSDL and decontamination efficacy between the VX and the hydrophilic OPC triethyl phosphonoacetate (TEPA). The epidermal membrane was exposed to 20, 75 or 90% OPC diluted in deionized water and the decontamination was initiated 5, 10, 30, 60 or 120min post-exposure. Early decontamination of VX with RSDL, initiated 5-10min after skin exposure, was very effective. Delayed decontamination initiated 30-60min post-exposure was less effective but still the amount of penetrated agent was significantly reduced, while further delayed start of decontamination to 120min resulted in very low efficacy. Comparing RSDL decontamination of VX with that of TEPA showed that the decontamination efficacy at high agent concentrations was higher for VX. The degradation mechanism of VX and TEPA during decontamination was dissected by 31 P NMR spectroscopy of the OPCs following reactions with RSDL and its three nucleophile components. The degradation rate was clearly associated with the high pH of the specific solution investigated; i.e. increased pH resulted in a more rapid degradation. In addition, the solubility of the OPC in RSDL also influenced the degradation rate since the degradation of VX was significantly faster when the NMR analysis was performed in the organic solvent acetonitrile compared to water. In conclusion, we have applied the in vitro flow-through diffusion cell for evaluation of skin decontamination procedures of human epidermis exposed to OPCs. It was demonstrated that early decontamination is crucial for efficient mitigation of epidermal penetration of VX and that almost complete removal of the nerve agent from the skin surface is possible. Our data also indicate that the pH of RSDL together with the solubility of OPC in RSDL are of primary importance for the decontamination efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

[Endoscopic diagnosis of local chemical burn of mucous membranes of the stomach, induced with the purpose of simulation of gastric ulcer].

PubMed

Byzov, N V; Plekhanov, V N

2013-01-01

With the purpose of improvement of diagnosis of induced gastric ulcer were examined 11 patients who took aggressive agents for simulation of gastric ulcer and 33 patients who took pseudo-aggressive agents. Observables, conduced diagnosis of local chemical burn of mucous coat of stomach during initial 6 days after taking aggressive agents. Stages of ulcerous process, resulting from local chemical burn of mucous coat of stomach, coressponds to real gactric ulcer. Gelatin capsule using as a container for delivery of aggressive agents, melts in stomach in 5-6 minutes after taking. Independent from body position, mucous coat of greater curvature of the stomach is damaged. It is impossible to simulate duodenal bulb ulcer using the gelatine capsule or ball made of breadcrumb. The last method of delivery of aggressive agent can damage the small intestine because of uncontrollability of the place of breaking the ball.

I Feel You: The Design and Evaluation of a Domotic Affect-Sensitive Spoken Conversational Agent

PubMed Central

Lutfi, Syaheerah Lebai; Fernández-Martínez, Fernando; Lorenzo-Trueba, Jaime; Barra-Chicote, Roberto; Montero, Juan Manuel

2013-01-01

We describe the work on infusion of emotion into a limited-task autonomous spoken conversational agent situated in the domestic environment, using a need-inspired task-independent emotion model (NEMO). In order to demonstrate the generation of affect through the use of the model, we describe the work of integrating it with a natural-language mixed-initiative HiFi-control spoken conversational agent (SCA). NEMO and the host system communicate externally, removing the need for the Dialog Manager to be modified, as is done in most existing dialog systems, in order to be adaptive. The first part of the paper concerns the integration between NEMO and the host agent. The second part summarizes the work on automatic affect prediction, namely, frustration and contentment, from dialog features, a non-conventional source, in the attempt of moving towards a more user-centric approach. The final part reports the evaluation results obtained from a user study, in which both versions of the agent (non-adaptive and emotionally-adaptive) were compared. The results provide substantial evidences with respect to the benefits of adding emotion in a spoken conversational agent, especially in mitigating users' frustrations and, ultimately, improving their satisfaction. PMID:23945740

A Systems Approach to Depaint Chemistry

DTIC Science & Technology

2009-02-01

continuous colored film by curing through solvent evaporation, oxidation, catylization or other means. – Vehicle: Film former, binder, resin or polymer...impart large changes in properties. – Suspending agents – Driers – Anti-Skinning Agents – Wetting Agents – Anti- Foaming Agents – Coalescing Agents ...volatile stripper inside the coating. Paint Release Agent Coating Removal Mechanism Zone1: PRA Layer Zone2: PRA Initial Permeation into coating system Epoxy

Agentic personality characteristics and coping: their relation to trait anxiety in college students.

PubMed

Weigold, Ingrid K; Robitschek, Christine

2011-04-01

Anxiety and its disorders, often present before adulthood, have high personal and societal costs for men and women. This study tested a mediation model in which 3 forms of coping mediate the relation of 3 agentic personality characteristics (i.e., traits associated with the belief that people can effectively exercise control over their lives) to lower levels of anxiety within 1 subgroup of young adults (i.e., college students). The agentic personality characteristics were (a) hardiness, (b) personal growth initiative, and (c) coping self-efficacy. The forms of dispositional coping were (a) problem-focused, (b) emotion-focused, and (c) avoidant. Results suggest that agentic personality characteristics differentially relate to forms of coping and trait anxiety. In addition, coping appears to fully mediate the relations of the personality characteristics to anxiety. The results imply that agentic personality characteristics and coping are important in decreasing and/or protecting against anxiety, in part because of how they relate to forms of coping, and suggest the need for more research. © 2011 American Orthopsychiatric Association.

Opinion formation of free speech on the directed social network

NASA Astrophysics Data System (ADS)

Su, Jiongming; Ma, Hongxu; Liu, Baohong; Li, Qi

2014-12-01

A dynamical model with continuous opinion is proposed to study how the speech order and the topology of directed social network affect the opinion formation of free speech. In the model, agents express their opinions one by one with random order (RO) or probability order (PO), other agents paying attentions to the speaking agent, receive provider's opinion, update their opinions and then express their new opinions in their turns. It is proved that with the same agent j repeats its opinion more, other agents who pay their attentions to j and include j's opinion in their confidence level at initial time, will continue approaching j's opinion. Simulation results reveal that on directed scale-free network: (1) the model for PO forms fewer opinion clusters, larger maximum cluster (MC), smaller standard deviation (SD), and needs less waiting time to reach a middle level of consensus than RO; (2) as the parameter of scale-free degree distribution decreases or the confidence level increases, the results often get better for both speech orders; (3) the differences between PO and RO get smaller as the size of network decreases.

Regulated expression of the MRP8 and MRP14 genes in human promyelocytic leukemic HL-60 cell treated with the differentiation-inducing agents mycophenolic acid and 1{alpha},25-Dihydroxyvitamin D{sub 3}

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

Warner-Bartnicki, A.L.; Murao, S.; Collart, F.R.

1992-12-31

The calcium-binding proteins MRP8 and MEP14 are present in mature monomyelocytic cells and are induced during differentiation. Previous studies have demonstrated that the proteins may mediate the growth arrest in differentiating HL-60 cells. We determined the levels of a protein complex (PC) containing MRP8 and MRP14 and investigated the mechanism by which the genes encoding these proteins are regulated in HL-60 cells treated with the differentiation-inducing agent mycophenorc acid (MPA)While the PC was barely detectable in untreated cells, MPA treatment resulted in elevated levels of the PC which were maximal at 3-4 d, and were found to directly parallel gainsmore » in the steady-state levels of MRP8 and MRP14 MRNA. Transcription studies with the use of nuclear run-on experiments revealed increased transcription initiation at the MRP8 and MRP14 promoters after MPA treatment. 1{alpha},25-Dihydroxyvitamin D{sub 3}, which induces HL-60 cell differentiation by another mechanism, was also found to increase transcription initiation at the MRP8 and MRP14 promoters. Our results suggest that this initiation is the major control of maturation agent-mediated increases in MRP8 and MRPl4 gene expression, and support a role for the PC in terminal differentiation of human monomyelocytic cells.« less

Agent Persuasion Mechanism of Acquaintance

NASA Astrophysics Data System (ADS)

Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

Agent persuasion can improve negotiation efficiency in dynamic environment based on its initiative and autonomy, and etc., which is being affected much more by acquaintance. Classification of acquaintance on agent persuasion is illustrated, and the agent persuasion model of acquaintance is also illustrated. Then the concept of agent persuasion degree of acquaintance is given. Finally, relative interactive mechanism is elaborated.

Effect of spent mushroom substrate as a bulking agent on gaseous emissions and compost quality during pig manure composting.

PubMed

Li, Shuyan; Li, Danyang; Li, Jijin; Li, Yangyang; Li, Guoxue; Zang, Bing; Li, Yun

2018-05-01

The aim of this study was to investigate the gaseous emissions (CH 4 , N 2 O, and NH 3 ) and compost quality during the pig manure composting by adding spent mushroom substrate (SMS) as a bulking agent. The control treatment was also studied using corn stalk (CS) as a bulking agent. The experiment was conducted in a pilot scale composting reactor under aerobic condition with the initial C/N ratio of 20. Results showed that bulking agents significantly affected gaseous emissions and compost quality. Using SMS as a bulking agent improved composting efficiency by shortening the time for maturity. SMS increased germination index and humic acid of the final compost (by 13.44 and 41.94%, respectively) compared with CS. Furthermore, composting with SMS as a bulking agent could reduce nitrogen loss, NH 3 , and N 2 O emissions (by 13.57, 35.56, and 46.48%, respectively) compared with the control. SMS slightly increased CH 4 emission about 1.1 times of the CS. However, a 33.95% decrease in the global warming potential of CH 4 and N 2 O was obtained by adding SMS treatment. These results indicate that SMS is a favorable bulking agent for reducing gaseous emissions and increasing compost quality.

Is fixed combination therapy appropriate for initial hypertension treatment?

PubMed

Elliott, William J

2002-08-01

Recent clinical trials in hypertension prove how seldom single drug therapy achieves target blood pressure (BP) and reduces cardiovascular morbidity and mortality. A natural response is the testing and marketing of fixed-dose combination products for hypertension, of which 14 have been approved in the United States since 1993. Currently, only five products are indicated by the Food and Drug Administration for initial therapy of hypertension; all include a diuretic. To achieve such an indication, studies must show not only safety and efficacy of the combination, but also BP lowering that is at least additive compared with the two agents given separately, as well as a "synergy" not present when each agent is given alone. Some advantages to initial combination therapy include greater BP reduction, improved adherence to pill taking, fewer side effects, and lower cost. The most likely candidates for initial combination therapy are patients with initial BP higher than 160/100 mm Hg, or those with a BP goal lower than the customary 140/90 mm Hg. These include patients with target organ damage, clinical cardiovascular disease, proteinuria, renal impairment, or diabetes mellitus. In many of these circumstances, an angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist is frequently recommended; adding a diuretic or calcium antagonist to it is much more likely to result in achievement of the BP goal. More research is being done to explore the combination of not only two representatives from classes of conventional agents, but also other drugs that may help address the multiple manifestations of the "metabolic syndrome" that often accompanies hypertension.

Counterbalancing the use of ultrasound contrast agents by a cavitation-regulated system.

PubMed

Desjouy, C; Fouqueray, M; Lo, C W; Muleki Seya, P; Lee, J L; Bera, J C; Chen, W S; Inserra, C

2015-09-01

The stochastic behavior of cavitation can lead to major problems of initiation and maintenance of cavitation during sonication, responsible of poor reproducibility of US-induced bioeffects in the context of sonoporation for instance. To overcome these disadvantages, the injection of ultrasound contrast agents as cavitation nuclei ensures fast initiation and lower acoustic intensities required for cavitation activity. More recently, regulated-cavitation devices based on the real-time modulation of the applied acoustic intensity have shown their potential to maintain a stable cavitation state during an ultrasonic shot, in continuous or pulsed wave conditions. In this paper is investigated the interest, in terms of cavitation activity, of using such regulated-cavitation device or injecting ultrasound contrast agents in the sonicated medium. When using fixed applied acoustic intensity, results showed that introducing ultrasound contrast agents increases reproducibility of cavitation activity (coefficient of variation 62% and 22% without and with UCA, respectively). Moreover, the use of the regulated-cavitation device ensures a given cavitation activity (coefficient of variation less 0.4% in presence of UCAs or not). This highlights the interest of controlling cavitation over time to free cavitation-based application from the use of UCAs. Interestingly, during a one minute sonication, while ultrasound contrast agents progressively disappear, the regulated-cavitation device counterbalance their destruction to sustain a stable inertial cavitation activity. Copyright © 2015 Elsevier B.V. All rights reserved.

19 CFR 201.15 - Attorneys or agents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 3 2013-04-01 2013-04-01 false Attorneys or agents. 201.15 Section 201.15 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION GENERAL RULES OF GENERAL APPLICATION Initiation and Conduct of Investigations § 201.15 Attorneys or agents. (a) In general. No register of attorneys or agents...

Children as Change Agents for Family Health

ERIC Educational Resources Information Center

Burrows, Lisette

2017-01-01

Purpose: The purpose of this paper is to explore ways in which children and young people are being positioned as change agents for families through school health promotion initiatives in New Zealand. Design/methodology/approach: The paper maps and describes the kinds of policies and initiatives that directly or indirectly regard children as…

Verbal Semantics Drives Early Anticipatory Eye Movements during the Comprehension of Verb-Initial Sentences.

PubMed

Sauppe, Sebastian

2016-01-01

Studies on anticipatory processes during sentence comprehension often focus on the prediction of postverbal direct objects. In subject-initial languages (the target of most studies so far), however, the position in the sentence, the syntactic function, and the semantic role of arguments are often conflated. For example, in the sentence "The frog will eat the fly" the syntactic object ("fly") is at the same time also the last word and the patient argument of the verb. It is therefore not apparent which kind of information listeners orient to for predictive processing during sentence comprehension. A visual world eye tracking study on the verb-initial language Tagalog (Austronesian) tested what kind of information listeners use to anticipate upcoming postverbal linguistic input. The grammatical structure of Tagalog allows to test whether listeners' anticipatory gaze behavior is guided by predictions of the linear order of words, by syntactic functions (e.g., subject/object), or by semantic roles (agent/patient). Participants heard sentences of the type "Eat frog fly" or "Eat fly frog" (both meaning "The frog will eat the fly") while looking at displays containing an agent referent ("frog"), a patient referent ("fly") and a distractor. The verb carried morphological marking that allowed the order and syntactic function of agent and patient to be inferred. After having heard the verb, listeners fixated on the agent irrespective of its syntactic function or position in the sentence. While hearing the first-mentioned argument, listeners fixated on the corresponding referent in the display accordingly and then initiated saccades to the last-mentioned referent before it was encountered. The results indicate that listeners used verbal semantics to identify referents and their semantic roles early; information about word order or syntactic functions did not influence anticipatory gaze behavior directly after the verb was heard. In this verb-initial language, event semantics takes early precedence during the comprehension of sentences, while arguments are anticipated temporally more local to when they are encountered. The current experiment thus helps to better understand anticipation during language processing by employing linguistic structures not available in previously studied subject-initial languages.

Deduction of initial strategy distributions of agents in mix-game models

NASA Astrophysics Data System (ADS)

Gou, Chengling

2006-11-01

This paper reports the effort of deducing the initial strategy distributions (ISDs) of agents in mix-game models that is used to predict a real financial time series generated from a target financial market. Using mix-games to predict Shanghai Index, we find that the time series of prediction accurate rates is sensitive to the ISDs of agents in group 2 who play a minority game, but less sensitive to the ISDs of agents in group 1 who play a majority game. And agents in group 2 tend to cluster in full strategy space (FSS) if the real financial time series has obvious tendency (upward or downward), otherwise they tend to scatter in FSS. We also find that the ISDs and the number of agents in group 1 influence the level of prediction accurate rates. Finally, this paper gives suggestion about further research.

A nonlinear merging protocol for consensus in multi-agent systems on signed and weighted graphs

NASA Astrophysics Data System (ADS)

Feng, Shasha; Wang, Li; Li, Yijia; Sun, Shiwen; Xia, Chengyi

2018-01-01

In this paper, we investigate the multi-agent consensus for networks with undirected graphs which are not connected, especially for the signed graph in which some edge weights are positive and some edges have negative weights, and the negative-weight graph whose edge weights are negative. We propose a novel nonlinear merging consensus protocol to drive the states of all agents to converge to the same state zero which is not dependent upon the initial states of agents. If the undirected graph whose edge weights are positive is connected, then the states of all agents converge to the same state more quickly when compared to most other protocols. While the undirected graph whose edge weights might be positive or negative is unconnected, the states of all agents can still converge to the same state zero under the premise that the undirected graph can be divided into several connected subgraphs with more than one node. Furthermore, we also discuss the impact of parameter r presented in our protocol. Current results can further deepen the understanding of consensus processes for multi-agent systems.

A distributed agent architecture for real-time knowledge-based systems: Real-time expert systems project, phase 1

NASA Technical Reports Server (NTRS)

Lee, S. Daniel

1990-01-01

We propose a distributed agent architecture (DAA) that can support a variety of paradigms based on both traditional real-time computing and artificial intelligence. DAA consists of distributed agents that are classified into two categories: reactive and cognitive. Reactive agents can be implemented directly in Ada to meet hard real-time requirements and be deployed on on-board embedded processors. A traditional real-time computing methodology under consideration is the rate monotonic theory that can guarantee schedulability based on analytical methods. AI techniques under consideration for reactive agents are approximate or anytime reasoning that can be implemented using Bayesian belief networks as in Guardian. Cognitive agents are traditional expert systems that can be implemented in ART-Ada to meet soft real-time requirements. During the initial design of cognitive agents, it is critical to consider the migration path that would allow initial deployment on ground-based workstations with eventual deployment on on-board processors. ART-Ada technology enables this migration while Lisp-based technologies make it difficult if not impossible. In addition to reactive and cognitive agents, a meta-level agent would be needed to coordinate multiple agents and to provide meta-level control.

Potential development of a new cotton-based antimicrobial wipe

USDA-ARS?s Scientific Manuscript database

The adsorption of alkyl-dimethyl-benzyl-ammonium chloride (ADBAC), a cationic surfactant commonly employed as an antimicrobial agent, on greige and bleached nonwoven cotton fabrics was investigated using UV/visible spectroscopy. Initial results have shown that greige cotton adsorbs roughly three tim...

Exclusion processes: Short-range correlations induced by adhesion and contact interactions

NASA Astrophysics Data System (ADS)

Ascolani, Gianluca; Badoual, Mathilde; Deroulers, Christophe

2013-01-01

We analyze the out-of-equilibrium behavior of exclusion processes where agents interact with their nearest neighbors, and we study the short-range correlations which develop because of the exclusion and other contact interactions. The form of interactions we focus on, including adhesion and contact-preserving interactions, is especially relevant for migration processes of living cells. We show the local agent density and nearest-neighbor two-point correlations resulting from simulations on two-dimensional lattices in the transient regime where agents invade an initially empty space from a source and in the stationary regime between a source and a sink. We compare the results of simulations with the corresponding quantities derived from the master equation of the exclusion processes, and in both cases, we show that, during the invasion of space by agents, a wave of correlations travels with velocity v(t)˜t-1/2. The relative placement of this wave to the agent density front and the time dependence of its height may be used to discriminate between different forms of contact interactions or to quantitatively estimate the intensity of interactions. We discuss, in the stationary density profile between a full and an empty reservoir of agents, the presence of a discontinuity close to the empty reservoir. Then we develop a method for deriving approximate hydrodynamic limits of the processes. From the resulting systems of partial differential equations, we recover the self-similar behavior of the agent density and correlations during space invasion.

An agent-based model identifies MRI regions of probable tumor invasion in a patient with glioblastoma

NASA Astrophysics Data System (ADS)

Chen, L. Leon; Ulmer, Stephan; Deisboeck, Thomas S.

2010-01-01

We present an application of a previously developed agent-based glioma model (Chen et al 2009 Biosystems 95 234-42) for predicting spatio-temporal tumor progression using a patient-specific MRI lattice derived from apparent diffusion coefficient (ADC) data. Agents representing collections of migrating glioma cells are initialized based upon voxels at the outer border of the tumor identified on T1-weighted (Gd+) MRI at an initial time point. These simulated migratory cells exhibit a specific biologically inspired spatial search paradigm, representing a weighting of the differential contribution from haptotactic permission and biomechanical resistance on the migration decision process. ADC data from 9 months after the initial tumor resection were used to select the best search paradigm for the simulation, which was initiated using data from 6 months after the initial operation. Using this search paradigm, 100 simulations were performed to derive a probabilistic map of tumor invasion locations. The simulation was able to successfully predict a recurrence in the dorsal/posterior aspect long before it was depicted on T1-weighted MRI, 18 months after the initial operation.

An agent-based model identifies MRI regions of probable tumor invasion in a patient with glioblastoma.

PubMed

Chen, L Leon; Ulmer, Stephan; Deisboeck, Thomas S

2010-01-21

We present an application of a previously developed agent-based glioma model (Chen et al 2009 Biosystems 95 234-42) for predicting spatio-temporal tumor progression using a patient-specific MRI lattice derived from apparent diffusion coefficient (ADC) data. Agents representing collections of migrating glioma cells are initialized based upon voxels at the outer border of the tumor identified on T1-weighted (Gd+) MRI at an initial time point. These simulated migratory cells exhibit a specific biologically inspired spatial search paradigm, representing a weighting of the differential contribution from haptotactic permission and biomechanical resistance on the migration decision process. ADC data from 9 months after the initial tumor resection were used to select the best search paradigm for the simulation, which was initiated using data from 6 months after the initial operation. Using this search paradigm, 100 simulations were performed to derive a probabilistic map of tumor invasion locations. The simulation was able to successfully predict a recurrence in the dorsal/posterior aspect long before it was depicted on T1-weighted MRI, 18 months after the initial operation.

Synchronization of multi-agent systems with metric-topological interactions.

PubMed

Wang, Lin; Chen, Guanrong

2016-09-01

A hybrid multi-agent systems model integrating the advantages of both metric interaction and topological interaction rules, called the metric-topological model, is developed. This model describes planar motions of mobile agents, where each agent can interact with all the agents within a circle of a constant radius, and can furthermore interact with some distant agents to reach a pre-assigned number of neighbors, if needed. Some sufficient conditions imposed only on system parameters and agent initial states are presented, which ensure achieving synchronization of the whole group of agents. It reveals the intrinsic relationships among the interaction range, the speed, the initial heading, and the density of the group. Moreover, robustness against variations of interaction range, density, and speed are investigated by comparing the motion patterns and performances of the hybrid metric-topological interaction model with the conventional metric-only and topological-only interaction models. Practically in all cases, the hybrid metric-topological interaction model has the best performance in the sense of achieving highest frequency of synchronization, fastest convergent rate, and smallest heading difference.

The impact of compaction, moisture content, particle size and type of bulking agent on initial physical properties of sludge-bulking agent mixtures before composting.

PubMed

Huet, J; Druilhe, C; Trémier, A; Benoist, J C; Debenest, G

2012-06-01

This study aimed to experimentally acquire evolution profiles between depth, bulk density, Free Air Space (FAS), air permeability and thermal conductivity in initial composting materials. The impact of two different moisture content, two particle size and two types of bulking agent on these four parameters was also evaluated. Bulk density and thermal conductivity both increased with depth while FAS and air permeability both decreased with it. Moreover, depth and moisture content had a significant impact on almost all the four physical parameters contrary to particle size and the type of bulking agent. Copyright © 2012 Elsevier Ltd. All rights reserved.

Data-driven agent-based modeling, with application to rooftop solar adoption

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

Zhang, Haifeng; Vorobeychik, Yevgeniy; Letchford, Joshua

Agent-based modeling is commonly used for studying complex system properties emergent from interactions among many agents. We present a novel data-driven agent-based modeling framework applied to forecasting individual and aggregate residential rooftop solar adoption in San Diego county. Our first step is to learn a model of individual agent behavior from combined data of individual adoption characteristics and property assessment. We then construct an agent-based simulation with the learned model embedded in artificial agents, and proceed to validate it using a holdout sequence of collective adoption decisions. We demonstrate that the resulting agent-based model successfully forecasts solar adoption trends andmore » provides a meaningful quantification of uncertainty about its predictions. We utilize our model to optimize two classes of policies aimed at spurring solar adoption: one that subsidizes the cost of adoption, and another that gives away free systems to low-income house- holds. We find that the optimal policies derived for the latter class are significantly more efficacious, whereas the policies similar to the current California Solar Initiative incentive scheme appear to have a limited impact on overall adoption trends.« less

Protecting Dynamic Mobile Agent against Denial of Service Attacks

NASA Astrophysics Data System (ADS)

Aggarwal, Mayank; Nipur, Pallavi

2010-11-01

Mobile Agents are softwares migrating from one node to another to fulfill the task of its owner. The introduction of mobile agents has reduced network latency, network traffic a lot but at the same time it has increased the vulnerability for attacks by malicious hosts. One such attack is `Denial of Service', once the agent is launched it is free to roam without any control of its owner, this on one hand decreases the cost of agent—owner interaction and on the other hand increases the chances of `Denial Of Service'. In Denial Of Service attack the malicious host may deny resources required by the agent and kill the agent, thus the result computed so far is lost and this may happen every time the agent visits any malicious host. In this paper we continued the work done in [10] in which the authors proposed techniques by which owner can detect the malicious host for `Denial Of Service' but they did not covered technique for dynamic routes i.e. where the host or agent initiate migrations to hosts which were not contained in the route composed by the owner. We introduced an algorithm and a model which can be useful for the above purpose.

Data-driven agent-based modeling, with application to rooftop solar adoption

DOE PAGES

Zhang, Haifeng; Vorobeychik, Yevgeniy; Letchford, Joshua; ...

2016-01-25

Agent-based modeling is commonly used for studying complex system properties emergent from interactions among many agents. We present a novel data-driven agent-based modeling framework applied to forecasting individual and aggregate residential rooftop solar adoption in San Diego county. Our first step is to learn a model of individual agent behavior from combined data of individual adoption characteristics and property assessment. We then construct an agent-based simulation with the learned model embedded in artificial agents, and proceed to validate it using a holdout sequence of collective adoption decisions. We demonstrate that the resulting agent-based model successfully forecasts solar adoption trends andmore » provides a meaningful quantification of uncertainty about its predictions. We utilize our model to optimize two classes of policies aimed at spurring solar adoption: one that subsidizes the cost of adoption, and another that gives away free systems to low-income house- holds. We find that the optimal policies derived for the latter class are significantly more efficacious, whereas the policies similar to the current California Solar Initiative incentive scheme appear to have a limited impact on overall adoption trends.« less

The role of alternative and natural agents, cryotherapy, and/or laser for management of alimentary mucositis.

PubMed

Migliorati, Cesar A; Oberle-Edwards, Loree; Schubert, Mark

2006-06-01

To review the literature and update the current guidelines of alternative/natural agents, cryotherapy, and/or laser therapy in the management of alimentary mucositis (AM). The original guidelines developed by the Multinational Association for Supportive Care in Cancer (MASCC)/International Society for Oral Oncology (ISOO) mucositis study group were the basis for this study. A medical librarian conducted an initial Medline search to identify research articles published between 2002 and 2005 in English language. A search term combination that included stomatitis, mucositis, mucous membrane, neoplasm, lasers, complimentary therapies, amino acids, antioxidants, vitamins, minerals, plant extracts, and cryotherapy was conducted. This initial search identified articles with a strong scientific methodology that included both preclinical and clinical research. Using standardized scoring forms, authors reviewed and scored individual articles. A consensus result of the review was achieved in a meeting of reviewers in June of 2005. The initial search identified a total of 167 new articles. Of these, 14 were selected and reviewed: alternative/natural therapy (one preclinical study); cryotherapy (four clinical studies); lasers (two clinical studies); and alternative/natural agents (seven clinical studies). A new guideline could be established for the use of cryotherapy in the management of AM in hematopoietic stem cell transplant (HSCT) patients receiving melphalan in the conditioning phase. The rapid progress in the understanding of AM created a need for new prevention and management protocols. Frequent literature review is now necessary to identify agents and protocols being developed in this important area of supportive care in cancer.

Model and simulation of Krause model in dynamic open network

NASA Astrophysics Data System (ADS)

Zhu, Meixia; Xie, Guangqiang

2017-08-01

The construction of the concept of evolution is an effective way to reveal the formation of group consensus. This study is based on the modeling paradigm of the HK model (Hegsekmann-Krause). This paper analyzes the evolution of multi - agent opinion in dynamic open networks with member mobility. The results of the simulation show that when the number of agents is constant, the interval distribution of the initial distribution will affect the number of the final view, The greater the distribution of opinions, the more the number of views formed eventually; The trust threshold has a decisive effect on the number of views, and there is a negative correlation between the trust threshold and the number of opinions clusters. The higher the connectivity of the initial activity group, the more easily the subjective opinion in the evolution of opinion to achieve rapid convergence. The more open the network is more conducive to the unity of view, increase and reduce the number of agents will not affect the consistency of the group effect, but not conducive to stability.

Competition Among Reputations in the 2D Sznajd Model: Spontaneous Emergence of Democratic States

NASA Astrophysics Data System (ADS)

Crokidakis, Nuno; Forgerini, Fabricio L.

2012-04-01

We propose a modification in the Sznajd sociophysics model defined on the square lattice. For this purpose, we consider reputation—a mechanism limiting the agents' persuasive power. The reputation is introduced as a time-dependent score, which can be positive or negative. This mechanism avoids dictatorship (full consensus, all spins parallel) for a wide range of model parameters. We consider two different situations: case 1, in which the agents' reputation increases for each persuaded neighbor, and case 2, in which the agents' reputation increases for each persuasion and decreases when a neighbor keeps his opinion. Our results show that the introduction of reputation avoids full consensus even for initial densities of up spins greater than 1/2. The relaxation times follow a log-normal-like distribution in both cases, but they are larger in case 2 due to the competition among reputations. In addition, we show that the usual phase transition occurs and depends on the initial concentration d of individuals with the same opinion, but the critical points d c in the two cases are different.

Nonsurgical Outpatient Therapies for the Management of Female Stress Urinary Incontinence: Long-Term Effectiveness and Durability

PubMed Central

Davila, G. Willy

2011-01-01

Objective. To evaluate long-term effectiveness and safety of conservative and minimally invasive outpatient treatments for female stress urinary incontinence (SUI) through a review of the literature. Methods. PubMed was searched for reports on prospective clinical trials with at least 12-month follow-up of minimally invasive treatments, pelvic floor rehabilitation, or pharmacotherapy in women with SUI. Each report was examined for long-term rates of effectiveness and safety. Results. Thirty-two clinical trial reports were included. Prospective long-term studies of pelvic floor rehabilitation were limited but indicated significant improvements with treatment adherence for at least 12 months. Poor initial tolerability with duloxetine resulted in substantial discontinuation. Most patients receiving transurethral radiofrequency collagen denaturation or urethral bulking agents reported significant long-term improvements, generally good tolerability, and safety. Conclusions. Conservative therapy is an appropriate initial approach for female SUI, but if therapy fails, radiofrequency collagen denaturation or bulking agents may be an attractive intermediate management step or alternative to surgery. PMID:21738529

Steroid plus antiviral treatment for Bell's palsy.

PubMed

Kang, H M; Jung, S Y; Byun, J Y; Park, M S; Yeo, S G

2015-05-01

The effectiveness of antiviral agents for the treatment of Bell's palsy is uncertain. We evaluated whether a steroid with an antiviral agent (S + A group) provided better recovery outcomes than a steroid alone (S group) in patients with Bell's palsy. A total of 1342 patients diagnosed with Bell's palsy who visited the Kyung Hee Medical Center in Seoul, Korea, from 2002 to 2012 were included in this study. Patients in the S + A group were treated with prednisolone and antiviral agents (n = 569) and those in the S group with prednisolone alone (n = 773). Outcomes were measured using the House-Brackmann (HB) scale according to age, initial disease severity, electroneurography (ENoG) findings and underlying comorbidities. The rate of recovery (HB grades I and II) with initially severe Bell's palsy (HB grades V and VI) was higher in the S + A than in the S group (P = 0.001). However, the rates of recovery were similar with initially moderate palsy (HB grades II-IV) (P = 0.502). In patients classified according to age and ENoG-determined severity of palsy, the overall recovery rate was higher in the S + A than in the S group, but the differences were not statistically significant (P > 0.05 for both). The recovery rate without diabetes mellitus (DM) and hypertension (HTN) was higher in the S + A group than in the S group (P = 0.031). But in the patients with HTN and DM, the difference in recovery rates between the S + A and S groups was not statistically significant (P = 0.805). Treatment with a steroid plus antiviral agent resulted in significantly higher recovery rates than steroid therapy alone in patients with initially severe Bell's palsy and without either HTN or DM, and a nonsignificant trend towards higher recovery rates in all patients with Bell's palsy in this study. Antiviral agents may therefore help in the treatment of Bell's palsy. © 2014 The Association for the Publication of the Journal of Internal Medicine.

Development of the Technologies for Stabilization Treatment of the Water of the Recycling Cooling Systems at Thermal Power Plants

NASA Astrophysics Data System (ADS)

Vlasov, S. M.; Chichirova, N. D.; Chichirov, A. A.; Vlasova, A. Yu.; Filimonova, A. A.; Prosvirnina, D. V.

2018-02-01

A turbine-condensate cooling system is one of the less stable and most hard-to-control systems of maintaining optimal water chemistry. A laboratory recycling cooling water test facility, UVO-0.3, was developed for physical simulation of innovative zero-discharge water chemistry conditions and improvement of technological flowcharts of stabilization treatment of the initial and circulating water of the recycling cooling systems at thermal power plants. Experiments were conducted in the UVO-0.3 facility to investigate the processes that occur in the recycling water supply system and master new technologies of stabilization of the initial and circulating water. It is shown that, when using untreated initial water, scaling cannot be prevented even under low concentration levels. The main reason for the activation of scale depositing is the desorption of carbon dioxide that results in alkalization of the circulating water and, as a consequence, a displacement of the chemical reaction equilibrium towards the formation of slightly soluble hardness ions. Some techniques, viz., liming and alkalization of the initial water and the by-pass treatment of the circulating water, are considered. New engineering solutions have been developed for reducing the amount of scale-forming substances in the initial and circulating water. The best results were obtained by pretreating the initial water with alkalizing agents and simultaneously bypassing and treating part of the circulating water. The obtained experimental data underlie the process flowcharts of stabilization treatment of the initial and circulating TPP water that ensure scale-free and noncorrosive operation and meet the corresponding environmental requirements. Under the bypassing, the specific rates of the agents and the residual hardness are reduced compared with the conventional pretreatment.

Radiolabelled D2 agonists as prolactinoma imaging agents. Final technical report, January 31, 1990--August 31, 1991

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

Otto, C.A.

1991-12-31

Research conducted in this terminal year of support centered on three distinct areas: mAChR ligand localization in pancreas and the effect of Ca{sup +2} on localization, continuation of assessment of quaternized and neutral mAChR ligands for possible use as PET myocardial imaging agents, and initiation of a study to determine the relationship of the nAChR receptor to the cellular receptor for measles virus. Several tables and figures illustrating the results are included.

Finite-time and fixed-time leader-following consensus for multi-agent systems with discontinuous inherent dynamics

NASA Astrophysics Data System (ADS)

Ning, Boda; Jin, Jiong; Zheng, Jinchuan; Man, Zhihong

2018-06-01

This paper is concerned with finite-time and fixed-time consensus of multi-agent systems in a leader-following framework. Different from conventional leader-following tracking approaches where inherent dynamics satisfying the Lipschitz continuous condition is required, a more generalised case is investigated: discontinuous inherent dynamics. By nonsmooth techniques, a nonlinear protocol is first proposed to achieve the finite-time leader-following consensus. Then, based on fixed-time stability strategies, the fixed-time leader-following consensus problem is solved. An upper bound of settling time is obtained by using a new protocol, and such a bound is independent of initial states, thereby providing additional options for designers in practical scenarios where initial conditions are unavailable. Finally, numerical simulations are provided to demonstrate the effectiveness of the theoretical results.

Effects of radical initiators, polymerization inhibitors, and other agents on the sonochemical unzipping of double-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Fukumori, Minoru; Hara, Shinnosuke; Ogawa, Takuji; Tanaka, Hirofumi

2018-03-01

The mechanism of graphene nanoribbon synthesis by the sonication-assisted unzipping of carbon nanotubes (CNTs) was investigated utilizing 4-methoxyphenol and 1,4-dimethoxybenzene as moieties of poly[(m-phenylenevinylene)-co-(2,5-dioctoxy-p-phenylenevinylene)]. The obtained results revealed that unzipping was promoted by 4-methoxyphenol owing to the facile abstraction of its phenolic hydrogen by sonication-generated radicals on CNTs, whereas 1,4-dimethoxybenzene did not facilitate unzipping, since its methoxy hydrogens were hardly abstracted. Moreover, unzipping was also facilitated by trans-stilbene, the double bond of which reacts with CNT radicals. Furthermore, we succeeded in using a general radical initiator, namely, 2,2‧-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride to promote unzipping, confirming that it is promoted by radical donors/trapping agents.

CHANGES IN LIPID-ENCAPSULATED MICROBUBBLE POPULATION DURING CONTINUOUS INFUSION AND METHODS TO MAINTAIN CONSISTENCY

PubMed Central

KAYA, MEHMET; GREGORY, THOMAS S.; DAYTON, PAUL A.

2009-01-01

Stabilized microbubbles are utilized as ultrasound contrast agents. These micron-sized gas capsules are injected into the bloodstream to provide contrast enhancement during ultrasound imaging. Some contrast imaging strategies, such as destruction-reperfusion, require a continuous injection of microbubbles over several minutes. Most quantitative imaging strategies rely on the ability to administer a consistent dose of contrast agent. Because of the buoyancy of these gas-filled agents, their spatial distribution within a syringe changes over time. The population of microbubbles that is pumped from a horizontal syringe outlet differs from initial population as the microbubbles float to the syringe top. In this manuscript, we study the changes in the population of a contrast agent that is pumped from a syringe due to microbubble floatation. Results are presented in terms of change in concentration and change in mean diameter, as a function of time, suspension medium, and syringe diameter. Data illustrate that the distribution of contrast agents injected from a syringe changes in both concentration and mean diameter over several minutes without mixing. We discuss the application of a mixing system and viscosity agents to keep the contrast solution more evenly distributed in a syringe. These results are significant for researchers utilizing microbubble contrast agents in continuous-infusion applications where it is important to maintain consistent contrast agent delivery rate, or in situations where the injection syringe cannot be mixed immediately prior to administration. PMID:19632760

Research on ultrasonic excitation for the removal of drilling fluid plug, paraffin deposition plug, polymer plug and inorganic scale plug for near-well ultrasonic processing technology.

PubMed

Wang, Zhenjun; Zeng, Jing; Song, Hao; Li, Feng

2017-05-01

Near-well ultrasonic processing technology attracts more attention due to its simple operation, high adaptability, low cost and no pollution to the formation. Although this technology has been investigated in detail through laboratory experiments and field tests, systematic and intensive researches are absent for certain major aspects, such as whether ultrasonic excitation is better than chemical agent for any plugs removal; whether ultrasound-chemical combination plug removal technology has the best plugs removal effect. In this paper, the comparison of removing drilling fluid plug, paraffin deposition plug, polymer plug and inorganic scale plug using ultrasonic excitation, chemical agent and ultrasound-chemical combination plug removal technology is investigated. Results show that the initial core permeability and ultrasonic frequency play a significant role in plug removal. Ultrasonic excitation and chemical agent have different impact on different plugs. The comparison results show that the effect of removing any plugs using ultrasound-chemicals composite plug removal technology is obviously better than that using ultrasonic excitation or chemical agent alone. Such conclusion proves that ultrasonic excitation and chemical agent can cause synergetic effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Designing Agent Collectives For Systems With Markovian Dynamics

NASA Technical Reports Server (NTRS)

Wolpert, David H.; Lawson, John W.

2004-01-01

The Collective Intelligence (COIN) framework concerns the design of collectives of agents so that as those agents strive to maximize their individual utility functions, their interaction causes a provided world utility function concerning the entire collective to be also maximized. Here we show how to extend that framework to scenarios having Markovian dynamics when no re-evolution of the system from counter-factual initial conditions (an often expensive calculation) is permitted. Our approach transforms the (time-extended) argument of each agent's utility function before evaluating that function. This transformation has benefits in scenarios not involving Markovian dynamics of an agent's utility function are observable. We investigate this transformation in simulations involving both hear and quadratic (nonlinear) dynamics. In addition, we find that a certain subset of these transformations, which result in utilities that have low opacity (analogous to having high signal to noise) but are not factored (analogous to not being incentive compatible), reliably improve performance over that arising with factored utilities. We also present a Taylor Series method for the fully general nonlinear case.

Use of atypical antipsychotics for treatment-resistant major depressive disorder.

PubMed

Papakostas, George I; Shelton, Richard C

2008-12-01

Despite the progressive increase in the number of pharmacologic agents with potential antidepressant activity, many patients suffering from major depressive disorder (MDD) continue to be symptomatic. Clearly, an urgent need exists to develop safer, better tolerated, and more effective treatments for MDD. Use of atypical antipsychotic agents as adjunctive treatment for treatment-resistant MDD (TRD) represents one such effort toward novel pharmacotherapy development. Atypical antipsychotic agents have been hypothesized to be beneficial in treating mood disorders, including TRD, as a result of their complex mechanisms of action. After an initial series of positive case reports, series, and small clinical trials, subsequent larger-scale projects have yielded conflicting results. However, more recently, larger-scale clinical trials have supported the effectiveness of at least some of these medications. This review summarizes the existing data regarding the effectiveness of these medications in treating TRD, including biochemical rationale and clinical data.

Evolution of Implicit and Explicit Communication in Mobile Robots

NASA Astrophysics Data System (ADS)

de Greeff, Joachim; Nolfi, Stefano

This work investigates the conditions in which a population of embodied agents evolved for the ability to display coordinated/cooperative skills can develop an ability to communicate, whether and to what extent the evolved communication system can complexify during the course of the evolutionary process, and how the characteristics of such communication system varies evolutionarily. The analysis of the obtained results indicates that evolving robots develop a capacity to access/generate information which has a communicative value, an ability to produce different signals encoding useful regularities, and an ability to react appropriately to explicit and implicit signals. The analysis of the obtained results allows us to formulate detailed hypothesis on the evolution of communication for what concern aspects such us: (i) how communication can emerge from a population of initially non-communicating agents, (ii) how communication systems can complexify, (iii) how signals/meanings can originate and how they can be grounded in agents' sensory-motor states.

A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway.

PubMed

Zhao, Hong; Guo, Yuming; Li, Shu; Han, Ruiqin; Ying, Jianming; Zhu, Hai; Wang, Yuanyuan; Yin, Li; Han, Yuqing; Sun, Lingzhi; Wang, Zhaoyi; Lin, Qingcong; Bi, Xinyu; Jiao, Yuchen; Jia, Hongying; Zhao, Jianjun; Huang, Zhen; Li, Zhiyu; Zhou, Jianguo; Song, Wei; Meng, Kun; Cai, Jianqiang

2015-10-13

Tumor-initiating cell (TIC) is a subpopulation of cells in tumors that are responsible for tumor initiation and progression. Recent studies indicate that hepatocellular carcinoma-initiating cells (HCICs) confer the high malignancy, recurrence and multi-drug resistance in hepatocellular carcinoma (HCC). In this study, we found that Icaritin, a prenylflavonoid derivative from Epimedium Genus, inhibited malignant growth of HCICs. Icaritin decreased the proportion of EpCAM-positive (a HCICs marker) cells, suppressed tumorsphere formation in vitro and tumor formation in vivo. We also found that Icaritin reduced expression of Interleukin-6 Receptors (IL-6Rs), attenuated both constitutive and IL-6-induced phosphorylation of Janus-activated kinases 2 (Jak2) and Signal transducer and activator of transcription 3 (Stat3), and inhibited Stat3 downstream genes, such as Bmi-1 and Oct4. The inhibitory activity of Icaritin in HCICs was augmented by siRNA-mediated silencing of Stat3 but attenuated by constitutive activation of Stat3.Taken together, our results indicate that Icaritin is able to inhibit malignant growth of HCICs and suggest that Icaritin may be developed into a novel therapeutic agent for effective treatment of HCC.

Competitive Dynamics on Complex Networks

PubMed Central

Zhao, Jiuhua; Liu, Qipeng; Wang, Xiaofan

2014-01-01

We consider a dynamical network model in which two competitors have fixed and different states, and each normal agent adjusts its state according to a distributed consensus protocol. The state of each normal agent converges to a steady value which is a convex combination of the competitors' states, and is independent of the initial states of agents. This implies that the competition result is fully determined by the network structure and positions of competitors in the network. We compute an Influence Matrix (IM) in which each element characterizing the influence of an agent on another agent in the network. We use the IM to predict the bias of each normal agent and thus predict which competitor will win. Furthermore, we compare the IM criterion with seven node centrality measures to predict the winner. We find that the competitor with higher Katz Centrality in an undirected network or higher PageRank in a directed network is most likely to be the winner. These findings may shed new light on the role of network structure in competition and to what extent could competitors adjust network structure so as to win the competition. PMID:25068622

Using an agent-based model to analyze the dynamic communication network of the immune response

PubMed Central

2011-01-01

Background The immune system behaves like a complex, dynamic network with interacting elements including leukocytes, cytokines, and chemokines. While the immune system is broadly distributed, leukocytes must communicate effectively to respond to a pathological challenge. The Basic Immune Simulator 2010 contains agents representing leukocytes and tissue cells, signals representing cytokines, chemokines, and pathogens, and virtual spaces representing organ tissue, lymphoid tissue, and blood. Agents interact dynamically in the compartments in response to infection of the virtual tissue. Agent behavior is imposed by logical rules derived from the scientific literature. The model captured the agent-to-agent contact history, and from this the network topology and the interactions resulting in successful versus failed viral clearance were identified. This model served to integrate existing knowledge and allowed us to examine the immune response from a novel perspective directed at exploiting complex dynamics, ultimately for the design of therapeutic interventions. Results Analyzing the evolution of agent-agent interactions at incremental time points from identical initial conditions revealed novel features of immune communication associated with successful and failed outcomes. There were fewer contacts between agents for simulations ending in viral elimination (win) versus persistent infection (loss), due to the removal of infected agents. However, early cellular interactions preceded successful clearance of infection. Specifically, more Dendritic Agent interactions with TCell and BCell Agents, and more BCell Agent interactions with TCell Agents early in the simulation were associated with the immune win outcome. The Dendritic Agents greatly influenced the outcome, confirming them as hub agents of the immune network. In addition, unexpectedly high frequencies of Dendritic Agent-self interactions occurred in the lymphoid compartment late in the loss outcomes. Conclusions An agent-based model capturing several key aspects of complex system dynamics was used to study the emergent properties of the immune response to viral infection. Specific patterns of interactions between leukocyte agents occurring early in the response significantly improved outcome. More interactions at later stages correlated with persistent inflammation and infection. These simulation experiments highlight the importance of commonly overlooked aspects of the immune response and provide insight into these processes at a resolution level exceeding the capabilities of current laboratory technologies. PMID:21247471

Experience Using Formal Methods for Specifying a Multi-Agent System

NASA Technical Reports Server (NTRS)

Rouff, Christopher; Rash, James; Hinchey, Michael; Szczur, Martha R. (Technical Monitor)

2000-01-01

The process and results of using formal methods to specify the Lights Out Ground Operations System (LOGOS) is presented in this paper. LOGOS is a prototype multi-agent system developed to show the feasibility of providing autonomy to satellite ground operations functions at NASA Goddard Space Flight Center (GSFC). After the initial implementation of LOGOS the development team decided to use formal methods to check for race conditions, deadlocks and omissions. The specification exercise revealed several omissions as well as race conditions. After completing the specification, the team concluded that certain tools would have made the specification process easier. This paper gives a sample specification of two of the agents in the LOGOS system and examples of omissions and race conditions found. It concludes with describing an architecture of tools that would better support the future specification of agents and other concurrent systems.

Preparation of Shrinkage Compensating Concrete with HCSA Expansive Agent

NASA Astrophysics Data System (ADS)

Li, Changcheng; Jia, Fujia

2017-10-01

Shrinkage compensating concrete (SCC) has become one of the best effective methods of preventing and reducing concrete cracking. SCC is prepared by HCSA high performance expansive agent for concrete which restrained expansion rate is optimized by 0.057%. Slump, compressive strength, restrained expansion rate and cracking resistance test were carried out on SCC. The results show that the initial slump of fresh SCC was about 220mm-230mm, while slump after 2 hours was 180mm-200mm. The restrained expansion rate of SCC increased with the mixing amount of expansive agent. After cured in water for 14 days, the restrained expansion rate of C35 and C40 SCC were 0.020%-0.032%. With the dosage of expansive agent increasing, restrained expansion rate of SCC increased, maximum compressive stress and cracking stress improved, cracking temperature fell, thus cracking resistance got effectively improvement.

Apoptosis and Self-Destruct: A Contribution to Autonomic Agents?

NASA Technical Reports Server (NTRS)

Sterritt, Roy; Hinchey, Mike

2004-01-01

Autonomic Computing (AC), a self-managing systems initiative based on the biological metaphor of the autonomic nervous system, is increasingly gaining momentum as the way forward in designing reliable systems. Agent technologies have been identified as a key enabler for engineering autonomicity in systems, both in terms of retrofitting autonomicity into legacy systems and designing new systems. The AC initiative provides an opportunity to consider other biological systems and principles in seeking new design strategies. This paper reports on one such investigation; utilizing the apoptosis metaphor of biological systems to provide a dynamic health indicator signal between autonomic agents.

Effect of a sequential treatment combining abaloparatide and alendronate for the management of postmenopausal osteoporosis.

PubMed

Reginster, J Y; Al Daghri, Nasser; Kaufman, Jean-Marc; Bruyère, Olivier

2018-02-01

The recently published results of the sequential treatment of postmenopausal osteoporotic women with subcutaneous abaloparatide (80 µg/day) (ABL) for 18 months followed by 6 months of oral alendronate (70 mg/week) (ALN) support the administration of an anti-resorptive agent after completion of a treatment course with an osteoanabolic agent. The ABL/ALN sequence resulted in greater bone mineral density gains at all skeletal sites and in a reduction of vertebral, non-vertebral, major and clinical fractures compared to what is observed after 18 months of placebo followed by 6 months of ALN. Whereas questions remained unanswered about the ideal anti-resorptive agent to be used after ABL, the optimal duration of the administration of the anti-resorptive drug or the potential interest of re-initiating a course of ABL after a limited administration of ALN, these results support the use of the ABL/ALN sequence in the management of postmenopausal osteoporosis.

[Community health agents: profile and education].

PubMed

Marzari, Carla Kowalski; Junges, José Roque; Selli, Lucilda

2011-01-01

This research discusses the profile and education of the community health agents. There is no clarity about the kind of professional needed and the appropriate training to the fulfillment of the function. The research is a case study with exploratory methodology and qualitative approach. The data was collected with a focused group, formed by ten agents, intentional selected from those with more time in service in Family Health Strategy teams from the municipality of Santa Maria, Rio Grande do Sul State. The discussions were recorded and transcribed by the researcher. The data was interpreted by content analysis. The results pointed to some important questions concerning the identity of the community health agents: integration on the health team, insertion in the community, profile and education. The profile which emerges from the research, is not different from the one proposed by the Ministry of Health. However, the difference is the professionalization, an initiative assumed by the agent, guided by reality, which he faces in his activity. The gaps, perceived in his formation, cause the agent to construct his professional identity, determined more by the technical aspect of the scientific knowledge than by his social competence as a community agent.

Cosine Kuramoto Based Distribution of a Convoy with Limit-Cycle Obstacle Avoidance Through the Use of Simulated Agents

NASA Astrophysics Data System (ADS)

Howerton, William

This thesis presents a method for the integration of complex network control algorithms with localized agent specific algorithms for maneuvering and obstacle avoidance. This method allows for successful implementation of group and agent specific behaviors. It has proven to be robust and will work for a variety of vehicle platforms. Initially, a review and implementation of two specific algorithms will be detailed. The first, a modified Kuramoto model was developed by Xu [1] which utilizes tools from graph theory to efficiently perform the task of distributing agents. The second algorithm developed by Kim [2] is an effective method for wheeled robots to avoid local obstacles using a limit-cycle navigation method. The results of implementing these methods on a test-bed of wheeled robots will be presented. Control issues related to outside disturbances not anticipated in the original theory are then discussed. A novel method of using simulated agents to separate the task of distributing agents from agent specific velocity and heading commands has been developed and implemented to address these issues. This new method can be used to combine various behaviors and is not limited to a specific control algorithm.

Approach for Autonomous Control of Unmanned Aerial Vehicle Using Intelligent Agents for Knowledge Creation

NASA Technical Reports Server (NTRS)

Dufrene, Warren R., Jr.

2004-01-01

This paper describes the development of a planned approach for Autonomous operation of an Unmanned Aerial Vehicle (UAV). A Hybrid approach will seek to provide Knowledge Generation through the application of Artificial Intelligence (AI) and Intelligent Agents (IA) for UAV control. The applications of several different types of AI techniques for flight are explored during this research effort. The research concentration is directed to the application of different AI methods within the UAV arena. By evaluating AI and biological system approaches. which include Expert Systems, Neural Networks. Intelligent Agents, Fuzzy Logic, and Complex Adaptive Systems, a new insight may be gained into the benefits of AI and CAS techniques applied to achieving true autonomous operation of these systems. Although flight systems were explored, the benefits should apply to many Unmanned Vehicles such as: Rovers. Ocean Explorers, Robots, and autonomous operation systems. A portion of the flight system is broken down into control agents that represent the intelligent agent approach used in AI. After the completion of a successful approach, a framework for applying an intelligent agent is presented. The initial results from simulation of a security agent for communication are presented.

Effect of bioadhesion on initial in vitro buoyancy of effervescent floating matrix tablets of ciprofloxacin HCL

PubMed Central

Negi, Jeetendra Singh; Trivedi, Abhinav; Khanduri, Praveen; Negi, Vandana; Kasliwal, Nikhil

2011-01-01

The purpose of this study was to investigate effect of bioadhesion on the initial in vitro buoyancy behaviour of effervescent matrix tablets of ciprofloxacin HCl (CIPRO). Tablets were prepared by direct compression using HPMC K4M and Carbopol 971P as hydrophilic-controlled release polymers, sodium bicarbonate (NaHCO3) as gas-generating agent, polyplasdone XL, Explotab and Ac-Di-Sol as swelling agents. Tablets were evaluated for normal and modified initial in vitro floating behavior, floating duration, swelling behavior and in vitro drug release studies. A modified buoyancy lag time for tablets was determined in order to include the effect of bioadhesion on initial buoyancy. The initial buoyancy was found depended on bioadhesion ability of tablets. The lowest modified buoyancy lag time of 20 seconds was obtained for Formulation F7 having both NaHCO3 and polyplasdone XL. The floating duration was also found dependent on concentration of NaHCO3 and swelling agents. The drug release of F7 was also sustained up to 12-hr duration with anomalous drug transport mechanism. PMID:22171304

Management of patients with multiple myeloma: emphasizing the role of high-dose therapy.

PubMed

Kyle, R A

2001-06-01

Treatment for multiple myeloma should not be given until the patient is symptomatic or at risk for the occurrence of complications of the disease. If the patient is younger than 70 years, the physician should seriously consider an autologous peripheral blood stem cell transplant. Most physicians initially administer vincristine/doxorubicin/dexamethasone (VAD) for 3 to 4 months and then collect the stem cells before exposure to alkylating agents. Following stem cell collection, one may proceed with high-dose chemotherapy and then infusion of the stem cells, or one can administer alkylating agents until a plateau is reached and delay transplantation until progressive disease occurs. There is no difference in overall survival between early and late transplantation, but the former avoids the cost and inconvenience of alkylating agent therapy. Double or tandem autologous stem cell transplants may produce better results, but the evidence is not strong. Almost all patients have a relapse after an autologous stem cell transplant, so efforts are being made to prolong the response with a2-interferon or dendritic cell therapy. Allogeneic bone marrow transplantation is feasible for only 5%-10% of patients, but the mortality is high and it is curative in only a small fraction of patients. Treatment with melphalan and prednisone results in an objective response in 50%-60% of patients. Combinations of alkylating agents produce a higher response rate, but there is no survival benefit. Thalidomide produces an objective response in about one third of patients with refractory disease. It currently is being studied in conjunction with dexamethasone for conventional initial therapy.

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

Perception Modelling of Visitors in Vargas Museum Using Agent-Based Simulation and Visibility Analysis

NASA Astrophysics Data System (ADS)

Carcellar, B. G., III

2017-10-01

Museum exhibit management is one of the usual undertakings of museum facilitators. Art works must be strategically placed to achieve maximum viewing from the visitors. The positioning of the artworks also highly influences the quality of experience of the visitors. One solution in such problems is to utilize GIS and Agent-Based Modelling (ABM). In ABM, persistent interacting objects are modelled as agents. These agents are given attributes and behaviors that describe their properties as well as their motion. In this study, ABM approach that incorporates GIS is utilized to perform analyticcal assessment on the placement of the artworks in the Vargas Museum. GIS serves as the backbone for the spatial aspect of the simulation such as the placement of the artwork exhibits, as well as possible obstructions to perception such as the columns, walls, and panel boards. Visibility Analysis is also done to the model in GIS to assess the overall visibility of the artworks. The ABM is done using the initial GIS outputs and GAMA, an open source ABM software. Visitors are modelled as agents, moving inside the museum following a specific decision tree. The simulation is done in three use cases: the 10 %, 20 %, and 30 % chance of having a visitor in the next minute. For the case of the said museum, the 10 % chance is determined to be the closest simulation case to the actual and the recommended minimum time to achieve a maximum artwork perception is 1 hour and 40 minutes. Initial assessment of the results shows that even after 3 hours of simulation, small parts of the exhibit show lack of viewers, due to its distance from the entrance. A more detailed decision tree for the visitor agents can be incorporated to have a more realistic simulation.

Novel polymers and method of preparing same

NASA Technical Reports Server (NTRS)

Hirshfield, S. M. (Inventor)

1973-01-01

Polymers are prepared with terminal functional groups by reacting a compound selected from the group consisting of lithium p-lithiophenoxide and tetrabutylammonium p-lithiophenoxide as an initiator with material such as butadiene. The resulting functionally terminated new polymers are then capable of reacting with coupling agents to form star polymers.

Using uncertainty and sensitivity analyses in socioecological agent-based models to improve their analytical performance and policy relevance.

PubMed

Ligmann-Zielinska, Arika; Kramer, Daniel B; Spence Cheruvelil, Kendra; Soranno, Patricia A

2014-01-01

Agent-based models (ABMs) have been widely used to study socioecological systems. They are useful for studying such systems because of their ability to incorporate micro-level behaviors among interacting agents, and to understand emergent phenomena due to these interactions. However, ABMs are inherently stochastic and require proper handling of uncertainty. We propose a simulation framework based on quantitative uncertainty and sensitivity analyses to build parsimonious ABMs that serve two purposes: exploration of the outcome space to simulate low-probability but high-consequence events that may have significant policy implications, and explanation of model behavior to describe the system with higher accuracy. The proposed framework is applied to the problem of modeling farmland conservation resulting in land use change. We employ output variance decomposition based on quasi-random sampling of the input space and perform three computational experiments. First, we perform uncertainty analysis to improve model legitimacy, where the distribution of results informs us about the expected value that can be validated against independent data, and provides information on the variance around this mean as well as the extreme results. In our last two computational experiments, we employ sensitivity analysis to produce two simpler versions of the ABM. First, input space is reduced only to inputs that produced the variance of the initial ABM, resulting in a model with output distribution similar to the initial model. Second, we refine the value of the most influential input, producing a model that maintains the mean of the output of initial ABM but with less spread. These simplifications can be used to 1) efficiently explore model outcomes, including outliers that may be important considerations in the design of robust policies, and 2) conduct explanatory analysis that exposes the smallest number of inputs influencing the steady state of the modeled system.

Using Uncertainty and Sensitivity Analyses in Socioecological Agent-Based Models to Improve Their Analytical Performance and Policy Relevance

PubMed Central

Ligmann-Zielinska, Arika; Kramer, Daniel B.; Spence Cheruvelil, Kendra; Soranno, Patricia A.

2014-01-01

Agent-based models (ABMs) have been widely used to study socioecological systems. They are useful for studying such systems because of their ability to incorporate micro-level behaviors among interacting agents, and to understand emergent phenomena due to these interactions. However, ABMs are inherently stochastic and require proper handling of uncertainty. We propose a simulation framework based on quantitative uncertainty and sensitivity analyses to build parsimonious ABMs that serve two purposes: exploration of the outcome space to simulate low-probability but high-consequence events that may have significant policy implications, and explanation of model behavior to describe the system with higher accuracy. The proposed framework is applied to the problem of modeling farmland conservation resulting in land use change. We employ output variance decomposition based on quasi-random sampling of the input space and perform three computational experiments. First, we perform uncertainty analysis to improve model legitimacy, where the distribution of results informs us about the expected value that can be validated against independent data, and provides information on the variance around this mean as well as the extreme results. In our last two computational experiments, we employ sensitivity analysis to produce two simpler versions of the ABM. First, input space is reduced only to inputs that produced the variance of the initial ABM, resulting in a model with output distribution similar to the initial model. Second, we refine the value of the most influential input, producing a model that maintains the mean of the output of initial ABM but with less spread. These simplifications can be used to 1) efficiently explore model outcomes, including outliers that may be important considerations in the design of robust policies, and 2) conduct explanatory analysis that exposes the smallest number of inputs influencing the steady state of the modeled system. PMID:25340764

Distributed Planning in a Mixed-Initiative Environment: Collaborative Technologies for Network Centric Operations

DTIC Science & Technology

2008-10-01

Agents in the DEEP architecture extend and use the Java Agent Development (JADE) framework. DEEP requires a distributed multi-agent system and a...framework to help simplify the implementation of this system. JADE was chosen because it is fully implemented in Java , and supports these requirements

How Students Create Motivationally Supportive Learning Environments for Themselves: The Concept of Agentic Engagement

ERIC Educational Resources Information Center

Reeve, Johnmarshall

2013-01-01

The present study introduced "agentic engagement" as a newly proposed student-initiated pathway to greater achievement and greater motivational support. Study 1 developed the brief, construct-congruent, and psychometrically strong Agentic Engagement Scale. Study 2 provided evidence for the scale's construct and predictive validity, as…

Toward Shared Working Space of Human and Robotic Agents Through Dipole Flow Field for Dependable Path Planning.

PubMed

Trinh, Lan Anh; Ekström, Mikael; Cürüklü, Baran

2018-01-01

Recent industrial developments in autonomous systems, or agents, which assume that humans and the agents share the same space or even work in close proximity, open for new challenges in robotics, especially in motion planning and control. In these settings, the control system should be able to provide these agents a reliable path following control when they are working in a group or in collaboration with one or several humans in complex and dynamic environments. In such scenarios, these agents are not only moving to reach their goals, i.e., locations, they are also aware of the movements of other entities to find a collision-free path. Thus, this paper proposes a dependable, i.e., safe, reliable and effective, path planning algorithm for a group of agents that share their working space with humans. Firstly, the method employs the Theta * algorithm to initialize the paths from a starting point to a goal for a set of agents. As Theta * algorithm is computationally heavy, it only reruns when there is a significant change of the environment. To deal with the movements of the agents, a static flow field along the configured path is defined. This field is used by the agents to navigate and reach their goals even if the planned trajectories are changed. Secondly, a dipole field is calculated to avoid the collision of agents with other agents and human subjects. In this approach, each agent is assumed to be a source of a magnetic dipole field in which the magnetic moment is aligned with the moving direction of the agent. The magnetic dipole-dipole interactions between these agents generate repulsive forces to help them to avoid collision. The effectiveness of the proposed approach has been evaluated with extensive simulations. The results show that the static flow field is able to drive agents to the goals with a small number of requirements to update the path of agents. Meanwhile, the dipole flow field plays an important role to prevent collisions. The combination of these two fields results in a safe path planning algorithm, with a deterministic outcome, to navigate agents to their desired goals.

42 CFR 493.1261 - Standard: Bacteriology.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) For antimicrobial susceptibility tests, the laboratory must check each batch of media and each lot number and shipment of antimicrobial agent(s) before, or concurrent with, initial use, using approved...

The Infectious Pathogenesis Of Prostate Cancer

DTIC Science & Technology

2011-04-01

agents in the genesis of inflammation. For prostate cancer, several lines of evidence point to a role of infections as important agents , although no...specific infection has consistently been identified. In this project, we are examining two specific infectious agents with respect to prostate cancer: T...Infectious agents are likely targets involved in the initiation and exacerbation of chronic inflammation, and infections can lead to increased risk of

The Unilateralist’s Curse and the Case for a Principle of Conformity

PubMed Central

Bostrom, Nick; Douglas, Thomas; Sandberg, Anders

2016-01-01

In some situations a number of agents each have the ability to undertake an initiative that would have significant effects on the others. Suppose that each of these agents is purely motivated by an altruistic concern for the common good. We show that if each agent acts on her own personal judgment as to whether the initiative should be undertaken, then the initiative will be undertaken more often than is optimal. We suggest that this phenomenon, which we call the unilateralist’s curse, arises in many contexts, including some that are important for public policy. To lift the curse, we propose a principle of conformity, which would discourage unilateralist action. We consider three different models for how this principle could be implemented, and respond to an objection that could be raised against it. PMID:27499570

Neoseiulus californicus (Acari: Phytoseiidae) as a potential control agent of Tetranychus urticae (Acari: Tetranychidae): effect of pest/predator ratio on pest abundance on strawberry.

PubMed

Greco, Nancy M; Sánchez, Norma E; Liljesthröm, Gerardo G

2005-01-01

Neoseiulus californicus (McGregor) is a promising agent for successful Tetranychus urticae Koch control through conservation techniques, in strawberry crops in La Plata (Buenos Aires, Argentina). In prey-predator interaction, initial relative densities have an important effect on system dynamics. The economic threshold level (ETL) used for this pest in the present study was 50 active mites per leaflet. In our laboratory experiments, initial T. urticae to N. californicus ratio had a significant effect on the population abundance of T. urticae at a 7-day period. When pest/predator ratio was 5/1 (at initial pest densities from 5 to 15 females/leaflet) the final number of active T. urticae/leaflet was significantly lower than the ETL, while at 20 females/leaflet this number did not differ from the ETL. At 7.5/1 ratio, the final number of active T. urticae/leaflet, at initial pest densities from 5 to 15 females/leaflet, reached the ETL without surpassing it. At 10/1 and 15/1 ratios, pest densities exceeded the ETL only at 15 initial T. urticae/leaflet. Most greenhouse and field observations were consistent with the predictions of a graphical model based on experimental results. This predator was very effective in limiting pest densities at a 7-day period and within the range of pest-predator ratios and absolute densities used in this study. Conservation of N. californicus promoting favorable pest/predator ratios may result in early control of T. urticae.

Risks of herpes zoster in patients with rheumatoid arthritis according to biologic disease-modifying therapy.

PubMed

Yun, Huifeng; Xie, Fenglong; Delzell, Elizabeth; Chen, Lang; Levitan, Emily B; Lewis, James D; Saag, Kenneth G; Beukelman, Timothy; Winthrop, Kevin; Baddley, John W; Curtis, Jeffrey R

2015-05-01

To evaluate whether the risks of herpes zoster (HZ) differed by biologic agents with different mechanisms of action (MOAs) in older rheumatoid arthritis (RA) patients. Using Medicare data from 2006-2011, among RA patients with prior biologic agent use and no history of cancer or other autoimmune diseases, this retrospective cohort study identified new treatment episodes of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Followup started on initiation of the new biologic agent and ended at any of the following: first incidence of HZ, a 30-day gap in current exposure, death, a diagnosis of other autoimmune disease or cancer, loss of insurance coverage, or December 31, 2011. We calculated the proportion of RA patients vaccinated for HZ in each calendar year prior to biologic agent initiation and HZ incidence rate for each biologic agent. We compared HZ risks among therapies using Cox regression adjusted for potential confounders. Of 29,129 new biologic treatment episodes, 28.7% used abatacept, 15.9% adalimumab, 14.8% rituximab, 12.4% infliximab, 12.2% etanercept, 6.1% tocilizumab, 5.8% certolizumab, and 4.4% golimumab. The proportion of RA patients vaccinated for HZ prior to biologic agent initiation ranged from 0.4% in 2007 to 4.1% in 2011. We identified 423 HZ diagnoses with the highest HZ incidence rate for certolizumab (2.45 per 100 person-years) and the lowest for golimumab (1.61 per 100 person-years). Neither the crude incidence rate nor the adjusted hazard ratio differed significantly among biologic agents. Glucocorticoid use had a significant association with HZ. Among older patients with RA, the HZ risk was similar across biologic agents, including those with different MOAs. © 2015, American College of Rheumatology.

Effects of payoff functions and preference distributions in an adaptive population

NASA Astrophysics Data System (ADS)

Yang, H. M.; Ting, Y. S.; Wong, K. Y. Michael

2008-03-01

Adaptive populations such as those in financial markets and distributed control can be modeled by the Minority Game. We consider how their dynamics depends on the agents’ initial preferences of strategies, when the agents use linear or quadratic payoff functions to evaluate their strategies. We find that the fluctuations of the population making certain decisions (the volatility) depends on the diversity of the distribution of the initial preferences of strategies. When the diversity decreases, more agents tend to adapt their strategies together. In systems with linear payoffs, this results in dynamical transitions from vanishing volatility to a nonvanishing one. For low signal dimensions, the dynamical transitions for the different signals do not take place at the same critical diversity. Rather, a cascade of dynamical transitions takes place when the diversity is reduced. In contrast, no phase transitions are found in systems with the quadratic payoffs. Instead, a basin boundary of attraction separates two groups of samples in the space of the agents’ decisions. Initial states inside this boundary converge to small volatility, while those outside diverge to a large one. Furthermore, when the preference distribution becomes more polarized, the dynamics becomes more erratic. All the above results are supported by good agreement between simulations and theory.

Agent planning in AgScala

NASA Astrophysics Data System (ADS)

Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

2013-10-01

Agent-oriented programming languages are designed to simplify the development of software agents, especially those that exhibit complex, intelligent behavior. This paper presents recent improvements of AgScala, an agent-oriented programming language based on Scala. AgScala includes declarative constructs for managing beliefs, actions and goals of intelligent agents. Combined with object-oriented and functional programming paradigms offered by Scala, it aims to be an efficient framework for developing both purely reactive, and more complex, deliberate agents. Instead of the Prolog back-end used initially, the new version of AgScala relies on Agent Planning Package, a more advanced system for automated planning and reasoning.

Physician reasons for nonpharmacologic treatment of hyperglycemia in older patients newly diagnosed with type 2 diabetes mellitus.

PubMed

Marrett, Elizabeth; Zhang, Qiaoyi; Kanitscheider, Claudia; Davies, Michael J; Radican, Larry; Feinglos, Mark N

2012-11-01

To identify reasons why primary care physicians (PCPs) do not treat older patients newly diagnosed with type 2 diabetes mellitus (T2DM) with antihyperglycemic agents following diagnosis. US PCPs were surveyed via the internet regarding their reasons for not treating patients aged >65 years diagnosed with T2DM and had not yet initiated antihyperglycemic therapy for ≥6 months after diagnosis. PCPs were requested to provide relevant clinical information for untreated older patients and select applicable reasons for not initiating treatment from a list of 35 possibilities, grouped into five categories. A total of 508 PCPs completed the online survey and provided complete clinical data for 770 patients. The reasons provided by the first-ranked physician for not initiating antihyperglycemic therapy were related to diet and exercise (57.5%); mild hyperglycemia (23.8%); patient's concerns (13.4%); concerns about antihyperglycemic agents (3.0%); and comorbidities and polypharmacy (2.3%). The "diet and exercise" category was the most common first-ranked non-treatment reason, regardless of recent hemoglobin A(1c) (HbA(1c)) stratum. Reasons within the "patient's concerns," "concerns related to antihyperglycemic agents," and "comorbidities and polypharmacy" categories tended to be selected more often as first-ranked reasons by physicians for patients with higher HbA(1c) values. Of the 158 patients whose physicians planned to initiate antihyperglycemic therapy within the next month, 54.4% already had a most recent HbA(1c) value above their physician-stated threshold for treatment initiation. In the PCPs studied, there was a tendency to select appropriate reasons for non-treatment with antihyperglycemic agents given their patients' glycemic status. However, there was inertia related to the initiation of pharmacological therapy in some older patients with newly diagnosed T2DM. Important factors included physicians' perceptions of "mild" hyperglycemia and the HbA(1c) threshold for using antihyperglycemic agents.

Cooperation in Human-Agent Systems to Support Resilience: A Microworld Experiment.

PubMed

Chiou, Erin K; Lee, John D

2016-09-01

This study uses a dyadic approach to understand human-agent cooperation and system resilience. Increasingly capable technology fundamentally changes human-machine relationships. Rather than reliance on or compliance with more or less reliable automation, we investigate interaction strategies with more or less cooperative agents. A joint-task microworld scenario was developed to explore the effects of agent cooperation on participant cooperation and system resilience. To assess the effects of agent cooperation on participant cooperation, 36 people coordinated with a more or less cooperative agent by requesting resources and responding to requests for resources in a dynamic task environment. Another 36 people were recruited to assess effects following a perturbation in their own hospital. Experiment 1 shows people reciprocated the cooperative behaviors of the agents; a low-cooperation agent led to less effective interactions and less resource sharing, whereas a high-cooperation agent led to more effective interactions and greater resource sharing. Experiment 2 shows that an initial fast-tempo perturbation undermined proactive cooperation-people tended to not request resources. However, the initial fast tempo had little effect on reactive cooperation-people tended to accept resource requests according to cooperation level. This study complements the supervisory control perspective of human-automation interaction by considering interdependence and cooperation rather than the more common focus on reliability and reliance. The cooperativeness of automated agents can influence the cooperativeness of human agents. Design and evaluation for resilience in teams involving increasingly autonomous agents should consider the cooperative behaviors of these agents. © 2016, Human Factors and Ergonomics Society.

Initial Evaluation of Burn Characteristics of Phenolic Foam Runway Brake Arrestor Material

DTIC Science & Technology

1993-12-01

foam immersed in a jet fuel fire when extinguished using 3-percent Aqueous Film Forming Foam ( AFFF ). Three pool...extinguishment time of phenolic foam immersed in a jet fuel fire, using 3-percent Aqueous Film Forming Foam ( AFFF ) extinguishing agent. The wind was negligible...percent Aqueous Film Forming Foam ( AFFF ) agent. This project is an initial assessment of the fire safety of phenolic foam

Evaluation of location and number of aid post for sustainable humanitarian relief using agent based modeling (ABM) and geographic information system (GIS)

NASA Astrophysics Data System (ADS)

Khair, Fauzi; Sopha, Bertha Maya

2017-12-01

One of the crucial phases in disaster management is the response phase or the emergency response phase. It requires a sustainable system and a well-integrated management system. Any errors in the system on this phase will impact on significant increase of the victims number as well as material damage caused. Policies related to the location of aid posts are important decisions. The facts show that there are many failures in the process of providing assistance to the refugees due to lack of preparation and determination of facilities and aid post location. Therefore, this study aims to evaluate the number and location of aid posts on Merapi eruption in 2010. This study uses an integration between Agent Based Modeling (ABM) and Geographic Information System (GIS) about evaluation of the number and location of the aid post using some scenarios. The ABM approach aims to describe the agents behaviour (refugees and volunteers) in the event of a disaster with their respective characteristics. While the spatial data, GIS useful to describe real condition of the Sleman regency road. Based on the simulation result, it shows alternative scenarios that combine DERU UGM post, Maguwoharjo Stadium, Tagana Post and Pakem Main Post has better result in handling and distributing aid to evacuation barrack compared to initial scenario. Alternative scenarios indicates the unmet demands are less than the initial scenario.

Detection/classification/quantification of chemical agents using an array of surface acoustic wave (SAW) devices

NASA Astrophysics Data System (ADS)

Milner, G. Martin

2005-05-01

ChemSentry is a portable system used to detect, identify, and quantify chemical warfare (CW) agents. Electro chemical (EC) cell sensor technology is used for blood agents and an array of surface acoustic wave (SAW) sensors is used for nerve and blister agents. The combination of the EC cell and the SAW array provides sufficient sensor information to detect, classify and quantify all CW agents of concern using smaller, lighter, lower cost units. Initial development of the SAW array and processing was a key challenge for ChemSentry requiring several years of fundamental testing of polymers and coating methods to finalize the sensor array design in 2001. Following the finalization of the SAW array, nearly three (3) years of intensive testing in both laboratory and field environments were required in order to gather sufficient data to fully understand the response characteristics. Virtually unbounded permutations of agent characteristics and environmental characteristics must be considered in order to operate against all agents and all environments of interest to the U.S. military and other potential users of ChemSentry. The resulting signal processing design matched to this extensive body of measured data (over 8,000 agent challenges and 10,000 hours of ambient data) is considered to be a significant advance in state-of-the-art for CW agent detection.

Security Measures to Protect Mobile Agents

NASA Astrophysics Data System (ADS)

Dadhich, Piyanka; Govil, M. C.; Dutta, Kamlesh

2010-11-01

The security issues of mobile agent systems have embarrassed its widespread implementation. Mobile agents that move around the network are not safe because the remote hosts that accommodate the agents initiates all kinds of attacks. These hosts try to analyze the agent's decision logic and their accumulated data. So, mobile agent security is the most challenging unsolved problems. The paper analyzes various security measures deeply. Security especially the attacks performed by hosts to the visiting mobile agent (the malicious hosts problem) is a major obstacle that prevents mobile agent technology from being widely adopted. Being the running environment for mobile agent, the host has full control over them and could easily perform many kinds of attacks against them.

Spreading of nonmotile bacteria on a hard agar plate: Comparison between agent-based and stochastic simulations

NASA Astrophysics Data System (ADS)

Rana, Navdeep; Ghosh, Pushpita; Perlekar, Prasad

2017-11-01

We study spreading of a nonmotile bacteria colony on a hard agar plate by using agent-based and continuum models. We show that the spreading dynamics depends on the initial nutrient concentration, the motility, and the inherent demographic noise. Population fluctuations are inherent in an agent-based model, whereas for the continuum model we model them by using a stochastic Langevin equation. We show that the intrinsic population fluctuations coupled with nonlinear diffusivity lead to a transition from a diffusion limited aggregation type of morphology to an Eden-like morphology on decreasing the initial nutrient concentration.

Development rate, consumption and host specificity of Carea varipes (Lepidoptera: Nolidae)

USDA-ARS?s Scientific Manuscript database

The Asian shrub Rhodomyrtus tomentosa is an invasive weed in Florida and Hawaii, USA. Surveys for natural enemies of this exotic shrub in Hong Kong, China resulted in the development of a laboratory colony and initial host range testing of Carea varipes as a potential biological control agent of R. ...

Detection of early changes in lung-cell cytology by flow-systems analysis techniques. Progress report, January 1--June 30, 1976

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

Steinkamp, J. A.; Hansen, K. M.; Wilson, J. S.

1976-08-01

This report summarizes results of preliminary experiments to develop cytological and biochemical indicators for estimating damage to respiratory epithelium exposed to toxic agents associated with the by-products of nonnuclear energy production using advanced flow-systems cell-analysis technologies. Since initiation of the program one year ago, progress has been made in obtaining adequate numbers of exfoliated lung cells from the Syrian hamster for flow analysis; cytological techniques developed on human exfoliated gynecological samples have been adapted to hamster lung epithelium for obtaining single-cell suspensions; and lung-cell samples have been initially characterized based on DNA content, total protein, nuclear and cytoplasmic size, andmore » multiangle light-scatter measurements. Preliminary results from measurements of the above parameters which recently became available are described in this report. As the flow-systems technology is adapted further to analysis of exfoliated lung cells, measurements of changes in physical and biochemical cellular properties as a function of exposure to toxic agents will be performed.« less

Dynamics of bounded confidence opinion in heterogeneous social networks: Concord against partial antagonism

NASA Astrophysics Data System (ADS)

Kurmyshev, Evguenii; Juárez, Héctor A.; González-Silva, Ricardo A.

2011-08-01

Bounded confidence models of opinion dynamics in social networks have been actively studied in recent years, in particular, opinion formation and extremism propagation along with other aspects of social dynamics. In this work, after an analysis of limitations of the Deffuant-Weisbuch (DW) bounded confidence, relative agreement model, we propose the mixed model that takes into account two psychological types of individuals. Concord agents (C-agents) are friendly people; they interact in a way that their opinions always get closer. Agents of the other psychological type show partial antagonism in their interaction (PA-agents). Opinion dynamics in heterogeneous social groups, consisting of agents of the two types, was studied on different social networks: Erdös-Rényi random graphs, small-world networks and complete graphs. Limit cases of the mixed model, pure C- and PA-societies, were also studied. We found that group opinion formation is, qualitatively, almost independent of the topology of networks used in this work. Opinion fragmentation, polarization and consensus are observed in the mixed model at different proportions of PA- and C-agents, depending on the value of initial opinion tolerance of agents. As for the opinion formation and arising of “dissidents”, the opinion dynamics of the C-agents society was found to be similar to that of the DW model, except for the rate of opinion convergence. Nevertheless, mixed societies showed dynamics and bifurcation patterns notably different to those of the DW model. The influence of biased initial conditions over opinion formation in heterogeneous social groups was also studied versus the initial value of opinion uncertainty, varying the proportion of the PA- to C-agents. Bifurcation diagrams showed an impressive evolution of collective opinion, in particular, radical changes of left to right consensus or vice versa at an opinion uncertainty value equal to 0.7 in the model with the PA/C mixture of population near 50/50.

Canine infection with Dirofilaria immitis, Borrelia burgdorferi, Anaplasma spp., and Ehrlichia spp. in the United States, 2010–2012

PubMed Central

2014-01-01

Background The geographic distribution of canine infection with vector-borne disease agents in the United States appears to be expanding. Methods To provide an updated assessment of geographic trends in canine infection with Dirofilaria immitis, Borrelia burgdorferi, Ehrlichia spp., and Anaplasma spp., we evaluated results from an average of 3,588,477 dogs tested annually by veterinarians throughout the United States from 2010 – 2012. Results As in an earlier summary report, the percent positive test results varied by agent and region, with antigen of D. immitis and antibody to Ehrlichia spp. most commonly identified in the Southeast (2.9% and 3.2%, respectively) and antibody to both B. burgdorferi and Anaplasma spp. most commonly identified in the Northeast (13.3% and 7.1%, respectively) and upper Midwest (4.4% and 3.9%, respectively). Percent positive test results for D. immitis antigen were lower in every region considered, including in the Southeast, than previously reported. Percent positive test results for antibodies to B. burgdorferi and Ehrlichia spp. were higher nationally than previously reported, and, for antibodies to Anaplasma spp., were higher in the Northeast but lower in the Midwest and West, than in the initial report. Annual reports of human cases of Lyme disease, ehrlichiosis, and anaplasmosis were associated with percent positive canine test results by state for each respective tick-borne disease agent (R2 = 0.701, 0.457, and 0.314, respectively). Within endemic areas, percent positive test results for all three tick-borne agents demonstrated evidence of geographic expansion. Conclusions Continued national monitoring of canine test results for vector-borne zoonotic agents is an important tool for accurately mapping the geographic distribution of these agents, and greatly aids our understanding of the veterinary and public health threats they pose. PMID:24886589

Histone deacetylase inhibitors: current status and overview of recent clinical trials.

PubMed

Ma, Xujun; Ezzeldin, Hany H; Diasio, Robert B

2009-10-01

Histone deacetylase (HDAC) inhibitors are a new group of anticancer agents that have a potential role in the regulation of gene expression, induction of cell death, apoptosis and cell cycle arrest of cancer cells by altering the acetylation status of chromatin and other non-histone proteins. In clinical trials, HDAC inhibitors have demonstrated promising antitumour activity as monotherapy in cutaneous T-cell lymphoma and other haematological malignancies. In solid tumours, several HDAC inhibitors have been shown to be efficacious as single agents; however, results of most clinical trials were in favour of using HDAC inhibitors either prior to the initiation of chemotherapy or in combination with other treatments. Currently, the molecular basis of response to HDAC inhibitors in patients is not fully understood. In this review, we summarize the current status of HDAC inhibitors, as single agents or in combination with other agents in different phases of clinical trials. In most of the clinical trials, HDAC inhibitors were tolerable and exerted biological or antitumor activity. HDAC inhibitors have been studied in phase I, II and III clinical trials with variable efficacy. The combination of HDAC inhibitors with other anticancer agents including epigenetic or chemotherapeutic agents demonstrated favourable clinical outcome.

Optimal Wonderful Life Utility Functions in Multi-Agent Systems

NASA Technical Reports Server (NTRS)

Wolpert, David H.; Tumer, Kagan; Swanson, Keith (Technical Monitor)

2000-01-01

The mathematics of Collective Intelligence (COINs) is concerned with the design of multi-agent systems so as to optimize an overall global utility function when those systems lack centralized communication and control. Typically in COINs each agent runs a distinct Reinforcement Learning (RL) algorithm, so that much of the design problem reduces to how best to initialize/update each agent's private utility function, as far as the ensuing value of the global utility is concerned. Traditional team game solutions to this problem assign to each agent the global utility as its private utility function. In previous work we used the COIN framework to derive the alternative Wonderful Life Utility (WLU), and experimentally established that having the agents use it induces global utility performance up to orders of magnitude superior to that induced by use of the team game utility. The WLU has a free parameter (the clamping parameter) which we simply set to zero in that previous work. Here we derive the optimal value of the clamping parameter, and demonstrate experimentally that using that optimal value can result in significantly improved performance over that of clamping to zero, over and above the improvement beyond traditional approaches.

Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.

PubMed

Head, R J; Fay, M F; Cosgrove, L; Y C Fung, K; Rundle-Thiele, D; Martin, J H

2017-12-02

Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O 6 -methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis. This review describes key juxtaposed drivers in the balance between alkylation induced mutagenesis and apoptosis. Mutations in MMR genes are the probable drivers for alkylation based drug resistance. Critical to this interaction are the dose-response and temporal interactions between adduct formation and MMR mutations. The precision in dose interval, dose-responses and temporal relationships dictate a role for alkylating agents in either promoting experimental tumour formation or inducing tumour cell death with chemotherapy. Importantly, this resultant loss of chemotherapeutic selective pressure provides opportunity to explore novel therapeutics and appropriate combinations to minimise alkylation based drug resistance and tumour relapse.

Designing Agent Collectives For Systems With Markovian Dynamics

NASA Technical Reports Server (NTRS)

Wolpert, David H.; Lawson, John W.; Clancy, Daniel (Technical Monitor)

2001-01-01

The "Collective Intelligence" (COIN) framework concerns the design of collectives of agents so that as those agents strive to maximize their individual utility functions, their interaction causes a provided "world" utility function concerning the entire collective to be also maximized. Here we show how to extend that framework to scenarios having Markovian dynamics when no re-evolution of the system from counter-factual initial conditions (an often expensive calculation) is permitted. Our approach transforms the (time-extended) argument of each agent's utility function before evaluating that function. This transformation has benefits in scenarios not involving Markovian dynamics, in particular scenarios where not all of the arguments of an agent's utility function are observable. We investigate this transformation in simulations involving both linear and quadratic (nonlinear) dynamics. In addition, we find that a certain subset of these transformations, which result in utilities that have low "opacity (analogous to having high signal to noise) but are not "factored" (analogous to not being incentive compatible), reliably improve performance over that arising with factored utilities. We also present a Taylor Series method for the fully general nonlinear case.

Effect of different bulking agents on water variation and thermal balance and their respective contribution to bio-generated heat during long-term storage sludge biodrying process.

PubMed

Liu, Tiantian; Cui, Chongwei; He, Junguo; Tang, Jian

2018-04-17

Biodrying was first used for the post-treatment of long-term storage sludge with vinasse as bulking agents. The effect of different bulking agents on water and heat variation and their respective contributions to bio-generated heat during storage sludge biodrying were investigated. Three different bulking agents (beer lees and distillers grains, with conventional straw used for comparison) were mixed with storage sludge for biodrying for an 18-day period. The results revealed the treatment with beer lees as bulking agent achieved the best performance with the highest water removal capacity (658 g kg -1 initial water). The extent of organic degradation in the mixture was related to the degradation ability of the bulking agents. The degradation of C- and H-containing materials (e.g., carboxylic acid) accounted for volatile solids (VS) loss. Water and thermal analyses showed that evaporation was the main way of water loss (accounting for 90%), while evaporation heat was the main component of heat consumption (accounting for 56.67-60.62%).The biodegradation of bulking agents contributed a high proportion of the bio-generated heat consumed by water evaporation (82.35-86.67%).

The Relation between Thematic Role Computing and Semantic Relatedness Processing during On-Line Sentence Comprehension

PubMed Central

Li, Xiaoqing; Zhao, Haiyan; Lu, Yong

2014-01-01

Sentence comprehension involves timely computing different types of relations between its verbs and noun arguments, such as morphosyntactic, semantic, and thematic relations. Here, we used EEG technique to investigate the potential differences in thematic role computing and lexical-semantic relatedness processing during on-line sentence comprehension, and the interaction between these two types of processes. Mandarin Chinese sentences were used as materials. The basic structure of those sentences is “Noun+Verb+‘le’+a two-character word”, with the Noun being the initial argument. The verb disambiguates the initial argument as an agent or a patient. Meanwhile, the initial argument and the verb are highly or lowly semantically related. The ERPs at the verbs revealed that: relative to the agent condition, the patient condition evoked a larger N400 only when the argument and verb were lowly semantically related; however, relative to the high-relatedness condition, the low-relatedness condition elicited a larger N400 regardless of the thematic relation; although both thematic role variation and semantic relatedness variation elicited N400 effects, the N400 effect elicited by the former was broadly distributed and reached maximum over the frontal electrodes, and the N400 effect elicited by the latter had a posterior distribution. In addition, the brain oscillations results showed that, although thematic role variation (patient vs. agent) induced power decreases around the beta frequency band (15–30 Hz), semantic relatedness variation (low-relatedness vs. high-relatedness) induced power increases in the theta frequency band (4–7 Hz). These results suggested that, in the sentence context, thematic role computing is modulated by the semantic relatedness between the verb and its argument; semantic relatedness processing, however, is in some degree independent from the thematic relations. Moreover, our results indicated that, during on-line sentence comprehension, thematic role computing and semantic relatedness processing are mediated by distinct neural systems. PMID:24755643

42 CFR 423.2274 - Broker and agent requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

....2274 Broker and agent requirements. Link to an amendment published at 76 FR 54635, Sept. 1, 2011. For...) Agents and brokers must be compensated as follows: (1) A Part D sponsor (or other entity on its behalf... (a)(1)(i), individuals enrolling in a PDP in 2009 are initially deemed to be in the first renewal...

Chemical Surface Washing Agents for Oil Spills: Update State-of-the-Art on Mechanisms of Action and Evaluation of Two Laboratory Effectiveness Tests.

EPA Science Inventory

Chemical surface washing agents are formulations designed to help release stranded oil from shoreline substrates.The U.S. Environmental Protection Agency (EPA), in response to the Oil Pollution Act of 1990, Initiated study of these cleaning agents. The project summarized here had...

Modeling Radicalization Phenomena in Heterogeneous Populations.

PubMed

Galam, Serge; Javarone, Marco Alberto

2016-01-01

The phenomenon of radicalization is investigated within a mixed population composed of core and sensitive subpopulations. The latest includes first to third generation immigrants. Respective ways of life may be partially incompatible. In case of a conflict core agents behave as inflexible about the issue. In contrast, sensitive agents can decide either to live peacefully adjusting their way of life to the core one, or to oppose it with eventually joining violent activities. The interplay dynamics between peaceful and opponent sensitive agents is driven by pairwise interactions. These interactions occur both within the sensitive population and by mixing with core agents. The update process is monitored using a Lotka-Volterra-like Ordinary Differential Equation. Given an initial tiny minority of opponents that coexist with both inflexible and peaceful agents, we investigate implications on the emergence of radicalization. Opponents try to turn peaceful agents to opponents driving radicalization. However, inflexible core agents may step in to bring back opponents to a peaceful choice thus weakening the phenomenon. The required minimum individual core involvement to actually curb radicalization is calculated. It is found to be a function of both the majority or minority status of the sensitive subpopulation with respect to the core subpopulation and the degree of activeness of opponents. The results highlight the instrumental role core agents can have to hinder radicalization within the sensitive subpopulation. Some hints are outlined to favor novel public policies towards social integration.

Modeling Radicalization Phenomena in Heterogeneous Populations

PubMed Central

2016-01-01

The phenomenon of radicalization is investigated within a mixed population composed of core and sensitive subpopulations. The latest includes first to third generation immigrants. Respective ways of life may be partially incompatible. In case of a conflict core agents behave as inflexible about the issue. In contrast, sensitive agents can decide either to live peacefully adjusting their way of life to the core one, or to oppose it with eventually joining violent activities. The interplay dynamics between peaceful and opponent sensitive agents is driven by pairwise interactions. These interactions occur both within the sensitive population and by mixing with core agents. The update process is monitored using a Lotka-Volterra-like Ordinary Differential Equation. Given an initial tiny minority of opponents that coexist with both inflexible and peaceful agents, we investigate implications on the emergence of radicalization. Opponents try to turn peaceful agents to opponents driving radicalization. However, inflexible core agents may step in to bring back opponents to a peaceful choice thus weakening the phenomenon. The required minimum individual core involvement to actually curb radicalization is calculated. It is found to be a function of both the majority or minority status of the sensitive subpopulation with respect to the core subpopulation and the degree of activeness of opponents. The results highlight the instrumental role core agents can have to hinder radicalization within the sensitive subpopulation. Some hints are outlined to favor novel public policies towards social integration. PMID:27166677

Personal protection during resuscitation of casualties contaminated with chemical or biological warfare agents--a survey of medical first responders.

PubMed

Brinker, Andrea; Prior, Kate; Schumacher, Jan

2009-01-01

The threat of mass casualties caused by an unconventional terrorist attack is a challenge for the public health system, with special implications for emergency medicine, anesthesia, and intensive care. Advanced life support of patients injured by chemical or biological warfare agents requires an adequate level of personal protection. The aim of this study was to evaluate the personal protection knowledge of emergency physicians and anesthetists who would be at the frontline of the initial health response to a chemical/biological warfare agent incident. After institutional review board approval, knowledge of personal protection measures among emergency medicine (n = 28) and anesthetics (n = 47) specialty registrars in the South Thames Region of the United Kingdom was surveyed using a standardized questionnaire. Participants were asked for the recommended level of personal protection if a chemical/biological warfare agent(s) casualty required advanced life support in the designated hospital resuscitation area. The best awareness within both groups was regarding severe acute respiratory syndrome, and fair knowledge was found regarding anthrax, plague, Ebola, and smallpox. In both groups, knowledge about personal protection requirements against chemical warfare agents was limited. Knowledge about personal protection measures for biological agents was acceptable, but was limited for chemical warfare agents. The results highlight the need to improve training and education regarding personal protection measures for medical first receivers.

Analysis of the heavy oil production technology effectiveness using natural thermal convection with heat agent recirculation method in reservoirs with varying initial water saturation

NASA Astrophysics Data System (ADS)

Osnos, V. B.; Kuneevsky, V. V.; Larionov, V. M.; Saifullin, E. R.; Gainetdinov, A. V.; Vankov, Yu V.; Larionova, I. V.

2017-01-01

The method of natural thermal convection with heat agent recirculation (NTC HAR) in oil reservoirs is described. The analysis of the effectiveness of this method for oil reservoir heating with the values of water saturation from 0 to 0.5 units is conducted. As the test element Ashalchinskoye oil field is taken. CMG STARS software was used for calculations. Dynamics of cumulative production, recovery factor and specific energy consumption per 1 m3 of crude oil produced in the application of the heat exchanger with heat agent in cases of different initial water saturation are defined and presented as graphs.

Do Low Molecular Weight Agents Cause More Severe Asthma than High Molecular Weight Agents?

PubMed

Meca, Olga; Cruz, María-Jesús; Sánchez-Ortiz, Mónica; González-Barcala, Francisco-Javier; Ojanguren, Iñigo; Munoz, Xavier

2016-01-01

The aim of this study was to analyse whether patients with occupational asthma (OA) caused by low molecular weight (LMW) agents differed from patients with OA caused by high molecular weight (HMW) with regard to risk factors, asthma presentation and severity, and response to various diagnostic tests. Seventy-eight patients with OA diagnosed by positive specific inhalation challenge (SIC) were included. Anthropometric characteristics, atopic status, occupation, latency periods, asthma severity according to the Global Initiative for Asthma (GINA) control classification, lung function tests and SIC results were analysed. OA was induced by an HMW agent in 23 patients (29%) and by an LMW agent in 55 (71%). A logistic regression analysis confirmed that patients with OA caused by LMW agents had a significantly higher risk of severity according to the GINA classification after adjusting for potential confounders (OR = 3.579, 95% CI 1.136-11.280; p = 0.029). During the SIC, most patients with OA caused by HMW agents presented an early reaction (82%), while in patients with OA caused by LMW agents the response was mainly late (73%) (p = 0.0001). Similarly, patients with OA caused by LMW agents experienced a greater degree of bronchial hyperresponsiveness, measured as the difference in the methacholine dose-response ratio (DRR) before and after SIC (1.77, range 0-16), compared with patients with OA caused by HMW agents (0.87, range 0-72), (p = 0.024). OA caused by LMW agents may be more severe than that caused by HMW agents. The severity of the condition may be determined by the different mechanisms of action of these agents.

Clinical Trials in Noninfectious Uveitis

PubMed Central

Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida

2015-01-01

The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763

Epidemiology and treatment approaches in management of invasive fungal infections

PubMed Central

Kriengkauykiat, Jane; Ito, James I; Dadwal, Sanjeet S

2011-01-01

Over the past 20 years, the number of invasive fungal infections has continued to persist, due primarily to the increased numbers of patients subjected to severe immunosuppression. Despite the development of more active, less toxic antifungal agents and the standard use of antifungal prophylaxis, invasive fungal infections (especially invasive mold infections) continue to be a significant factor in hematopoietic cell and solid organ transplantation outcomes, resulting in high mortality rates. Since the use of fluconazole as standard prophylaxis in the hematopoietic cell transplantation setting, invasive candidiasis has come under control, but no mold-active antifungal agent (except for posaconazole in the setting of acute myelogenous leukemia and myelodysplastic syndrome) has been shown to improve the survival rate over fluconazole. With the advent of new azole and echinocandin agents, we have seen the emergence of more azole-resistant and echinocandin-resistant fungi. The recent increase in zygomycosis seen in the hematopoietic cell transplantation setting may be due to the increased use of voriconazole. This has implications for the empiric approach to pulmonary invasive mold infections when zygomycosis cannot be ruled out. It is imperative that an amphotericin B product, an antifungal that has never developed resistance in over 50 years, be initiated. The clinical presentations of invasive mold infections and invasive candidiasis can be nonspecific and the diagnostic tests insensitive, so a high index of suspicion and immediate initiation of empiric therapy is required. Unfortunately, our currently available serologic tests do not predict infection ahead of disease, and, therefore cannot be used to initiate “preemptive” therapy. Also, the Aspergillus galactomannan test gives a false negative result in patients receiving antimold prophylaxis, ie, virtually all of our patients with hematologic malignancy and hematopoietic cell transplant recipients. We may eventually be able to select patients at highest risk for invasive fungal infections for prophylaxis by genetic testing. However, with our current armamentarium of antifungal agents and widespread use of prophylaxis in high-risk groups (hematologic malignancy, hematopoietic cell transplantation), we continue to see high incidence and mortality rates, and our future hope lies in reversing the immunosuppression or augmenting the immune system of these severely immunocompromised hosts by developing and utilizing immunotherapy, immunoprophylaxis, and vaccines. PMID:21750627

Drought stress leads to systemic induced susceptibility to a nectrotrophic fungus associated with mountain pine beetle in Pinus banksiana seedlings.

PubMed

Klutsch, Jennifer G; Shamoun, Simon Francis; Erbilgin, Nadir

2017-01-01

Conifers have complex defense responses to initial attacks by insects and pathogens that can have cascading effects on success of subsequent colonizers. However, drought can affect a plant's ability to respond to biotic agents by potentially altering the resources needed for the energetically costly production of induced defense chemicals. We investigated the impact of reduced water on induced chemical defenses of jack pine (Pinus banksiana) seedlings from initial attack by biotic agents and resistance to subsequent challenge inoculation with a pathogenic fungal associate of mountain pine beetle (Dendroctonus ponderosae), Grosmannia clavigera. Applications of phytohormones (methyl salicylate and methyl jasmonate) and G. clavigera were used for initial induction of defenses. Monoterpene concentrations varied with initial induction from fungal and phytohormone application while watering treatment had no effect. Seedlings treated with G. clavigera and methyl jasmonate had the greatest monoterpene concentrations compared to the control and methyl salicylate-treated seedlings. However, the monoterpene response to the challenge inoculation varied with watering treatments, not with prior induction treatments, with lower monoterpene concentrations in fungal lesions on seedlings in the low to moderate watering treatments compared to normal watering treatment. Furthermore, prior induction from phytohormones resulted in systemic cross-induction of resistance to G. clavigera under normal watering treatment but susceptibility under low watering treatment. Seedlings stressed by low water conditions, which also had lower stomatal conductance than seedlings in the normal watering treatment, likely allocated resources to initial defense response but were left unable to acquire further resources for subsequent responses. Our results demonstrate that drought can affect interactions among tree-infesting organisms through systemic cross-induction of susceptibility.

Drought stress leads to systemic induced susceptibility to a nectrotrophic fungus associated with mountain pine beetle in Pinus banksiana seedlings

PubMed Central

Shamoun, Simon Francis; Erbilgin, Nadir

2017-01-01

Conifers have complex defense responses to initial attacks by insects and pathogens that can have cascading effects on success of subsequent colonizers. However, drought can affect a plant’s ability to respond to biotic agents by potentially altering the resources needed for the energetically costly production of induced defense chemicals. We investigated the impact of reduced water on induced chemical defenses of jack pine (Pinus banksiana) seedlings from initial attack by biotic agents and resistance to subsequent challenge inoculation with a pathogenic fungal associate of mountain pine beetle (Dendroctonus ponderosae), Grosmannia clavigera. Applications of phytohormones (methyl salicylate and methyl jasmonate) and G. clavigera were used for initial induction of defenses. Monoterpene concentrations varied with initial induction from fungal and phytohormone application while watering treatment had no effect. Seedlings treated with G. clavigera and methyl jasmonate had the greatest monoterpene concentrations compared to the control and methyl salicylate-treated seedlings. However, the monoterpene response to the challenge inoculation varied with watering treatments, not with prior induction treatments, with lower monoterpene concentrations in fungal lesions on seedlings in the low to moderate watering treatments compared to normal watering treatment. Furthermore, prior induction from phytohormones resulted in systemic cross-induction of resistance to G. clavigera under normal watering treatment but susceptibility under low watering treatment. Seedlings stressed by low water conditions, which also had lower stomatal conductance than seedlings in the normal watering treatment, likely allocated resources to initial defense response but were left unable to acquire further resources for subsequent responses. Our results demonstrate that drought can affect interactions among tree-infesting organisms through systemic cross-induction of susceptibility. PMID:29216258

Cytocompatibility and Mechanical Properties of Short Phosphate Glass Fibre Reinforced Polylactic Acid (PLA) Composites: Effect of Coupling Agent Mediated Interface

PubMed Central

Hasan, Muhammad Sami; Ahmed, Ifty; Parsons, Andrew; Walker, Gavin; Scotchford, Colin

2012-01-01

In this study three chemical agents Amino-propyl-triethoxy-silane (APS), sorbitol ended PLA oligomer (SPLA) and Hexamethylene diisocyanate (HDI) were identified to be used as coupling agents to react with the phosphate glass fibre (PGF) reinforcement and the polylactic acid (PLA) polymer matrix of the composite. Composites were prepared with short chopped strand fibres (l = 20 mm, ϕ = 20 µm) in a random arrangement within PLA matrix. Improved, initial composite flexural strength (~20 MPa) was observed for APS treated fibres, which was suggested to be due to enhanced bonding between the fibres and polymer matrix. Both APS and HDI treated fibres were suggested to be covalently linked with the PLA matrix. The hydrophobicity induced by these coupling agents (HDI, APS) helped to resist hydrolysis of the interface and thus retained their mechanical properties for an extended period of time as compared to non-treated control. Approximately 70% of initial strength and 65% of initial modulus was retained by HDI treated fibre composites in contrast to the control, where only ~50% of strength and modulus was retained after 28 days of immersion in PBS at 37 °C. All coupling agent treated and control composites demonstrated good cytocompatibility which was comparable to the tissue culture polystyrene (TCP) control, supporting the use of these materials as coupling agent’s within medical implant devices. PMID:24955744

Preparation and characterization of (St-DVB-MAA) ion exchange resins

NASA Astrophysics Data System (ADS)

Jiang, Shanquan; Sun, Xiangwei; Ling, Lixing; Wang, Shumin; Wu, Wufeng; Cheng, Shihong; Hu, Yue; Zhong, Chunyan

2017-08-01

In this paper, used polyvinyl alcohol as dispersing agent, Benzoyl peroxide as initiator of polymerization, Divinyl benzene as cross-linking agent, Styrene and 2-Methylpropenoic acid as monomer, ion exchange resin (copolymer of St-DVB-MAA)were prepared by suspension polymerization on 80°C. The structures, components and properties of the prepared composite micro gels were characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA). The experiment of ion exchange was conducted by resin to deal with copper ions in the solution. The result showed that performance of the ion exchange capacity was excellent, which impacted by pH.

[New drugs in the treatment of multiple myeloma].

PubMed

Oriol, Albert; Motlló, Cristina

2014-09-15

Progress in the treatment of multiple myeloma in the last decade has been able to delay, but ultimately not to prevent, the development of resistances and most patients still die of the disease or its related complications. New drugs have been developed including new alkylating agents, proteasome inhibitors and immunomodulators but also monoclonal antibodies and drugs with new mechanisms of action. Hopefully, this new generation of targeted agents will improve the results of the initial therapy, avoid relapses and development of resistances and provide better and less toxic options for the relapsed and refractory patient. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Single cell imaging of Bruton's Tyrosine Kinase using an irreversible inhibitor

NASA Astrophysics Data System (ADS)

Turetsky, Anna; Kim, Eunha; Kohler, Rainer H.; Miller, Miles A.; Weissleder, Ralph

2014-04-01

A number of Bruton's tyrosine kinase (BTK) inhibitors are currently in development, yet it has been difficult to visualize BTK expression and pharmacological inhibition in vivo in real time. We synthesized a fluorescent, irreversible BTK binder based on the drug Ibrutinib and characterized its behavior in cells and in vivo. We show a 200 nM affinity of the imaging agent, high selectivity, and irreversible binding to its target following initial washout, resulting in surprisingly high target-to-background ratios. In vivo, the imaging agent rapidly distributed to BTK expressing tumor cells, but also to BTK-positive tumor-associated host cells.

Method for producing small hollow spheres

DOEpatents

Hendricks, C.D.

1979-01-09

Method is disclosed for producing small hollow spheres of glass, metal or plastic, wherein the sphere material is mixed with or contains as part of the composition a blowing agent which decomposes at high temperature (T [approx gt] 600 C). As the temperature is quickly raised, the blowing agent decomposes and the resulting gas expands from within, thus forming a hollow sphere of controllable thickness. The thus produced hollow spheres (20 to 10[sup 3] [mu]m) have a variety of application, and are particularly useful in the fabrication of targets for laser implosion such as neutron sources, laser fusion physics studies, and laser initiated fusion power plants. 1 fig.

Method and apparatus for producing small hollow spheres

DOEpatents

Hendricks, Charles D.

1979-01-01

Method and apparatus for producing small hollow spheres of glass, metal or plastic, wherein the sphere material is mixed with or contains as part of the composition a blowing agent which decomposes at high temperature (T.gtoreq.600.degree. C.). As the temperature is quickly raised, the blowing agent decomposes and the resulting gas expands from within, thus forming a hollow sphere of controllable thickness. The thus produced hollow spheres (20 to 10.sup.3 .mu.m) have a variety of application, and are particularly useful in the fabrication of targets for laser implosion such as neutron sources, laser fusion physics studies, and laser initiated fusion power plants.

Method for producing small hollow spheres

DOEpatents

Hendricks, Charles D. [Livermore, CA

1979-01-09

Method for producing small hollow spheres of glass, metal or plastic, wherein the sphere material is mixed with or contains as part of the composition a blowing agent which decomposes at high temperature (T .gtorsim. 600.degree. C). As the temperature is quickly raised, the blowing agent decomposes and the resulting gas expands from within, thus forming a hollow sphere of controllable thickness. The thus produced hollow spheres (20 to 10.sup.3 .mu.m) have a variety of application, and are particularly useful in the fabrication of targets for laser implosion such as neutron sources, laser fusion physics studies, and laser initiated fusion power plants.

Relative diffusion of paramagnetic metal complexes of MRI contrast agents in an isotropic hydrogel medium.

PubMed

Weerakoon, Bimali Sanjeevani; Osuga, Toshiaki

2017-03-01

The observation of molecular diffusion by means of magnetic resonance imaging (MRI) is significant in the evaluation of the metabolic activity of living tissues. Series of MRI examinations were conducted on a diffusion model to study the behaviour of the diffusion process of different-molecular-weight (MW) paramagnetic MRI contrast agents in an isotropic agar hydrogel medium. The model consisted of a solidified 1 % agar gel with an initial concentration of 0.5 mmol/L contrast solution layered on top of the gel. The diffusion process was monitored at pre-determined time intervals of immediately, 1, 6, 9, 23, and 48 h after introduction of the contrast agents onto the agar gel with a T1-weighted spin-echo (SE) pulse sequence. Three types of paramagnetic contrast agents, Gd-DTPA with a MW of 547.57 g/mol, Prohance with a MW of 558.69 g/mol and MnCl 2 with a MW of 125.84 g/mol, resulted in an approximate average diffusional displacement ratio of 1:1:2 per hour, respectively, within 48 h of the experiment. Therefore, the results of this study supported the hypothesis that the rate of the diffusion process of MRI contrast agents in the agar hydrogel medium is inversely related to their MWs. However, more repetitions are necessary under various types of experimental conditions and also with various types of contrast media of different MWs for further confirmation and validation of these results.

Gossip-based solutions for discrete rendezvous in populations of communicating agents.

PubMed

Hollander, Christopher D; Wu, Annie S

2014-01-01

The objective of the rendezvous problem is to construct a method that enables a population of agents to agree on a spatial (and possibly temporal) meeting location. We introduce the buffered gossip algorithm as a general solution to the rendezvous problem in a discrete domain with direct communication between decentralized agents. We compare the performance of the buffered gossip algorithm against the well known uniform gossip algorithm. We believe that a buffered solution is preferable to an unbuffered solution, such as the uniform gossip algorithm, because the use of a buffer allows an agent to use multiple information sources when determining its desired rendezvous point, and that access to multiple information sources may improve agent decision making by reinforcing or contradicting an initial choice. To show that the buffered gossip algorithm is an actual solution for the rendezvous problem, we construct a theoretical proof of convergence and derive the conditions under which the buffered gossip algorithm is guaranteed to produce a consensus on rendezvous location. We use these results to verify that the uniform gossip algorithm also solves the rendezvous problem. We then use a multi-agent simulation to conduct a series of simulation experiments to compare the performance between the buffered and uniform gossip algorithms. Our results suggest that the buffered gossip algorithm can solve the rendezvous problem faster than the uniform gossip algorithm; however, the relative performance between these two solutions depends on the specific constraints of the problem and the parameters of the buffered gossip algorithm.

Gossip-Based Solutions for Discrete Rendezvous in Populations of Communicating Agents

PubMed Central

Hollander, Christopher D.; Wu, Annie S.

2014-01-01

The objective of the rendezvous problem is to construct a method that enables a population of agents to agree on a spatial (and possibly temporal) meeting location. We introduce the buffered gossip algorithm as a general solution to the rendezvous problem in a discrete domain with direct communication between decentralized agents. We compare the performance of the buffered gossip algorithm against the well known uniform gossip algorithm. We believe that a buffered solution is preferable to an unbuffered solution, such as the uniform gossip algorithm, because the use of a buffer allows an agent to use multiple information sources when determining its desired rendezvous point, and that access to multiple information sources may improve agent decision making by reinforcing or contradicting an initial choice. To show that the buffered gossip algorithm is an actual solution for the rendezvous problem, we construct a theoretical proof of convergence and derive the conditions under which the buffered gossip algorithm is guaranteed to produce a consensus on rendezvous location. We use these results to verify that the uniform gossip algorithm also solves the rendezvous problem. We then use a multi-agent simulation to conduct a series of simulation experiments to compare the performance between the buffered and uniform gossip algorithms. Our results suggest that the buffered gossip algorithm can solve the rendezvous problem faster than the uniform gossip algorithm; however, the relative performance between these two solutions depends on the specific constraints of the problem and the parameters of the buffered gossip algorithm. PMID:25397882

Initial formal toxicity evaluation of APC-2, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate in preparation for a first-in-man clinical trial

NASA Astrophysics Data System (ADS)

Bugaj, Joseph E.; Dorshow, Richard B.

2014-03-01

The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated APC-2, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in preparation. A battery of formal toxicity tests necessary for regulatory clearance to proceed with a clinical trial has been recently completed on this new fluorescent tracer agent. These include single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Blood samples were collected to assess pharmacokinetic parameters including half-life, area under the curve, and clearance. Urine samples were collected to assess distribution. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent APC-2 have resulted in no demonstrable pathological test article concerns.

Dual-contrast agent photon-counting computed tomography of the heart: initial experience.

PubMed

Symons, Rolf; Cork, Tyler E; Lakshmanan, Manu N; Evers, Robert; Davies-Venn, Cynthia; Rice, Kelly A; Thomas, Marvin L; Liu, Chia-Ying; Kappler, Steffen; Ulzheimer, Stefan; Sandfort, Veit; Bluemke, David A; Pourmorteza, Amir

2017-08-01

To determine the feasibility of dual-contrast agent imaging of the heart using photon-counting detector (PCD) computed tomography (CT) to simultaneously assess both first-pass and late enhancement of the myocardium. An occlusion-reperfusion canine model of myocardial infarction was used. Gadolinium-based contrast was injected 10 min prior to PCD CT. Iodinated contrast was infused immediately prior to PCD CT, thus capturing late gadolinium enhancement as well as first-pass iodine enhancement. Gadolinium and iodine maps were calculated using a linear material decomposition technique and compared to single-energy (conventional) images. PCD images were compared to in vivo and ex vivo magnetic resonance imaging (MRI) and histology. For infarct versus remote myocardium, contrast-to-noise ratio (CNR) was maximal on late enhancement gadolinium maps (CNR 9.0 ± 0.8, 6.6 ± 0.7, and 0.4 ± 0.4, p < 0.001 for gadolinium maps, single-energy images, and iodine maps, respectively). For infarct versus blood pool, CNR was maximum for iodine maps (CNR 11.8 ± 1.3, 3.8 ± 1.0, and 1.3 ± 0.4, p < 0.001 for iodine maps, gadolinium maps, and single-energy images, respectively). Combined first-pass iodine and late gadolinium maps allowed quantitative separation of blood pool, scar, and remote myocardium. MRI and histology analysis confirmed accurate PCD CT delineation of scar. Simultaneous multi-contrast agent cardiac imaging is feasible with photon-counting detector CT. These initial proof-of-concept results may provide incentives to develop new k-edge contrast agents, to investigate possible interactions between multiple simultaneously administered contrast agents, and to ultimately bring them to clinical practice.

$1.8 Million and counting: how volatile agent education has decreased our spending $1000 per day.

PubMed

Miller, Scott A; Aschenbrenner, Carol A; Traunero, Justin R; Bauman, Loren A; Lobell, Samuel S; Kelly, Jeffrey S; Reynolds, John E

2016-12-01

Volatile anesthetic agents comprise a substantial portion of every hospital's pharmacy budget. Challenged with an initiative to lower anesthetic drug expenditures, we developed an education-based intervention focused on reducing volatile anesthetic costs while preserving access to all available volatile anesthetics. When postintervention evaluation demonstrated a dramatic year-over-year reduction in volatile agent acquisition costs, we undertook a retrospective analysis of volatile anesthetic purchasing data using time series analysis to determine the impact of our educational initiative. We obtained detailed volatile anesthetic purchasing data from the Central Supply of Wake Forest Baptist Health from 2007 to 2014 and integrated these data with the time course of our educational intervention. Aggregate volatile anesthetic purchasing data were analyzed for 7 consecutive fiscal years. The educational initiative emphasized tissue partition coefficients of volatile anesthetics in adipose tissue and muscle and their impact on case management. We used an interrupted time series analysis of monthly cost per unit data using autoregressive integrated moving average modeling, with the monthly cost per unit being the amount spent per bottle of anesthetic agent per month. The cost per unit decreased significantly after the intervention (t=-6.73, P<.001). The autoregressive integrated moving average model predicted that the average cost per unit decreased $48 after the intervention, with 95% confidence interval of $34 to $62. As evident from the data, the purchasing of desflurane and sevoflurane decreased, whereas that of isoflurane increased. An educational initiative focused solely on the selection of volatile anesthetic agent per case significantly reduced volatile anesthetic expense at a tertiary medical center. This approach appears promising for application in other hospitals in the rapidly evolving, value-added health care environment. We were able to accomplish this with instruction on tissue partition coefficients and each agent's individual cost per MAC-hour delivered. Copyright © 2016 Elsevier Inc. All rights reserved.

Disseminated histoplasmosis in an African pygmy hedgehog.

PubMed

Snider, Timothy A; Joyner, Priscilla H; Clinkenbeard, Kenneth D

2008-01-01

A 2-year-old captive-bred sexually intact female African pygmy hedgehog (Atelerix albiventris) was evaluated because of vague signs of illness including inappetence, weakness, lethargy, and weight loss over a 20-day period. Abnormalities detected via initial clinicopathologic analyses included anemia, thrombocytopenia, leukopenia, hypoproteinemia, and hypoglycemia. Results of a fecal flotation test were negative. Three weeks after the initial evaluation, splenomegaly was detected via palpation and ultrasonography. The hedgehog was treated with broad-spectrum antibacterial agents, resulting in an initially favorable response. Fenbendazole was also administered against possible occult parasitic infestation. After 3 weeks of illness, the hedgehog's condition had worsened and supportive care and administration of additional antibacterial agents were instituted. The hedgehog died, and pathologic examinations revealed severe splenomegaly; granulomatous infiltrates were evident in multiple organs, and Histoplasma capsulatum yeasts were detected intralesionally. Histoplasmosis can develop in a wide range of mammalian species. African pygmy hedgehogs are becoming increasingly popular as exotic pets, and vague signs of illness and splenomegaly are often attributed to hemolymphatic malignancies, which are somewhat common in this species. Practitioners should be aware that similar clinical signs may be associated with histoplasmosis in these animals. Although the hedgehog of this report was confined indoors, it originated from an area where histoplasmosis was endemic; this indicates that the disease should be included as a differential diagnosis for hedgehogs that develop vague signs of illness and are known to originate from such geographic regions.

Method of making low work function component

DOEpatents

Robinson, Vance [Niskayuna, NY; Weaver, Stanton Earl [Northville, NY; Michael, Joseph Darryl [Delmar, NY

2011-11-15

A method for fabricating a component is disclosed. The method includes: providing a member having an effective work function of an initial value, disposing a sacrificial layer on a surface of the member, disposing a first agent within the member to obtain a predetermined concentration of the agent at said surface of the member, annealing the member, and removing the sacrificial layer to expose said surface of the member, wherein said surface has a post-process effective work function that is different from the initial value.

Effects of asphalt cement rejuvenating agents : final report.

DOT National Transportation Integrated Search

1980-08-01

Louisiana's initial work in the recycling of asphaltic concrete pavements has demonstrated the need to obtain a base of knowledge in the area of rejuvenating age-hardened reclaimed asphalt cement. In this report, eight rejuvenating agents are examine...

75 FR 66352 - Glycine From the People's Republic of China: Initiation of Antidumping Anti-circumvention Inquiry

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

... agent, re-absorbable amino acid, chemical intermediate, and a metal complexing agent. Glycine is... and Chiyuen International Trading Ltd., a manufacturer in the PRC of amino acetic acid (i.e., glycine...

Prediction, events, and the advantage of Agents: The processing of semantic roles in visual narrative

PubMed Central

Cohn, Neil; Paczynski, Martin

2013-01-01

Agents consistently appear prior to Patients in sentences, manual signs, and drawings, and Agents are responded to faster when presented in visual depictions of events. We hypothesized that this “Agent advantage” reflects Agents’ role in event structure. We investigated this question by manipulating the depictions of Agents and Patients in preparatory actions in a wordless visual narrative. We found that Agents elicited a greater degree of predictions regarding upcoming events than Patients, that Agents are viewed longer than Patients, independent of serial order, and that visual depictions of actions are processed more quickly following the presentation of an Agent versus a Patient. Taken together these findings support the notion that Agents initiate the building of event representation. We suggest that Agent First orders facilitate the interpretation of events as they unfold and that the saliency of Agents within visual representations of events is driven by anticipation of upcoming events. PMID:23959023

ACOUSTIC CHARACTERIZATION AND PHARAMACOKINETIC ANALYSES OF NEW NANOBUBBLE ULTRASOUND CONTRAST AGENTS

PubMed Central

Wu, Hanping; Rognin, Nicolas G.; Krupka, Tianyi M.; Solorio, Luis; Yoshiara, Hiroki; Guenette, Gilles; Sanders, Christoher; Kamiyama, Naohisa; Exner, Agata A.

2013-01-01

In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rate in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma. PMID:23932272

Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents.

PubMed

Wu, Hanping; Rognin, Nicolas G; Krupka, Tianyi M; Solorio, Luis; Yoshiara, Hiroki; Guenette, Gilles; Sanders, Christopher; Kamiyama, Naohisa; Exner, Agata A

2013-11-01

In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rates in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Amplification of bovine papillomavirus DNA by N-methyl-N'-nitro-N-nitrosoguanidine, ultraviolet irradiation, or infection with herpes simplex virus

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

Schmitt, J.; Schlehofer, J.R.; Mergener, K.

1989-09-01

Treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or irradiation with ultraviolet light (uv254 nm) induces amplification of integrated as well as episomal sequences of bovine papillomavirus (BPV) type 1 DNA in BPV-1-transformed mouse C127 cells (i.e., ID13 cells). This is shown by filter in situ hybridization and Southern blot analysis of cellular DNA. Similarly, infection of ID13 cells with herpes simplex virus (HSV) type 1 which has been shown to be mutagenic for host cell DNA leads to amplification of BPV DNA sequences. In contrast to this induction of DNA amplification by initiators, treatment of ID13 cells with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)more » does not result in increased synthesis of BPV DNA nor does TPA treatment modulate the initiator-induced DNA amplification. Similar to other cell systems infection with adeno-associated virus (AAV) type 2 inhibits BPV-1 DNA amplification irrespective of the inducing agent. In contrast to initiator-induced DNA amplification, treatment with carcinogen (MNNG) or tumor promoters or combination of MNNG and promoter of C127 cells prior to transformation by BPV-1 does not lead to an increase in the number of transformed foci. The induction of amplification of papillomavirus DNA by initiating agents possibly represents one of the mechanisms by which the observed synergism between papillomavirus infection and initiators in tumorigenesis might occur.« less

Cancer Risk-Assessment of Radiation Damage in Ataxia Telangiectasia Heterozygous Human Breast Epithelial Cell Cultures

NASA Technical Reports Server (NTRS)

Applewhite, Lisa C.

2002-01-01

This paper describes the study of the markers of cellular changes that are found during the onset of carcinogenesis. Several of the biological factors are markers of stress response, oncoprotein expression, and differentiation factors. Oxidative stress response agents such as heat shock proteins (HSPs) protect cells from oxidative stresses such as ionizing radiation. The onocoprotein HER-2/neu, a specific breast cancer marker, indicates early onset of cancer. Additional structural and morphogenetic markers of differentiation were considered in order to determine initial cellular changes at the initial onset of cancer. As an additional consideration, all-trans retinoic acid (RA), a differentiation agent, was considered because of its known role in regulating normal differentiation and inhibiting tumor proliferation via specific nuclear receptors. This paper discusses study and results of the preliminary analyses of gamma irradiation of AT heterozygous human breast epithelial cells (WH). Comparisons are also made of the effects various RA concentrations post-irradiation.

Tumor shrinkage and objective response rates: gold standard for oncology efficacy screening trials, or an outdated end point?

PubMed

Bradbury, Penelope; Seymour, Lesley

2009-01-01

Phase II clinical trials have long been used to screen new cancer therapeutics for antitumor activity ("efficacy") worthy of further evaluation. Traditionally, the primary end point used in these screening trials has been objective response rate (RR), with the desired rate being arbitrarily set by the researchers before initiation of the trial. For cytotoxic agents, especially in common tumor types, response has been a reasonably robust and validated surrogate of benefit. Phase II trials with response as an end point have a modest sample size (15-40 patients) and are completed rapidly allowing early decisions regarding future development of a given agent. More recently, a number of new agents have proven successful in pivotal phase III studies, despite a low or very modest RR demonstrated in early clinical trials. Researchers have postulated that these novel agents, as a class, may not induce significant regression of tumors, and that the use of RR as an end point for phase II studies will result in false negative results, and point out that not all available data is used in making the decision. Others have pointed out that even novel agents have proven unsuccessful in pivotal trials if objective responses are not demonstrated in early clinical trials. We review here the historical and current information regarding objective tumor response.

Hippuristanol - A potent steroid inhibitor of eukaryotic initiation factor 4A

PubMed Central

Cencic, Regina; Pelletier, Jerry

2016-01-01

ABSTRACT Protein synthesis and its regulatory signaling pathways play essential roles in the initiation and maintenance of the cancer phenotype. Insight obtained over the last 3 decades on the mechanisms regulating translation in normal and transformed cells have revealed that perturbed control in cancer cells may offer an Achilles' heel for the development of novel anti-neoplastic agents. Several small molecule inhibitors have been identified and characterized that target translation initiation – more specifically, the rate-limiting step where ribosomes are recruited to mRNA templates. Among these, hippuristanol, a polyhydroxysteroid from the gorgonian Isis hippuris has been found to inhibit translation initiation by blocking the activity of eukaryotic initiation factor (eIF) 4A, an essential RNA helicase involved in this process. Herein, we highlight the biological properties of this compound, its potential development as an anti-cancer agent, and its use to validate eIF4A as an anti-neoplastic target. PMID:27335721

Development of Novel Decontamination Techniques for Chemical Agents (GB, VX, HD) Contaminated Facilities. Phase II. Laboratory Evaluation of Novel Agent Decontamination Concepts

DTIC Science & Technology

1985-06-21

mild steel, unpainted mild steel, and porous (i.e., concrete and unglazed porcelain ) test coupons contaminated with agent to a hot-gas composition near...unpainted *’ mild steel, painted stainless steel, concrete, and unglazed porcelain * coupons contaminated with HD, GB, or VX. The detectable limit for the Sub...similar decontamination efficiency was observable in the concrete and unglazed porcelain tests for an initial dose level of 1.8 mg agent/g of material

An Advanced Computational Approach to System of Systems Analysis & Architecting Using Agent-Based Behavioral Model

DTIC Science & Technology

2012-09-30

System N Agent « datatype » SoS Architecture -Receives Capabilities1 -Provides Capabilities1 1 -Provides Capabilities1 1 -Provides Capabilities1 -Updates 1...fitness, or objective function. The structure of the SoS Agent is depicted in Figure 10. SoS Agent Architecture « datatype » Initial SoS...Architecture «subsystem» Fuzzy Inference Engine FAM « datatype » Affordability « datatype » Flexibility « datatype » Performance « datatype » Robustness Input Input

Mu Opioids and Their Receptors: Evolution of a Concept

PubMed Central

Pan, Ying-Xian

2013-01-01

Opiates are among the oldest medications available to manage a number of medical problems. Although pain is the current focus, early use initially focused upon the treatment of dysentery. Opium contains high concentrations of both morphine and codeine, along with thebaine, which is used in the synthesis of a number of semisynthetic opioid analgesics. Thus, it is not surprising that new agents were initially based upon the morphine scaffold. The concept of multiple opioid receptors was first suggested almost 50 years ago (Martin, 1967), opening the possibility of new classes of drugs, but the morphine-like agents have remained the mainstay in the medical management of pain. Termed mu, our understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years. Early pharmacological studies identified three major classes of receptors, helped by the discovery of endogenous opioid peptides and receptor subtypes—primarily through the synthesis of novel agents. These chemical biologic approaches were then eclipsed by the molecular biology revolution, which now reveals a complexity of the morphine-like agents and their receptors that had not been previously appreciated. PMID:24076545

Impact of varying analytical methodologies on grain particle size determination.

PubMed

Kalivoda, J R; Jones, C K; Stark, C R

2017-01-01

The determination of particle size is an important quality control measurement for feed manufacturers, nutritionists, and producers. The current approved method for determining the geometric mean diameter by weight (d) and geometric standard deviation (S) of grains is standard ANSI/ASAE S319.4. This method controls many variables, including the suggested quantity of initial material and the type, number, and size of sieves. However, the method allows for variations in sieving time, sieve agitators, and the use of a dispersion agent. The objective of this experiment was to determine which method of particle size analysis best estimated the particle size of various cereal grain types. Eighteen samples of either corn, sorghum, or wheat were ground and analyzed using different variations of the approved method. Treatments were arranged in a 5 × 3 factorial arrangement with 5 sieving methods: 1) 10-min sieving time with sieve agitators and no dispersion agent, 2) 10-min sieving time with sieve agitators and dispersion agent, 3) 15-min sieving time with no sieve agitators or dispersion agent, 4) 15-min sieving time with sieve agitators and no dispersion agent, and 5) 15-min sieving time with sieve agitators and dispersion agent conducted in 3 grain types (ground corn, sorghum, and wheat) with 4 replicates per treatment. The analytical method that resulted in the lowest d and greatest S was considered desirable because it was presumably representative of increased movement of particles to their appropriate sieve. Analytical method affected d and S ( ≤ 0.05) measured by both standards. Inclusion of sieve agitators and dispersion agent in the sieve stack resulted in the lowest d, regardless of sieving time. Inclusion of dispersion agent reduced d ( ≤ 0.05) by 32 and 36 µm when shaken for 10 and 15 min, respectively, compared to the same sample analyzed without dispersion agent. The addition of the dispersion agent also increased S. The dispersion agent increased the quantity of very fine particles collected in the pan; therefore, S was significantly greater ( ≤ 0.05). Corn and sorghum ground using the same mill parameters had similar d ( > 0.05), but wheat ground using the same mill parameters was 120 to 104 µm larger ( ≤ 0.05) than corn and sorghum, respectively. Both sieve agitators and dispersion agent should be included when conducting particle size analysis. The results indicate that 10 and 15 min of sieving time produced similar results.

Time-trends in the prescribing of gastroprotective agents to primary care patients initiating low-dose aspirin or non-steroidal anti-inflammatory drugs: a population-based cohort study

PubMed Central

Warlé-van Herwaarden, Margaretha F; Koffeman, Aafke R; Valkhoff, Vera E; ’t Jong, Geert W; Kramers, Cornelis; Sturkenboom, Miriam C; De Smet, Peter A G M

2015-01-01

Aims Low-dose aspirin (LDA) and non-steroidal-anti-inflammatory drugs (NSAIDs) both increase the risk of upper gastrointestinal events (UGIEs). In the Netherlands, recommendations regarding the prescription of gastroprotective agents (GPAs) in LDA users were first issued in 2009 in the HARM-Wrestling consensus. National guidelines on gastroprotective strategies (GPSs) in NSAID users were issued in the first part of the preceding. The aim of the present study was to examine time-trends in GPSs in patients initiating LDA and those initiating NSAIDs between 2000 and 2012. Methods Within a large electronic primary healthcare database, two cohorts were selected: (i) patients newly prescribed LDA and (ii) patients newly prescribed NSAIDs between 2000 and 2012. Patients who had been prescribed a GPA in the previous six months were excluded. For both cohorts, patients’ risk of a UGIE was classified as low, moderate or high, based on the HARM-Wrestling consensus, and the presence of an adequate GPSwas determined. Results A total of 37 578 patients were included in the LDA cohort and 352 025 patients in the NSAID cohort. In both cohorts, an increase in GPSs was observed over time, but prescription of GPAs was lower in the LDA cohort. By 2012, an adequate GPS was present in 31.8% of high-risk LDA initiators, vs. 48.0% of high-risk NSAID initiators. Conclusions Despite a comparable risk of UGIEs, GPSs are prescribed less in high-risk LDA initiators than in high-risk NSAID initiators. For both groups of patients, there is still room for improvement in guideline adherence. PMID:25777983

Initiator and Photocatalyst-Free Visible Light Induced One-Pot Reaction: Concurrent RAFT Polymerization and CuAAC Click Reaction.

PubMed

Wang, Jie; Wang, Xinbo; Xue, Wentao; Chen, Gaojian; Zhang, Weidong; Zhu, Xiulin

2016-05-01

A new, visible light-catalyzed, one-pot and one-step reaction is successfully employed to design well-controlled side-chain functionalized polymers, by the combination of ambient temperature revisible addtion-fragmentation chain transfer (RAFT) polymerization and click chemistry. Polymerizations are well controlled in a living way under the irradiation of visible light-emitting diode (LED) light without photocatalyst and initiator, using the trithiocarbonate agent as iniferter (initiator-transfer agent-terminator) agent at ambient temperature. Fourier transfer infrared spectroscopy (FT-IR), NMR, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) data confirm the successful one-pot reaction. Compared to the reported zero-valent metal-catalyzed one-pot reaction, the polymerization rate is much faster than that of the click reaction, and the visible light-catalyzed one-pot reaction can be freely and easily regulated by turning on and off the light. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reduction of serum TARC levels in atopic dermatitis by topical anti-inflammatory treatments.

PubMed

Yasukochi, Yumi; Nakahara, Takeshi; Abe, Takeru; Kido-Nakahara, Makiko; Kohda, Futoshi; Takeuchi, Satoshi; Hagihara, Akihito; Furue, Masutaka

2014-09-01

Serum thymus and activation-regulated chemokine (TARC) levels are associated with the disease activity of patients with atopic dermatitis (AD) and sensitively reflect short-term changes in skin conditions. The main treatment for AD is topical agent application. This study investigated the relationship between serum TARC levels and the dosage of topical agents, including corticosteroids and/or tacrolimus, in patients with AD. The serum TARC levels of 56 AD patients and the amounts of topical agents prescribed to them were investigated retrospectively. The weekly reduction in serum TARC levels and weekly dosage of topical agents among AD patients were compared and their associations were evaluated. The dosage of topical agents was closely related to serum TARC levels. One gram of strong rank steroid or the equivalent amount of steroid/tacrolimus is required to reduce serum TARC levels by 9.94 pg/mL weekly in moderate to severe AD patients. Higher initial TARC levels require more topical agent, which results in a more rapid decrease in TARC levels. The serum TARC levels and eosinophil numbers in peripheral blood are significantly correlated. Serum TARC level improvement and topical agent dosage are strongly correlated. TARC and eosinophil numbers are significantly correlated, but the wider range of TARC levels seems to be clinically more useful for monitoring AD severity. The serum TARC level is a very sensitive biomarker for monitoring the severity and treatment response in AD.

How watching Pinocchio movies changes our subjective experience of extrapersonal space.

PubMed

Fini, Chiara; Committeri, Giorgia; Müller, Barbara C N; Deschrijver, Eliane; Brass, Marcel

2015-01-01

The way we experience the space around us is highly subjective. It has been shown that motion potentialities that are intrinsic to our body influence our space categorization. Furthermore, we have recently demonstrated that in the extrapersonal space, our categorization also depends on the movement potential of other agents. When we have to categorize the space as "Near" or "Far" between a reference and a target, the space categorized as "Near" is wider if the reference corresponds to a biological agent that has the potential to walk, instead of a biological and non-biological agent that cannot walk. But what exactly drives this "Near space extension"? In the present paper, we tested whether abstract beliefs about the biological nature of an agent determine how we categorize the space between the agent and an object. Participants were asked to first read a Pinocchio story and watch a correspondent video in which Pinocchio acts like a real human, in order to become more transported into the initial story. Then they had to categorize the location ("Near" or "Far") of a target object located at progressively increasing or decreasing distances from a non-biological agent (i.e., a wooden dummy) and from a biological agent (i.e., a human-like avatar). The results indicate that being transported into the Pinocchio story, induces an equal "Near" space threshold with both the avatar and the wooden dummy as reference frames.

Initiation of pharmacotherapy for post-traumatic stress disorder among veterans from Iraq and Afghanistan: a dimensional, symptom cluster approach

PubMed Central

Rosenheck, Robert; Mohamed, Somaia; Pietrzak, Robert; Hoff, Rani

2016-01-01

Background The pharmacological treatment of post-traumatic stress disorder (PTSD) is extremely challenging, as no specific agent has been developed exclusively to treat this disorder. Thus, there are growing concerns among the public, providers and consumers associated with its use as the efficacy of some agents is still in question. Aims We applied a dimensional and symptom cluster-based approach to better understand how the heterogeneous phenotypic presentation of PTSD may relate to the initiation of pharmacotherapy for PTSD initial episode. Method US veterans who served in the conflicts in Iraq and Afghanistan and received an initial PTSD diagnosis at the US Veterans Health Administration between 2008 and 2011 were included in this study. Veterans were followed for 365 days from initial PTSD diagnosis to identify initiation for antidepressants, anxiolytics/sedatives/hypnotics, antipsychotics and prazosin. Multivariable analyses were used to assess the relationship between the severity of unique PTSD symptom clusters and receiving prescriptions from each medication class, as well as the time from diagnosis to first prescription. Results Increased severity of emotional numbing symptoms was independently associated with the prescription of antidepressants, and they were prescribed after a substantially shorter period of time than other medications. Anxiolytics/sedatives/hypnotics prescription was associated with heightened re-experiencing symptoms and sleep difficulties. Antipsychotics were associated with elevated re-experiencing and numbing symptoms and prazosin with reported nightmares. Conclusions Prescribing practices for military-related PTSD appear to follow US VA/DoD clinical guidelines. Results of this study suggest that a novel dimensional and symptom cluster-based approach to classifying the phenotypic presentation of military-related PTSD symptoms may help inform prescribing patterns for PTSD. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:27703791

Personalizing initial therapy in acute myeloid leukemia: incorporating novel agents into clinical practice

PubMed Central

DeStefano, Christin B.; Hourigan, Christopher S.

2018-01-01

While the past decade has seen a revolution in understanding of the genetic and molecular etiology of the disease, in clinical practice, initial therapy for acute myeloid leukemia (AML) patients has been a relatively straightforward choice between intensive combination cytotoxic induction therapy as used for decades or less-intensive hypomethylating therapy. The year 2017, however, witnessed US Food and Drug Administration approvals of midostaurin, enasidenib, gemtuzumab ozogamicin and CPX-351 for AML patients, with many other promising agents currently in clinical trials. This review discusses these options, highlights unanswered questions regarding optimal combinations and proposes some suggested approaches for the personalization of initial therapy for AML patients. PMID:29713444

Production of morphology-controllable porous hyaluronic acid particles using a spray-drying method.

PubMed

Iskandar, Ferry; Nandiyanto, Asep Bayu Dani; Widiyastuti, W; Young, Lee Sin; Okuyama, Kikuo; Gradon, Leon

2009-05-01

Hyaluronic acid (HA) porous particles with controllable porosity and pore size, ranging from 100 to 300 nm, were successfully prepared using a colloidal templating and spray-drying method. HA powder and polystyrene latex (PSL) particles, which were used as the precursor and templating agent, respectively, were mixed in aqueous solution and spray-dried using a two-fluid nozzle system to produce HA and PSL composite particles. Water was evaporated during spray-drying using heated air with a temperature of 120 degrees C. This simple process was completed within several seconds. The prepared particles were collected and washed with an organic solvent to dissolve the PSL templating agent. The porosity and pore size of the resulting particles were easily controlled by changing the initial mass ratio of precursor to templating agent, i.e., HA to PSL, and by altering the size of the PSL template particles.

A Protein Aggregation Based Test for Screening of the Agents Affecting Thermostability of Proteins

PubMed Central

Eronina, Tatyana; Borzova, Vera; Maloletkina, Olga; Kleymenov, Sergey; Asryants, Regina; Markossian, Kira; Kurganov, Boris

2011-01-01

To search for agents affecting thermal stability of proteins, a test based on the registration of protein aggregation in the regime of heating with a constant rate was used. The initial parts of the dependences of the light scattering intensity (I) on temperature (T) were analyzed using the following empiric equation: I = K agg(T−T 0)2, where K agg is the parameter characterizing the initial rate of aggregation and T 0 is a temperature at which the initial increase in the light scattering intensity is registered. The aggregation data are interpreted in the frame of the model assuming the formation of the start aggregates at the initial stages of the aggregation process. Parameter T 0 corresponds to the moment of the origination of the start aggregates. The applicability of the proposed approach was demonstrated on the examples of thermal aggregation of glycogen phosphorylase b from rabbit skeletal muscles and bovine liver glutamate dehydrogenase studied in the presence of agents of different chemical nature. The elaborated approach to the study of protein aggregation may be used for rapid identification of small molecules that interact with protein targets. PMID:21760963

Definition of an Ontology Matching Algorithm for Context Integration in Smart Cities

PubMed Central

Otero-Cerdeira, Lorena; Rodríguez-Martínez, Francisco J.; Gómez-Rodríguez, Alma

2014-01-01

In this paper we describe a novel proposal in the field of smart cities: using an ontology matching algorithm to guarantee the automatic information exchange between the agents and the smart city. A smart city is composed by different types of agents that behave as producers and/or consumers of the information in the smart city. In our proposal, the data from the context is obtained by sensor and device agents while users interact with the smart city by means of user or system agents. The knowledge of each agent, as well as the smart city's knowledge, is semantically represented using different ontologies. To have an open city, that is fully accessible to any agent and therefore to provide enhanced services to the users, there is the need to ensure a seamless communication between agents and the city, regardless of their inner knowledge representations, i.e., ontologies. To meet this goal we use ontology matching techniques, specifically we have defined a new ontology matching algorithm called OntoPhil to be deployed within a smart city, which has never been done before. OntoPhil was tested on the benchmarks provided by the well known evaluation initiative, Ontology Alignment Evaluation Initiative, and also compared to other matching algorithms, although these algorithms were not specifically designed for smart cities. Additionally, specific tests involving a smart city's ontology and different types of agents were conducted to validate the usefulness of OntoPhil in the smart city environment. PMID:25494353

Definition of an Ontology Matching Algorithm for Context Integration in Smart Cities.

PubMed

Otero-Cerdeira, Lorena; Rodríguez-Martínez, Francisco J; Gómez-Rodríguez, Alma

2014-12-08

In this paper we describe a novel proposal in the field of smart cities: using an ontology matching algorithm to guarantee the automatic information exchange between the agents and the smart city. A smart city is composed by different types of agents that behave as producers and/or consumers of the information in the smart city. In our proposal, the data from the context is obtained by sensor and device agents while users interact with the smart city by means of user or system agents. The knowledge of each agent, as well as the smart city's knowledge, is semantically represented using different ontologies. To have an open city, that is fully accessible to any agent and therefore to provide enhanced services to the users, there is the need to ensure a seamless communication between agents and the city, regardless of their inner knowledge representations, i.e., ontologies. To meet this goal we use ontology matching techniques, specifically we have defined a new ontology matching algorithm called OntoPhil to be deployed within a smart city, which has never been done before. OntoPhil was tested on the benchmarks provided by the well known evaluation initiative, Ontology Alignment Evaluation Initiative, and also compared to other matching algorithms, although these algorithms were not specifically designed for smart cities. Additionally, specific tests involving a smart city's ontology and different types of agents were conducted to validate the usefulness of OntoPhil in the smart city environment.

Application Transparent HTTP Over a Disruption Tolerant Smartnet

DTIC Science & Technology

2014-09-01

American Standard Code for Information Interchange BP Bundle Protocol BPA bundle protocol agent CLA convergence layer adapters CPU central processing...forwarding them through the plugin pipeline. The initial version of the DTNInput plugin uses the BBN Spindle bundle protocol agent ( BPA ) implementation

A flocking algorithm for multi-agent systems with connectivity preservation under hybrid metric-topological interactions.

PubMed

He, Chenlong; Feng, Zuren; Ren, Zhigang

2018-01-01

In this paper, we propose a connectivity-preserving flocking algorithm for multi-agent systems in which the neighbor set of each agent is determined by the hybrid metric-topological distance so that the interaction topology can be represented as the range-limited Delaunay graph, which combines the properties of the commonly used disk graph and Delaunay graph. As a result, the proposed flocking algorithm has the following advantages over the existing ones. First, range-limited Delaunay graph is sparser than the disk graph so that the information exchange among agents is reduced significantly. Second, some links irrelevant to the connectivity can be dynamically deleted during the evolution of the system. Thus, the proposed flocking algorithm is more flexible than existing algorithms, where links are not allowed to be disconnected once they are created. Finally, the multi-agent system spontaneously generates a regular quasi-lattice formation without imposing the constraint on the ratio of the sensing range of the agent to the desired distance between two adjacent agents. With the interaction topology induced by the hybrid distance, the proposed flocking algorithm can still be implemented in a distributed manner. We prove that the proposed flocking algorithm can steer the multi-agent system to a stable flocking motion, provided the initial interaction topology of multi-agent systems is connected and the hysteresis in link addition is smaller than a derived upper bound. The correctness and effectiveness of the proposed algorithm are verified by extensive numerical simulations, where the flocking algorithms based on the disk and Delaunay graph are compared.

A flocking algorithm for multi-agent systems with connectivity preservation under hybrid metric-topological interactions

PubMed Central

Feng, Zuren; Ren, Zhigang

2018-01-01

In this paper, we propose a connectivity-preserving flocking algorithm for multi-agent systems in which the neighbor set of each agent is determined by the hybrid metric-topological distance so that the interaction topology can be represented as the range-limited Delaunay graph, which combines the properties of the commonly used disk graph and Delaunay graph. As a result, the proposed flocking algorithm has the following advantages over the existing ones. First, range-limited Delaunay graph is sparser than the disk graph so that the information exchange among agents is reduced significantly. Second, some links irrelevant to the connectivity can be dynamically deleted during the evolution of the system. Thus, the proposed flocking algorithm is more flexible than existing algorithms, where links are not allowed to be disconnected once they are created. Finally, the multi-agent system spontaneously generates a regular quasi-lattice formation without imposing the constraint on the ratio of the sensing range of the agent to the desired distance between two adjacent agents. With the interaction topology induced by the hybrid distance, the proposed flocking algorithm can still be implemented in a distributed manner. We prove that the proposed flocking algorithm can steer the multi-agent system to a stable flocking motion, provided the initial interaction topology of multi-agent systems is connected and the hysteresis in link addition is smaller than a derived upper bound. The correctness and effectiveness of the proposed algorithm are verified by extensive numerical simulations, where the flocking algorithms based on the disk and Delaunay graph are compared. PMID:29462217

Prediction, events, and the advantage of agents: the processing of semantic roles in visual narrative.

PubMed

Cohn, Neil; Paczynski, Martin

2013-11-01

Agents consistently appear prior to Patients in sentences, manual signs, and drawings, and Agents are responded to faster when presented in visual depictions of events. We hypothesized that this "Agent advantage" reflects Agents' role in event structure. We investigated this question by manipulating the depictions of Agents and Patients in preparatory actions in wordless visual narratives. We found that Agents elicited a greater degree of predictions regarding upcoming events than Patients, that Agents are viewed longer than Patients, independent of serial order, and that visual depictions of actions are processed more quickly following the presentation of an Agent vs. a Patient. Taken together these findings support the notion that Agents initiate the building of event representation. We suggest that Agent First orders facilitate the interpretation of events as they unfold and that the saliency of Agents within visual representations of events is driven by anticipation of upcoming events. Copyright © 2013 Elsevier Inc. All rights reserved.

Soman increases neuronal COX-2 levels: possible link between seizures and protracted neuronal damage.

PubMed

Angoa-Pérez, Mariana; Kreipke, Christian W; Thomas, David M; Van Shura, Kerry E; Lyman, Megan; McDonough, John H; Kuhn, Donald M

2010-12-01

Nerve agent-induced seizures cause neuronal damage in brain limbic and cortical circuits leading to persistent behavioral and cognitive deficits. Without aggressive anticholinergic and benzodiazepine therapy, seizures can be prolonged and neuronal damage progresses for extended periods of time. The objective of this study was to determine the effects of the nerve agent soman on expression of cyclooxygenase-2 (COX-2), the initial enzyme in the biosynthetic pathway of the proinflammatory prostaglandins and a factor that has been implicated in seizure initiation and propagation. Rats were exposed to a toxic dose of soman and scored behaviorally for seizure intensity. Expression of COX-2 was determined throughout brain from 4h to 7 days after exposure by immunohistochemistry and immunoblotting. Microglial activation and astrogliosis were assessed microscopically over the same time-course. Soman increased COX-2 expression in brain regions known to be damaged by nerve agents (e.g., hippocampus, amygdala, piriform cortex and thalamus). COX-2 expression was induced in neurons, and not in microglia or astrocytes, and remained elevated through 7 days. The magnitude of COX-2 induction was correlated with seizure intensity. COX-1 expression was not changed by soman. Increased expression of neuronal COX-2 by soman is a late-developing response relative to other signs of acute physiological distress caused by nerve agents. COX-2-mediated production of prostaglandins is a consequence of the seizure-induced neuronal damage, even after survival of the initial cholinergic crisis is assured. COX-2 inhibitors should be considered as adjunct therapy in nerve agent poisoning to minimize nerve agent-induced seizure activity. Published by Elsevier B.V.

Stable target opinion through power-law bias in information exchange

NASA Astrophysics Data System (ADS)

Datta, Amitava

2018-04-01

We study a model of binary decision making when a certain population of agents is initially seeded with two different opinions, "+" and "-," with fractions p1 and p2, respectively, p1+p2=1 . Individuals can reverse their initial opinion only once based on this information exchange. We study this model on a completely connected network, where any pair of agents can exchange information, and a two-dimensional square lattice with periodic boundary conditions, where information exchange is possible only between the nearest neighbors. We propose a model in which each agent maintains two counters of opposite opinions and accepts opinions of other agents with a power-law bias until a threshold is reached, when they fix their final opinion. Our model is inspired by the study of negativity bias and positive-negative asymmetry, which has been known in the psychology literature for a long time. Our model can achieve a stable intermediate mix of positive and negative opinions in a population. In particular, we show that it is possible to achieve close to any fraction p3, 0 ≤p3≤1 , of "-" opinion starting from an initial fraction p1 of "-" opinion by applying a bias through adjusting the power-law exponent of p3.

Stable target opinion through power-law bias in information exchange.

PubMed

Datta, Amitava

2018-04-01

We study a model of binary decision making when a certain population of agents is initially seeded with two different opinions, "+" and "-," with fractions p_{1} and p_{2}, respectively, p_{1}+p_{2}=1. Individuals can reverse their initial opinion only once based on this information exchange. We study this model on a completely connected network, where any pair of agents can exchange information, and a two-dimensional square lattice with periodic boundary conditions, where information exchange is possible only between the nearest neighbors. We propose a model in which each agent maintains two counters of opposite opinions and accepts opinions of other agents with a power-law bias until a threshold is reached, when they fix their final opinion. Our model is inspired by the study of negativity bias and positive-negative asymmetry, which has been known in the psychology literature for a long time. Our model can achieve a stable intermediate mix of positive and negative opinions in a population. In particular, we show that it is possible to achieve close to any fraction p_{3}, 0≤p_{3}≤1, of "-" opinion starting from an initial fraction p_{1} of "-" opinion by applying a bias through adjusting the power-law exponent of p_{3}.

A case report of tinea pedis caused by Trichosporon faecale in Iran

PubMed Central

Fallahi, Ali akbar; Moazeni, Maryam; Noorbakhsh, Fatemeh; Kordbacheh, Parivash; Zaini, Farideh; Mirhendi, Hossein; Zeraati, Hojjat; Rezaie, Sassan

2012-01-01

Trichosporon species are known as the causative agents of cutaneous infections and are involved in systemic, localized, as well as disseminated mycoses particularly in immunocompromised patients. Here we report a case of tinea pedis infection caused by Trichosporon faecale in a healthy 29-year-old woman in the north of Iran. Macroscopic and microscopic characteristics using direct examination as well as culture method revealed the causative agent as Trichosporon species. Molecular analysis of the internal transcribed spacer region validated the initial result and indicated that this case of tinea pedis was caused by T. faecale. The patient was recovered after treatment with topical myconazole accompanied with oral fluconazole. PMID:24371737

Bipartite consensus for multi-agent systems with antagonistic interactions and communication delays

NASA Astrophysics Data System (ADS)

Guo, Xing; Lu, Jianquan; Alsaedi, Ahmed; Alsaadi, Fuad E.

2018-04-01

This paper studies the consensus problems over signed digraphs with arbitrary finite communication delays. For the considered system, the information flow is directed and only locally delayed information can be used for each node. We derive that bipartite consensus of this system can be realized when the associated signed digraph is strongly connected. Furthermore, for structurally balanced networks, this paper studies the pinning partite consensus for the considered system. we design a pinning scheme to pin any one agent in the signed network, and obtain that the network achieves pinning bipartite consensus with any initial conditions. Finally, two examples are provided to demonstrate the effectiveness of our main results.

A high resolution agent-based model to support walk-bicycle infrastructure investment decisions: A case study with New York City

DOE PAGES

Aziz, H. M. Abdul; Park, Byung H.; Morton, April M.; ...

2017-11-24

Active transportation modes--walk and bicycle--are central for low carbon transport, healthy living, and complete streets initiative. Building a community with amenable walk and bicycle facilities asks for smart planning and investments. It is critical to investigate the impact of infrastructure building or expansion on the overall walk and bicycle mode usage prior to making investment choices utilizing public tax money. This research developed an agent-based model to support investment decisions that allows to assess the impact of changes in walk-bike infrastructures at a high spatial resolution (e.g., block group level). The agent-based model (ABM) utilizes data from a synthetic populationmore » simulator generating agents with corresponding socio-demographic characteristics, and integrates facility attributes regarding walking and bicycling (e.g., sidewalk width, bike lane length) into the mode choice decision making process. Moreover, the ABM accounts for the effect of social interactions among agents who live and work at the same geographic locations. Finally, GIS-based maps are developed at block group resolution that allows exploring the effect of walk-bike infrastructure related investments. The results from New York City case study indicate that infrastructure investments such as widening sidewalk and increasing bike lane network can positively influence the active transportation mode choices. In addition, the level of impact varies with geographic locations--different boroughs of New York City will have different impacts. Lastly, social promotions resulting in higher social interaction among agents can reinforce the impacts of infrastructure changes.« less

A high resolution agent-based model to support walk-bicycle infrastructure investment decisions: A case study with New York City

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

Aziz, H. M. Abdul; Park, Byung H.; Morton, April M.

Active transportation modes--walk and bicycle--are central for low carbon transport, healthy living, and complete streets initiative. Building a community with amenable walk and bicycle facilities asks for smart planning and investments. It is critical to investigate the impact of infrastructure building or expansion on the overall walk and bicycle mode usage prior to making investment choices utilizing public tax money. This research developed an agent-based model to support investment decisions that allows to assess the impact of changes in walk-bike infrastructures at a high spatial resolution (e.g., block group level). The agent-based model (ABM) utilizes data from a synthetic populationmore » simulator generating agents with corresponding socio-demographic characteristics, and integrates facility attributes regarding walking and bicycling (e.g., sidewalk width, bike lane length) into the mode choice decision making process. Moreover, the ABM accounts for the effect of social interactions among agents who live and work at the same geographic locations. Finally, GIS-based maps are developed at block group resolution that allows exploring the effect of walk-bike infrastructure related investments. The results from New York City case study indicate that infrastructure investments such as widening sidewalk and increasing bike lane network can positively influence the active transportation mode choices. In addition, the level of impact varies with geographic locations--different boroughs of New York City will have different impacts. Lastly, social promotions resulting in higher social interaction among agents can reinforce the impacts of infrastructure changes.« less

Effective Coordination of Multiple Intelligent Agents for Command and Control

DTIC Science & Technology

2003-09-01

System Architecture As an initial problem domain in E - commerce , we chose collective book purchasing. In the university setting, relatively large numbers... a coalition server, an auctioneer agent, a set of supplier agents, and a web- based interface 9 for end users. The system is based on a simple...buyers are able to request and sellers to respond to a list of items, within a particular category. Sellers present

Pathogenesis of achalasia cardia.

PubMed

Ghoshal, Uday C; Daschakraborty, Sunil B; Singh, Renu

2012-06-28

Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down's syndrome and Parkinson's disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus.

Pathogenesis of achalasia cardia

PubMed Central

Ghoshal, Uday C; Daschakraborty, Sunil B; Singh, Renu

2012-01-01

Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down’s syndrome and Parkinson’s disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus. PMID:22791940

Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents

PubMed Central

Sullivan, Jack M.; Yau, Edwin H.; Kolniak, Tiffany A.; Sheflin, Lowell G.; Taggart, R. Thomas; Abdelmaksoud, Heba E.

2011-01-01

Post-transcriptional gene silencing (PTGS) agents such as ribozymes, RNAi and antisense have substantial potential for gene therapy of human retinal degenerations. These technologies are used to knockdown a specific target RNA and its cognate protein. The disease target mRNA may be a mutant mRNA causing an autosomal dominant retinal degeneration or a normal mRNA that is overexpressed in certain diseases. All PTGS technologies depend upon the initial critical annealing event of the PTGS ligand to the target RNA. This event requires that the PTGS agent is in a conformational state able to support hybridization and that the target have a large and accessible single-stranded platform to allow rapid annealing, although such platforms are rare. We address the biocomplexity that currently limits PTGS therapeutic development with particular emphasis on biophysical variables that influence cellular performance. We address the different strategies that can be used for development of PTGS agents intended for therapeutic translation. These issues apply generally to the development of PTGS agents for retinal, ocular, or systemic diseases. This review should assist the interested reader to rapidly appreciate critical variables in PTGS development and facilitate initial design and testing of such agents against new targets of clinical interest. PMID:21785698

Chemoprevention of esophageal squamous cell carcinoma

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

Stoner, Gary D.; Wang Lishu; Chen Tong

2007-11-01

Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, andmore » to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.« less

Comparative Safety of Antidepressant Agents for Children and Adolescents Regarding Suicidal Acts

PubMed Central

Schneeweiss, Sebastian; Patrick, Amanda R.; Solomon, Daniel H.; Dormuth, Colin R.; Miller, Matt; Mehta, Jyotsna; Lee, Jennifer C.; Wang, Philip S.

2010-01-01

OBJECTIVE The objective of this study was to assess the risk of suicide attempts and suicides after initiation of antidepressant medication use by children and adolescents, for individual agents. METHODS We conducted a 9-year cohort study by using population-wide data from British Columbia. We identified new users of antidepressants who were 10 to 18 years of age with a recorded diagnosis of depression. Study outcomes were hospitalization attributable to intentional self-harm and suicide death. RESULTS Of 20 906 children who initiated antidepressant therapy, 16 774 (80%) had no previous antidepressant use. During the first year of use, we observed 266 attempted and 3 completed suicides, which yielded an event rate of 27.04 suicidal acts per 1000 person-years (95% confidence interval [CI]: 23.9–30.5 suicidal acts per 1000 person-years). There were no meaningful differences in the rate ratios (RRs) comparing fluoxetine with citalopram (RR: 0.97 [95% CI: 0.54–1.76]), fluvoxamine (RR: 1.05 [95% CI: 0.46–2.43]), paroxetine (RR: 0.80 [95% CI: 0.47–1.37]), and sertraline (RR: 1.02 [95% CI: 0.56–1.84]). Tricyclic agents showed risks similar to those of selective serotonin reuptake inhibitors (RR: 0.92 [95% CI: 0.43–2.00]). CONCLUSION Our finding of equal event rates among antidepressant agents supports the decision of the Food and Drug Administration to include all antidepressants in the black box warning regarding potentially increased suicidality risk for children and adolescents beginning use of antidepressants. PMID:20385637

The multi-criteria optimization for the formation of the multiple-valued logic model of a robotic agent

NASA Astrophysics Data System (ADS)

Bykovsky, A. Yu; Sherbakov, A. A.

2016-08-01

The C-valued Allen-Givone algebra is the attractive tool for modeling of a robotic agent, but it requires the consensus method of minimization for the simplification of logic expressions. This procedure substitutes some undefined states of the function for the maximal truth value, thus extending the initially given truth table. This further creates the problem of different formal representations for the same initially given function. The multi-criteria optimization is proposed for the deliberate choice of undefined states and model formation.

Absorbent Analysis of Anniston Chemical Agent Disposal Facility Munition Demilitarization Building (MDB) Banks 1 and 2 Filter Samples Following Completion of The GB Agent and VX Rocket Campaigns

DTIC Science & Technology

2013-01-01

adsorbed on wet carbon (13 wt% water ). Left to right: initial and t = 6, 13, and 16 days ..............................3 2. 31 P MAS NMR spectra...obtained for 10 wt% VX adsorbed on wet carbon (13 wt% water ) Left to right: initial and t = 24 days ...............................................4...of feed air. Each Class A Type II filter contained approximately 48.2 lb of granular, activated, coconut shell-based carbon. A given filter bank

Formal Consistency Verification of Deliberative Agents with Respect to Communication Protocols

NASA Technical Reports Server (NTRS)

Ramirez, Jaime; deAntonio, Angelica

2004-01-01

The aim of this paper is to show a method that is able to detect inconsistencies in the reasoning carried out by a deliberative agent. The agent is supposed to be provided with a hybrid Knowledge Base expressed in a language called CCR-2, based on production rules and hierarchies of frames, which permits the representation of non-monotonic reasoning, uncertain reasoning and arithmetic constraints in the rules. The method can give a specification of the scenarios in which the agent would deduce an inconsistency. We define a scenario to be a description of the initial agent s state (in the agent life cycle), a deductive tree of rule firings, and a partially ordered set of messages and/or stimuli that the agent must receive from other agents and/or the environment. Moreover, the method will make sure that the scenarios will be valid w.r.t. the communication protocols in which the agent is involved.

Design for interaction between humans and intelligent systems during real-time fault management

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Schreckenghost, Debra L.; Thronesbery, Carroll G.

1992-01-01

Initial results are reported to provide guidance and assistance for designers of intelligent systems and their human interfaces. The objective is to achieve more effective human-computer interaction (HCI) for real time fault management support systems. Studies of the development of intelligent fault management systems within NASA have resulted in a new perspective of the user. If the user is viewed as one of the subsystems in a heterogeneous, distributed system, system design becomes the design of a flexible architecture for accomplishing system tasks with both human and computer agents. HCI requirements and design should be distinguished from user interface (displays and controls) requirements and design. Effective HCI design for multi-agent systems requires explicit identification of activities and information that support coordination and communication between agents. The effects are characterized of HCI design on overall system design and approaches are identified to addressing HCI requirements in system design. The results include definition of (1) guidance based on information level requirements analysis of HCI, (2) high level requirements for a design methodology that integrates the HCI perspective into system design, and (3) requirements for embedding HCI design tools into intelligent system development environments.

A Diversity Research Initiative: How Diverse Undergraduate Students Become Researchers, Change Agents, and Members of a Research Community.

ERIC Educational Resources Information Center

Kingston-Mann, Esther, Ed.

This report presents information on the University of Massachusetts Boston's Diversity Research Initiative (DRI). Section 1, "Essays by Participant Observers," includes "Building a Diversity Research Initiative: An Introduction" (Esther Kingston-Mann); "Diversity Imperative: Reflections on the Diversity Research…

Optimization of food waste hydrolysis in leach bed coupled with methanogenic reactor: effect of pH and bulking agent.

PubMed

Xu, Su Yun; Lam, Hoi Pui; Karthikeyan, O Parthiba; Wong, Jonathan W C

2011-02-01

The effects of pH and bulking agents on hydrolysis/acidogenesis of food waste were studied using leach bed reactor (LBR) coupled with methanogenic up-flow anaerobic sludge blanket (UASB) reactor. The hydrolysis rate under regulated pH (6.0) was studied and compared with unregulated one during initial experiment. Then, the efficacies of five different bulking agents, i.e. plastic full particles, plastic hollow sphere, bottom ash, wood chip and saw dust were experimented under the regulated pH condition. Leachate recirculation with 50% water replacement was practiced throughout the experiment. Results proved that the daily leachate recirculation with pH control (6.0) accelerated the hydrolysis rate (59% higher volatile fatty acids) and methane production (up to 88%) compared to that of control without pH control. Furthermore, bottom ash improved the reactor alkalinity, which internally buffered the system that improved the methane production rate (0.182 l CH(4)/g VS(added)) than other bulking agents. Copyright © 2010 Elsevier Ltd. All rights reserved.

Hybrid neural intelligent system to predict business failure in small-to-medium-size enterprises.

PubMed

Borrajo, M Lourdes; Baruque, Bruno; Corchado, Emilio; Bajo, Javier; Corchado, Juan M

2011-08-01

During the last years there has been a growing need of developing innovative tools that can help small to medium sized enterprises to predict business failure as well as financial crisis. In this study we present a novel hybrid intelligent system aimed at monitoring the modus operandi of the companies and predicting possible failures. This system is implemented by means of a neural-based multi-agent system that models the different actors of the companies as agents. The core of the multi-agent system is a type of agent that incorporates a case-based reasoning system and automates the business control process and failure prediction. The stages of the case-based reasoning system are implemented by means of web services: the retrieval stage uses an innovative weighted voting summarization of self-organizing maps ensembles-based method and the reuse stage is implemented by means of a radial basis function neural network. An initial prototype was developed and the results obtained related to small and medium enterprises in a real scenario are presented.

Learning to select useful landmarks.

PubMed

Greiner, R; Isukapalli, R

1996-01-01

To navigate effectively, an autonomous agent must be able to quickly and accurately determine its current location. Given an initial estimate of its position (perhaps based on dead-reckoning) and an image taken of a known environment, our agent first attempts to locate a set of landmarks (real-world objects at known locations), then uses their angular separation to obtain an improved estimate of its current position. Unfortunately, some landmarks may not be visible, or worse, may be confused with other landmarks, resulting in both time wasted in searching for the undetected landmarks, and in further errors in the agent's estimate of its position. To address these problems, we propose a method that uses previous experiences to learn a selection function that, given the set of landmarks that might be visible, returns the subset that can be used to reliably provide an accurate registration of the agent's position. We use statistical techniques to prove that the learned selection function is, with high probability, effectively at a local optimum in the space of such functions. This paper also presents empirical evidence, using real-world data, that demonstrate the effectiveness of our approach.

DYNACLIPS (DYNAmic CLIPS): A dynamic knowledge exchange tool for intelligent agents

NASA Technical Reports Server (NTRS)

Cengeloglu, Yilmaz; Khajenoori, Soheil; Linton, Darrell

1994-01-01

In a dynamic environment, intelligent agents must be responsive to unanticipated conditions. When such conditions occur, an intelligent agent may have to stop a previously planned and scheduled course of actions and replan, reschedule, start new activities and initiate a new problem solving process to successfully respond to the new conditions. Problems occur when an intelligent agent does not have enough knowledge to properly respond to the new situation. DYNACLIPS is an implementation of a framework for dynamic knowledge exchange among intelligent agents. Each intelligent agent is a CLIPS shell and runs a separate process under SunOS operating system. Intelligent agents can exchange facts, rules, and CLIPS commands at run time. Knowledge exchange among intelligent agents at run times does not effect execution of either sender and receiver intelligent agent. Intelligent agents can keep the knowledge temporarily or permanently. In other words, knowledge exchange among intelligent agents would allow for a form of learning to be accomplished.

Thermal Destruction Of CB Contaminants Bound On Building ...

EPA Pesticide Factsheets

Symposium Paper An experimental and theoretical program has been initiated by the U.S. EPA to investigate issues of chemical/biological agent destruction in incineration systems when the agent in question is bound on common porous building interior materials. This program includes 3-dimensional computational fluid dynamics modeling with matrix-bound agent destruction kinetics, bench-scale experiments to determine agent destruction kinetics while bound on various matrices, and pilot-scale experiments to scale-up the bench-scale experiments to a more practical scale. Finally, model predictions are made to predict agent destruction and combustion conditions in two full-scale incineration systems that are typical of modern combustor design.

Palonosetron (Aloxi): a second-generation 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting

PubMed Central

2006-01-01

In July 2003, the Food and Drug Administration approved palonosetron hydrochloride injection for the treatment of chemotherapy-induced nausea and vomiting (CINV). The newest agent in the class of 5-HT3 receptor antagonists (5-HT3RAs), palonosetron differs from other agents in its class by its higher receptor-binding affinity and longer half-life. These pharmacological properties have resulted in improved antiemetic activity in clinical trials, particularly in the treatment of delayed CINV following moderate emetogenic chemotherapy. Based on the results of these clinical studies, palonosetron is the only 5-HT3RA approved for delayed CINV. Palonosetron is given as a single 0.25-mg intravenous dose 30 minutes before the initial dose of chemotherapy. Headache and constipation were the most common adverse events reported with palonosetron therapy. PMID:17106506

Efficacy of Yeast' Vacuoles as Antimicrobial Agents to Escherichia coli Bacteremia in Rat.

PubMed

Yoon, Jihee; Cho, Ho-Seong; Park, Chul; Park, Byoung-Yong; Kim, Yang-Hoon; Min, Jiho

2017-01-01

Yeast vacuoles, lysosomes, are cell organelles that have antimicrobial activity against several bacteria in vitro. Lysosomes have a potential application to the treatment of pathogens such as antibiotics in vivo. Therefore, the in vivo efficacy of lysosomes was examined in a rat infection model against pathogenic Escherichia coli with varying susceptibilities to standard antimicrobial agents. Before in vivo testing, the concentration-dependent safety of lysosomes was confirmed by blood test and histopathology of normal rats. The therapeutic efficacy of lysosomes was examined in terms of the survival of E. coli in infected rat blood. The complete blood count and histopathology results were affected by the lysosomes concentration. In addition, the E. coli growth was inhibited by the initial injection of lysosomes. These results support the use of lysosomes as a bacterial inhibitor of an infected rat model.

Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway.

PubMed

Bhui, Kulpreet; Prasad, Sahdeo; George, Jasmine; Shukla, Yogeshwer

2009-09-18

Chemoprevention impels the pursuit for either single targeted or cocktail of multi-targeted agents. Bromelain, potential agent in this regard, is a pharmacologically active compound, present in stems and fruits of pineapple (Ananas cosmosus), endowed with anti-inflammatory, anti-invasive and anti-metastatic properties. Herein, we report the anti tumor-initiating effects of bromelain in 2-stage mouse skin tumorigenesis model. Pre-treatment of bromelain resulted in reduction in cumulative number of tumors (CNT) and average number of tumors per mouse. Preventive effect was also comprehended in terms of reduction in tumor volume up to a tune of approximately 65%. Components of the cell signaling pathways, connecting proteins involved in cell death were targeted. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in Bcl-2. A marked inhibition in cyclooxygenase-2 (Cox-2) expression and inactivation of nuclear factor-kappa B (NF-kappaB) was recorded, as phosphorylation and consequent degradation of I kappa B alpha was blocked by bromelain. Also, bromelain treatment curtailed extracellular signal regulated protein kinase (ERK1/2), p38 mitogen-activated protein kinase (MAPK) and Akt activity. The basis of anti tumor-initiating activity of bromelain was revealed by its time dependent reduction in DNA nick formation and increase in percentage prevention. Thus, modulation of inappropriate cell signaling cascades driven by bromelain is a coherent approach in achieving chemoprevention.

Institutional Researchers as Change Agents

ERIC Educational Resources Information Center

Swing, Randy L.

2009-01-01

The future challenge and opportunity for institutional researchers is to serve as change agents with involvement in initiating, implementing, and evaluating campus work. Institutional researchers are poised to excel at doing so because of the array of technical skills they routinely apply to existing institutional research roles. Their work…

[Results of a regional survey on the treatment of rhizomelic pseudopolyarthritis and temporal arteritis. Apropos of 242 cases treated by various modalities with synthetic antimalarials, corticoids and non-steroidal anti-inflammatory agents].

PubMed

David-Chaussé, J; Dehais, J; Leman, A

1983-01-01

The authors report the results of a retrospective therapeutic survey concerning 176 cases of rhizomelic pseudopolyarthritis (RPP) and 66 cases of temporal arteritis (TA). Of 128 cases of RPP treated initially by synthetic anti-malarials (SAM) and non-steroidal anti-inflammatory agents (NSAI), 66 were followed up until cure which was obtained after a mean of 23 months and 3 subsequently received brief steroid therapy. 45 cases of RPP were treated initially with corticosteroids. They were generally associated with SAM which enabled early weaning of the steroids, towards the 8 th month, or at least reducing the dose. Cure was obtained within 24 months. Three patients were treated by NSAI and gold therapy. After cure, 5 cases of recurrence and 1 case of TA were observed. 40 cases of TA were initially treated with SAM and NSAI. Twenty cures were obtained within a mean of 28 months. 4 patients later received brief corticosteroid therapy because of an extension of the signs, including two cases of ocular manifestations with a resolving course. Of 25 cases of TA initially treated with steroids, 20 received SAM in combination, or in relay which enabled either steroids, weaning towards the 14th month or a reduction in the dose of steroids. Cure was obtained in an average of 35 months. One case of impaired visual acuity occurred during corticosteroid treatment. Immunosuppressants were used in one patient. No cases of recurrence were observed. Iatrogenic complications with SAM were rare, generally benign and reversible, in contrast to those associated with corticosteroid therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Establishing Research and Management Priorities for Monoecious Hydrilla

DTIC Science & Technology

2014-01-01

strategies. While use of high stocking rates of non-selective sterile grass carp (Ctenopharyngodon idella) has successfully controlled hydrilla in many...discussions of classical biological control agents (e.g. insects that feed specifically on hydrilla) did not yield any promising near-term candidates...possible. Diver- assisted dredging techniques and hand removal techniques were explored on the infestation in the Lake Cayuga inlet; initial results were

Outcome of tacrolimus and vedolizumab after corticosteroid and anti-TNF failure in paediatric severe colitis.

PubMed

Hamel, Blaise; Wu, May; Hamel, Elizabeth O; Bass, Dorsey M; Park, K T

2018-01-01

Severe colitis flare from ulcerative colitis (UC) or Crohn's disease (CD) may be refractory to corticosteroids and antitumour necrosis factor (TNF) agents resulting in high colectomy rates. We aimed to describe the utility of tacrolimus to prevent colectomy during second-line vedolizumab initiation after corticosteroid and anti-TNF treatment failure in paediatric severe colitis. A retrospective cohort analysis was performed between 1 October 2014 and 31 October 2016 at a single tertiary care centre. Inclusion criteria were patients with severe colitis who received tacrolimus before or during vedolizumab induction and previous exposure to anti-TNF therapy with or without corticosteroids. The initiation of tacrolimus was clinician dependent based on an institutional protocol. Twelve patients (10 UC, two CD; median age 16 years; three female) received at least one dose of vedolizumab 10 mg/kg (max of 300 mg) due to anti-TNF therapy failure and persistent flare not responsive to corticosteroids. Of the 12 patients, eight (67%) and four (33%) had failed one or two anti-TNF agents, respectively. Tacrolimus was initiated for acute disease severity during hospitalisation (58%) or ongoing flare during outpatient care (42%). 9 (75%) of 12 patients avoided colectomy or inflammatory bowel disease-related surgery at 24 weeks and eight (68%) continued on vedolizumab maintenance with no adverse events out to 80 weeks. We report real-world data on the outcome of tacrolimus around vedolizumab initiation in paediatric UC or CD after corticosteroid and anti-TNF therapy treatment failure. Our pilot experience indicates a potential benefit of concomitant tacrolimus when initiating vedolizumab therapy.

Combination therapy in combating cancer

PubMed Central

Mokhtari, Reza Bayat; Homayouni, Tina S.; Baluch, Narges; Morgatskaya, Evgeniya; Kumar, Sushil; Das, Bikul; Yeger, Herman

2017-01-01

Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival rates for most metastatic cancers are still quite low, and the process of developing a new anti-cancer drug is costly and extremely time-consuming. Therefore, new strategies that target the survival pathways that provide efficient and effective results at an affordable cost are being considered. One such approach incorporates repurposing therapeutic agents initially used for the treatment of different diseases other than cancer. This approach is effective primarily when the FDA-approved agent targets similar pathways found in cancer. Because one of the drugs used in combination therapy is already FDA-approved, overall costs of combination therapy research are reduced. This increases cost efficiency of therapy, thereby benefiting the “medically underserved”. In addition, an approach that combines repurposed pharmaceutical agents with other therapeutics has shown promising results in mitigating tumour burden. In this systematic review, we discuss important pathways commonly targeted in cancer therapy. Furthermore, we also review important repurposed or primary anti-cancer agents that have gained popularity in clinical trials and research since 2012. PMID:28410237

Trends in surgical management and pre-operative urodynamics in female medicare beneficiaries with mixed incontinence.

PubMed

Chughtai, Bilal; Hauser, Nicholas; Anger, Jennifer; Asfaw, Tirsit; Laor, Leanna; Mao, Jialin; Lee, Richard; Te, Alexis; Kaplan, Steven; Sedrakyan, Art

2017-02-01

We sought to examine the surgical trends and utilization of treatment for mixed urinary incontinence among female Medicare beneficiaries. Data was obtained from a 5% national random sample of outpatient and carrier claims from 2000 to 2011. Included were female patients 65 and older, diagnosed with mixed urinary incontinence, who underwent surgical treatment identified by Current Procedural Terminology, Fourth Edition (CPT-4) codes. Urodynamics (UDS) before initial and secondary procedure were also identified using CPT-4 codes. Procedural trends and utilization of UDS were analyzed. Utilization of UDS increased during the study period, from 38.4% to 74.0% prior to initial surgical intervention, and from 28.6% to 62.5% preceding re-intervention. Sling surgery (63.0%) and injectable bulking agents (28.0%) were the most common surgical treatments adopted, followed by sacral nerve stimulation (SNS) (4.8%) and Burch (4.0%) procedures. Re-intervention was performed in 4.0% of patients initially treated with sling procedures and 21.3% of patients treated with bulking agents, the majority of whom (51.7% and 76.3%, respectively) underwent injection of a bulking agent. Risk of re-intervention was not different among those who did or did not receive urodynamic tests prior to the initial procedure (8.5% vs. 9.3%) CONCLUSIONS: Sling and bulk agents are the most common treatment for MUI. Preoperative urodynamic testing was not related to risk of re-intervention following surgery for mixed urinary incontinence in this cohort. Neurourol. Urodynam. 36:422-425, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Evolvable mathematical models: A new artificial Intelligence paradigm

NASA Astrophysics Data System (ADS)

Grouchy, Paul

We develop a novel Artificial Intelligence paradigm to generate autonomously artificial agents as mathematical models of behaviour. Agent/environment inputs are mapped to agent outputs via equation trees which are evolved in a manner similar to Symbolic Regression in Genetic Programming. Equations are comprised of only the four basic mathematical operators, addition, subtraction, multiplication and division, as well as input and output variables and constants. From these operations, equations can be constructed that approximate any analytic function. These Evolvable Mathematical Models (EMMs) are tested and compared to their Artificial Neural Network (ANN) counterparts on two benchmarking tasks: the double-pole balancing without velocity information benchmark and the challenging discrete Double-T Maze experiments with homing. The results from these experiments show that EMMs are capable of solving tasks typically solved by ANNs, and that they have the ability to produce agents that demonstrate learning behaviours. To further explore the capabilities of EMMs, as well as to investigate the evolutionary origins of communication, we develop NoiseWorld, an Artificial Life simulation in which interagent communication emerges and evolves from initially noncommunicating EMM-based agents. Agents develop the capability to transmit their x and y position information over a one-dimensional channel via a complex, dialogue-based communication scheme. These evolved communication schemes are analyzed and their evolutionary trajectories examined, yielding significant insight into the emergence and subsequent evolution of cooperative communication. Evolved agents from NoiseWorld are successfully transferred onto physical robots, demonstrating the transferability of EMM-based AIs from simulation into physical reality.

UCP1 in adipose tissues: two steps to full browning.

PubMed

Kalinovich, Anastasia V; de Jong, Jasper M A; Cannon, Barbara; Nedergaard, Jan

2017-03-01

The possibility that brown adipose tissue thermogenesis can be recruited in order to combat the development of obesity has led to a high interest in the identification of "browning agents", i.e. agents that increase the amount and activity of UCP1 in brown and brite/beige adipose tissues. However, functional analysis of the browning process yields confusingly different results when the analysis is performed in one of two alternative steps. Thus, in one of the steps, using cold acclimation as a potent model browning agent, we find that if the browning process is followed in mice initially housed at 21 °C (the most common procedure), there is only weak molecular evidence for increases in UCP1 gene expression or UCP1 protein abundance in classical brown adipose tissue; however, in brite/beige adipose depots, there are large increases, apparently associating functional browning with events only in the brite/beige tissues. Contrastingly, in another step, if the process is followed starting with mice initially housed at 30 °C (thermoneutrality for mice, thus similar to normal human conditions), large increases in UCP1 gene expression and UCP1 protein abundance are observed in the classical brown adipose tissue depots; there is then practically no observable UCP1 gene expression in brite/beige tissues. This apparent conundrum can be resolved when it is realized that the classical brown adipose tissue at 21 °C is already essentially fully differentiated and thus expands extensively through proliferation upon further browning induction, rather than by further enhancing cellular differentiation. When the limiting factor for thermogenesis, i.e. the total amount of UCP1 protein per depot, is analyzed, classical brown adipose tissue is by far the predominant site for the browning process, irrespective of which of the two steps is analyzed. There are to date no published data demonstrating that alternative browning agents would selectively promote brite/beige tissues versus classical brown tissue to a higher degree than does cold acclimation. Thus, to restrict investigations to examine adipose tissue depots where only a limited part of the adaptation process occurs (i.e. the brite/beige tissues) and to use initial conditions different from the thermoneutrality normally experienced by adult humans may seriously hamper the identification of therapeutically valid browning agents. The data presented here have therefore important implications for the analysis of the potential of browning agents and the nature of human brown adipose tissue. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Remineralization of initial enamel caries in vitro using a novel peptide based on amelogenin

NASA Astrophysics Data System (ADS)

Li, Danxue; Lv, Xueping; Tu, Huanxin; Zhou, Xuedong; Yu, Haiyang; Zhang, Linglin

2015-09-01

Dental caries is the most common oral disease with high incidence, widely spread and can seriously affect the health of oral cavity and the whole body. Current caries prevention measures such as fluoride treatment, antimicrobial agents, and traditional Chinese herbal, have limitations to some extent. Here we design and synthesize a novel peptide based on the amelogenin, and assess its ability to promote the remineralization of initial enamel caries lesions. We used enamel blocks to form initial lesions, and then subjected to 12-day pH cycling in the presence of peptide, NaF and HEPES buffer. Enamel treated with peptide or NaF had shallower, narrower lesions, thicker remineralized surfaces and less mineral loss than enamel treated with HEPES. This peptide can promote the remineralization of initial enamel caries and inhibit the progress of caries. It is a promising anti-caries agent with various research prospects and practical application value.

Incentivising effort in governance of public hospitals: Development of a delegation-based alternative to activity-based remuneration.

PubMed

Søgaard, Rikke; Kristensen, Søren Rud; Bech, Mickael

2015-08-01

This paper is a first examination of the development of an alternative to activity-based remuneration in public hospitals, which is currently being tested at nine hospital departments in a Danish region. The objective is to examine the process of delegating the authority of designing new incentive schemes from the principal (the regional government) to the agents (the hospital departments). We adopt a theoretical framework where, when deciding about delegation, the principal should trade off an initiative effect against the potential cost of loss of control. The initiative effect is evaluated by studying the development process and the resulting incentive schemes for each of the departments. Similarly, the potential cost of loss of control is evaluated by assessing the congruence between focus of the new incentive schemes and the principal's objectives. We observe a high impact of the effort incentive in the form of innovative and ambitious selection of projects by the agents, leading to nine very different solutions across departments. However, we also observe some incongruence between the principal's stated objectives and the revealed private interests of the agents. Although this is a baseline study involving high uncertainty about the future, the findings point at some issues with the delegation approach that could lead to inefficient outcomes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Synthesis and biological evaluation of (99m)Tc-DMP-NGA as a novel hepatic asialoglycoprotein receptor imaging agent.

PubMed

Yang, Wenjiang; Mou, Tiantian; Zhang, Xianzhong; Wang, Xuebin

2010-01-01

A novel bifunctional coupling agents-biomolecular compound DMP-NGA was prepared by coupling the SATP with galactosyl-neoglycoalbumin (NGA). The DMP-NGA was labeled with technetium-99m, and the radiochemical purity in excess of 98% after purified with HPLC. In vivo biodistribution showed that (99m)Tc-DMP-NGA had very high initial liver uptake with good retention. The liver accumulated 99.35+/-9.77%, 74.25+/-3.03%, 52.47+/-7.58% of the injected dose per gram at 5, 30 and 120min after injection, respectively. It had relative higher initial liver uptake and much lower blood uptake than that of (99m)Tc-GSA. The liver/blood ratio reached 83.4 at 30min post-injection, while the ratio of liver/kidney was 14.4. The uptakes in other organs in the abdomen were also slightly low. In addition, the hepatic uptake of (99m)Tc-DMP-NGA was blocked by preinjecting free GSA as blocking agent. The result indicates that (99m)Tc-DMP-NGA has specific binding to ASGP receptor. Images acquired with Kodak In-Vivo Imaging System FX Pro showed significant difference before and after inhibition. The promising biological properties of (99m)Tc-DMP-NGA afford potential applications in liver receptor imaging for assessment of hepatocyte function.

Collective circular motion in synchronized and balanced formations with second-order rotational dynamics

NASA Astrophysics Data System (ADS)

Jain, Anoop; Ghose, Debasish

2018-01-01

This paper considers collective circular motion of multi-agent systems in which all the agents are required to traverse different circles or a common circle at a prescribed angular velocity. It is required to achieve these collective motions with the heading angles of the agents synchronized or balanced. In synchronization, the agents and their centroid have a common velocity direction, while in balancing, the movement of agents causes the location of the centroid to become stationary. The agents are initially considered to move at unit speed around individual circles at different angular velocities. It is assumed that the agents are subjected to limited communication constraints, and exchange relative information according to a time-invariant undirected graph. We present suitable feedback control laws for each of these motion coordination tasks by considering a second-order rotational dynamics of the agent. Simulations are given to illustrate the theoretical findings.

46 CFR Sec. 2 - Voyage numbers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... voyage No. 1 having the prefixed designation NSA and followed by the General Agents' abbreviated designation and voyage number, as NSA-1/ABC-1. (b) The continuity of NSA voyage numbers shall not change with... General Agent shall affix his abbreviated designation and initial voyage numbers, as NSA-13/XYZ-1. ...

46 CFR Sec. 2 - Voyage numbers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... voyage No. 1 having the prefixed designation NSA and followed by the General Agents' abbreviated designation and voyage number, as NSA-1/ABC-1. (b) The continuity of NSA voyage numbers shall not change with... General Agent shall affix his abbreviated designation and initial voyage numbers, as NSA-13/XYZ-1. ...

46 CFR Sec. 2 - Voyage numbers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... voyage No. 1 having the prefixed designation NSA and followed by the General Agents' abbreviated designation and voyage number, as NSA-1/ABC-1. (b) The continuity of NSA voyage numbers shall not change with... General Agent shall affix his abbreviated designation and initial voyage numbers, as NSA-13/XYZ-1. ...

46 CFR Sec. 2 - Voyage numbers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... voyage No. 1 having the prefixed designation NSA and followed by the General Agents' abbreviated designation and voyage number, as NSA-1/ABC-1. (b) The continuity of NSA voyage numbers shall not change with... General Agent shall affix his abbreviated designation and initial voyage numbers, as NSA-13/XYZ-1. ...

46 CFR Sec. 2 - Voyage numbers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... voyage No. 1 having the prefixed designation NSA and followed by the General Agents' abbreviated designation and voyage number, as NSA-1/ABC-1. (b) The continuity of NSA voyage numbers shall not change with... General Agent shall affix his abbreviated designation and initial voyage numbers, as NSA-13/XYZ-1. ...

Intelligent Agents: Information Strategies for the Information Society.

ERIC Educational Resources Information Center

Garcia-Sierra, A. J.

In the workplace of today which is increasingly being overloaded with information, the concept of intelligent information agents has been widely prescribed. This paper briefly looks at the United Kingdom Government's Information Society Initiative which has been fueled by the realization that information is the key component of the ongoing…

MOOCs as Change Agents to Boost Innovation in Higher Education Learning Arenas

ERIC Educational Resources Information Center

Ossiannilsson, Ebba; Altinay, Fahriye; Altinay, Zehra

2016-01-01

Massive open online courses (MOOCs) provide opportunities for learners to benefit from initiatives that are promoted by prestigious universities worldwide. The introduction of MOOCs in 2008 has since then transformed education globally. Consequently, MOOCs should be acknowledged as a pedagogical innovation and recognized as change agents and…

Application of Grazing-Inspired Guidance Laws to Autonomous Information Gathering

DTIC Science & Technology

2014-09-01

paths by expressing it as the Selective Traveling Salesman Problem subject to dynamic constraints. Tisdale et al. [11] utilized a receding horizon ap...vehicle failures by halving the initial fuel level on selected agents. Note that simulations start with agents 50s travel time away from where they

Predictors of the discharge dosage of an atypical antipsychotic agent among hospitalized, treatment-naive, first-episode psychosis patients in naturalistic, public-sector settings.

PubMed

Compton, Michael T; Kelley, Mary E; Lloyd, Robert Brett; McClam, Tamela; Ramsay, Claire E; Haggard, Patrick J; Augustin, Sara

2011-02-01

Little is known about determinants of second-generation antipsychotic dosages during initial hospitalization of first-episode psychosis. This study examined potential predictors of dosage of an atypical antipsychotic agent, risperidone, at hospital discharge after initial evaluation and treatment of first-episode nonaffective psychosis in 3 naturalistic, public-sector treatment settings. The number of psychotropic agents prescribed and discharge antipsychotic dosage were abstracted from the medical record. Demographic and extensive clinical characteristics were assessed through a clinical research study conducted at the 3 sites. One-way analyses of variance, trend tests using specific linear combinations of estimates, and χ² tests assessed for associations between atypical antipsychotic dosage and 5 hypothesized predictors, as well as 12 exploratory variables. Among 155 hospitalized first-episode patients, 121 (78.1%) were discharged on risperidone, and subsequent analyses focused on that subset. The mean risperidone dosage among those 121 patients was 4.26 mg; 31 received 1 to 2 mg, 45 received 3 to 4 mg, 37 received 5 to 6 mg, and 8 received more than 6 mg. Analyses suggested that older age at hospitalization, the number of psychotropic agents prescribed, excited symptoms, and premorbid social functioning may be predictors of the discharge dosage. Although several factors emerged, in general, predictors of discharge dosages of second-generation agents, here exemplified by risperidone, in real-world practice settings remain to be clarified. Given the importance of antipsychotic initiation during first hospitalization, future research should test an even broader array of potential predictors.

Costly punishment and cooperation in the evolutionary snowdrift game

NASA Astrophysics Data System (ADS)

Xu, C.; Ji, M.; Yap, Yee Jiun; Zheng, Da-Fang; Hui, P. M.

2011-05-01

The role of punishments in promoting cooperation is an important issue. We incorporate costly punishments into the snowdrift game (SG) by introducing a third punishing (P) character, and study the effects. The punishers, who carry basically a cooperative (C) character, are willing to pay a cost α so as to punish a non-cooperative (D) opponent by β. Depending on the initial fractions of the characters, α, β, and the cost-to-benefit ratio r in the SG, the three-character system evolves into a steady state consisting either only of C and P characters or only of C and D characters, in a well-mixed population. The former situation represents an enhancement in cooperation relative to the SG, while the latter is similar to the SG. The dynamics in approaching these different steady states are found to be different. Analytically, the key features in the dynamics and the steady states observed in simulations are captured by a set of differential equations. The sensitivity to the initial distribution of characters is studied by depicting the flow in a phase portrait and analyzing the nature of fixed points. The analysis also shows the role of P-character agents in preventing a system from invasion by D-character agents. Starting from a population consisting only of C and P agents, a D-character agent intended to invade the system cannot survive when the initial fraction of P agents is greater than r/β. Our model, defined intentionally as a simulation algorithm, can be readily generalized to incorporate many interesting effects, such as those in a networked population.

Survey of rheumatologists on the use of the Philippine Guidelines on the Screening for Tuberculosis prior to use of Biologic Agents.

PubMed

Aquino-Villamin, Melissa; Tankeh-Torres, Sandra; Lichauco, Juan Javier

2016-11-01

The use of biologic agents has become an important option in treating patients with rheumatoid arthritis. However, these drugs have been associated with an increased risk of tuberculosis (TB) reactivation. Local guidelines for TB screening prior to the use of biologic agents were developed to address this issue. This study is a survey describing the compliance of Filipino rheumatologists to these guidelines. Eighty-seven rheumatologists in the Philippines were given the questionnaire and responses from 61 rheumatologists were included in the analysis. All respondents agree that patients should be screened prior to giving the biologic agents. Local guidelines recommend screening with tuberculin skin test (TST) and chest radiograph. However, cut-off values considered for a positive TST and timing of initiation of biologic agents after starting TB prophylaxis and treatment varied among respondents. In addition, screening of close household contacts were only performed by 41 (69.5%) respondents. There were 11 respondents who reported 16 patients developing TB during or after receiving biologic agents, despite adherence to the guidelines. This survey describes the compliance rate of Filipino rheumatologists in applying current local recommendations for TB screening prior to initiating biologic agents. The incidence of new TB cases despite the current guidelines emphasizes the importance of compliance and the need to revise the guidelines based on updated existing literature. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Reflectance confocal microscopy of tinea nigra: comparing images with dermoscopy and mycological examination results.

PubMed

Veasey, John Verrinder; Avila, Ricardo Bertozzi de; Ferreira, Marcus Antônio Maia de Olivas; Lazzarini, Rosana

2017-01-01

Tinea nigra is a superficial mycosis whose diagnosis is confirmed by isolating the infectious agent Hortae werneckii through mycological examinations. In vivo reflectance confocal microscopy, initially used in melanocytic dermatosis, has been used with skin infectious diseases to identify the parasite at the cellular level. We report, for the first time in the scientific literature, the use of reflectance confocal microscopy in a case of tinea nigra and compare its findings to dermoscopy and mycological examination results.

Reflectance confocal microscopy of tinea nigra: comparing images with dermoscopy and mycological examination results*

PubMed Central

Veasey, John Verrinder; de Avila, Ricardo Bertozzi; Ferreira, Marcus Antônio Maia de Olivas; Lazzarini, Rosana

2017-01-01

Tinea nigra is a superficial mycosis whose diagnosis is confirmed by isolating the infectious agent Hortae werneckii through mycological examinations. In vivo reflectance confocal microscopy, initially used in melanocytic dermatosis, has been used with skin infectious diseases to identify the parasite at the cellular level. We report, for the first time in the scientific literature, the use of reflectance confocal microscopy in a case of tinea nigra and compare its findings to dermoscopy and mycological examination results. PMID:28954116

Knowledge Representation for Decision Making Agents

DTIC Science & Technology

2013-07-15

knowledge map. This knowledge map is a dictionary data structure called tmap in the code. It represents a network of locations with a number [0,1...fillRandom(): Informed initial tmap distribution (randomly generated per node) with belief one. • initialBelief = 3 uses fillCenter(): normal...triggered on AllMyFMsHaveBeenInitialized. 2. Executes main.py • Initializes knowledge map labeled tmap . • Calls initialize search() – resets distanceTot and

Theoretical effect of hyperventilation on speed of recovery and risk of rehypnotization following recovery - a GasMan® simulation

PubMed Central

2012-01-01

Background Hyperventilation may be used to hasten recovery from general anesthesia with potent inhaled anesthetics. However, its effect may be less pronounced with the newer, less soluble agents, and it may result in rehypnotization if subsequent hypoventilation occurs because more residual anesthetic will be available in the body for redistribution to the central nervous system. We used GasMan® simulations to examine these issues. Methods One MAC of isoflurane, sevoflurane, or desflurane was administered to a fictitious 70 kg patient for 8 h with normoventilation (alveolar minute ventilation [VA] 5 L.min-1), resulting in full saturation of the vessel rich group (VRG) and >95% saturation of the muscle group. After 8 h, agent administration was stopped, and fresh gas flow was increased to 10 L.min-1 to avoid rebreathing. At that same time, we continued with one simulation where normoventilation was maintained, while in a second simulation hyperventilation was instituted (10 L.min-1). We determined the time needed for the partial pressure in the VRG (FVRG; representing the central nervous system) to reach 0.3 MAC (MACawake). After reaching MACawake in the VRG, several degrees of hypoventilation were instituted (VA of 2.5, 1.5, 1, and 0.5 L.min-1) to determine whether FVRG would increase above 0.3 MAC(= rehypnotization). Results Time to reach 0.3 MAC in the VRG with normoventilation was 14 min 42 s with isoflurane, 9 min 12 s with sevoflurane, and 6 min 12 s with desflurane. Hyperventilation reduced these recovery times by 30, 18, and 13% for isoflurane, sevoflurane, and desflurane, respectively. Rehypnotization was observed with VA of 0.5 L.min-1 with desflurane, 0.5 and 1 L.min-1 with sevoflurane, and 0.5, 1, 1.5, and 2.5 L.min-1 with isoflurane. Only with isoflurane did initial hyperventilation slightly increase the risk of rehypnotization. Conclusions These GasMan® simulations confirm that the use of hyperventilation to hasten recovery is marginally beneficial with the newer, less soluble agents. In addition, subsequent hypoventilation results in rehypnotization only with more soluble agents, unless hypoventilation is severe. Also, initial hyperventilation does not increase the risk of rehypnotization with less soluble agents when subsequent hypoventilation occurs. Well-controlled clinical studies are required to validate these simulations. PMID:22989260

Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial.

PubMed

Davies, M; Lavalle-González, F; Storms, F; Gomis, R

2008-05-01

For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycaemic control, necessitating insulin therapy. Fear of hypoglycaemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS, glargine, Sanofi-aventis, Paris, France) therapy using two treatment algorithms. This subgroup analysis investigated the initiation of once-daily glargine therapy in patients suboptimally controlled on multiple OADs. This study was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose < or =100 mg/dl (< or =5.5 mmol/l). Algorithms were compared for incidence of severe hypoglycaemia [requiring assistance and blood glucose <50 mg/dl (<2.8 mmol/l)] and baseline to end-point change in haemoglobin A(1c) (HbA(1c)). Of the 4961 patients enrolled in the study, 865 were included in this subgroup analysis: 340 received glargine plus 1 OAD and 525 received glargine plus >1 OAD. Incidence of severe hypoglycaemia was <1%. HbA(1c) decreased significantly between baseline and end-point for patients receiving glargine plus 1 OAD (-1.4%, p < 0.001; algorithm 1 -1.3% vs. algorithm 2 -1.5%; p = 0.03) and glargine plus >1 OAD (-1.7%, p < 0.001; algorithm 1 -1.5% vs. algorithm 2 -1.8%; p = 0.001). This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA(1c) with a low risk of hypoglycaemia. The greater reduction in HbA(1c) was seen in patients randomized to the patient-driven algorithm (algorithm 2) on 1 or >1 OAD.

A pilot study: the efficacy of virgin coconut oil as ocular rewetting agent on rabbit eyes.

PubMed

Mutalib, Haliza Abdul; Kaur, Sharanjeet; Ghazali, Ahmad Rohi; Chinn Hooi, Ng; Safie, Nor Hasanah

2015-01-01

Purpose. An open-label pilot study of virgin coconut oil (VCO) was conducted to determine the safety of the agent as ocular rewetting eye drops on rabbits. Methods. Efficacy of the VCO was assessed by measuring NIBUT, anterior eye assessment, corneal staining, pH, and Schirmer value before instillation and at 30 min, 60 min, and two weeks after instillation. Friedman test was used to analyse any changes in all the measurable variables over the period of time. Results. Only conjunctival redness with instillation of saline agent showed significant difference over the period of time (P < 0.05). However, further statistical analysis had shown no significant difference at 30 min, 60 min, and two weeks compared to initial measurement (P > 0.05). There were no changes in the NIBUT, limbal redness, palpebral conjunctiva redness, corneal staining, pH, and Schirmer value over the period of time for each agent (P > 0.05). Conclusion. VCO acts as safe rewetting eye drops as it has shown no significant difference in the measurable parameter compared to commercial brand eye drops and saline. These study data suggest that VCO is safe to be used as ocular rewetting agent on human being.

Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

PubMed Central

Das, Rina; Hammamieh, Rasha; Neill, Roger; Ludwig, George V; Eker, Steven; Lincoln, Patrick; Ramamoorthy, Preveen; Dhokalia, Apsara; Mani, Sachin; Mendis, Chanaka; Cummings, Christiano; Kearney, Brian; Royaee, Atabak; Huang, Xiao-Zhe; Paranavitana, Chrysanthi; Smith, Leonard; Peel, Sheila; Kanesa-Thasan, Niranjan; Hoover, David; Lindler, Luther E; Yang, David; Henchal, Erik; Jett, Marti

2008-01-01

Background Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs. Methods To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays. Results We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin. Conclusion Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents. PMID:18667072

Update on the pharmacological treatment of adult myositis.

PubMed

Oddis, C V

2016-07-01

The management of patients with idiopathic inflammatory myopathy (IIM) remains a challenge given the systemic features beyond active myositis. That is, recognizing the inflammatory arthropathy, varying dermatomyositis rashes, and overt and occult features of interstitial lung disease in addition to myositis adds to the complexity of diagnosis and treatment of IIM. However, clinicians now have available many more immunosuppressive drugs as well as biologic agents for use in patients with myositis and other autoimmune diseases. Here, the use of these agents is reviewed and support based on available published literature is provided even though many studies have been small and results somewhat anecdotal. Glucocorticoids remain the initial treatment of choice in most instances and methotrexate and azathioprine are often used early in the treatment course. These agents are followed by other immunosuppressive drugs, for example mycophenolate mofetil, tacrolimus, cyclosporine and cyclophosphamide, some of which are used alone while combinations of these agents also provide an effective option. There is more rationale for the use of biologic agents such as rituximab from a mechanistic perspective and, given the incorporation of validated core set measures in assessing myositis patients, we can look forward to better designed clinical trials in the future. © 2016 The Association for the Publication of the Journal of Internal Medicine.

Correlation between information diffusion and opinion evolution on social media

NASA Astrophysics Data System (ADS)

Xiong, Fei; Liu, Yun; Zhang, Zhenjiang

2014-12-01

Information diffusion and opinion evolution are often treated as two independent processes. Opinion models assume the topic reaches each agent and agents initially have their own ideas. In fact, the processes of information diffusion and opinion evolution often intertwine with each other. Whether the influence between these two processes plays a role in the system state is unclear. In this paper, we collected more than one million real data from a well-known social platform, and analysed large-scale user diffusion behaviour and opinion formation. We found that user inter-event time follows a two-scaling power-law distribution with two different power exponents. Public opinion stabilizes quickly and evolves toward the direction of convergence, but the consensus state is prevented by a few opponents. We propose a three-state opinion model accompanied by information diffusion. Agents form and exchange their opinions during information diffusion. Conversely, agents' opinions also influence their diffusion actions. Simulations show that the model with a correlation of the two processes produces similar statistical characteristics as empirical results. A fast epidemic process drives individual opinions to converge more obviously. Unlike previous epidemic models, the number of infected agents does not always increase with the update rate, but has a peak with an intermediate value of the rate.

A Pilot Study: The Efficacy of Virgin Coconut Oil as Ocular Rewetting Agent on Rabbit Eyes

PubMed Central

Mutalib, Haliza Abdul; Kaur, Sharanjeet; Ghazali, Ahmad Rohi; Chinn Hooi, Ng; Safie, Nor Hasanah

2015-01-01

Purpose. An open-label pilot study of virgin coconut oil (VCO) was conducted to determine the safety of the agent as ocular rewetting eye drops on rabbits. Methods. Efficacy of the VCO was assessed by measuring NIBUT, anterior eye assessment, corneal staining, pH, and Schirmer value before instillation and at 30 min, 60 min, and two weeks after instillation. Friedman test was used to analyse any changes in all the measurable variables over the period of time. Results. Only conjunctival redness with instillation of saline agent showed significant difference over the period of time (P < 0.05). However, further statistical analysis had shown no significant difference at 30 min, 60 min, and two weeks compared to initial measurement (P > 0.05). There were no changes in the NIBUT, limbal redness, palpebral conjunctiva redness, corneal staining, pH, and Schirmer value over the period of time for each agent (P > 0.05). Conclusion. VCO acts as safe rewetting eye drops as it has shown no significant difference in the measurable parameter compared to commercial brand eye drops and saline. These study data suggest that VCO is safe to be used as ocular rewetting agent on human being. PMID:25802534

VMAT2 inhibitors for the treatment of tardive dyskinesia.

PubMed

Scorr, Laura M; Factor, Stewart A

2018-06-15

Tardive dyskinesia (TD) is an often disabling hyperkinetic movement disorder caused by exposure to dopamine receptor blocking agents. Although initially thought to most commonly occur with typical antipsychotics, the incidence is likely similar with atypical antipsychotics and antiemetics such as metoclopramide. Increased prescribing of these agents as well as low rates of remission have contributed to a rising prevalence of TD. Although this condition was described nearly 60 years ago, it is only within the past year that two novel therapeutic agents were FDA approved. Characterization of the VMAT2 inhibitor tetrabenazine, which was identified as a therapeutic agent for TD in older clinical trials, has yielded two distinct pharmacologic strategies to optimize response. The first strategy, used to create deutetrabenazine, employed deuterization of tetrabenazine to stabilize the pharmacokinetics and eliminate high peak plasma levels. The second strategy was the creation of a prodrug, valbenazine, for the two most active isoforms of tetrabenazine that also resulted in more stable pharmacokinetics and eliminated peak plasma levels. Both agents have been demonstrated to be effective and safe for the treatment of TD in multicenter, controlled trials and their development has led to a resurgence of interest in the characterization and treatment of this movement disorder. Copyright © 2018 Elsevier B.V. All rights reserved.

Specialty Tier-Level Cost Sharing and Biologic Agent Use in the Medicare Part D Initial Coverage Period Among Beneficiaries With Rheumatoid Arthritis.

PubMed

Doshi, Jalpa A; Hu, Tianyan; Li, Pengxiang; Pettit, Amy R; Yu, Xinyan; Blum, Marissa

2016-11-01

To examine associations between specialty tier-level cost sharing and use of biologic agents for rheumatoid arthritis (RA) during Medicare Part D's initial coverage period (ICP). This was a retrospective study using 2007-2010 5% sample Medicare files to examine RA patients with use of a Part D RA biologic agent in the prior year. Patients without low-income subsidies (non-LIS group), who faced specialty tier-level cost sharing, were compared to a control group of low-income subsidy patients (LIS group), who faced nominal out-of-pocket costs in the ICP. Outcomes included use of a Part D or Part B RA biologic agent during the ICP and presence of a ≥30-day continuous gap in treatment among Part D biologic agent users in the ICP. Risk-adjusted outcomes were estimated using logistic regressions, controlling for patient demographic, clinical, and Part D plan characteristics. On average, a 30-day Part D biologic agent supply cost the non-LIS group $484 out of pocket (29.9% cost sharing) versus $5 (0.3% cost sharing) for the LIS group. The non-LIS group was less likely to fill Part D biologic agents (61.2% versus 72.7%, odds ratio [OR] 0.58 [95% confidence interval (95% CI) 0.46-0.72]; P < 0.001), more than twice as likely to receive Part B biologic agents (9.9% versus 4.4%, OR 2.41 [95% CI 1.61-3.60]; P < 0.001), and less likely to use any biologic agent (70.1% versus 76.9%, OR 0.69 [95% CI 0.55-0.88]; P = 0.002). The non-LIS subgroup filling Part D biologic agents had approximately twice the odds of a gap in both Part D biologic agent and any biologic agent availability. Specialty tier-level cost sharing was associated with interruptions in RA biologic agent treatment among Medicare patients. © 2016, American College of Rheumatology.

Emotional recognition from the speech signal for a virtual education agent

NASA Astrophysics Data System (ADS)

Tickle, A.; Raghu, S.; Elshaw, M.

2013-06-01

This paper explores the extraction of features from the speech wave to perform intelligent emotion recognition. A feature extract tool (openSmile) was used to obtain a baseline set of 998 acoustic features from a set of emotional speech recordings from a microphone. The initial features were reduced to the most important ones so recognition of emotions using a supervised neural network could be performed. Given that the future use of virtual education agents lies with making the agents more interactive, developing agents with the capability to recognise and adapt to the emotional state of humans is an important step.

Use of the interior cavity of the P22 capsid for site-specific initiation of atom-transfer radical polymerization with high-density cargo loading

NASA Astrophysics Data System (ADS)

Lucon, Janice; Qazi, Shefah; Uchida, Masaki; Bedwell, Gregory J.; Lafrance, Ben; Prevelige, Peter E.; Douglas, Trevor

2012-10-01

Virus-like particles (VLPs) have emerged as important and versatile architectures for chemical manipulation in the development of functional hybrid nanostructures. Here we demonstrate a successful site-selective initiation of atom-transfer radical polymerization reactions to form an addressable polymer constrained within the interior cavity of a VLP. Potentially, this protein-polymer hybrid of P22 and cross-linked poly(2-aminoethyl methacrylate) could be useful as a new high-density delivery vehicle for the encapsulation and delivery of small-molecule cargos. In particular, the encapsulated polymer can act as a scaffold for the attachment of small functional molecules, such as fluorescein dye or the magnetic resonance imaging (MRI) contrast agent Gd-diethylenetriaminepentacetate, through reactions with its pendant primary amine groups. Using this approach, a significant increase in the labelling density of the VLP, compared to that of previous modifications of VLPs, can be achieved. These results highlight the use of multimeric protein-polymer conjugates for their potential utility in the development of VLP-based MRI contrast agents with the possibility of loading other cargos.

[Cefazolin efficacy and antibiotic sensitivity against pathogenic bacteria in pediatric with acute upper urinary tract infection].

PubMed

Fuke, Toshiya; Abe, Yoshifusa; Hoshino, Akihiro; Oto, Hideyasu; Sakai, Naho; Murayama, Junichiro; Yoshida, Koichiro; Itabashi, Kazuo

2010-05-01

Acute upper urinary tract infection may cause sepsis, especially in neonates and infants, mandating the choice of appropriate, effective antibacterials minimizing increasing bacterial resistance. Frequently prescribing broad-spectrum cephalosporinin is one such example. Different antibacterial therapies are initiated clinically due to treatment protocol differences among institutions, disease severity, etc. We studied the efficacy of cefazolin (CEZ), a first-generation cephalosporin, as first-line parenteral treatment in acute upper urinary tract infection. We found that 88.9% of microbial infections have indications for CEZ. CEZ efficacy is 91.3%, and 97.2% of urine cultures show negative results. Escherichia coli sensitivity to antibacterial agents is 90.9% of the minimal inhibitory concentration (MIC) < 4 for CEZ, 93.9% of MIC < 1 for ceftazidime (CAZ), 63.6% of MIC < 4 for ampicillin, and 81.8% of MIC < 2 for gentamicin. CEZ thus has the same efficacy as CAZ and is more effective than other antibacterial agents against E. coli. We concluded that CEZ is an effective antibacterial in initial antibacterial pediatric therapy in acute upper urinary tract infection.

Little by Little Does the Trick: Design and Construction of a Discrete Event Agent-Based Simulation Framework

DTIC Science & Technology

2007-12-01

model. Finally, we build a small agent-based model using the component architecture to demonstrate the library’s functionality. 15. NUMBER OF...and a Behavioral model. Finally, we build a small agent-based model using the component architecture to demonstrate the library’s functionality...prototypes an architectural design which is generalizable, reusable, and extensible. We have created an initial set of model elements that demonstrate

Standing sedation in African elephants (Loxodonta africana) using detomidine-butorphanol combinations.

PubMed

Neiffer, Donald L; Miller, Michele A; Weber, Martha; Stetter, Mark; Fontenot, Deidre K; Robbins, P K; Pye, Geoffrey W

2005-06-01

Standing sedation was provided for 14 clinical procedures in three African elephants (Loxodonta africana) managed by combined protected and modified-protected contact and trained through operant conditioning. An initial hand-injection of detomidine hydrochloride and butorphanol tartrate at a ratio of 1:1 on a microg:microg basis was administered intramuscularly, with a dosage range of 50-70 mg (12.9-19.7 microg/kg) for each drug. The initial injection resulted in adequate sedation for initiation and completion of eight procedures, whereas supplemental doses were required for the remaining procedures. The dosage range for the supplemental injections of each drug was 4.0-7.3 microg/kg. Initial effect was noted within 3.0-25 min (mean = 11.6 min, SD +/- 5.9 min), with maximal effect occurring at 25-30 min for those procedures not requiring supplementation. In all but one procedure, this effect was maintained until the end of the procedure, which ranged from 47 to 98 min (mean = 74.7 min, SD +/- 18.8 min). No cardiac or respiratory depression was appreciated. Recovery after administration of reversal agents was rapid and complete, ranging from 2 to 20 min (mean = 9.0 min, SD +/- 7.0 min). On the basis of the authors' experience, recommended dosage ranges for reversal agents would be intravenous yohimbine (73.4-98.5 microg/kg), intravenous naltrexone (48.9-98.5 microg/kg), and intramuscular naltrexone (73.4-98.5 microg/kg). Approximately one-third to one-half of the total naltrexone dose should be administered intravenously. Mild adverse side effects limited to the gastrointestinal tract were observed in association with five procedures including abdominal distention with or without transient anorexia. Administration of reversal agents, encouraging exercise and water consumption, and administration of flunixin meglumine were helpful in the resolution of signs. In addition to gastrointestinal signs, slight ataxia was observed before initiation of surgical stimulation during one procedure in which 19.7 microg/kg of each drug was administered. On the basis of the procedures that did not require supplementation to initiate treatment and taking into consideration the potential for ataxia at higher doses, a starting dosage range of 14.7-16.2 microg/kg of both detomidine and butorphanol in a ratio of 1:1 on a microg:microg basis administered i.m. simultaneously is recommended.

High performance UV and thermal cure hybrid epoxy adhesive

NASA Astrophysics Data System (ADS)

Chen, C. F.; Iwasaki, S.; Kanari, M.; Li, B.; Wang, C.; Lu, D. Q.

2017-06-01

New type one component UV and thermal curable hybrid epoxy adhesive was successfully developed. The hybrid epoxy adhesive is complete initiator free composition. Neither photo-initiator nor thermal initiator is contained. The hybrid adhesive is mainly composed of special designed liquid bismaleimide, partially acrylated epoxy resin, acrylic monomer, epoxy resin and latent curing agent. Its UV light and thermal cure behavior was studied by FT-IR spectroscopy and FT-Raman spectroscopy. Adhesive samples cured at UV only, thermal only and UV + thermal cure conditions were investigated. By calculated conversion rate of double bond in both acrylic component and maleimide compound, satisfactory light curability of the hybrid epoxy adhesive was confirmed quantitatively. The investigation results also showed that its UV cure components, acrylic and bismalimide, possess good thermal curability too. The initiator free hybrid epoxy adhesive showed satisfactory UV curability, good thermal curability and high adhesion performance.

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative.

PubMed

Dick, Andrew D; Rosenbaum, James T; Al-Dhibi, Hassan A; Belfort, Rubens; Brézin, Antoine P; Chee, Soon Phaik; Davis, Janet L; Ramanan, Athimalaipet V; Sonoda, Koh-Hei; Carreño, Ester; Nascimento, Heloisa; Salah, Sawsen; Salek, Sherveen; Siak, Jay; Steeples, Laura

2018-05-01

An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Necroulcerative hemorrhagic gastritis in a cat secondary to the administration of 3% hydrogen peroxide as an emetic agent.

PubMed

Obr, Teresa D; Fry, Joanna K; Lee, Justine A; Hottinger, Heidi A

2017-09-01

To describe a case of necroulcerative gastritis in a cat secondary to administration of 3% hydrogen peroxide as an emetic agent. A 10-year-old neutered male domestic shorthair was evaluated for hematemesis less than 24 hours following ingestion of a piece of foam. The pet owner had administered 2 doses of 0.5-1.0 tablespoons (7.5-15 mL) of 3% hydrogen peroxide in an attempt to induce emesis at home; emesis was achieved and produced the foam foreign body. Due to the presence of protracted vomiting and hematemesis, the patient was then presented to an emergency facility for further diagnostics and treatment. Initial blood work was normal on presentation, and advanced imaging of the abdomen was performed. An exploratory laparotomy revealed no foreign material in the gastrointestinal tract; however, severe ulceration of approximately 60% of the gastric mucosa was observed around the cardia and extended from the fundus down through the body of the stomach to the lesser curvature. Due to the severity of ulceration and presumed poor prognosis, the patient was euthanized intraoperatively. Histopathology of the stomach wall was consistent with severe confluent necroulcerative and hemorrhagic pleocellular gastritis, presumed to be secondary to administration of 3% hydrogen peroxide, which was used as the primary emetic agent in this case. The oral administration of 3% hydrogen peroxide solution in cats can result in necroulcerative gastritis as a possible sequel. While hydrogen peroxide is considered a safe emetic agent in dogs, its use in cats is not recommended. As a result, the use of emetic agents in cats should be limited to veterinary administration, using alternative, safer emetic agents such as alpha-adrenergic agonists. © Veterinary Emergency and Critical Care Society 2017.

Curtailing the high rate of late-stage attrition of investigational therapeutics against unprecedented targets in patients with lung and other malignancies.

PubMed

Rowinsky, Eric K

2004-06-15

A greater understanding of the pathogenesis and biology of cancer coupled with major advances in biotechnology has resulted in the identification of rationally designed, target-based (RDTB) anticancer therapeutics, ushering in new therapeutic opportunities and high expectations for the future as well as developmental challenges. Because these agents appear to principally target malignant cells, it is expected that they will produce less toxicity at clinically effective doses than nonspecific cytotoxic agents, but their target requirements are likely to be much more stringent. The innate complexity of the networks that contain elements targeted by these agents also decreases the probability that any single therapeutic manipulation will result in robust clinical activity and success when used alone, particularly in patients with solid malignancies that have multiple relevant signaling aberrations. In contrast, proof of principle and robust antitumor activity may be most efficiently demonstrated in nonrandomized evaluations involving tumors that are principally driven by aberrations of the specific target. The predominant therapeutic manifestation of RDTB agents in preclinical studies is due to decreased tumor growth rates and will likely be similar in the clinic; however, such manifestations are not readily detectable and quantifiable using nonrandomized clinical evaluations. To curtail the increasing rate of late-stage attrition of RDTB agents, which, if maintained, will stymie progress in cancer therapy, the design of initial nonrandomized evaluations, particularly the selection of tumors and patients, must be guided by the principal biological features of the agents. Next, evaluations, some of which must be randomized, can be performed in a wide range of tumor types, depending on the presence and relevance of the target. To validate the concept of RDTB therapeutics and to realize their full potential, radically different development, evaluation, and regulatory paradigms must be adopted.

Phentermine and topiramate for the management of obesity: a review

PubMed Central

Cosentino, Gina; Conrad, Ariane O; Uwaifo, Gabriel I

2013-01-01

Obesity is now a major public health concern worldwide with increasing prevalence and a growing list of comorbidities and complications. The morbidity, mortality and reduced productivity associated with obesity and its complications result in a major burden to health care costs. Obesity is a complex chronic medical syndrome often with multiple different etiologic factors in individual patients. The long term successful management of obesity remains particularly challenging and invariably requires a multifaceted approach including lifestyle and behavioral modification, increased physical activity, and adjunctive pharmacotherapy. Bariatric surgery remains a last resort though at present it has the best results for achieving sustained robust weight loss. Obesity pharmacotherapy has been very limited in its role for long term obesity management because of the past history of several failed agents as well as the fact that presently available agents are few, and generally utilized as monotherapy. The recent FDA approval of the fixed drug combination of phentermine and extended release topiramate (topiramate-ER) (trade name Qsymia™) marks the first FDA approved combination pharmacotherapeutic agent for obesity since the Phen-Fen combination of the 1990s. This review details the history and clinical trial basis for the use of both phentermine and topiramate in obesity therapeutics as well as the results of clinical trials of their combination for obesity treatment in humans. The initial clinical approval trials offer evidence that this fixed drug combination offers synergistic potential for effective, robust and sustained weight loss with mean weight loss of at least 10% of baseline achieved and sustained for up to 2 years in over 50% of subjects treated. It is anticipated that this agent will be the first in a new trend of multi-agent combination therapy for the chronic adjunctive management of obesity. PMID:23630412

Evidence-Based Guidelines for Empirical Therapy of Neutropenic Fever in Korea

PubMed Central

Kim, Sung-Han; Kim, Soo Young; Kim, Chung-Jong; Park, Wan Beom; Song, Young Goo; Choi, Jung-Hyun

2011-01-01

Neutrophils play an important role in immunological function. Neutropenic patients are vulnerable to infection, and except fever is present, inflammatory reactions are scarce in many cases. Additionally, because infections can worsen rapidly, early evaluation and treatments are especially important in febrile neutropenic patients. In cases in which febrile neutropenia is anticipated due to anticancer chemotherapy, antibiotic prophylaxis can be used, based on the risk of infection. Antifungal prophylaxis may also be considered if long-term neutropenia or mucosal damage is expected. When fever is observed in patients suspected to have neutropenia, an adequate physical examination and blood and sputum cultures should be performed. Initial antibiotics should be chosen by considering the risk of complications following the infection; if the risk is low, oral antibiotics can be used. For initial intravenous antibiotics, monotherapy with a broad-spectrum antibiotic or combination therapy with two antibiotics is recommended. At 3-5 days after beginning the initial antibiotic therapy, the condition of the patient is assessed again to determine whether the fever has subsided or symptoms have worsened. If the patient's condition has improved, intravenous antibiotics can be replaced with oral antibiotics; if the condition has deteriorated, a change of antibiotics or addition of antifungal agents should be considered. If the causative microorganism is identified, initial antimicrobial or antifungal agents should be changed accordingly. When the cause is not detected, the initial agents should continue to be used until the neutrophil count recovers. PMID:21716917

Hypertension management: rationale for triple therapy based on mechanisms of action.

PubMed

Neutel, Joel M; Smith, David H G

2013-10-01

An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill, fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control. © 2012 John Wiley & Sons Ltd.

Initiation of biological agents in patients with ankylosing spondylitis: results of a Delphi study by the ASAS Group

PubMed Central

Pham, T; van der Heijde, D; Calin, A; Khan, M; van der Linden, S.; Bellamy, N; Dougados, M

2003-01-01

Background: There is ample evidence of important symptomatic efficacy of tumour necrosis factor α (TNFα) inhibition in ankylosing spondylitis (AS). Moreover, studies suggest that anti-TNF could be considered as the first disease controlling antirheumatic treatment (DC-ART) for AS. Objective: To determine precisely which patients with AS are most likely to benefit from anti-TNFα treatment because of the cost and possible long term side effects of such treatment. Methods: Assessment in Ankylosing Spondylitis (ASAS) members were asked to use a Delphi technique to name the characteristics of patients with AS for whom they would start DC-ART, in three different clinical presentations (isolated axial involvement, peripheral arthritis, enthesitis). Results: Among the 62 invited ASAS members, more than 50% actively participated in the four phases of definition according to the Delphi technique. For each of the three clinical presentations, a combination of five to six domains was proposed, with an evaluation instrument and a cut off point defining a minimum level of activity for each domain. Conclusion: This study provides a profile for a patient with AS for considering initiation of biological agents that reflects the opinion of the ASAS members, using a Delphi exercise. Further studies are required to assess their relevance and their consistency with clinical practice. PMID:12922951

Linking MODFLOW with an agent-based land-use model to support decision making

USGS Publications Warehouse

Reeves, H.W.; Zellner, M.L.

2010-01-01

The U.S. Geological Survey numerical groundwater flow model, MODFLOW, was integrated with an agent-based land-use model to yield a simulator for environmental planning studies. Ultimately, this integrated simulator will be used as a means to organize information, illustrate potential system responses, and facilitate communication within a participatory modeling framework. Initial results show the potential system response to different zoning policy scenarios in terms of the spatial patterns of development, which is referred to as urban form, and consequent impacts on groundwater levels. These results illustrate how the integrated simulator is capable of representing the complexity of the system. From a groundwater modeling perspective, the most important aspect of the integration is that the simulator generates stresses on the groundwater system within the simulation in contrast to the traditional approach that requires the user to specify the stresses through time. Copyright ?? 2010 The Author(s). Journal compilation ?? 2010 National Ground Water Association.

Symptoms of Gulf War veterans possibly exposed to organophosphate chemical warfare agents at Khamisiyah, Iraq.

PubMed

McCauley, L A; Rischitelli, G; Lambert, W E; Lasarev, M; Sticker, D L; Spencer, P S

2001-01-01

During the 1991 Gulf War, some Allied troops were potentially exposed to sarin/cyclosarin as the result of the destruction of Iraqi munitions at Khamisiyah. To evaluate the prevalence of past and current symptoms known to be associated with exposure to these chemical warfare agents, the authors conducted a computer-assisted telephone survey of 2,918 U.S. Gulf War veterans. Veterans who had participated in or witnessed the demolition in 1991 were more likely to report historical or extant symptoms than were veterans from other military units. These results should be viewed cautiously because they are based on symptoms recalled nine years after the event without precise characterization of exposure. Nonetheless, the findings suggest that symptoms consistent with low-level sarin exposure may have initially occurred, and health effects may have persisted in the veterans who were nearest to the demolition activity. Further research is warranted.

Deliberate or unintended: Intentions modulate empathic responses to others' economic payoffs in social interactions.

PubMed

Ma, Qingguo; Meng, Liang; Shen, Qiang

2017-12-01

Previous studies examining empathy have revealed the neural substrates of how the physical pain of others is represented in the human brain. However, little is known about the empathic modulation of behavioral and neural responses to others' economic payoffs, especially in the social context. In the present study, we engaged participants in a revised Dictator Game as observers who observe the powerless players receiving varied offers proposed by the dominant players, establishing the link between empathy and fairness perception. Results showed that unfair division schemes elicited a more pronounced FRN than fair ones only if a human agent proposed the initial offer. In addition, observers sacrificed their own payments to adjust unfair proposals, especially when a human agent proposed the offer. Thus, results of the current study demonstrated that perceived intention modulates behavioral and neural responses to others' economic payoffs in social interactions.

A hybrid model for opinion formation

NASA Astrophysics Data System (ADS)

Borra, Domenica; Lorenzi, Tommaso

2013-06-01

This paper presents a hybrid model for opinion formation in a large group of agents exposed to the persuasive action of a small number of strong opinion leaders. The model is defined by coupling a finite difference equation for the dynamics of leaders opinion with a continuous integro-differential equation for the dynamics of the others. Such a definition stems from the idea that the leaders are few and tend to retain original opinions, so that their dynamics occur on a longer time scale with respect to the one of the other agents. A general well-posedness result is established for the initial value problem linked to the model. The asymptotic behavior in time of the related solution is characterized for some general parameter settings, which mimic distinct social scenarios, where different emerging behaviors can be observed. Analytical results are illustrated and extended through numerical simulations.

Final Report

NASA Technical Reports Server (NTRS)

1995-01-01

This cooperative agreement explored the novel polymerization of vinylsilane, alone and in combination with other alkenylsilanes, alkylsilanes, and/or crosslinking agents, using dimethyltitanocene as homogeneous catalyst. The reactions were found to be initiated photochemically under mild conditions, and no hydrogen gas was evolved when alkenylsilanes were polymerized. The polymers were found to have predominately a carbosilane-type backbone containing -SiH2-CH2-CH2-Si and -SiH2-CH(CH3)-Si type linkages. The mechanism of polymerization was found to be step-growth. Despite the relatively low molecular weight of the polymer (M(sub n) - 500 and M(sub W) - 1500), pyrolysis resulted in conversion to C-rich SiC ceramic in high char yields (-60%). Copolymerization with methylsilane resulted in higher chars and more crystalline polymer. Addition of crosslinking agents such as polybutadiene or methyltrivinylsilane increased the viscosity of the polymer produced and enabled application as coatings to fiber toes.

Comparison between maximum radial expansion of ultrasound contrast agents and experimental postexcitation signal results.

PubMed

King, Daniel A; O'Brien, William D

2011-01-01

Experimental postexcitation signal data of collapsing Definity microbubbles are compared with the Marmottant theoretical model for large amplitude oscillations of ultrasound contrast agents (UCAs). After taking into account the insonifying pulse characteristics and size distribution of the population of UCAs, a good comparison between simulated results and previously measured experimental data is obtained by determining a threshold maximum radial expansion (Rmax) to indicate the onset of postexcitation. This threshold Rmax is found to range from 3.4 to 8.0 times the initial bubble radius, R0, depending on insonification frequency. These values are well above the typical free bubble inertial cavitation threshold commonly chosen at 2R0. The close agreement between the experiment and models suggests that lipid-shelled UCAs behave as unshelled bubbles during most of a large amplitude cavitation cycle, as proposed in the Marmottant equation.

Characterization of seed nuclei in glucagon aggregation using light scattering methods and field-flow fractionation

PubMed Central

Hoppe, Cindy C; Nguyen, Lida T; Kirsch, Lee E; Wiencek, John M

2008-01-01

Background Glucagon is a peptide hormone with many uses as a therapeutic agent, including the emergency treatment of hypoglycemia. Physical instability of glucagon in solution leads to problems with the manufacture, formulation, and delivery of this pharmaceutical product. Glucagon has been shown to aggregate and form fibrils and gels in vitro. Small oligomeric precursors serve to initiate and nucleate the aggregation process. In this study, these initial aggregates, or seed nuclei, are characterized in bulk solution using light scattering methods and field-flow fractionation. Results High molecular weight aggregates of glucagon were detected in otherwise monomeric solutions using light scattering techniques. These aggregates were detected upon initial mixing of glucagon powder in dilute HCl and NaOH. In the pharmaceutically relevant case of acidic glucagon, the removal of aggregates by filtration significantly slowed the aggregation process. Field-flow fractionation was used to separate aggregates from monomeric glucagon and determine relative mass. The molar mass of the large aggregates was shown to grow appreciably over time as the glucagon solutions gelled. Conclusion The results of this study indicate that initial glucagon solutions are predominantly monomeric, but contain small quantities of large aggregates. These results suggest that the initial aggregates are seed nuclei, or intermediates which catalyze the aggregation process, even at low concentrations. PMID:18613970

South Carolina's Model for Initiating Hispanic 4-H Clubs

ERIC Educational Resources Information Center

Lippert, Robert; Rembert, Kellye

2012-01-01

Over the past 5 years, through the initiative of several county Extension agents, South Carolina 4-H has established a successful model for bringing Hispanic youth into our program. We have found the most effective method is to initiate contact and establish partnerships with the principals and ESOL instructors in the local schools. Through this…

Scientific and Popular Health Knowledge in the Education Work of Community Health Agents in Rio de Janeiro Shantytowns

ERIC Educational Resources Information Center

Zanchetta, M. S.; Kolawole Salami, B.; Perreault, M.; Leite, L. C.

2012-01-01

Health education for socially marginalized populations challenges the efficacy of existing strategies and methods, and the pertinence of the educational and philosophical principles that underpin them. The Brazilian Community Health Agents Initiative (CHAI) hires residents of deprived marginalized communities to undertake health promotion and…

Bootstrapping Cognition from Behavior--A Computerized Thought Experiment

ERIC Educational Resources Information Center

Moller, Ralf; Schenck, Wolfram

2008-01-01

We show that simple perceptual competences can emerge from an internal simulation of action effects and are thus grounded in behavior. A simulated agent learns to distinguish between dead ends and corridors without the necessity to represent these concepts in the sensory domain. Initially, the agent is only endowed with a simple value system and…

Are three colonies of Neostromboceros albicomus, a candidate biological control agent for Lygodium microphyllum, the same host biotype?

USDA-ARS?s Scientific Manuscript database

Three colonies of Neostromboceros albicomus, a candidate biological control agent of Lygodium microphyllum, were barcoded using the D2 expansion domain, to determine which of two biotypes they represented. The first colony, collected in 2005 & 2007, was used for the initial host range testing. Colon...

Computation of the target state and feedback controls for time optimal consensus in multi-agent systems

NASA Astrophysics Data System (ADS)

Mulla, Ameer K.; Patil, Deepak U.; Chakraborty, Debraj

2018-02-01

N identical agents with bounded inputs aim to reach a common target state (consensus) in the minimum possible time. Algorithms for computing this time-optimal consensus point, the control law to be used by each agent and the time taken for the consensus to occur, are proposed. Two types of multi-agent systems are considered, namely (1) coupled single-integrator agents on a plane and, (2) double-integrator agents on a line. At the initial time instant, each agent is assumed to have access to the state information of all the other agents. An algorithm, using convexity of attainable sets and Helly's theorem, is proposed, to compute the final consensus target state and the minimum time to achieve this consensus. Further, parts of the computation are parallelised amongst the agents such that each agent has to perform computations of O(N2) run time complexity. Finally, local feedback time-optimal control laws are synthesised to drive each agent to the target point in minimum time. During this part of the operation, the controller for each agent uses measurements of only its own states and does not need to communicate with any neighbouring agents.

The next generation of sepsis trials: What’s next after the demise of recombinant human activated Protein C?

PubMed Central

Opal, Steven M.; Dellinger, R. Phillip; Vincent, Jean-Louis; Masur, Henry; Angus, Derek C.

2014-01-01

Progress in the development of novel therapeutics to treat sepsis has come to virtual standstill. While enormous strides have been made in the understanding of basic molecular mechanisms that underlie the pathophysiology of sepsis, a distressingly long list of novel therapeutic agents have been tested in large clinical trials over the past 25 years without a single, specific, immunomodulating agent showing consistent benefit in sepsis trials. The only novel anti-sepsis agent to successfully complete a phase 3 sepsis trial, human recombinant activated protein C, was recently taken off the market after a follow up placebo-controlled trial (PROWESS SHOCK) failed to replicate the results of the initial registration trial (PROWESS) performed 10 yr earlier. We must critically re-examine our basic approach in the preclinical and clinical evaluation of new sepsis therapies. We propose 12 specific recommendations that if implemented could improve the outlook for developing new drugs for sepsis. PMID:24717456

Influence of aluminium nitride as a foaming agent on the preparation of foam glass-ceramics from high-titanium blast furnace slag

NASA Astrophysics Data System (ADS)

Shi, Huan; Feng, Ke-qin; Wang, Hai-bo; Chen, Chang-hong; Zhou, Hong-ling

2016-05-01

To effectively reuse high-titanium blast furnace slag (TS), foam glass-ceramics were successfully prepared by powder sintering at 1000°C. TS and waste glass were used as the main raw materials, aluminium nitride (AlN) as the foaming agent, and borax as the fluxing agent. The influence of the amount of AlN added (1wt%-5wt%) on the crystalline phases, microstructure, and properties of the produced foam glass-ceramics was studied. The results showed that the main crystal phases were perovskite, diopside, and augite. With increasing AlN content, a transformation from diopside to augite occurred and the crystallinity of the pyroxene phases slightly decreased. Initially, the average pore size and porosity of the foam glass-ceramics increased and subsequently decreased; similarly, their bulk density and compressive strength decreased and subsequently increased. The optimal properties were obtained when the foam glass-ceramics were prepared by adding 4wt% AlN.

Pairing of heterochromatin in response to cellular stress.

PubMed

Abdel-Halim, H I; Mullenders, L H F; Boei, J J W A

2006-07-01

We previously reported that exposure of human cells to DNA-damaging agents (X-rays and mitomycin C (MMC)) induces pairing of the homologous paracentromeric heterochromatin of chromosome 9 (9q12-13). Here, we show that UV irradiation and also heat shock treatment of human cells lead to similar effects. Since the various agents induce very different types and frequencies of damage to cellular constituents, the data suggest a general stress response as the underlying mechanism. Moreover, local UV irradiation experiments revealed that pairing of heterochromatin is an event that can be triggered without induction of DNA damage in the heterochromatic sequences. The repair deficient xeroderma pigmentosum cells (group F) previously shown to fail pairing after MMC displayed elevated pairing after heat shock treatment but not after UV exposure. Taken together, the present results indicate that pairing of heterochromatin following exposure to DNA-damaging agents is initiated by a general stress response and that the sensing of stress or the maintenance of the paired status of the heterochromatin might be dependent on DNA repair.

Emerging insights into resistance to BRAF inhibitors in melanoma.

PubMed

Bucheit, Amanda D; Davies, Michael A

2014-02-01

Melanoma is the most aggressive form of skin cancer. The treatment of patients with advanced melanoma is rapidly evolving due to an improved understanding of molecular drivers of this disease. Somatic mutations in BRAF are the most common genetic alteration found in these tumors. Recently, two different mutant-selective small molecule inhibitors of BRAF, vemurafenib and dabrafenib, have gained regulatory approval based on positive results in randomized phase III trials. While the development of these agents represents a landmark in the treatment of melanoma, the benefit of these agents is limited by the frequent and rapid onset of resistance. The identification of several molecular mechanisms of resistance to BRAF inhibitors is rapidly leading to the clinical testing of combinatorial strategies to improve the clinical benefit of these agents. These mechanisms, and the lessons learned from the initial testing of the BRAF inhibitors, provide multiple insights that may facilitate the development of targeted therapies against other oncogenic mutations in melanoma, as well as in other cancers. Copyright © 2013 Elsevier Inc. All rights reserved.

Detection of early changes in lung cell cytology by flow-systems analysis techniques. Progress report, January 1--December 31, 1978. [Resulting from exposure to toxic agents associated with production and use of synthetic fuels from oil shale and coal

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

Steinkamp, J.A.; Wilson, J.S.; Svitra, Z.V.

1979-02-01

This report summarizes ongoing experiments to develop cytological and biochemical indicators for measuring damage to respiratory tract cells of experimental animals exposed by inhalation to environmental toxic agents. The specific goal is to apply flow cytometric methods to analyze and detect changes in lung epithelium as a function of exposure to toxic agents associated with the production and utilization of synthetic fuels from oil shale and coal. During the past 6 months, hamsters were exposed to raw and spent oil shale particulates, silica dust, and ozone, and DNA content measurements were performed on lung cell samples. Although initial shale exposuresmore » did not yield the expected results, recent data show atypical changes in DNA content per cell distributions. Ozone exposures also were expanded to include DNA measurements and cytology, ranging up to 72 h postexposure. Progress was achieved in developing a new method for quantitating pulmonary macrophage phagocytosis in rats using micron-sized fluorescent spheres. New methods for determining alkaline phosphatase, DNA content, and protein also were under development. Plans are to continue developing cytological and biochemical markers for measuring atypical cellular changes, including macrophage function, and to emphasize exposing experimental animals to particulates and gaseous agents for studying dose-damage relationships.« less

Antithrombotic agents intake prior to injury does not affect outcome after a traumatic brain injury in hospitalized elderly patients.

PubMed

Julien, Jessica; Alsideiri, Ghusn; Marcoux, Judith; Hasen, Mohammed; Correa, José A; Feyz, Mitra; Maleki, Mohammed; de Guise, Elaine

2017-04-01

The purpose of this study is to investigate the effect of risk factors including International Normalized Ratio (INR) as well as the Partial Thromboplastin Time (PTT) scores on several outcomes, including hospital length of stay (LOS) and The Extended Glasgow Outcome Scale (GOSE) following TBI in the elderly population. Data were retrospectively collected on patients (n=982) aged 65 and above who were admitted post TBI to the McGill University Health Centre-Montreal General Hospital from 2000 to 2011. Age, Injury Severity Score (ISS), Glasgow Coma Scale score (GCS), type of trauma (isolated TBI vs polytrauma including TBI), initial CT scan results according to the Marshall Classification and the INR and PTT scores and prescriptions of antiplatelet or anticoagulant agents (AP/AC) were collected. Results also indicated that age, ISS and GSC score have an effect on the GOSE score. We also found that taking AC/AP has an effect on GOSE outcome, but that this effects depends on PTT, with lower odds of a worse outcome for those taking AC/AP agents as the PTT value goes up. However, this effect only becomes significant as the PTT value reaches 60 and above. Age and injury severity rather than antithrombotic agent intake are associated with adverse acute outcome such as GOSE in hospitalized elderly TBI patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dual PET and Near-Infrared Fluorescence Imaging Probes as Tools for Imaging in Oncology

PubMed Central

An, Fei-Fei; Chan, Mark; Kommidi, Harikrishna; Ting, Richard

2016-01-01

OBJECTIVE The purpose of this article is to summarize advances in PET fluorescence resolution, agent design, and preclinical imaging that make a growing case for clinical PET fluorescence imaging. CONCLUSION Existing SPECT, PET, fluorescence, and MRI contrast imaging techniques are already deeply integrated into the management of cancer, from initial diagnosis to the observation and management of metastases. Combined positron-emitting fluorescent contrast agents can convey new or substantial benefits that improve on these proven clinical contrast agents. PMID:27223168

The effect of five kinds of surface treatment agents on the bond strength to various ceramics with thermocycle aging.

PubMed

Noda, Yukari; Nakajima, Masatoshi; Takahashi, Masahiro; Mamanee, Teerapong; Hosaka, Keiichi; Takagaki, Tomohiro; Ikeda, Masaomi; Foxton, Richard M; Tagami, Junji

2017-11-29

This study evaluated the effects of ceramic surface treatment agents on shear bond strengths to ceramic materials with and without thermocycling. Ceramic plates were prepared from feldspathic ceramic; AAA, lithium disilicate ceramic material; IPS e.max Press, zirconia ceramic; Lava. Ceramic surfaces were pretreated with one of five surface treatment agents (Clearfil PhotoBond mixed with Porcelainbond activator (PB), Clearfil SE One mixed with Porcelainbond activator (SO), Ceramic Primer (CP), Universal Primer (UP), Scotchbond Universal (SU)), and then a resin cement (Clapearl DC) was filled. After 0, 5,000, and 10,000 thermocycles, micro-shear bond strengths between ceramic-cement interfaces were determined. SU exhibited significantly lower initial bond strength to AAA and e.max than PB, SO, CP, and UP. For Lava, PB, SO, CP and SU exhibited higher initial bond strengths than UP. Thermocycles reduced bond strengths to all the ceramic materials with any surface treatment.

Using web technology and Java mobile software agents to manage outside referrals.

PubMed Central

Murphy, S. N.; Ng, T.; Sittig, D. F.; Barnett, G. O.

1998-01-01

A prototype, web-based referral application was created with the objective of providing outside primary care providers (PCP's) the means to refer patients to the Massachusetts General Hospital and the Brigham and Women's Hospital. The application was designed to achieve the two primary objectives of providing the consultant with enough data to make decisions even at the initial visit, and providing the PCP with a prompt response from the consultant. The system uses a web browser/server to initiate the referral and Java mobile software agents to support the workflow of the referral. This combination provides a light client implementation that can run on a wide variety of hardware and software platforms found in the office of the PCP. The implementation can guarantee a high degree of security for the computer of the PCP. Agents can be adapted to support the wide variety of data types that may be used in referral transactions, including reports with complex presentation needs and scanned (faxed) images Agents can be delivered to the PCP as running applications that can perform ongoing queries and alerts at the office of the PCP. Finally, the agent architecture is designed to scale in a natural and seamless manner for unforeseen future needs. PMID:9929190

Utilization of nonsteroidal anti-inflammatory drugs and antisecretory agents: a managed care claims analysis.

PubMed

Ofman, Joshua J; Badamgarav, Enkhe; Henning, James M; Knight, Kevin; Laine, Loren

2004-06-15

To describe patients initiating nonsteroidal anti-inflammatory drug (NSAID) therapy with regard to gastrointestinal and cardiac risks and patterns of antisecretory agent use, and to explore the relation between therapy type and subsequent outcomes. We studied patients aged 18 years or older who had continuous coverage from 1998 to 2001 and who had initiated treatment with cyclooxygenase-2 (COX-2) selective inhibitors or nonselective NSAIDs. Patients were categorized with respect to gastrointestinal and cardiac risk profiles. Proton pump inhibitor use within 15 days of initiating NSAID therapy was considered prophylactic. Logistic regression analysis was used to evaluate associations between treatment and hospitalization events, cardiac events, and health care costs. We identified 106,564 eligible NSAID initiators: 65.2% used COX-2 inhibitors and 34.8% used traditional NSAIDs. Users of COX-2 inhibitors were more likely to be at higher risk of gastrointestinal bleeding and cardiac events than were NSAID users. Proton pump inhibitor prophylaxis was most common among users of COX-2 inhibitors, but was only 11% in patients at high risk of gastrointestinal bleeding. There were no differences among treatment groups in terms of gastrointestinal or cardiac events. Initiation of COX-2 inhibitor therapy was associated with greater total health care costs. Although we found that COX-2 inhibitors were used more frequently than were traditional NSAIDs in certain groups of patients with varying cardiac or gastrointestinal risk, we did not find that their use resulted in reductions in clinical events, cotherapy with proton pump inhibitors, or costs, suggesting that a better understanding of the relation between NSAID treatment strategies and outcomes in patients with differing risk characteristics is needed.

Evolution of tag-based cooperation on Erdős-Rényi random graphs

NASA Astrophysics Data System (ADS)

Lima, F. W. S.; Hadzibeganovic, Tarik; Stauffer, Dietrich

2014-12-01

Here, we study an agent-based model of the evolution of tag-mediated cooperation on Erdős-Rényi random graphs. In our model, agents with heritable phenotypic traits play pairwise Prisoner's Dilemma-like games and follow one of the four possible strategies: Ethnocentric, altruistic, egoistic and cosmopolitan. Ethnocentric and cosmopolitan strategies are conditional, i.e. their selection depends upon the shared phenotypic similarity among interacting agents. The remaining two strategies are always unconditional, meaning that egoists always defect while altruists always cooperate. Our simulations revealed that ethnocentrism can win in both early and later evolutionary stages on directed random graphs when reproduction of artificial agents was asexual; however, under the sexual mode of reproduction on a directed random graph, we found that altruists dominate initially for a rather short period of time, whereas ethnocentrics and egoists suppress other strategists and compete for dominance in the intermediate and later evolutionary stages. Among our results, we also find surprisingly regular oscillations which are not damped in the course of time even after half a million Monte Carlo steps. Unlike most previous studies, our findings highlight conditions under which ethnocentrism is less stable or suppressed by other competing strategies.

Cell lineage tracing in the developing enteric nervous system: superstars revealed by experiment and simulation

PubMed Central

Cheeseman, Bevan L.; Zhang, Dongcheng; Binder, Benjamin J.; Newgreen, Donald F.; Landman, Kerry A.

2014-01-01

Cell lineage tracing is a powerful tool for understanding how proliferation and differentiation of individual cells contribute to population behaviour. In the developing enteric nervous system (ENS), enteric neural crest (ENC) cells move and undergo massive population expansion by cell division within self-growing mesenchymal tissue. We show that single ENC cells labelled to follow clonality in the intestine reveal extraordinary and unpredictable variation in number and position of descendant cells, even though ENS development is highly predictable at the population level. We use an agent-based model to simulate ENC colonization and obtain agent lineage tracing data, which we analyse using econometric data analysis tools. In all realizations, a small proportion of identical initial agents accounts for a substantial proportion of the total final agent population. We term these individuals superstars. Their existence is consistent across individual realizations and is robust to changes in model parameters. This inequality of outcome is amplified at elevated proliferation rate. The experiments and model suggest that stochastic competition for resources is an important concept when understanding biological processes which feature high levels of cell proliferation. The results have implications for cell-fate processes in the ENS. PMID:24501272

Analysis of Influence of Foaming Mixture Components on Structure and Properties of Foam Glass

NASA Astrophysics Data System (ADS)

Karandashova, N. S.; Goltsman, B. M.; Yatsenko, E. A.

2017-11-01

It is recommended to use high-quality thermal insulation materials to increase the energy efficiency of buildings. One of the best thermal insulation materials is foam glass - durable, porous material that is resistant to almost any effect of substance. Glass foaming is a complex process depending on the foaming mode and the initial mixture composition. This paper discusses the influence of all components of the mixture - glass powder, foaming agent, enveloping material and water - on the foam glass structure. It was determined that glass powder is the basis of the future material. A foaming agent forms a gas phase in the process of thermal decomposition. This aforementioned gas foams the viscous glass mass. The unreacted residue thus changes a colour of the material. The enveloping agent slows the foaming agent decomposition preventing its premature burning out and, in addition, helps to accelerate the sintering of glass particles. The introduction of water reduces the viscosity of the foaming mixture making it evenly distributed and also promotes the formation of water gas that additionally foams the glass mass. The optimal composition for producing the foam glass with the density of 150 kg/m3 is defined according to the results of the research.

Mechanisms of infection in the respiratory tract.

PubMed

Baskerville, A

1981-12-01

Related to its potential vulnerability the respiratory tract has a very complex and effective defence apparatus. The interaction between these defence mechanisms and certain characteristics of aetiological agents results in a pattern in which initial infections by these agents tend to occur at specific sites in the tract. Infections in which the primary portal of entry is in the upper respiratory tract include Bordetella bronchiseptica and Haemophilus spp in pigs; Pasteurella spp in cattle, sheep, pigs; Mycoplasma spp in cattle, sheep, pigs and poultry; equine herpesvirus 1 in horses; infectious bovine rhinotracheitis in cattle; parainfluenza 3 in cattle and sheep; infectious laryngo-tracheitis and infectious bronchitis in poultry; feline viral rhinotracheitis and calicivirus in cats; Aujeszky's disease virus and swine influenza in pigs; and equine influenza in horses. Infections in which the primary portal of entry is in the lower respiratory tract include Aspergillus fumigatus in poultry and mammals, respiratory syncytial virus in cattle, distemper virus in dogs and adenovirus in cattle and dogs. A fuller understanding of the interactions between an agent and the host at the point of entry would make it much easier to develop effective vaccines and therapeutic agents.

Distributed cooperative H∞ optimal tracking control of MIMO nonlinear multi-agent systems in strict-feedback form via adaptive dynamic programming

NASA Astrophysics Data System (ADS)

Luy, N. T.

2018-04-01

The design of distributed cooperative H∞ optimal controllers for multi-agent systems is a major challenge when the agents' models are uncertain multi-input and multi-output nonlinear systems in strict-feedback form in the presence of external disturbances. In this paper, first, the distributed cooperative H∞ optimal tracking problem is transformed into controlling the cooperative tracking error dynamics in affine form. Second, control schemes and online algorithms are proposed via adaptive dynamic programming (ADP) and the theory of zero-sum differential graphical games. The schemes use only one neural network (NN) for each agent instead of three from ADP to reduce computational complexity as well as avoid choosing initial NN weights for stabilising controllers. It is shown that despite not using knowledge of cooperative internal dynamics, the proposed algorithms not only approximate values to Nash equilibrium but also guarantee all signals, such as the NN weight approximation errors and the cooperative tracking errors in the closed-loop system, to be uniformly ultimately bounded. Finally, the effectiveness of the proposed method is shown by simulation results of an application to wheeled mobile multi-robot systems.

Fluorescence Detection of KRAS2 mRNA Hybridization in Lung Cancer Cells with PNA-Peptides Containing an Internal Thiazole Orange

PubMed Central

2015-01-01

We previously developed reporter-peptide nucleic acid (PNA)-peptides for sequence-specific radioimaging and fluorescence imaging of particular mRNAs in cells and tumors. However, a direct test for PNA-peptide hybridization with RNA in the cytoplasm would be desirable. Thiazole orange (TO) dye at the 5′ end of a hybridization agent shows a strong increase in fluorescence quantum yield when stacked upon a 5′ terminal base pair, in solution and in cells. We hypothesized that hybridization agents with an internal TO could distinguish a single base mutation in RNA. Thus, we designed KRAS2 PNA-IGF1 tetrapeptide agents with an internal TO adjacent to the middle base of the 12th codon, a frequent site of cancer-initiating mutations. Our molecular dynamics calculations predicted a disordered bulge with weaker hybridization resulting from a single RNA mismatch. We observed that single-stranded PNA-IGF1 tetrapeptide agents with an internal TO showed low fluorescence, but fluorescence escalated 5–6-fold upon hybridization with KRAS2 RNA. Circular dichroism melting curves showed ∼10 °C higher Tm for fully complementary vs single base mismatch TO-PNA-peptide agent duplexes with KRAS2 RNA. Fluorescence measurements of treated human lung cancer cells similarly showed elevated cytoplasmic fluorescence intensity with fully complementary vs single base mismatch agents. Sequence-specific elevation of internal TO fluorescence is consistent with our hypothesis of detecting cytoplasmic PNA-peptide:RNA hybridization if a mutant agent encounters the corresponding mutant mRNA. PMID:25180641

Waldenstrom Macroglobulinemia☆

PubMed Central

Leleu, Xavier; Roccaro, Aldo M.; Moreau, Anne-Sophie; Dupire, Sophie; Robu, Daniela; Gay, Julie; Hatjiharissi, Evdoxia; Burwik, Nicholas; Ghobrial, Irene M.

2011-01-01

In the past years, new developments have occurred both in the understanding of the biology of Waldenstrom Macroglobulinemia (WM) and in therapeutic options for WM. WM is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with demonstration of an IgM monoclonal gammopathy. Despite advances in therapy, WM remains incurable, with 5–6 years median overall survival of patients in symptomatic WM. Therapy is postponed for asymptomatic patients, and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. No specific agent or regimen has been shown to be superior to another for treatment of WM. As such, novel therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. These efforts have led to the development of several novel agents including the proteasome inhibitor bortezomib, and several Akt/mTor inhibitors, perifosine and Rad001, and immunomodulatory agents such as thalidomide and lenalidomide. Studies with monoclonal antibodies are ongoing and promising including the use of alemtuzumab, SGN-70, and the APRIL/BLYS blocking protein TACI-Ig atacicept. Other agents currently being tested in clinical trials include the PKC inhibitor enzastaurin, the natural product resveratrol, as well as the statin simvastatin. This report provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM. PMID:18555588

Impact of memory on opinion dynamics

NASA Astrophysics Data System (ADS)

Jędrzejewski, Arkadiusz; Sznajd-Weron, Katarzyna

2018-09-01

We investigate an agent-based model of opinion dynamics with two types of social response: conformity and independence. Conformity is introduced to the model analogously as in the Sznajd model or q-voter model, which means that only unanimous group exerts peer pressure on individuals. The novelty, in relation to previous versions of the q-voter model, is memory possessed by each agent and external noise T, which plays the role of social temperature. Each agent has its own memories of past experiences related to the social costs and benefits of being independent or conformist. If an agent was awarded in past more for being independent, it will have a greater tendency to be independent than conformist and vice versa. We will show that depending on the social temperature T the system spontaneously organizes into one of two regimes. Below a certain critical social temperature Tc, all agents in the society acquire personal traits (so called person state). Some of them become permanent conformists and others start to behave forever independently. This means that initially homogeneous population becomes heterogeneous, and agents respond differently to social influence. For T >Tc, all agents with equal probabilities behave independently or conform to peer pressure (so called situation state). This regime change between person and situation state, which reminds the idea of an annealed vs. quenched disorder, affects also public opinion. Particularly interesting results are obtained for individualistic societies, in which public opinion is non-monotonic function of T, which means that there is an optimal social temperature for which an agreement in the society is the highest.

A randomized prospective study of desflurane versus isoflurane in minimal flow anesthesia using “equilibration time” as the change-over point to minimal flow

PubMed Central

Mallik, Tanuja; Aneja, S; Tope, R; Muralidhar, V

2012-01-01

Background: In the administration of minimal flow anesthesia, traditionally a fixed time period of high flow has been used before changing over to minimal flow. However, newer studies have used “equilibration time” of a volatile anesthetic agent as the change-over point. Materials and Methods: A randomized prospective study was conducted on 60 patients, who were divided into two groups of 30 patients each. Two volatile inhalational anesthetic agents were compared. Group I received desflurane (n = 30) and group II isoflurane (n = 30). Both the groups received an initial high flow till equilibration between inspired (Fi) and expired (Fe) agent concentration were achieved, which was defined as Fe/Fi = 0.8. The mean (SD) equilibration time was obtained for both the agent. Then, a drift in end-tidal agent concentration during the minimal flow anesthesia and recovery profile was noted. Results: The mean equilibration time obtained for desflurane and isoflurane were 4.96 ± 1.60 and 16.96 ± 9.64 min (P < 0.001). The drift in end-tidal agent concentration over time was minimal in the desflurane group (P = 0.065). Recovery time was 5.70 ± 2.78 min in the desflurane group and 8.06 ± 31 min in the isoflurane group (P = 0.004). Conclusion: Use of equilibration time of the volatile anesthetic agent as a change-over point, from high flow to minimal flow, can help us use minimal flow anesthesia, in a more efficient way. PMID:23225926

Laser ablation of basal cell carcinomas guided by confocal microscopy

NASA Astrophysics Data System (ADS)

Sierra, Heidy; Cordova, Miguel; Nehal, Kishwer; Rossi, Anthony; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

2016-02-01

Laser ablation offers precise and fast removal of superficial and early nodular types of basal cell carcinomas (BCCs). Nevertheless, the lack of histological confirmation has been a limitation. Reflectance confocal microscopy (RCM) imaging combined with a contrast agent can offer cellular-level histology-like feedback to detect the presence (or absence) of residual BCC directly on the patient. We conducted an ex vivo bench-top study to provide a set of effective ablation parameters (fluence, number of passes) to remove superficial BCCs while also controlling thermal coagulation post-ablation to allow uptake of contrast agent. The results for an Er:YAG laser (2.9 um and pulse duration 250us) show that with 6 passes of 25 J/cm2, thermal coagulation can be effectively controlled, to allow both the uptake of acetic acid (contrast agent) and detection of residual (or absence) BCCs. Confirmation was provided with histological examination. An initial in vivo study on 35 patients shows that the uptake of contrast agent aluminum chloride) and imaging quality is similar to that observed in the ex vivo study. The detection of the presence of residual tumor or complete clearance was confirmed in 10 wounds with (additional) histology and in 25 lesions with follow-up imaging. Our results indicate that resolution is sufficient but further development and use of appropriate contrast agent are necessary to improve sensitivity and specificity. Advances in RCM technology for imaging of lateral and deep margins directly on the patient may provide less invasive, faster and less expensive image-guided approaches for treatment of BCCs.

Modeling the transport of cryoprotective agents in articular cartilage for cryopreservation

NASA Astrophysics Data System (ADS)

Torqabeh, Alireza Abazari

Loading vitrifiable concentrations of cryoprotective agents is an important step for cryopreservation of biological tissues by vitrification for research and transplantation purposes. This may be done by immersing the tissue in a cryoprotective agent (CPA) solution, and increasing the concentration, continuously or in multiple steps, and simultaneously decreasing the temperature to decrease the toxicity effects of the cryoprotective agent on the tissue cellular system. During cryoprotective agent loading, osmotic water movement from the tissue to the surrounding solution, and the resultant tissue shrinkage and stress-strain in the tissue matrix as well as on the cellular system can significantly alter the outcome of the cryopreservation protocol. In this thesis, a biomechanical model for articular cartilage is developed to account for the transport of the cryoprotective agent, the nonideal-nondilute properties of the vitrifiable solutions, the osmotic water movement and the resultant tissue shrinkage and stress-strain in the tissue matrix, and the osmotic volume change of the chondrocytes, during cryoprotective agent loading in the cartilage matrix. Four essential transport parameters needed for the model were specified, the values of which were obtained uniquely by fitting the model to experimental data from porcine articular cartilage. Then, it was shown that using real nonuniform initial distributions of water and fixed charges in cartilage, measured separately in this thesis using MRI, in the model can significantly affect the model predictions. The model predictions for dimethyl sulfoxide diffusion in porcine articular cartilage were verified by comparing to spatially and temporally resolved measurements of dimethyl sulfoxide concentration in porcine articular cartilage using a spectral MRI technique, developed for this purpose and novel to the field of cryobiology. It was demonstrated in this thesis that the developed mathematical model provides a novel tool for studying transport phenomena in cartilage during cryopreservation protocols, and can make accurate predictions for the quantities of interest for applications in the cryopreservation of articular cartilage.

An equation-free approach to agent-based computation: Bifurcation analysis and control of stationary states

NASA Astrophysics Data System (ADS)

Siettos, C. I.; Gear, C. W.; Kevrekidis, I. G.

2012-08-01

We show how the equation-free approach can be exploited to enable agent-based simulators to perform system-level computations such as bifurcation, stability analysis and controller design. We illustrate these tasks through an event-driven agent-based model describing the dynamic behaviour of many interacting investors in the presence of mimesis. Using short bursts of appropriately initialized runs of the detailed, agent-based simulator, we construct the coarse-grained bifurcation diagram of the (expected) density of agents and investigate the stability of its multiple solution branches. When the mimetic coupling between agents becomes strong enough, the stable stationary state loses its stability at a coarse turning point bifurcation. We also demonstrate how the framework can be used to design a wash-out dynamic controller that stabilizes open-loop unstable stationary states even under model uncertainty.

Agent-Supported Mission Operations Teamwork

NASA Technical Reports Server (NTRS)

Malin, Jane T.

2003-01-01

This slide presentation reviews the development of software agents to support of mission operations teamwork. The goals of the work was to make automation by agents easy to use, supervise and direct, manage information and communication to decrease distraction, interruptions, workload and errors, reduce mission impact of off-nominal situations and increase morale and decrease turnover. The accomplishments or the project are: 1. Collaborative agents - mixed initiative and creation of instructions for mediating agent 2. Methods for prototyping, evaluating and evolving socio-technical systems 3. Technology infusion: teamwork tools in mISSIons 4. Demonstrations in simulation testbed An example of the use of agent is given, the use of an agent to monitor a N2 tank leak. An incomplete instruction to the agent is handled with mediating assistants, or Intelligent Briefing and Response Assistant (IBRA). The IBRA Engine also watches data stream for triggers and executes Act-Whenever actions. There is also a Briefing and Response Instruction (BRI) which is easy for a discipline specialist to create through a BRI editor.

Scoping Planning Agents With Shared Models

NASA Technical Reports Server (NTRS)

Bedrax-Weiss, Tania; Frank, Jeremy D.; Jonsson, Ari K.; McGann, Conor

2003-01-01

In this paper we provide a formal framework to define the scope of planning agents based on a single declarative model. Having multiple agents sharing a single model provides numerous advantages that lead to reduced development costs and increase reliability of the system. We formally define planning in terms of extensions of an initial partial plan, and a set of flaws that make the plan unacceptable. A Flaw Filter (FF) allows us to identify those flaws relevant to an agent. Flaw filters motivate the Plan Identification Function (PIF), which specifies when an agent is is ready hand control to another agent for further work. PIFs define a set of plan extensions that can be generated from a model and a plan request. FFs and PIFs can be used to define the scope of agents without changing the model. We describe an implementation of PIFsand FFswithin the context of EUROPA, a constraint-based planning architecture, and show how it can be used to easily design many different agents.

Evacuation Simulation in Kalayaan Residence Hall, up Diliman Using Gama Simulation Software

NASA Astrophysics Data System (ADS)

Claridades, A. R. C.; Villanueva, J. K. S.; Macatulad, E. G.

2016-09-01

Agent-Based Modeling (ABM) has recently been adopted in some studies for the modelling of events as a dynamic system given a set of events and parameters. In principle, ABM employs individual agents with assigned attributes and behaviors and simulates their behavior around their environment and interaction with other agents. This can be a useful tool in both micro and macroscale-applications. In this study, a model initially created and applied to an academic building was implemented in a dormitory. In particular, this research integrates three-dimensional Geographic Information System (GIS) with GAMA as the multi-agent based evacuation simulation and is implemented in Kalayaan Residence Hall. A three-dimensional GIS model is created based on the floor plans and demographic data of the dorm, including respective pathways as networks, rooms, floors, exits and appropriate attributes. This model is then re-implemented in GAMA. Different states of the agents and their effect on their evacuation time were then observed. GAMA simulation with varying path width was also implemented. It has been found out that compared to their original states, panic, eating and studying will hasten evacuation, and on the other hand, sleeping and being on the bathrooms will be impedances. It is also concluded that evacuation time will be halved when path widths are doubled, however it is recommended for further studies for pathways to be modeled as spaces instead of lines. A more scientific basis for predicting agent behavior in these states is also recommended for more realistic results.

Opinion dynamics in two dimensions: domain coarsening leads to stable bi-polarization and anomalous scaling exponents

NASA Astrophysics Data System (ADS)

Velásquez-Rojas, F.; Vazquez, F.

2018-04-01

We study an opinion dynamics model that explores the competition between persuasion and compromise in a population of agents with nearest-neighbor interactions on a two-dimensional square lattice. Each agent can hold either a positive or a negative opinion orientation, and can have two levels of intensity—moderate and extremist. When two interacting agents have the same orientation they become extremists with persuasion probability p, while if they have opposite orientations they become moderate with compromise probability q. These updating rules lead to the formation of same-opinion domains with a coarsening dynamics that depends on the ratio r  =  p/q. The population initially evolves to a centralized state for small r, where domains are composed of moderate agents and coarsening is without surface tension, and to a bi-polarized state for large r, where domains are formed by extremist agents and coarsening is driven by curvature. Consensus in an extreme opinion is finally reached in a time that scales with the population size N and r as for small r and as for large r. Bi-polarization could be quite stable when the system falls into a striped state where agents organize into single-opinion horizontal, vertical or diagonal bands. An analysis of the stripe dynamics towards consensus allows us to obtain an approximate expression for τ, which shows that the exponent 1.64 is a result of the diffusion of the stripe interfaces combined with their roughness properties.

New methodology for specific inhalation challenges with occupational agents

PubMed Central

2010-01-01

Background Inhalation challenges are used for diagnosing occupational asthma (OA). The initial methodology consisted of a "realistic" exposure without monitoring nor controlling exposure. Our aim was to design an equipment, called the GenaSIC, that allows the generation of various agents regardless of the formulation and to assess the feasibility of its use in patients investigated for OA. Results GenaSIC can generate lactose, flour, malt, isocyanates, formaldehyde and N-butyl acetate with precise and fairly stable concentrations. Using N-butyl-acetate as a control agent and real time measurement, we show that normal breathing has a negligible effect on the concentration. We exposed forty-four different subjects to a control agent and/or to a suspected occupational agent. Nineteen of the subjects were only exposed to N-butyl acetate as a control agent without experiencing any significant irritant effect (no significant changes in spirometry thereafter). Eight subjects who were exposed to both N-butyl acetate and formaldehyde did not show significant reactions. Seven subjects were exposed to dry particles (flour in six instances, malt in the other) and five showed immediate asthmatic reactions which changes in FEV1 from 20% to a maximum of 28%. Finally, ten subjects were exposed to isocyanates, four of whom showed a positive reaction, including one subject with immediate maximum changes in FEV1 of 22%. Conclusion GenaSIC offers the possibility of reliable and safe exposures to dry particles, formaldehyde and isocyanates in the investigation of OA. PMID:20534154

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors).

PubMed

Winthrop, K L; Mariette, X; Silva, J T; Benamu, E; Calabrese, L H; Dumusc, A; Smolen, J S; Aguado, J M; Fernández-Ruiz, M

2018-06-01

The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate risk of infection and no specific prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-α agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection. Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Agent-based model of angiogenesis simulates capillary sprout initiation in multicellular networks

PubMed Central

Walpole, J.; Chappell, J.C.; Cluceru, J.G.; Mac Gabhann, F.; Bautch, V.L.; Peirce, S. M.

2015-01-01

Many biological processes are controlled by both deterministic and stochastic influences. However, efforts to model these systems often rely on either purely stochastic or purely rule-based methods. To better understand the balance between stochasticity and determinism in biological processes a computational approach that incorporates both influences may afford additional insight into underlying biological mechanisms that give rise to emergent system properties. We apply a combined approach to the simulation and study of angiogenesis, the growth of new blood vessels from existing networks. This complex multicellular process begins with selection of an initiating endothelial cell, or tip cell, which sprouts from the parent vessels in response to stimulation by exogenous cues. We have constructed an agent-based model of sprouting angiogenesis to evaluate endothelial cell sprout initiation frequency and location, and we have experimentally validated it using high-resolution time-lapse confocal microscopy. ABM simulations were then compared to a Monte Carlo model, revealing that purely stochastic simulations could not generate sprout locations as accurately as the rule-informed agent-based model. These findings support the use of rule-based approaches for modeling the complex mechanisms underlying sprouting angiogenesis over purely stochastic methods. PMID:26158406

Agent-based model of angiogenesis simulates capillary sprout initiation in multicellular networks.

PubMed

Walpole, J; Chappell, J C; Cluceru, J G; Mac Gabhann, F; Bautch, V L; Peirce, S M

2015-09-01

Many biological processes are controlled by both deterministic and stochastic influences. However, efforts to model these systems often rely on either purely stochastic or purely rule-based methods. To better understand the balance between stochasticity and determinism in biological processes a computational approach that incorporates both influences may afford additional insight into underlying biological mechanisms that give rise to emergent system properties. We apply a combined approach to the simulation and study of angiogenesis, the growth of new blood vessels from existing networks. This complex multicellular process begins with selection of an initiating endothelial cell, or tip cell, which sprouts from the parent vessels in response to stimulation by exogenous cues. We have constructed an agent-based model of sprouting angiogenesis to evaluate endothelial cell sprout initiation frequency and location, and we have experimentally validated it using high-resolution time-lapse confocal microscopy. ABM simulations were then compared to a Monte Carlo model, revealing that purely stochastic simulations could not generate sprout locations as accurately as the rule-informed agent-based model. These findings support the use of rule-based approaches for modeling the complex mechanisms underlying sprouting angiogenesis over purely stochastic methods.

Hemostatic action of polyurethane foam with 55% polyethylene glycol compared to collagen and gelatin.

PubMed

Broekema, Ferdinand I; van Oeveren, Wim; Boerendonk, Andrea; Sharma, Prashant K; Bos, Rudolf R M

2016-08-12

For most topical hemostatic agents the mechanism of hemostatic action is not fully understood. This work aimed to investigate the hemostatic mechanism of action and viscoelastic properties of polyurethane foam (PU) in comparison to the widely used collagen and gelatin. The hemostatic mechanism of action of the materials was tested using human whole blood and platelet-poor plasma (PPP). The ability of the hemostatic agent to exert pressure on the wound was quantified in terms of its viscoelastic properties both under dry and wet conditions using a low load compression tester (LLCT). It has been shown that collagen and PU initiate hemostasis through both thrombocyte aggregation and contact activation of the coagulation cascade. Gelatin did not show improved thrombocyte aggregation or initiation of the coagulation cascade compared to the negative control group. PU is more firm under wet conditions and shows more springback than collagen and gelatin. We conclude that PU is promising as a topical hemostatic agent because it initiates both the coagulation cascade and thrombocyte aggregation. Furthermore, it has favorable viscoelastic properties compared to collagen and gelatin which leads to increased pressure on a wound.

42 CFR 422.2274 - Broker and agent requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... (that is, non-employee) or employed. (a) Agents and brokers must be compensated as follows: (1) An MA...) For renewals, must be an amount equal to 50 percent of the initial compensation in paragraph (a)(1)(i... for enrollment of a beneficiary into a plan, if any, must be made in accordance with paragraph (a)(1...

42 CFR 422.2274 - Broker and agent requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... (that is, non-employee) or employed. (a) Agents and brokers must be compensated as follows: (1) An MA...) For renewals, must be an amount equal to 50 percent of the initial compensation in paragraph (a)(1)(i... for enrollment of a beneficiary into a plan, if any, must be made in accordance with paragraph (a)(1...

42 CFR 423.2274 - Broker and agent requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... (that is, non-employee) or employed. (a) Agents and brokers must be compensated as follows: (1) A Part D...) For renewals, must be an amount equal to 50 percent of the initial compensation in paragraph (a)(1)(i... of a beneficiary into a plan, if any, must be made in accordance with paragraph (a)(1) of this...

42 CFR 423.2274 - Broker and agent requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... (that is, non-employee) or employed. (a) Agents and brokers must be compensated as follows: (1) A Part D...) For renewals, must be an amount equal to 50 percent of the initial compensation in paragraph (a)(1)(i... of a beneficiary into a plan, if any, must be made in accordance with paragraph (a)(1) of this...

An effective intervention algorithm for promoting cooperation in the prisoner's dilemma game with multiple stable states

NASA Astrophysics Data System (ADS)

Li, Y. S.; Xu, C.; Hui, P. M.

2018-07-01

Multiple stable states, hysteresis, sensitivity to initial distributions, and a control algorithm for promoting cooperation are studied in an evolutionary prisoner's dilemma with agents connected into a regular random network. A system could evolve into states of different cooperative frequencies xc in different runs, even starting with the same initial cooperative frequency xc(in) and payoff parameters. For a large reward R, some values of xc(in) either take the system to a group of low cooperative frequency (LCF) states or to a few high cooperative frequency (HCF) states. These states differ by their network structures, with cooperative players connected into ring-like structure in LCF states and compact clusters in HCF states. Hysteresis in xc is observed when R is swept down and up, when the final state of the previous R is used as the initial state of the next R. The analysis led us to propose a closed pack cluster algorithm that gives HCF states effectively. The algorithm intervenes the system at some point in time by selectively switching some non-cooperative D-agents into cooperative C-agents at the peripheral of an existing cluster of C-agents. It ensures protection of a small C-cluster from which more cooperation can be induced. Practically, a governing body may first allow a society to evolve freely and then derive suitable policy to promote selected pockets of good practices for attaining a higher level of common good.

Mass diffusion coefficient measurement for vitreous humor using FEM and MRI

NASA Astrophysics Data System (ADS)

Rattanakijsuntorn, Komsan; Penkova, Anita; Sadha, Satwindar S.

2018-01-01

In early studies, the ‘contour method’ for determining the diffusion coefficient of the vitreous humor was developed. This technique relied on careful injection of an MRI contrast agent (surrogate drug) into the vitreous humor of fresh bovine eyes, and tracking the contours of the contrast agent in time. In addition, an analytical solution was developed for the theoretical contours built on point source model for the injected surrogate drug. The match between theoretical and experimental contours as a least square fit, while floating the diffusion coefficient, led to the value of the diffusion coefficient. This method had its limitation that the initial injection of the surrogate had to be spherical or ellipsoidal because of the analytical result based on the point-source model. With a new finite element model for the analysis in this study, the technique is much less restrictive and handles irregular shapes of the initial bolus. The fresh bovine eyes were used for drug diffusion study in the vitreous and three contrast agents of different molecular masses: gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA, 938 Da), non-ionic gadoteridol (Prohance, 559 Da), and bovine albumin conjugated with gadolinium (Galbumin, 74 kDa) were used as drug surrogates to visualize the diffusion process by MRI. The 3D finite element model was developed to determine the diffusion coefficients of these surrogates with the images from MRI. This method can be used for other types of bioporous media provided the concentration profile can be visualized (by methods such as MRI or fluorescence).

Theoretical effect of hyperventilation on speed of recovery and risk of rehypnotization following recovery - a GasMan® simulation.

PubMed

De Wolf, Andre M; Van Zundert, Tom C; De Cooman, Sofie; Hendrickx, Jan F

2012-09-18

Hyperventilation may be used to hasten recovery from general anesthesia with potent inhaled anesthetics. However, its effect may be less pronounced with the newer, less soluble agents, and it may result in rehypnotization if subsequent hypoventilation occurs because more residual anesthetic will be available in the body for redistribution to the central nervous system. We used GasMan® simulations to examine these issues. One MAC of isoflurane, sevoflurane, or desflurane was administered to a fictitious 70 kg patient for 8 h with normoventilation (alveolar minute ventilation [VA] 5 L.min-1), resulting in full saturation of the vessel rich group (VRG) and >95% saturation of the muscle group. After 8 h, agent administration was stopped, and fresh gas flow was increased to 10 L.min-1 to avoid rebreathing. At that same time, we continued with one simulation where normoventilation was maintained, while in a second simulation hyperventilation was instituted (10 L.min-1). We determined the time needed for the partial pressure in the VRG (FVRG; representing the central nervous system) to reach 0.3 MAC (MACawake). After reaching MACawake in the VRG, several degrees of hypoventilation were instituted (VA of 2.5, 1.5, 1, and 0.5 L.min-1) to determine whether FVRG would increase above 0.3 MAC(= rehypnotization). Time to reach 0.3 MAC in the VRG with normoventilation was 14 min 42 s with isoflurane, 9 min 12 s with sevoflurane, and 6 min 12 s with desflurane. Hyperventilation reduced these recovery times by 30, 18, and 13% for isoflurane, sevoflurane, and desflurane, respectively. Rehypnotization was observed with VA of 0.5 L.min-1 with desflurane, 0.5 and 1 L.min-1 with sevoflurane, and 0.5, 1, 1.5, and 2.5 L.min-1 with isoflurane. Only with isoflurane did initial hyperventilation slightly increase the risk of rehypnotization. These GasMan® simulations confirm that the use of hyperventilation to hasten recovery is marginally beneficial with the newer, less soluble agents. In addition, subsequent hypoventilation results in rehypnotization only with more soluble agents, unless hypoventilation is severe. Also, initial hyperventilation does not increase the risk of rehypnotization with less soluble agents when subsequent hypoventilation occurs. Well-controlled clinical studies are required to validate these simulations.

Activation of human herpesvirus replication by apoptosis.

PubMed

Prasad, Alka; Remick, Jill; Zeichner, Steven L

2013-10-01

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.

Activation of Human Herpesvirus Replication by Apoptosis

PubMed Central

Prasad, Alka; Remick, Jill

2013-01-01

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance. PMID:23885073

Nitrogen Trifluoride-Based Fluoride- Volatility Separations Process: Initial Studies

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

McNamara, Bruce K.; Scheele, Randall D.; Casella, Andrew M.

2011-09-28

This document describes the results of our investigations on the potential use of nitrogen trifluoride as the fluorinating and oxidizing agent in fluoride volatility-based used nuclear fuel reprocessing. The conceptual process uses differences in reaction temperatures between nitrogen trifluoride and fuel constituents that produce volatile fluorides to achieve separations and recover valuable constituents. We provide results from our thermodynamic evaluations, thermo-analytical experiments, kinetic models, and provide a preliminary process flowsheet. The evaluations found that nitrogen trifluoride can effectively produce volatile fluorides at different temperatures dependent on the fuel constituent.

Microvascular changes during acne lesion initiation and scarring is revealed in vivo using optical microangiography

NASA Astrophysics Data System (ADS)

Baran, Utku; Li, Yuandong; Choi, Woo J.; Wang, Ruikang K.

2015-02-01

Acne is a common skin disease in society and often leads to scarring. In this paper, we demonstrate the capabilities of swept-source optical coherence tomography (SS-OCT) in detecting specific features of acne lesion initiation and scarring on human facial skin in vivo over 30 days. Optical microangiography (OMAG) technique made it possible to image 3D tissue microvasculature changes up to 1 mm depth in vivo without the need of exogenous contrast agents in ~10 seconds. The presented results show promise to facilitate clinical trials of treatment and prognosis of acne vulgaris by detecting cutaneous microvasculature and structural changes within human skin in vivo.

Ontology of Earth's nonlinear dynamic complex systems

NASA Astrophysics Data System (ADS)

Babaie, Hassan; Davarpanah, Armita

2017-04-01

As a complex system, Earth and its major integrated and dynamically interacting subsystems (e.g., hydrosphere, atmosphere) display nonlinear behavior in response to internal and external influences. The Earth Nonlinear Dynamic Complex Systems (ENDCS) ontology formally represents the semantics of the knowledge about the nonlinear system element (agent) behavior, function, and structure, inter-agent and agent-environment feedback loops, and the emergent collective properties of the whole complex system as the result of interaction of the agents with other agents and their environment. It also models nonlinear concepts such as aperiodic, random chaotic behavior, sensitivity to initial conditions, bifurcation of dynamic processes, levels of organization, self-organization, aggregated and isolated functionality, and emergence of collective complex behavior at the system level. By incorporating several existing ontologies, the ENDCS ontology represents the dynamic system variables and the rules of transformation of their state, emergent state, and other features of complex systems such as the trajectories in state (phase) space (attractor and strange attractor), basins of attractions, basin divide (separatrix), fractal dimension, and system's interface to its environment. The ontology also defines different object properties that change the system behavior, function, and structure and trigger instability. ENDCS will help to integrate the data and knowledge related to the five complex subsystems of Earth by annotating common data types, unifying the semantics of shared terminology, and facilitating interoperability among different fields of Earth science.

Multiagent Systems Based Modeling and Implementation of Dynamic Energy Management of Smart Microgrid Using MACSimJX.

PubMed

Raju, Leo; Milton, R S; Mahadevan, Senthilkumaran

The objective of this paper is implementation of multiagent system (MAS) for the advanced distributed energy management and demand side management of a solar microgrid. Initially, Java agent development environment (JADE) frame work is used to implement MAS based dynamic energy management of solar microgrid. Due to unstable nature of MATLAB, when dealing with multithreading environment, MAS operating in JADE is linked with the MATLAB using a middle ware called Multiagent Control Using Simulink with Jade Extension (MACSimJX). MACSimJX allows the solar microgrid components designed with MATLAB to be controlled by the corresponding agents of MAS. The microgrid environment variables are captured through sensors and given to agents through MATLAB/Simulink and after the agent operations in JADE, the results are given to the actuators through MATLAB for the implementation of dynamic operation in solar microgrid. MAS operating in JADE maximizes operational efficiency of solar microgrid by decentralized approach and increase in runtime efficiency due to JADE. Autonomous demand side management is implemented for optimizing the power exchange between main grid and microgrid with intermittent nature of solar power, randomness of load, and variation of noncritical load and grid price. These dynamics are considered for every time step and complex environment simulation is designed to emulate the distributed microgrid operations and evaluate the impact of agent operations.

Multiagent Systems Based Modeling and Implementation of Dynamic Energy Management of Smart Microgrid Using MACSimJX

PubMed Central

Raju, Leo; Milton, R. S.; Mahadevan, Senthilkumaran

2016-01-01

The objective of this paper is implementation of multiagent system (MAS) for the advanced distributed energy management and demand side management of a solar microgrid. Initially, Java agent development environment (JADE) frame work is used to implement MAS based dynamic energy management of solar microgrid. Due to unstable nature of MATLAB, when dealing with multithreading environment, MAS operating in JADE is linked with the MATLAB using a middle ware called Multiagent Control Using Simulink with Jade Extension (MACSimJX). MACSimJX allows the solar microgrid components designed with MATLAB to be controlled by the corresponding agents of MAS. The microgrid environment variables are captured through sensors and given to agents through MATLAB/Simulink and after the agent operations in JADE, the results are given to the actuators through MATLAB for the implementation of dynamic operation in solar microgrid. MAS operating in JADE maximizes operational efficiency of solar microgrid by decentralized approach and increase in runtime efficiency due to JADE. Autonomous demand side management is implemented for optimizing the power exchange between main grid and microgrid with intermittent nature of solar power, randomness of load, and variation of noncritical load and grid price. These dynamics are considered for every time step and complex environment simulation is designed to emulate the distributed microgrid operations and evaluate the impact of agent operations. PMID:27127802

Chemical analysis of DC745 Materials: DEV Lot 1 reinvestigation; barcodes P053387, P053388, and P053389

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

Dirmyer, Matthew R.

This report serves as a follow up to our initial development lot 1 chemical analysis report (LA-UR-16-21970). The purpose of that report was to determine whether or not certain combinations of resin lots and curing agent lots resulted in chemical differences in the final material. One finding of that report suggested that pad P053389 was different from the three other pads analyzed. This report consists of chemical analysis of P053387, P053388, and a reinvestigation of P053389 all of which came from the potentially suspect combination of resin and curing agents lot. The goal of this report is to determine whethermore » the observations relating to P053389 were isolated to that particular pad or systemic to that combination of resin and curing agent lot. The following suite of analyses were performed on the pads: Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared Spectroscopy (FT-IR), and Solid State Nuclear Magnetic Resonance (NMR). The overall conclusions of the study are that pads P053387 and P053388 behave more consistently with the pads of other resin lot and curing agent lot combinations and that the chemical observations made regarding pad P053389 are isolated to that pad and not representative of an issue with that resin lot and curing agent lot combination.« less

Dentin Biomodification: Strategies, Renewable Resources and Clinical Applications

PubMed Central

Bedran-Russo, Ana K.; Pauli, Guido F.; Chen, Shao-Nong; McAlpine, James; Castellan, Carina S.; Phansalkar, Rasika S; Aguiar, Thaiane R.; Vidal, Cristina M.P.; Napotilano, José; Nam, Joo-Won; Leme, Ariene A.

2014-01-01

Objectives The biomodification of dentin is a biomimetic approach, mediated by bioactive agents, to enhance and reinforce the dentin by locally altering the biochemistry and biomechanical properties. This review provides an overview of key dentin matrix components, targeting effects of biomodification strategies, the chemistry of renewable natural sources, and current research on their potential clinical applications. Methods The PubMed database and collected literature were used as a resource for peer-reviewed articles to highlight the topics of dentin hierarchical structure, biomodification agents, and laboratorial investigations of their clinical applications. In addition, new data is presented on laboratorial methods for the standardization of proanthocyanidin-rich preparations as a renewable source of plant-derived biomodification agents. Results Biomodification agents can be categorized as physical methods and chemical agents. Synthetic and naturally occurring chemical strategies present distinctive mechanism of interaction with the tissue. Initially thought to be driven only by inter- or intra-molecular collagen induced non-enzymatic collagen cross-linking, multiple interactions with other dentin components are fundamental for the long-term biomechanics and biostability of the tissue. Oligomeric proanthocyanidins show promising bioactivity, and their chemical complexity requires systematic evaluation of the active compounds to produce a fully standardized intervention material from renewable resource, prior to their detailed clinical evaluation. Significance Understanding the hierarchical structure of dentin and the targeting effect of the bioactive compounds will establish their use in both dentin-biomaterials interface and caries management. PMID:24309436

Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine.

PubMed

Hussain, Arif; Mohsin, Javeria; Prabhu, Sathyen Alwin; Begum, Salema; Nusri, Qurrat El-Ain; Harish, Geetganga; Javed, Elham; Khan, Munawwar Ali; Sharma, Chhavi

2013-01-01

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- and time-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index (CI) <1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicity to normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment.

Curcumin: a promising agent targeting cancer stem cells.

PubMed

Zang, Shufei; Liu, Tao; Shi, Junping; Qiao, Liang

2014-01-01

Cancer stem cells are a subset of cells that are responsible for cancer initiation and relapse. They are generally resistant to the current anticancer agents. Successful anticancer therapy must consist of approaches that can target not only the differentiated cancer cells, but also cancer stem cells. Emerging evidence suggested that the dietary agent curcumin exerted its anti-cancer activities via targeting cancer stem cells of various origins such as those of colorectal cancer, pancreatic cancer, breast cancer, brain cancer, and head and neck cancer. In order to enhance the therapeutic potential of curcumin, this agent has been modified or used in combination with other agents in the experimental therapy for many cancers. In this mini-review, we discussed the effect of curcumin and its derivatives in eliminating cancer stem cells and the possible underlying mechanisms.

Infectious Agents Trigger Trophic Cascades.

PubMed

Buck, Julia C; Ripple, William J

2017-09-01

Most demonstrated trophic cascades originate with predators, but infectious agents can also cause top-down indirect effects in ecosystems. Here we synthesize the literature on trophic cascades initiated by infectious agents including parasitoids, pathogens, parasitic castrators, macroparasites, and trophically transmitted parasites. Like predators, infectious agents can cause density-mediated and trait-mediated indirect effects through their direct consumptive and nonconsumptive effects respectively. Unlike most predators, however, infectious agents are not fully and immediately lethal to their victims, so their consumptive effects can also trigger trait-mediated indirect effects. We find that the frequency of trophic cascades reported for different consumer types scales with consumer lethality. Furthermore, we emphasize the value of uniting predator-prey and parasite-host theory under a general consumer-resource framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

Agent-based simulation of a financial market

NASA Astrophysics Data System (ADS)

Raberto, Marco; Cincotti, Silvano; Focardi, Sergio M.; Marchesi, Michele

2001-10-01

This paper introduces an agent-based artificial financial market in which heterogeneous agents trade one single asset through a realistic trading mechanism for price formation. Agents are initially endowed with a finite amount of cash and a given finite portfolio of assets. There is no money-creation process; the total available cash is conserved in time. In each period, agents make random buy and sell decisions that are constrained by available resources, subject to clustering, and dependent on the volatility of previous periods. The model proposed herein is able to reproduce the leptokurtic shape of the probability density of log price returns and the clustering of volatility. Implemented using extreme programming and object-oriented technology, the simulator is a flexible computational experimental facility that can find applications in both academic and industrial research projects.

A review of nateglinide in the management of patients with type 2 diabetes

PubMed Central

Tentolouris, Nicholas; Voulgari, Christina; Katsilambros, Nicholas

2007-01-01

Impaired insulin secretion occurs early in the pathogenesis of type 2 diabetes mellitus (T2DM) and is chronic and progressive, resulting initially in impaired glucose tolerance (IGT) and eventually in T2DM. As most patients with T2DM have both insulin resistance and insulin deficiency, therapy for T2DM should aim to control not only fasting, but also postprandial plasma glucose levels. While oral glucose-lowering treatment with metformin and thiazolidinediones corrects fasting plasma glucose, these agents do not address the problem of mealtime glucose spikes that have been shown to trigger atherogenic processes. Nateglinide is a derivative of the amino acid D-phenylalanine, which acts directly on the pancreatic β-cells to stimulate insulin secretion. Nateglinide monotherapy controls significantly mealtime hyperglycemia and results in improved overall glycemic control in patients with T2DM by reducing glycosylated hemoglobin (HbA1c) levels. The combination of nateglinide with insulin-sensitising agents, such as metformin and thiazolidinediones, targets both insulin deficiency and insulin resistance and results in reductions in HbA1c that could not be achieved by monotherapy with other antidiabetic agents. In prediabetic subjects with IGT, nateglinide restores early insulin secretion and reduces postprandial hyperglycemia. Nateglinide has an excellent safety and tolerability profile and provides a lifetime flexibility that other antidiabetic agents could not accomplish. The aim of this review is to identify nateglinide as an effective “gate-keeper” in T2DM, since it restores early-phase insulin secretion and prevents mealtime glucose spikes throughout the day and to evaluate the results of ongoing research into its potential role in delaying the progression to overt diabetes and reducing its complications and mortality. PMID:18200800

Advances in acrylic-alkyd hybrid synthesis and characterization

NASA Astrophysics Data System (ADS)

Dziczkowski, Jamie

2008-10-01

In situ graft acrylic-alkyd hybrid resins were formed by polymerizing acrylic and acrylic-mixed monomers in the presence of alkyds by introduction of a free radical initiator to promote graft formation. Two-dimensional NMR, specifically gradient heteronuclear multiple quantum coherence (gHMQC), was used to clarify specific graft sites of the hybrid materials. Both individual and mixed-monomer systems were produced to determine any individual monomer preferences and to model current acrylic-alkyd systems. Different classes of initiators were used to determine any initiator effects on graft location. The 2D-NMR results confirm grafting at doubly allylic hydrogens located on the fatty acid chains and the polyol segment of the alkyd backbone. The gHMQC spectra show no evidence of grafting across double bonds on either pendant fatty acid groups or THPA unsaturation sites for any of the monomer or mixed monomer systems. It was also determined that choice of initiator has no effect on graft location. In addition, a design of experiments using response surface methodology was utilized to obtain a better understanding of this commercially available class of materials and relate both the chemical and physical properties to one another. A Box-Behnkin design was used, varying the oil length of the alkyd phase, the degree of unsaturation in the polyester backbone, and acrylic to alkyd ratio. Acrylic-alkyd hybrid resins were reduced with an amine/water mixture. Hydrolytic stability was tested and viscoelastic properties were obtained to determine crosslink density. Cured films were prepared and basic coatings properties were evaluated. It was found that the oil length of the alkyd is the most dominant factor for final coatings properties of the resins. Acrylic to alkyd ratio mainly influences the resin properties such as acid number, average molecular weight, and hydrolytic stability. The degree of unsaturation in the alkyd backbone has minimal effects on resin and film performance. Reversible-addition fragmentation polymerization techniques were employed to create a new class of acrylic-alkyd hybrid materials. Medium and long oil alkyds made from the monoglyceride process using soybean oil, glycerol, and phthalic anhydride were modified with a RAFT chain transfer agent. The alkyd macro-RAFT agents were reached by end-capping a medium oil soya-based alkyd with a carboxy-functional trithiocarbonate. The alkyd macro-RAFT agents were then used to create acrylic-alkyd block structures by polymerizing different acrylic monomers, including both acrylates and methacrylates in the presence of the macro-RAFT agent and 2, 2'-azobisisobutyronitrile (AIBN). Co-acrylic segments were reached by complete polymerization of one monomer followed by the addition of a second monomer and additional free radical initiator. The alkyds, macro-RAFT agents and, acrylic-alkyd blocks were characterized by size-exclusion chromatography (SEC), FTIR, and 1H-NMR. Pseudo-first-order kinetics behavior and conversion vs. molecular weight plots show that the RAFT-mediated reaction afforded a more controlled process for the synthesis of acrylated-alkyd materials. Preliminary coatings tests showed that material properties of acrylated-alkyds achieved by RAFT polymerization exhibit good overall coatings properties including adhesion, gloss, hardness, and impact resistance.

Finite-time consensus for multi-agent systems with globally bounded convergence time under directed communication graphs

NASA Astrophysics Data System (ADS)

Fu, Junjie; Wang, Jin-zhi

2017-09-01

In this paper, we study the finite-time consensus problems with globally bounded convergence time also known as fixed-time consensus problems for multi-agent systems subject to directed communication graphs. Two new distributed control strategies are proposed such that leaderless and leader-follower consensus are achieved with convergence time independent on the initial conditions of the agents. Fixed-time formation generation and formation tracking problems are also solved as the generalizations. Simulation examples are provided to demonstrate the performance of the new controllers.

The role of chemotherapy in the treatment of malignant astrocytomas.

PubMed

Mathieu, David; Fortin, David

2006-05-01

Malignant astrocytomas are aggressive neoplasms with a dismal prognosis despite optimal treatment. Maximal resective surgery is traditionally complemented by radiation therapy. Chemotherapy is now used on patients as initial therapy when their functional status is congruent with further treatment. The classic agents used are nitrosoureas, but temozolomide has taken the front seat recently, with recent data demonstrating increased survival when this agent is used concurrently with radiation therapy in newly diagnosed glioblastoma patients. A new class of agents, refered to as biological modifiers, are increasingly used in clinical trials in an effort to affect the intrinsic biologic aberrations harboured by tumor cells. These drugs comprise differentiation agents, anti-angiogenic agents, matrix-metalloproteinase inhibitors and signal transduction inhibitors, among others. This article reviews the standard cytotoxic agents that have been used to treat malignant astrocytomas, and the different combination regimens offering promise. In addition, recent advances with biological modifiers are also discussed.

Does estrogen play a role in response to adjuvant bone-targeted therapies?

PubMed Central

Russell, Kent; Amir, Eitan; Paterson, Alexander; Josse, Robert; Addison, Christina; Kuchuk, Iryna; Clemons, Mark

2013-01-01

Bone remains the most common site of breast cancer recurrence. The results of population studies, pre-clinical research and clinical studies in patients with metastatic disease provided a rationale for testing bone-targeted agents in the adjuvant setting. Despite the initial optimism, results from eight prospectively designed, randomized control studies powered to assess the value of adjuvant bone-targeted therapy in early breast cancer are conflicting. Data have shown that, where benefit exists, it tends to be in women with a “low estrogen environment”, either through menopause or suppression of ovarian function. In this manuscript, we review clinical data supporting the hypothesis that estrogen levels may play a part in explaining the response of patients to bone-targeted agents in the adjuvant setting. The results presented to date suggest that there may be data supporting a unifying role for estrogen in adjuvant trials. However, in the absence of any prospective randomized trials in which estrogen data has been systematically collected we cannot specifically answer this question. We await the results of the Oxford overview analysis of individual patient data with interest. PMID:26909288

42 CFR 423.2274 - Broker and agent requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

...: (a) Agents and brokers must be compensated as follows: (1) A Part D sponsor (or other entity on its... (a)(1)(i), individuals enrolling in a PDP in 2009 are initially deemed to be in the first renewal..., “like plan type” means PDP replaced with another PDP, MA or MA-PD replaced with another MA or MA-PD, or...

Creating a System for Data-Driven Decision-Making: Applying the Principal-Agent Framework

ERIC Educational Resources Information Center

Wohlstetter, Priscilla; Datnow, Amanda; Park, Vicki

2008-01-01

The purpose of this article is to improve our understanding of data-driven decision-making strategies that are initiated at the district or system level. We apply principal-agent theory to the analysis of qualitative data gathered in a case study of 4 urban school systems. Our findings suggest educators at the school level need not only systemic…

Decision theory with resource-bounded agents.

PubMed

Halpern, Joseph Y; Pass, Rafael; Seeman, Lior

2014-04-01

There have been two major lines of research aimed at capturing resource-bounded players in game theory. The first, initiated by Rubinstein (), charges an agent for doing costly computation; the second, initiated by Neyman (), does not charge for computation, but limits the computation that agents can do, typically by modeling agents as finite automata. We review recent work on applying both approaches in the context of decision theory. For the first approach, we take the objects of choice in a decision problem to be Turing machines, and charge players for the "complexity" of the Turing machine chosen (e.g., its running time). This approach can be used to explain well-known phenomena like first-impression-matters biases (i.e., people tend to put more weight on evidence they hear early on) and belief polarization (two people with different prior beliefs, hearing the same evidence, can end up with diametrically opposed conclusions) as the outcomes of quite rational decisions. For the second approach, we model people as finite automata, and provide a simple algorithm that, on a problem that captures a number of settings of interest, provably performs optimally as the number of states in the automaton increases. Copyright © 2014 Cognitive Science Society, Inc.

A new class of finite-time nonlinear consensus protocols for multi-agent systems

NASA Astrophysics Data System (ADS)

Zuo, Zongyu; Tie, Lin

2014-02-01

This paper is devoted to investigating the finite-time consensus problem for a multi-agent system in networks with undirected topology. A new class of global continuous time-invariant consensus protocols is constructed for each single-integrator agent dynamics with the aid of Lyapunov functions. In particular, it is shown that the settling time of the proposed new class of finite-time consensus protocols is upper bounded for arbitrary initial conditions. This makes it possible for network consensus problems that the convergence time is designed and estimated offline for a given undirected information flow and a group volume of agents. Finally, a numerical simulation example is presented as a proof of concept.

Effects of diversity on multiagent systems: Minority games

NASA Astrophysics Data System (ADS)

Wong, K. Y. Michael; Lim, S. W.; Gao, Zhuo

2005-06-01

We consider a version of large population games whose agents compete for resources using strategies with adaptable preferences. The games can be used to model economic markets, ecosystems, or distributed control. Diversity of initial preferences of strategies is introduced by randomly assigning biases to the strategies of different agents. We find that diversity among the agents reduces their maladaptive behavior. We find interesting scaling relations with diversity for the variance and other parameters such as the convergence time, the fraction of fickle agents, and the variance of wealth, illustrating their dynamical origin. When diversity increases, the scaling dynamics is modified by kinetic sampling and waiting effects. Analyses yield excellent agreement with simulations.

Adsorption study of a macro-RAFT agent onto SiO2-coated Gd2O3:Eu3+ nanorods: Requirements and limitations

NASA Astrophysics Data System (ADS)

Zou, Hua; Melro, Liliana; de Camargo Chaparro, Thaissa; de Souza Filho, Isnaldi Rodrigues; Ananias, Duarte; Bourgeat-Lami, Elodie; dos Santos, Amilton Martins; Barros-Timmons, Ana

2017-02-01

The use of a macromolecular RAFT (macro-RAFT) agent to encapsulate anisotropic nano-objects via emulsion polymerization is an emerging route to prepare polymer/inorganic colloidal nanocomposites. However, a number of requirements have to be fulfilled. This work aims at highlighting the effects of the preparative procedure and dispersion method on the amount of macro-RAFT agent adsorbed onto SiO2-coated Gd2O3:Eu3+ nanorods. The adsorption of macro-RAFT agent was studied using the depletion method with UV-vis spectrophotometry. Measurements were performed at a fixed concentration of nanorods and varying concentrations of the macro-RAFT agent in aqueous dispersion at room temperature. The adsorption isotherms showed that for the same initial macro-RAFT agent concentration, the highest adsorption capacity of the macro-RAFT agent on nanorods was usually achieved for non-calcined thin SiO2-coated nanorods under mild bath sonication.

A review of optical pacing with infrared light

NASA Astrophysics Data System (ADS)

Ford, S. M.; Watanabe, M.; Jenkins, M. W.

2018-02-01

Optical pacing (OP) uses pulsed infrared light to initiate heartbeats in electrically excitable cardiac tissues without employing exogenous agents. OP is an alternative approach to electrical pacing that may overcome some its disadvantages for some applications. In this review, we discuss the initial demonstrations, mechanisms, safety, advantages and applications of OP.

Context transfer in reinforcement learning using action-value functions.

PubMed

Mousavi, Amin; Nadjar Araabi, Babak; Nili Ahmadabadi, Majid

2014-01-01

This paper discusses the notion of context transfer in reinforcement learning tasks. Context transfer, as defined in this paper, implies knowledge transfer between source and target tasks that share the same environment dynamics and reward function but have different states or action spaces. In other words, the agents learn the same task while using different sensors and actuators. This requires the existence of an underlying common Markov decision process (MDP) to which all the agents' MDPs can be mapped. This is formulated in terms of the notion of MDP homomorphism. The learning framework is Q-learning. To transfer the knowledge between these tasks, the feature space is used as a translator and is expressed as a partial mapping between the state-action spaces of different tasks. The Q-values learned during the learning process of the source tasks are mapped to the sets of Q-values for the target task. These transferred Q-values are merged together and used to initialize the learning process of the target task. An interval-based approach is used to represent and merge the knowledge of the source tasks. Empirical results show that the transferred initialization can be beneficial to the learning process of the target task.

Enhancing the quality of aged latent fingerprints developed by superglue fuming: loss and replenishment of initiator.

PubMed

Wargacki, Stephen P; Lewis, Linda A; Dadmun, Mark D

2008-09-01

The recovery and identification of latent fingerprints from a crime scene are crucial to many investigations. The cyanoacrylate (superglue) fuming method (CFM), which develops fingerprints by growing a polymer coating over the print residue, is a powerful method but encounters severe limitations when prints are aged or exposed to harsh environmental conditions. We examine the aging process and how the changes that occur to a fingerprint residue over time influence the growth of polymer during development. We identify loss of initiator by erosion and degradation that, when coupled with a loss of water from the print residue, result in a decreased ability to polymerize ethylcyanoacrylate. Then, we present a methodology by which the ability of aged latent fingerprints to polymerize ethylcyanoacrylate is recovered. Two print enhancement agents, acetic acid and ammonia, are demonstrated to improve the growth of polymer from the print ridges by over an order of magnitude, while retaining the integrity of the print structure. Comparison between the two enhancement agents indicate that the enhancement occurs due to ridge coating by the ammonia or acetic acid and pH control of the latent print.

Evaluation of the Mental Healthiness Aging Initiative: community program to promote awareness about mental health and aging issues.

PubMed

Zanjani, Faika; Kruger, Tina; Murray, Deborah

2012-04-01

The objective of this study is to evaluate the Mental Healthiness Aging Initiative, designed to promote community awareness and knowledge about mental health and aging issues. This study occurred during 2007-2009 in 67 of 120 counties in Kentucky. A rural region (11 counties) received the intervention, consisting of focus groups, Extension Agent training, and television-based social marketing campaign. Partial-intervention counties (29 counties) received only the television-based social marketing campaign. The control counties (27 counties) received no intervention activities. Results indicated that the intervention counties agreed more with being able to assist elder adults with a potential mental illness. Also, the intervention counties understood the risk of consuming alcohol and medications better, but had a poorer recognition of drinking problems in elder adults. These findings need to be considered within study limitations, such as measurement error, degree of intervention exposure, and regional differences across intervention groups. The study demonstrates that community interventions on mental health awareness and knowledge are feasible within majority rural regions, with Extension Agents being gatekeepers, for promoting positive messages about mental health and aging issues.

Context Transfer in Reinforcement Learning Using Action-Value Functions

PubMed Central

Mousavi, Amin; Nadjar Araabi, Babak; Nili Ahmadabadi, Majid

2014-01-01

This paper discusses the notion of context transfer in reinforcement learning tasks. Context transfer, as defined in this paper, implies knowledge transfer between source and target tasks that share the same environment dynamics and reward function but have different states or action spaces. In other words, the agents learn the same task while using different sensors and actuators. This requires the existence of an underlying common Markov decision process (MDP) to which all the agents' MDPs can be mapped. This is formulated in terms of the notion of MDP homomorphism. The learning framework is Q-learning. To transfer the knowledge between these tasks, the feature space is used as a translator and is expressed as a partial mapping between the state-action spaces of different tasks. The Q-values learned during the learning process of the source tasks are mapped to the sets of Q-values for the target task. These transferred Q-values are merged together and used to initialize the learning process of the target task. An interval-based approach is used to represent and merge the knowledge of the source tasks. Empirical results show that the transferred initialization can be beneficial to the learning process of the target task. PMID:25610457

[Reservation forms of plague infectious agent in Tuva natural focus].

PubMed

Bazanova, L P; Innokent'eva, T I

2012-01-01

Data characterizing the reservation forms of plague infectious agent in Tuva natural focus are presented in the review. Yersinia pestis was shown to persist most of the year in Citellophilus tesquorum altaicus imago --the main carrier, getting into the animal organism only for a short time. An increased ability to aggregate in autumn and accumulate in clumps of C. tesquorum altaicus females that are more adapted to survive the cold season compared with males promote the persistence of the microorganism. The plague infectious agent in the altered form survives in the organism of females not only the winter period but also longer periods of time that is demonstrated by the facts of detection of it after 646 days of staying in the carrier. Moreover Yersinia pestis can persist for more than 400 days in the substrate of the nest of long-tailed ground squirrel infected by excrements and corpses of plague fleas. The substrate of the nest infected in summer-autumn period of the previous year may determine the primary infection of ground squirrels by plague infectious agent in the next epizootic season. On ground squirrels infected during contact with nest substrate, infection of intact fleas may be possible, and so the initiation of a new cycle of transmission of the infectious agent. Adaptation of the plague infectious agent to unfavorable existence conditions in the carrier is expressed in the changes of its morphology and ultrastructure that is evidenced by the facts of isolation of the infectious agent from corpses of fleas situated in the substrate, in the L-form, as well as results of phase-contrast and electron microscopy of the digestive tract of C. tesquorum altaicus.

Subharmonic emissions from microbubbles: effect of the driving pulse shape.

PubMed

Biagi, Elena; Breschi, Luca; Vannacci, Enrico; Masotti, Leonardo

2006-11-01

The aims of this work are to investigate the response of the ultrasonic contrast agents (UCA) insonified by different arbitrary-shaped pulses at different acoustic pressures and concentration of the contrast agent focusing on subharmonic emission. A transmission setup was developed in order to insonify the contrast agent contained in a measurement chamber. The transmitted ultrasonic signals were generated by an arbitrary wave generator connected to a linear power amplifier able to drive a single-element transducer. The transmitted ultrasonic pulses that passed through the contrast agent-filled chamber were received by a second transducer or a hydrophone aligned with the first one. The radio frequency (RF) signals were acquired by fast echographic multiparameters multi-image novel apparatus (FEMMINA), which is an echographic platform able to acquire ultrasonic signals in a real-time modality. Three sets of ultrasonic signals were devised in order to evaluate subharmonic response of the contrast agent respect with sinusoidal burst signals used as reference pulses. A decreasing up to 30 dB in subharmonic response was detected for a Gaussian-shaped pulse; differences in subharmonic emission up to 21 dB were detected for a composite pulse (two-tone burst) for different acoustic pressures and concentrations. Results from this experimentation demonstrated that the transmitted pulse shape strongly affects subharmonic emission in spite of a second harmonic one. In particular, the smoothness of the initial portion of the shaped pulses can inhibit subharmonic generation from the contrast agents respect with a reference sinusoidal burst signal. It also was shown that subharmonic generation is influenced by the amplitude and the concentration of the contrast agent for each set of the shaped pulses. Subharmonic emissions that derive from a nonlinear mechanism involving nonlinear coupling among different oscillation modes are strongly affected by the shape of the ultrasonic driving pulse.

Overcoming resistance to molecularly targeted anticancer therapies: Rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies.

PubMed

Tortora, Giampaolo; Bianco, Roberto; Daniele, Gennaro; Ciardiello, Fortunato; McCubrey, James A; Ricciardi, Maria Rosaria; Ciuffreda, Ludovica; Cognetti, Francesco; Tafuri, Agostino; Milella, Michele

2007-06-01

Accumulating evidence suggests that cancer can be envisioned as a "signaling disease", in which alterations in the cellular genome affect the expression and/or function of oncogenes and tumour suppressor genes. This ultimately disrupts the physiologic transmission of biochemical signals that normally regulate cell growth, differentiation and programmed cell death (apoptosis). From a clinical standpoint, signal transduction inhibition as a therapeutic strategy for human malignancies has recently achieved remarkable success. However, as additional drugs move forward into the clinical arena, intrinsic and acquired resistance to "targeted" agents becomes an issue for their clinical utility. One way to overcome resistance to targeted agents is to identify genetic and epigenetic aberrations underlying sensitivity/resistance, thus enabling the selection of patients that will most likely benefit from a specific therapy. Since resistance often ensues as a result of the concomitant activation of multiple, often overlapping, signaling pathways, another possibility is to interfere with multiple, cross-talking pathways involved in growth and survival control in a rational, mechanism-based, fashion. These concepts may be usefully applied, among others, to agents that target two major signal transduction pathways: the one initiated by epidermal growth factor receptor (EGFR) signaling and the one converging on mitogen-activated protein kinase (MAPK) activation. Here, we review the molecular mechanisms of sensitivity/resistance to EGFR inhibitors, as well as the rationale for combining them with other targeted agents, in an attempt to overcome resistance. In the second part of the paper, we review MAPK-targeted agents, focusing on their therapeutic potential in haematologic malignancies, and examine the prospects for combinations of MAPK inhibitors with cytotoxic agents or other signal transduction-targeted agents to obtain synergistic anti-tumour effects.

Overcoming resistance to molecularly targeted anticancer therapies: rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies

PubMed Central

Tortora, Giampaolo; Bianco, Roberto; Daniele, Gennaro; Ciardiello, Fortunato; McCubrey, James A; Ricciardi, Maria Rosaria; Ciuffreda, Ludovica; Cognetti, Francesco; Tafuri, Agostino; Milella, Michele

2007-01-01

Accumulating evidence suggests that cancer can be envisioned as a “signaling disease”, in which alterations in the cellular genome affect the expression and/or function of oncogenes and tumour suppressor genes. This ultimately disrupts the physiologic transmission of biochemical signals that normally regulate cell growth, differentiation and programmed cell death (apoptosis). From a clinical standpoint, signal transduction inhibition as a therapeutic strategy for human malignancies has recently achieved remarkable success. However, as additional drugs move forward into the clinical arena, intrinsic and acquired resistance to “targeted” agents becomes an issue for their clinical utility. One way to overcome resistance to targeted agents is to identify genetic and epigenetic aberrations underlying sensitivity/resistance, thus enabling the selection of patients that will most likely benefit from a specific therapy. Since resistance often ensues as a result of the concomitant activation of multiple, often overlapping, signaling pathways, another possibility is to interfere with multiple, cross-talking pathways involved in growth and survival control in a rational, mechanism-based, fashion. These concepts may be usefully applied, among others, to agents that target two major signal transduction pathways: the one initiated by epidermal growth factor receptor (EGFR) signaling and the one converging on mitogen-activated protein kinase (MAPK) activation. Here we review the molecular mechanisms of sensitivity/resistance to EGFR inhibitors, as well as the rationale for combining them with other targeted agents, in an attempt to overcome resistance. In the second part of the paper, we review MAPK-targeted agents, focusing on their therapeutic potential in hematologic malignancies, and examine the prospects for combinations of MAPK inhibitors with cytotoxic agents or other signal transduction-targeted agents to obtain synergistic anti-tumour effects. PMID:17482503

Diagnostic and Therapeutic Radiopharmaceutical Agents for Selective Discrimination of Prostate Cancer

DTIC Science & Technology

2008-10-01

complexing a M(CO)3 (Re,99mTc) organometallic species to target prostate cancer for imaging and therapy . The project has been successful in developing and...couple flutamide derivatives with new ligand systems. New methods were investigated on a fundamental level prior to functionalization with the ...based on the current results of the first generation compounds. The 2+1 approach was initially investigated for coupling the Tc(CO)3 to a multi

Coevolutionary network approach to cultural dynamics controlled by intolerance

NASA Astrophysics Data System (ADS)

Gracia-Lázaro, Carlos; Quijandría, Fernando; Hernández, Laura; Floría, Luis Mario; Moreno, Yamir

2011-12-01

Starting from Axelrod's model of cultural dissemination, we introduce a rewiring probability, enabling agents to cut the links with their unfriendly neighbors if their cultural similarity is below a tolerance parameter. For low values of tolerance, rewiring promotes the convergence to a frozen monocultural state. However, intermediate tolerance values prevent rewiring once the network is fragmented, resulting in a multicultural society even for values of initial cultural diversity in which the original Axelrod model reaches globalization.

Transforming Leadership in the FBI: A Recommendation for Strategic Change

DTIC Science & Technology

2007-03-01

move to another part of the country (rather than to innovate or to further develop bureau programs). The management system as it existed when I...Supervisory Special Agent Roger Trott who currently serves as the Executive Director of the FBI National Academy Associates. Trott championed the cause of...initiatives occurring in recent times have happened as a result of Trot’s foresight. When asked if the FBI is an organization that is well-led, Trott had

Chemical Stockpile Disposal Program. Chemical Agent and Munition Disposal. Summary of the U.S. Army’s Experience

DTIC Science & Technology

1987-09-21

a difficult process to control; continuous generation of acidic products results in the possibility of side reactions and in gaseous by- products . Ion...dissolved in hydrochlorlo acid. The acid chlorination forms non-toxic reaction products as per Figure 3-3. (2) To initiate the neutralization process ...et al, "Emission and Control of By- Products From Hazarduus Waste Combustion Processes ", Land Disposal, Remedial Action, Incineration and Treatment

Evaluation of Disinfection Techniques for, and Their Effects on, Rectal Thermocouple Catheters1

PubMed Central

Maher, J. T.; Rogers, M. R.; Peterson, D. W.

1961-01-01

The antibacterial activities of an iodophor (Wescodyne G), a quaternary ammonium compound (Roccal), and an iodine tincture as agents for the cold disinfection of rectal catheters contaminated in vitro were determined. Following thorough cleaning with an alcoholic solution of soft soap, each of the three disinfectants tested showed satisfactory results (100% kill) in 5 min against the enteric test bacteria (Escherichia coli and Salmonella typhosa) as well as a test species of the genus Pseudomonas, among the bacteria most resistant to surface-active agents. An aqueous solution of Wescodyne G containing 75 ppm available iodine was used both as a wiping solution and for subsequent disinfection of rectal catheters contaminated in vivo. Total bacterial destruction was found to follow a 60-min soak preceded by the wiping procedure. Rectal catheters subjected to prolonged immersion in each of the test disinfectants were found to be essentially unaffected, retaining their initial calibrations within a permissible tolerance. Neither Roccal nor Wescodyne G solutions were found to measurably attack bare thermocouples. Alcoholic iodine 0.5% did, however, exert a deteriorating effect on bare thermocouples in a short time, as measured by change in resistance characteristics. The results of this study have led to the recommendation that Wescodyne G containing 75 ppm available iodine be used in standing operating procedures for the initial cleaning and subsequent disinfection of rectal thermocouple catheters. Images Fig. 1 PMID:13765378

Timing and Characteristics of Cumulative Evidence Available on Novel Therapeutic Agents Receiving Food and Drug Administration Accelerated Approval.

PubMed

Naci, Huseyin; Wouters, Olivier J; Gupta, Radhika; Ioannidis, John P A

2017-06-01

Policy Points: Randomized trials-the gold standard of evaluating effectiveness-constitute a small minority of existing evidence on agents given accelerated approval. One-third of randomized trials are in therapeutic areas outside of FDA approval and less than half evaluate the therapeutic benefits of these agents but use them instead as common backbone treatments. Agents receiving accelerated approval are often tested concurrently in several therapeutic areas. For most agents, no substantial time lag is apparent between the average start dates of randomized trials evaluating their effectiveness and those using them as part of background therapies. There appears to be a tendency for therapeutic agents receiving accelerated approval to quickly become an integral component of standard treatment, despite potential shortcomings in their evidence base. Therapeutic agents treating serious conditions are eligible for Food and Drug Administration (FDA) accelerated approval. The clinical evidence accrued on agents receiving accelerated approval has not been systematically evaluated. Our objective was to assess the timing and characteristics of available studies. We first identified clinical studies of novel therapeutic agents receiving accelerated approval. We then (1) categorized those studies as randomized or nonrandomized, (2) explored whether they evaluated the FDA-approved indications, and (3) documented the available treatment comparisons. We also meta-analyzed the difference in start times between randomized studies that (1) did or did not evaluate approved indications and (2) were or were not designed to evaluate the agent's effectiveness. In total, 37 novel therapeutic agents received accelerated approval between 2000 and 2013. Our search of ClinicalTrials.gov identified 7,757 studies, which included 1,258,315 participants. Only one-third of identified studies were randomized controlled trials. Of 1,631 randomized trials with advanced recruitment status, 906 were conducted in therapeutic areas for which agents received initial accelerated approval, 202 were in supplemental indications, and 523 were outside approved indications. Only 411 out of 906 (45.4%) trials were designed to test the effectiveness of agents that received accelerated approval ("evaluation" trials); others used these agents as common background treatment in both arms ("background" trials). There was no detectable lag between average start times of trials conducted within and outside initially approved indications. Evaluation trials started on average 1.52 years (95% CI: 0.87 to 2.17) earlier than background trials. Cumulative evidence on agents with accelerated approvals has major limitations. Most clinical studies including these agents are small and nonrandomized, and about a third are conducted in unapproved areas, typically concurrently with those conducted in approved areas. Most randomized trials including these therapeutic agents are not designed to directly evaluate their clinical benefits but to incorporate them as standard treatment. © 2017 Milbank Memorial Fund.

Home composting using different ratios of bulking agent to food waste.

PubMed

Guidoni, Lucas Lourenço Castiglioni; Marques, Roger Vasques; Moncks, Rodrigo Bilhalva; Botelho, Fabiana Torma; da Paz, Matheus Francisco; Corrêa, Luciara Bilhalva; Corrêa, Érico Kunde

2018-02-01

The negative environmental impacts associated with home composting may be due to the absence of a defined operation criteria for the degradation process. In addition to the potentially low environmental impact in terms of energy and water usage, which is minimal to the manufacture of the composting unit and avoiding the processing and transportation of waste or byproduct, composting at home can also promote a reduction in the emission of unpleasant gases. The proportion of the food waste and bulking agents in the composting mixture may be decisive to fulfill good practices of waste stabilization. The aim of this study was to investigate how different ratios of bulking agent and organic household waste can affect the progress and outcome of the composting process. Three treatments, varying in the ratio of rice husk: raw fruit and vegetable leftovers (70:30, 50:50, 30:70; v:v) were used in a home composting system on a pilot scale. Results show that the proportion of starting materials used in the composting mixture influenced the degradation of organic matter, nitrogen dynamics of the process and its toxicity on germinating plants. The proportions with greater amounts of food waste had higher concentrations of mineral matter, higher peak temperature, and a better initial carbon-to-nitrogen ratio, while the proportion containing 70% of bulking agent lacked odors and leachate generation and showed a low nitrogen loss. A higher proportion of food waste presented better conditions for microbiological development and less time to obtain characteristics of matured composts. A higher proportion of bulking agents resulted in favorable conditions for household handling and less potential for environmental impacts. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Cybernetic Approach to the Modeling of Agent Communities

NASA Technical Reports Server (NTRS)

Truszkowski, Walt; Karlin, Jay

2000-01-01

In an earlier paper [1] examples of agent technology in a NASA context were presented. Both groundbased and space-based applications were addressed. This paper continues the discussion of one aspect of the Goddard Space Flight Center's continuing efforts to develop a community of agents that can support both ground-based and space-based systems autonomy. The paper focuses on an approach to agent-community modeling based on the theory of viable systems developed by Stafford Beer. It gives the status of an initial attempt to capture some of the agent-community behaviors in a viable system context. This paper is expository in nature and focuses on a discussion of the modeling of some of the underlying concepts and infrastructure that will serve as the basis of more detailed investigative work into the behavior of agent communities. The paper is organized as follows. First, a general introduction to agent community requirements is presented. Secondly, a brief introduction to the cybernetic concept of a viable system is given. This concept forms the foundation of the modeling approach. Then the concept of an agent community is modeled in the cybernetic context.

Overcoming Chloroquine Resistance in Malaria: Design, Synthesis, and Structure-Activity Relationships of Novel Hybrid Compounds

PubMed Central

Boudhar, Aicha; Ng, Xiao Wei; Loh, Chiew Yee; Chia, Wan Ni; Tan, Zhi Ming; Nosten, Francois

2016-01-01

Resistance to antimalarial therapies, including artemisinin, has emerged as a significant challenge. Reversal of acquired resistance can be achieved using agents that resensitize resistant parasites to a previously efficacious therapy. Building on our initial work describing novel chemoreversal agents (CRAs) that resensitize resistant parasites to chloroquine (CQ), we herein report new hybrid single agents as an innovative strategy in the battle against resistant malaria. Synthetically linking a CRA scaffold to chloroquine produces hybrid compounds with restored potency toward a range of resistant malaria parasites. A preferred compound, compound 35, showed broad activity and good potency against seven strains resistant to chloroquine and artemisinin. Assessment of aqueous solubility, membrane permeability, and in vitro toxicity in a hepatocyte line and a cardiomyocyte line indicates that compound 35 has a good therapeutic window and favorable drug-like properties. This study provides initial support for CQ-CRA hybrid compounds as a potential treatment for resistant malaria. PMID:26953199

Goal striving within agentic and communal roles: separate but functionally similar pathways to enhanced well-being.

PubMed

Sheldon, Kennon M; Cooper, M Lynne

2008-06-01

Do agency and communion strivings provide functionally similar but predictively independent pathways to enhanced well-being? We tested this idea via a year-long study of 493 diverse community adults. Our process model, based on self-determination and motive disposition theories, fit the data well. First, the need for achievement predicted initial autonomous motivation for agentic (work and school) role-goals and the need for intimacy predicted felt autonomy for communal (relationship and parenting) goals. For both agentic and communal goals, autonomous motivation predicted corresponding initial expectancies that predicted later goal attainment. Finally, each type of attainment predicted improved adjustment or role-satisfaction over the year. Besides being similar across agency and communion, the model was also similar across race and gender, except that the beneficial effects of communal goal attainment were stronger for high need for intimacy women and Blacks. Implications for agency/communion theories, motivation theories, and theories of well-being are discussed.

Do two and three year old children use an incremental first-NP-as-agent bias to process active transitive and passive sentences?: A permutation analysis

PubMed Central

Chang, Franklin; Rowland, Caroline; Ferguson, Heather; Pine, Julian

2017-01-01

We used eye-tracking to investigate if and when children show an incremental bias to assume that the first noun phrase in a sentence is the agent (first-NP-as-agent bias) while processing the meaning of English active and passive transitive sentences. We also investigated whether children can override this bias to successfully distinguish active from passive sentences, after processing the remainder of the sentence frame. For this second question we used eye-tracking (Study 1) and forced-choice pointing (Study 2). For both studies, we used a paradigm in which participants simultaneously saw two novel actions with reversed agent-patient relations while listening to active and passive sentences. We compared English-speaking 25-month-olds and 41-month-olds in between-subjects sentence structure conditions (Active Transitive Condition vs. Passive Condition). A permutation analysis found that both age groups showed a bias to incrementally map the first noun in a sentence onto an agent role. Regarding the second question, 25-month-olds showed some evidence of distinguishing the two structures in the eye-tracking study. However, the 25-month-olds did not distinguish active from passive sentences in the forced choice pointing task. In contrast, the 41-month-old children did reanalyse their initial first-NP-as-agent bias to the extent that they clearly distinguished between active and passive sentences both in the eye-tracking data and in the pointing task. The results are discussed in relation to the development of syntactic (re)parsing. PMID:29049390

In vitro analysis of the physical properties of contact lens blister pack solutions.

PubMed

Menzies, Kara L; Jones, Lyndon

2011-04-01

Since the initial development of silicone hydrogels, many modifications to the bulk and surface properties of the lenses have been undertaken to improve the wettability and comfort of the lenses. Recently, manufacturers have incorporated various "wetting agents" or surface-active agents into the blister packaging solutions (BPSs) of the lenses to improve initial comfort of the lens on eye. The purpose of this study was to measure and compare the pH, surface tension (ST), viscosity, and osmolality of BPSs for a variety of silicone hydrogel and polyHEMA-based hydrogel lenses. In addition, two saline solutions were tested for comparison purposes. The pH, osmolality, ST, and viscosity were measured for the BPSs for lotrafilcon B and lotrafilcon A and lotrafilcon B with a "modified BPS" (m-lotrafilcon A, m-lotrafilcon B) (CIBA Vision, Duluth, GA); balafilcon A (Bausch & Lomb, Rochester, NY); galyfilcon A, senofilcon A, and narafilcon A (Johnson & Johnson, Jacksonville, FL); and comfilcon A and enfilcon A (CooperVision, Pleasanton, CA) and BPSs from two conventional polyHEMA-based materials-etafilcon A (Johnson & Johnson) and omafilcon A (CooperVision). The two saline solutions tested were Unisol (Alcon, Fort Worth, TX) and Softwear Saline (CIBA Vision). The pH results for the two saline solutions and all BPSs remained in the pH range of tears (6.6-7.8). The ST of the modified BPS was significantly lower (p < 0.01) than the original non-modified BPS. Viscosity measurements ranged between 0.90 and 1.00 cP for all BPSs and saline solutions, except for the modified BPS, which had significantly higher viscosities (p < 0.001). Osmolality measurements were not significantly different (p > 0.05) between BPSs made by the same manufacturer but were significantly different compared with BPSs made by different manufacturers (p < 0.05). The incorporation of wetting agents and surfactants into BPSs does alter the physical properties of the BPSs, which may have clinical implications regarding initial in-eye comfort.

Current concepts in the pharmacological management of obesity.

PubMed

Carek, P J; Dickerson, L M

1999-06-01

The pharmacological management of obesity has gained increasing attention as new weight loss treatments are approved and a significant proportion of the public strives to lose weight. Obesity is associated with a high mortality rate, multiple chronic medical conditions, and carries an enormous financial burden. Obesity is a multifactorial condition, most often due to an imbalance in energy intake and expenditure. Despite the greater focus on management of obesity, weight loss remains a difficult goal to achieve. Obesity is a chronic medical condition that may require long term treatment, therefore the risks and benefits of all pharmacological agents must be carefully considered. Noradrenergic appetite suppressants (ie. phenyl-propanolamine, phentermine) result in weight loss but stimulatory effects limit their use. The serotonergic agents (fenfluramine, dexfenfluramine) were effective weight loss drugs, but were voluntarily withdrawn from the US market last year because of cardiovascular and pulmonary complications. The combination noradrenergic/serotonergic agent sibutramine is indicated for the management of obesity, particularly in the presence of other cardiovascular risk factors. Modest weight loss is achieved with sibutramine, although weight gain is significant after discontinuation. In addition, long term safety data are not yet available. The thermogenic combination of ephedrine plus caffeine is minimally effective, and adverse effects are usually transient. Other thermogenic agents, such as beta3-agonists, are still under investigation. Agents may alter digestion through lipase inhibition (orlistat) or fat substitution (olestra). Orlistat decreases systemic absorption of dietary fat, decreasing body weight and cholesterol. Olestra is a fat substitute that has been incorporated into snack foods. Olestra substitution for dietary fat has not been studied as a weight loss strategy, although olestra has no caloric value and may be beneficial. The use of orlistat and olestra may be limited by gastrointestinal adverse effects. Finally, the manipulation of leptin and neuropeptide Y are under investigation for the treatment of obesity. Pharmacological agents should be used as an aid to a structured diet and exercise regimen in the treatment of obesity. Weight loss agents may result in initial weight loss, but sustained weight loss is not always achieved even with continuation of treatment. The effect of weight loss obtained while using pharmacotherapeutic agents on morbidity and mortality has not been established. Therefore, diet and exercise should be the focus of any weight loss programme. There is a continued need for safe and effective pharmacotherapeutic agents for the treatment of obesity.

Identification of cancer specific ligands from one-bead one compound combinatorial libraries to develop theranostics agents against oral squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Yang, Frances Fan

Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent disease worldwide. One-bead one-compound (OBOC) combinatorial technology is a powerful method to identify peptidomimetic ligands against a variety of receptors on cell surfaces. We therefore hypothesized that cancer specific ligands against OSCC might be identified and can be conjugated to optical dyes or nanocarriers to develop theranostic agents against OSCC. Material and methods: Different OSCC cell lines were incubated with OBOC libraries and beads with cell binding were sorted and then screened with normal human cells to identify peptide-beads binding to different OSCC cell lines but not binding to normal human cells. The molecular probes of OSCC were developed by biotinylating the carboxyl end of the ligands. OSCC theranostic agents were developed by decorating LLY13 with NPs and evaluated by using orthotopic bioluminescent oral cancer model. Results: Six OSCC specific ligands were discovered. Initial peptide-histochemistry study indicated that LLY12 and LLY13 were able to specifically detect OSCC cells grown on chamber slides at the concentration of 1 muM. In addition, LLY13 was found to penetrate into the OSCC cells and accumulate in the cytoplasm, and nucleus. After screened with a panel of integrin antibodies, only anti-alpha3 antibody was able to block most of OSCC cells binding to the LLY13 beads. OSCC theranostic agents developed using targeting LLY13 micelles (25+/- 4nm in diameter) were more efficient in binding to HSC-3 cancer cells compared to non-targeting micelles. Ex vivo images demonstrated that xenografts from the mice with targeting micelles appeared to have higher signals than the non-targeting groups. Conclusion: LLY13 has promising in vitro and in vivo targeting activity against OSCC. In addition, LLY13 is also able to penetrate into cancer cells via endocytosis. Initial study indicated that alpha3 integrin might partially be the corresponding receptor involved for LLY13's binding to oral cancer cells. OSCC ligands developed from this study may become potential candidates for the development of OSCC targeted theranostic agents.

Ancestor of land plants acquired the DNA-3-methyladenine glycosylase (MAG) gene from bacteria through horizontal gene transfer.

PubMed

Fang, Huimin; Huangfu, Liexiang; Chen, Rujia; Li, Pengcheng; Xu, Shuhui; Zhang, Enying; Cao, Wei; Liu, Li; Yao, Youli; Liang, Guohua; Xu, Chenwu; Zhou, Yong; Yang, Zefeng

2017-08-24

The origin and evolution of land plants was an important event in the history of life and initiated the establishment of modern terrestrial ecosystems. From water to terrestrial environments, plants needed to overcome the enhanced ultraviolet (UV) radiation and many other DNA-damaging agents. Evolving new genes with the function of DNA repair is critical for the origin and radiation of land plants. In bacteria, the DNA-3-methyladenine glycosylase (MAG) recognizes of a variety of base lesions and initiates the process of the base excision repair for damaged DNA. The homologs of MAG gene are present in all major lineages of streptophytes, and both the phylogenic and sequence similarity analyses revealed that green plant MAG gene originated through an ancient horizontal gene transfer (HGT) event from bacteria. Experimental evidence demonstrated that the expression of the maize ZmMAG gene was induced by UV and zeocin, both of which are known as DNA-damaging agents. Further investigation revealed that Streptophyta MAG genes had undergone positive selection during the initial evolutionary period in the ancestor of land plants. Our findings demonstrated that the ancient HGT of MAG to the ancestor of land plants probably played an important role in preadaptation to DNA-damaging agents in terrestrial environments.

Environmental risk factors for pancreatic cancer: an update.

PubMed

Barone, Elisa; Corrado, Alda; Gemignani, Federica; Landi, Stefano

2016-11-01

Pancreatic cancer (PC) is one of the most aggressive diseases. Only 10 % of all PC cases are thought to be due to genetic factors. Here, we analyzed the most recently published case-control association studies, meta-analyses, and cohort studies with the aim to summarize the main environmental factors that could have a role in PC. Among the most dangerous agents involved in the initiation phase, there are the inhalation of cigarette smoke, and the exposure to mutagenic nitrosamines, organ-chlorinated compounds, heavy metals, and ionizing radiations. Moreover, pancreatitis, high doses of alcohol drinking, the body microbial infections, obesity, diabetes, gallstones and/or cholecystectomy, and the accumulation of asbestos fibers seem to play a crucial role in the progression of the disease. However, some of these agents act both as initiators and promoters in pancreatic acinar cells. Protective agents include dietary flavonoids, marine omega-3, vitamin D, fruit, vegetables, and the habit of regular physical activity. The identification of the factors involved in PC initiation and progression could be of help in establishing novel therapeutic approaches by targeting the molecular signaling pathways responsive to these stimuli. Moreover, the identification of these factors could facilitate the development of strategies for an early diagnosis or measures of risk reduction for high-risk people.

Blindness and social trust: The effect of early visual deprivation on judgments of trustworthiness.

PubMed

Ferrari, C; Vecchi, T; Merabet, L B; Cattaneo, Z

2017-10-01

Investigating the impact of early visual deprivation on evaluations related to social trust has received little attention to date. This is despite consistent evidence suggesting that early onset blindness may interfere with the normal development of social skills. In this study, we investigated whether early blindness affects judgments of trustworthiness regarding the actions of an agent, with trustworthiness representing the fundamental dimension in the social evaluation. Specifically, we compared performance between a group of early blind individuals with that of sighted controls in their evaluation of trustworthiness of an agent after hearing a pair of two positive or two negative social behaviors (impression formation). Participants then repeated the same evaluation following the presentation of a third (consistent or inconsistent) behavior regarding the same agent (impression updating). Overall, blind individuals tended to give similar evaluations compared to their sighted counterparts. However, they also valued positive behaviors significantly more than sighted controls when forming their impression of an agent's trustworthiness. Moreover, when inconsistent information was provided, blind individuals were more prone to revise their initial evaluation compared to controls. These results suggest that early visual deprivation may have a dramatic effect on the evaluation of social factors such as trustworthiness. Copyright © 2017 Elsevier Inc. All rights reserved.

The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging

NASA Astrophysics Data System (ADS)

Xing, Zhanwen; Wang, Jinrui; Ke, Hengte; Zhao, Bo; Yue, Xiuli; Dai, Zhifei; Liu, Jibin

2010-04-01

Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors.

Prevention and treatment of cancer targeting chronic inflammation: research progress, potential agents, clinical studies and mechanisms.

PubMed

Zhang, Yong; Kong, Weijia; Jiang, Jiandong

2017-06-01

Numerous experimental and clinical studies indicate that chronic inflammation is closely related to the initiation, progression, and spread of cancer, in which proinflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α), and transcription factors, such as nuclear factor-κB (NF-κB), and signal transducer and activator of transcription 3 (STAT3), play pivotal roles. Stimulated by proinflammatory cytokines, NF-κB and STAT3 can modulate the expression of target genes, most of which are oncogenic ones, and promote the survival, proliferation, invasion, and metastasis of cancer cells. Now it is generally accepted that inflammation-related molecules and pathways are useful targets for the prevention and treatment of cancer. In this review, we summarize the relationship between chronic inflammation and cancer and describe some potentially useful agents including aspirin, meformin, statins, and some natural products (green tea catechins, andrographolide, curcumin) for their cancer prevention and treatment activities targeting chronic inflammation. The results of typical clinical studies are included, and the influences of these agents on the proinflammatory cytokines and inflammation-related pathways are discussed. Data from the present review support that agents targeting chronic inflammation may have a broad application prospect for the prevention and treatment of cancer in the future.

Agent-based Model for the Coupled Human-Climate System

NASA Astrophysics Data System (ADS)

Zvoleff, A.; Werner, B.

2006-12-01

Integrated assessment models have been used to predict the outcome of coupled economic growth, resource use, greenhouse gas emissions and climate change, both for scientific and policy purposes. These models generally have employed significant simplifications that suppress nonlinearities and the possibility of multiple equilibria in both their economic (DeCanio, 2005) and climate (Schneider and Kuntz-Duriseti, 2002) components. As one step toward exploring general features of the nonlinear dynamics of the coupled system, we have developed a series of variations on the well studied RICE and DICE models, which employ different forms of agent-based market dynamics and "climate surprises." Markets are introduced through the replacement of the production function of the DICE/RICE models with an agent-based market modeling the interactions of producers, policymakers, and consumer agents. Technological change and population growth are treated endogenously. Climate surprises are representations of positive (for example, ice sheet collapse) or negative (for example, increased aerosols from desertification) feedbacks that are turned on with probability depending on warming. Initial results point toward the possibility of large amplitude instabilities in the coupled human-climate system owing to the mismatch between short outlook market dynamics and long term climate responses. Implications for predictability of future climate will be discussed. Supported by the Andrew W Mellon Foundation and the UC Academic Senate.

[Bacteremia and sepsis in patients hospitalized at the Dr. Fran Mihaljevíc Clinic for Infectious Diseases in Zagreb 1987-1991].

PubMed

Skerk, V; Schönwald, S; Bobinac, E; Bejuk, D; Zrinsćak, J

1995-01-01

A total number of 836 episodes of bacteremia and fungemia were examined in 823 hospitalized patients in the University Hospital of Infectious Diseases "Dr Fran Mihaljević" Zagreb from the beginning of 1987 to the end of 1991. Twenty-five percent of them were nosocomial bacteremias and 5% were polymicrobial bacteremias. The most frequently isolated causative agents were Salmonella spp. (26%), Escherichia coli (17%), Streptococcus pneumoniae (11%) and Staphylococcus aureus (8%). There were 34% of gram-positive bacteremias. The increased frequency of nosocomial bacteremias caused by coagulase-negative staphylococci was recorded. The frequency of coagulase-negative staphylococci strains resistant to gentamicin and Klebsiella spp. strains resistant to cefotaxime was increased. Shock was present in 19% of episodes. Relation between septic shock occurrence and causative agent of bacteremia was not proved. Mortality in patients with bacteremia was 13%, and total mortality was 20%. The outcome of the disease was in direct relation with causative agent of bacteremia. The initial empiric antimicrobial therapy was prolonged in 91% of episodes of bacteremia after blood culture results were known.

New perspectives of cobalt tris(bipyridine) system: anti-cancer effect and its collateral sensitivity towards multidrug-resistant (MDR) cancers

PubMed Central

Mok, Simon Wing Fai; Liu, Hauwei; Zeng, Wu; Han, Yu; Gordillo-Martinez, Flora; Chan, Wai-Kit; Wong, Keith Man-Chung; Wong, Vincent Kam Wai

2017-01-01

Platinating compounds including cisplatin, carboplatin, and oxaliplatin are common chemotherapeutic agents, however, patients developed resistance to these clinical agents after initial therapeutic treatments. Therefore, different approaches have been applied to identify novel therapeutic agents, molecular mechanisms, and targets for overcoming drug resistance. In this study, we have identified a panel of cobalt complexes that were able to specifically induce collateral sensitivity in taxol-resistant and p53-deficient cancer cells. Consistently, our reported anti-cancer functions of cobalt complexes 1–6 towards multidrug-resistant cancers have suggested the protective and non-toxic properties of cobalt metal-ions based compounds in anti-cancer therapies. As demonstrated in xenograft mouse model, our results also confirmed the identified cobalt complex 2 was able to suppress tumor growth in vivo. The anti-cancer effect of the cobalt complex 2 was further demonstrated to be exerted via the induction of autophagy, cell cycle arrest, and inhibition of cell invasion and P-glycoprotein (P-gp) activity. These data have provided alternative metal ion compounds for targeting drug resistance cancers in chemotherapies. PMID:28903398

Plague.

PubMed

Lazarus, Angeline A; Decker, Catherine F

2004-03-01

In the United States, plague poses a threat to humans from the infected animals in the endemic areas of the Western states. Plague may also be used in the near future as an agent of warfare or terrorism. Although the presentation of bubonic plague may be less of a problem, the septicemic and pneumonic forms present challenges to early diagnosis and prompt treatment. The major threat of plague as an agent of terrorism will probably be through the inhalational route. which could result in many cases of the pneumonic form, requiring early recognition and initiation of appropriate therapy. In a mass-casualty scenario, the clinician should be aware of the potential agents of biowarfare and be familiar with the treatment and prophylaxis recommendations outlined by the CDC. It is also prudent to employ universal precautions and respiratory isolation when treating patients with any unknown exposure. In endemic areas, personal protective measures such as use of insecticides, insect repellants, and prompt prophylaxis in cases of exposure to plague are recommended for reducing the incidence of infection. The author also recommends review of CDC website on bioterrorism (http://www.bt.cdc.gov) to keep informed of plague updates.

Detection of early changes in lung cell cytology by flow-systems analysis techniques, July 1--December 31, 1975

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

Steinkamp, J.A.; Ingram, M.; Hansen, K.M.

1976-03-01

This report summarizes results of preliminary experiments to demonstrate the feasibility of using automated flow-systems analysis in detecting early changes of respiratory epithelium exposed to physical and chemical agents associated with the by-products of nonnuclear energy production. The Syrian hamster was selected as the experimental test animal to begin investigation of the effects of toxic agents to cells of the respiratory tract. Since initiation of the program approximately six months ago, the goals have been acquisition of adequate numbers of exfoliated cells from the lung; adaptation of cytological techniques developed on human exfoliated gynecological samples to hamster lung epithelium formore » obtaining single-cell suspensions; utilization of existing cell staining methods to measure DNA content in lung cells; and analysis of DNA content and cell size. As the flow-system cell analysis technology is adapted to the measurement of exfoliated lung cells, rapid and quantitative determination of early changes in the physical and biochemical cellular properties will be attempted as a function of exposure to the toxic agents. (auth)« less

Continuum mechanics analysis of fracture progression in the vitrified cryoprotective agent DP6

PubMed Central

Steif, Paul S.; Palastro, Matthew C.; Rabin, Yoed

2008-01-01

As part of an ongoing effort to study the continuum mechanics effects associated with cryopreservation, the current report focuses on the prediction of fracture formation in cryoprotective agents. Fractures had been previously observed in 1 mℓ samples of the cryoprotective agent cocktail DP6, contained in a standard 15 mℓ glass vial, and subjected to various cooling rates. These experimental observations were obtained by means of a cryomacroscope, which has been recently presented by the current research team. High and low cooling rates were found to produce very distinct patterns of cracking. The current study seeks to explain the observed patterns on the basis of stresses predicted from finite element analysis, which relies on a simple viscoelastic constitutive model and on estimates of the critical stress for cracking. The current study demonstrates that the stress which results in instantaneous fracture at low cooling rates is consistent with the stress to initiate fracture at high cooling rate. This consistency supports the credibility of the proposed constitutive model and analysis, and the unified criterion for fracturing, that is, a critical stress threshold. PMID:18412493

Lead recovery from waste CRT funnel glass by high-temperature melting process.

PubMed

Hu, Biao; Hui, Wenlong

2018-02-05

In this research, a novel and effective process for waste CRT funnel glass treatment was developed. The key to this process is removal of lead from the CRT funnel glass by high-temperature melting process. Sodium carbonate powder was used as a fusion agent, sodium sulfide serves as a catalytic agent and carbon powder acts as reducing agent. Experimental results showed that lead recovery rate increased with an increase in the amount of added sodium carbonate, sodium sulfide, carbonate, temperature and holding time initially, and then reached a stable value. The maximum lead recovery rate was approximately 94%, when the optimum adding amount of sodium carbonate, sodium sulfide, carbonate, temperature and holding time were 25%, 8%, 3.6%, 1200°C and 120min, respectively. In the high-temperature melting process, lead silicate in the funnel glass was firstly reduced, and then removed. The glass slag can be made into sodium and potassium silicate by hydrolysis process. This study proposed a practical and economical process for recovery of lead and utilization of waste glass slag. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel morphology change of Au-Methotrexate conjugates: From nanochains to discrete nanoparticles.

PubMed

Wang, Wei-Yuan; Zhao, Xiu-Fen; Ju, Xiao-Han; Wang, Yu; Wang, Lin; Li, Shu-Ping; Li, Xiao-Dong

2016-12-30

A novel morphology change of Au-methotrexate (Au-MTX) conjugates that could transform from nanochains to discrete nanoparticles was achieved by a simple, one-pot, and hydrothermal growth method. Herein, MTX was used efficiently as a complex-forming agent, reducing agent, capping agent, and importantly a targeting anticancer drug. The formation mechanism suggested a similarity with the molecular imprinting technology. The Au-MTX complex induced the MTX molecules to selectively adsorb on different crystal facets of gold nanoparticles (AuNPs) and then formed gold nanospheres. Moreover, the abundantly binding MTX molecules promoted directional alignment of these gold nanospheres to further form nanochains. More interestingly, the linear structures gradually changed into discrete nanoparticles by adding different amount of ethylene diamine tetra (methylene phosphonic acid) (EDTMPA) into the initial reaction solution, which likely arose from the strong electrostatic effect of the negatively charged phosphonic acid groups. Compared with the as-prepared nanochains, the resultant discrete nanoparticles showed almost equal drug loading capacity but with higher drug release control, colloidal stability, and in vitro anticancer activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Epigenetic therapy potential of suberoylanilide hydroxamic acid on invasive human non-small cell lung cancer cells.

PubMed

Zhang, Shirong; Wu, Kan; Feng, Jianguo; Wu, Zhibing; Deng, Qinghua; Guo, Chao; Xia, Bing; Zhang, Jing; Huang, Haixiu; Zhu, Lucheng; Zhang, Ke; Shen, Binghui; Chen, Xufeng; Ma, Shenglin

2016-10-18

Metastasis is the reason for most cancer death, and a crucial primary step for cancer metastasis is invasion of the surrounding tissue, which may be initiated by some rare tumor cells that escape the heterogeneous primary tumor. In this study, we isolated invasive subpopulations of cancer cells from human non-small cell lung cancer (NSCLC) H460 and H1299 cell lines, and determined the gene expression profiles and the responses of these invasive cancer cells to treatments of ionizing radiation and chemotherapeutic agents. The subpopulation of highly invasive NSCLC cells showed epigenetic signatures of epithelial-mesenchymal transition, cancer cell stemness, increased DNA damage repair and cell survival signaling. We also investigated the epigenetic therapy potential of suberoylanilide hydroxamic acid (SAHA) on invasive cancer cells, and found that SAHA suppresses cancer cell invasiveness and sensitizes cancer cells to treatments of IR and chemotherapeutic agents. Our results provide guidelines for identification of metastatic predictors and for clinical management of NSCLC. This study also suggests a beneficial clinical potential of SAHA as a chemotherapeutic agent for NSCLC patients.

Granular activated carbon as nucleating agent for aerobic sludge granulation: Effect of GAC size on velocity field differences (GAC versus flocs) and aggregation behavior.

PubMed

Zhou, Jia-Heng; Zhao, Hang; Hu, Miao; Yu, Hai-Tian; Xu, Xiang-Yang; Vidonish, Julia; Alvarez, Pedro J J; Zhu, Liang

2015-12-01

Initial cell aggregation plays an important role in the formation of aerobic granules. In this study, three parallel aerobic granular sludge reactors treating low-strength wastewater were established using granular activated carbon (GAC) of different sizes as the nucleating agent. A novel visual quantitative evaluation method was used to discern how GAC size affects velocity field differences (GAC versus flocs) and aggregation behavior during sludge granulation. Results showed that sludge granulation was significantly enhanced by addition of 0.2mm GAC. However, there was no obvious improvement in granulation in reactor amended with 0.6mm GAC. Hydraulic analysis revealed that increase of GAC size enhanced the velocity field difference between flocs and GAC, which decreased the lifecycle and fraction of flocs-GAC aggregates. Overall, based on analysis of aggregation behavior, GAC of suitable sizes (0.2mm) can serve as the nucleating agent to accelerate flocs-GAC coaggregation and formation of aerobic granules. Copyright © 2015 Elsevier Ltd. All rights reserved.

Significance of Clostridium spiroforme in the enteritis-complex of commercial rabbits.

PubMed

Peeters, J E; Geeroms, R; Carman, R J; Wilkins, T D

1986-06-01

Commercial rabbits showing clinical signs of enteritis-complex were examined for the presence of Clostridium spiroforme and its iota-like toxin. The bacterium was detected by Gram stain in 52.4% of 149 cecal samples and iota-like toxin in 7.4%. From 29 strains of C. spiroforme tested, 26 were toxigenic, originating from 24 of 29 rabbitries. In 13.4% of the samples, C. spiroforme was present as the only known disease agent. Gross and microscopic lesions were similar to those described in the literature. In the other samples, C. spiroforme was associated with attaching effacing Escherichia coli (29.5%), Bacillus piliformis (10.3%), rotaviruses (25.6%), coronavirus (2.6%), Eimeria spp. (44.9%) and cryptosporidia (6.4%). In 33.3% of C. spiroforme-containing samples, more than one of these agents was present. There was no significant difference between the presence of these organisms in C. spiroforme-positive and negative samples. On the basis of these results as well as that of previous data, we suggest that C. spiroforme-mediated diarrhea is favoured by maldigestion, initiated by infectious agents and/or nutritional factors.

Ibrutinib for the treatment of mantle cell lymphoma.

PubMed

Herrera, Alex F; Jacobsen, Eric D

2014-11-01

Ibrutinib (PCI-32765)--a potent, covalent inhibitor of Bruton tyrosine kinase (BTK), an important kinase in the B-cell receptor signaling pathway--was recently approved by the FDA for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The drug was granted accelerated approval based on the findings of an international, multicenter, single-arm phase II study that enrolled patients with relapsed or refractory MCL. In the study, ibrutinib (560 mg daily) was well tolerated as a single agent and resulted in an overall response rate of 68% and an estimated median response duration of 17.5 months. Ibrutinib's response rate and duration of response compare favorably with those for other novel agents approved for the treatment of relapsed or refractory MCL, while being less toxic than most chemotherapy or chemoimmunotherapy regimens. Ibrutinib is currently being studied in combination with chemoimmunotherapy, monoclonal antibody therapy, and novel agents in both the initial and the relapsed/refractory treatment settings. We review the mechanism of action, preclinical and clinical development, and the role of ibrutinib in the context of other available treatments. ©2014 American Association for Cancer Research.

Immune thrombocytopenia: No longer ‘idiopathic’

PubMed Central

McCRAE, KEITH

2012-01-01

Immune thrombocytopenia (ITP) is a common hematologic disorder. Its pathogenesis involves both accelerated platelet destruction and impaired platelet production. First-line agents are usually effective initially but do not provide long-term responses. Splenectomy remains an effective long-term therapy, as does rituximab (Rituxan) in a subset of patients. Thrombopoietic agents offer a new alternative, although their place in the overall management of ITP remains uncertain. PMID:21632906

THE FAMILY AGENT, A TRAINING MANUAL AND PROGRAM EVALUATION OF A NEW CAREER IN SOCIAL SERVICE.

ERIC Educational Resources Information Center

LAZAR, JOYCE B.

THE PERSONNEL OF THE FAMILY AGENT PROGRAMS WERE WOMEN OF COMFORTABLE MEANS WHO HAD TEN TO TWENTY HOURS A WEEK AVAILABLE FOR SERVICE TO THE POOR. THE TRAINING PROGRAM DESCRIBED IS DIVIDED INTO TWO PHASES--INITIAL TRAINING AND INSERVICE TRAINING. SUBJECTS COVERED INCLUDE--(1) CONCEPTS OF THE WAR ON POVERTY, (2) THE NATURE OF POVERTY, (3) THE CULTURE…

NIE Final Report. Vermont Special Purpose Grant, January 1979 through September 1979 [and] Evaluation of the Resource Agent Program.

ERIC Educational Resources Information Center

Perry, Mary; Miller, Pamela A.

Vermont's adaptation of a federal Resource Agent Program (RAP), designed to meet the in-service training needs of teachers, is described in this final report. Part of a complete dissemination system, RAP was funded as a pilot program to initiate a collection of Vermont-originated resources to be entered into a state educational database. Described…

Education as an Agent of Social Evolution: The Educational Projects of Patrick Geddes in Late-Victorian Scotland

ERIC Educational Resources Information Center

Sutherland, Douglas

2009-01-01

This paper examines the educational projects of Patrick Geddes in late-Victorian Scotland. Initially a natural scientist, Geddes drew on an eclectic mix of social theory to develop his own ideas on social evolution. For him education was a vital agent of social change which, he believed, had the potential to develop active citizens whose…

Building Level Principals as Change Agents in a Response to Intervention Reform Initiative

ERIC Educational Resources Information Center

Ninni, Kristen

2010-01-01

The purpose of this study was to examine the role of the principal in a systems change effort. Utilizing Response to Intervention (RtI) as a means of studying principals as change agents, this researcher examined the principals' ability to implement and sustain a reform effort such as RtI as perceived by the principal, problem solving team, and…

Toxicity of silver nanoparticles in zebrafish models

NASA Astrophysics Data System (ADS)

Asharani, P. V.; Lian Wu, Yi; Gong, Zhiyuan; Valiyaveettil, Suresh

2008-06-01

This study was initiated to enhance our insight on the health and environmental impact of silver nanoparticles (Ag-np). Using starch and bovine serum albumin (BSA) as capping agents, silver nanoparticles were synthesized to study their deleterious effects and distribution pattern in zebrafish embryos (Danio rerio). Toxicological endpoints like mortality, hatching, pericardial edema and heart rate were recorded. A concentration-dependent increase in mortality and hatching delay was observed in Ag-np treated embryos. Additionally, nanoparticle treatments resulted in concentration-dependent toxicity, typified by phenotypes that had abnormal body axes, twisted notochord, slow blood flow, pericardial edema and cardiac arrhythmia. Ag+ ions and stabilizing agents showed no significant defects in developing embryos. Transmission electron microscopy (TEM) of the embryos demonstrated that nanoparticles were distributed in the brain, heart, yolk and blood of embryos as evident from the electron-dispersive x-ray analysis (EDS). Furthermore, the acridine orange staining showed an increased apoptosis in Ag-np treated embryos. These results suggest that silver nanoparticles induce a dose-dependent toxicity in embryos, which hinders normal development.

Twice-daily dosing of temozolomide in combination with fotemustine for the treatment of patients with refractory glioblastoma.

PubMed

Santoni, M; Paccapelo, A; Burattini, L; Onofri, A; Cascinu, S

2012-03-01

Alkylating agents, such as temozolomide (TMZ) and fotemustine (FTM) are widely used in recurrent glioblastoma (GBM) regimes. Several strategies have been proposed to prevent resistance to these agents, by combining or sequencing them. We report the results of a pilot study of patients with refractory GBM receiving a regime of twice-daily dosing of temozolomide administered on day 1, (with an initial oral dose of 200 mg/m(2) and a second oral dose of 75 mg/m(2) 12 h later), followed by fotemustine in a single i.v. infusion at 75 mg/m(2) on day 2, repeated every four weeks. Enrolment was stopped at 15 patients due to lack of effectiveness of this schedule for patients with GBM. Toxicity was mild, with no grade 4 side effects reported. Results indicate that our temozolomide -FTM combined schedule is not effective, although well tolerated, in non responsive patients with GBM. Further strategies are required to improve the outcome of these patients.

An adaptive critic-based scheme for consensus control of nonlinear multi-agent systems

NASA Astrophysics Data System (ADS)

Heydari, Ali; Balakrishnan, S. N.

2014-12-01

The problem of decentralised consensus control of a network of heterogeneous nonlinear systems is formulated as an optimal tracking problem and a solution is proposed using an approximate dynamic programming based neurocontroller. The neurocontroller training comprises an initial offline training phase and an online re-optimisation phase to account for the fact that the reference signal subject to tracking is not fully known and available ahead of time, i.e., during the offline training phase. As long as the dynamics of the agents are controllable, and the communication graph has a directed spanning tree, this scheme guarantees the synchronisation/consensus even under switching communication topology and directed communication graph. Finally, an aerospace application is selected for the evaluation of the performance of the method. Simulation results demonstrate the potential of the scheme.

Ultimate fate of constrained voters

NASA Astrophysics Data System (ADS)

Vazquez, F.; Redner, S.

2004-09-01

We examine the ultimate fate of individual opinions in a socially interacting population of leftists, centrists and rightists. In an elemental interaction between agents, a centrist and a leftist can both become centrists or both become leftists with equal rates (and similarly for a centrist and a rightist). However leftists and rightists do not interact. This interaction step between pairs of agents is applied repeatedly until the system can no longer evolve. In the mean-field limit, we determine the exact probability that the system reaches consensus (either leftist, rightist or centrist) or a frozen mixture of leftists and rightists as a function of the initial composition of the population. We also determine the mean time until the final state is reached. Some implications of our results for the ultimate fate in a limit of the Axelrod model are discussed.

Intelligent Information Fusion in the Aviation Domain: A Semantic-Web based Approach

NASA Technical Reports Server (NTRS)

Ashish, Naveen; Goforth, Andre

2005-01-01

Information fusion from multiple sources is a critical requirement for System Wide Information Management in the National Airspace (NAS). NASA and the FAA envision creating an "integrated pool" of information originally coming from different sources, which users, intelligent agents and NAS decision support tools can tap into. In this paper we present the results of our initial investigations into the requirements and prototype development of such an integrated information pool for the NAS. We have attempted to ascertain key requirements for such an integrated pool based on a survey of DSS tools that will benefit from this integrated pool. We then advocate key technologies from computer science research areas such as the semantic web, information integration, and intelligent agents that we believe are well suited to achieving the envisioned system wide information management capabilities.

Cost Comparison of Urate-Lowering Therapies in Patients with Gout and Moderate-to-Severe Chronic Kidney Disease.

PubMed

Mitri, Ghaith; Wittbrodt, Eric T; Turpin, Robin S; Tidwell, Beni A; Schulman, Kathy L

2016-04-01

Patients with chronic kidney disease (CKD) are at increased risk for developing gout and having refractory disease. Gout flare prevention relies heavily on urate-lowering therapies such as allopurinol and febuxostat, but clinical decision making in patients with moderate-to-severe CKD is complicated by significant comorbidity and the scarcity of real-world cost-effectiveness studies. To compare total and disease-specific health care expenditures by line of therapy in allopurinol and febuxostat initiators after diagnosis with gout and moderate-to-severe CKD. A retrospective observational cohort study was conducted to compare mean monthly health care cost (in 2012 U.S. dollars) among gout patients with CKD (stage 3 or 4) who initiated allopurinol or febuxostat. The primary outcome was total mean monthly health care expenditures, and the secondary outcome was disease-specific (gout, diabetes, renal, and cardiovascular disease [CVD]) expenditures. Gout patients (ICD-9-CM 274.xx) aged ≥ 18 years with concurrent CKD (stage 3 or 4) were selected from the MarketScan databases (January 2009-June 2012) upon allopurinol or febuxostat initiation. Patients were followed until disenrollment, discontinuation of the qualifying study agent, or use of the alternate study agent. Patients initiating allopurinol were subsequently propensity score-matched (1:1) to patients initiating febuxostat. Five generalized linear models (GLMs) were developed, each controlling for propensity score, to identify the incremental costs (vs. allopurinol) associated with febuxostat initiation in first-line (without prior allopurinol exposure) and second-line (with prior allopurinol exposure) settings. Propensity score matching yielded 2 cohorts, each with 1,486 patients (64.6% male, mean [SD] age 67.4 [12.8] years). Post-match, 74.6% of patients had stage 3 CKD; 82.9% had CVD; and 42.1% had diabetes. The post-match sample was well balanced on numerous comorbidities and medication exposures with the following exception: 50.0% of febuxostat initiators were treated in the second-line setting; that is, they had baseline exposure to allopurinol, whereas only 4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM results suggest that first-line febuxostat users incurred significantly (P = 0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs. $1,487). Febuxostat initiators in both settings had significantly (P < 0.001) higher gout-specific cost, due to higher febuxostat acquisition cost. Increased gout-specific cost in the first-line febuxostat cohort was offset by significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86 vs. $216). There were no significant differences in either renal or CVD costs (adjusted) between allopurinol initiators treated almost exclusively in the first-line setting and second-line febuxostat patients. Gout patients with concurrent CKD, initiating treatment with febuxostat in a first-line setting, incurred significantly less total cost than patients initiating allopurinol during the first exposure to each agent. Conversely, patients treated with second-line febuxostat following allopurinol incurred significantly higher total cost than patients initiating allopurinol. There was no significant difference in total cost between the agents across line of therapy. Although study findings suggest the potential for CVD and renal-related savings to offset febuxostat's higher acquisition cost in gout patients with moderate-to-severe CKD, this is the first such retrospective evaluation. Future research is warranted to both demonstrate the durability of study findings and to better elucidate the mechanism by which associated cost offsets occur. No outside funding supported this study. Turpin is an employee of Takeda Pharmaceuticals U.S.A. Mitri and Wittbrodt were employees of Takeda Pharmaceuticals U.S.A. at the time of this study. Tidwell and Schulman are employees of Outcomes Research Solutions, consultants to Takeda Pharmaceuticals U.S.A. All authors contributed to the design of the study and to the writing and review of the manuscript. All authors read and approved the final manuscript. Tidwell and Schulman collected the data, and all authors participated in data interpretation.

Agent-based assessment of stormwater re-use potential of low-impact development control facilities at the site of Vlasina Lake, Serbia.

PubMed

Blagojević, Borislava; Milićević, Dragan; Potić, Olivera

2013-01-01

Vlasina Lake in south-east Serbia is classified as an Area of Distinct Land Use and, as such, is subject to high environmental protection standards applied in the Master Plan. Two open channels for stormwater and sediment transportation to two large detention basins with pumping stations for water evacuation into the lake were envisaged in the Master Plan. In the preliminary design, the stormwater system was quite different: wherever possible, on-site natural features were used for allocation of ponds, and drainage channels were led through existing road culverts. The applied design concept has been low impact development (LID), which led to potential blue-green corridors, recognized by project stakeholders. The paper studies the possibility of using ponds as a key element of both the LID concept and the blue-green corridors approach. For that purpose, an initial Vlasina Lake site agent-based simulation model has been created. A realistic physical model is included, and simulation results for two hypothetical climatic and socio-economic scenarios are presented. From the experience in creating the agent-based model, and based on the simulation results, recommendations are given for further work. It is shown that ponds have potential for the investigated water re-use purposes.

Occupational hypersensitivity pneumonitis: an EAACI position paper.

PubMed

Quirce, S; Vandenplas, O; Campo, P; Cruz, M J; de Blay, F; Koschel, D; Moscato, G; Pala, G; Raulf, M; Sastre, J; Siracusa, A; Tarlo, S M; Walusiak-Skorupa, J; Cormier, Y

2016-06-01

The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modifying influence of swine-serum-induced liver fibrosis on development of preneoplastic lesions in rat liver.

PubMed

Wada, S; Kato, T; Mutai, M; Ozaki, K; Yamaguchi, S; Kim, D J; Baba-Toriyama, H; Asamoto, M; Ito, N; Tsuda, H

1996-03-01

Modifying effects of fibrosis or a cirrhotic state, caused by treatment with swine serum (SS), on the induction of preneoplastic focal lesions were assessed in a rat medium-term liver bioassay model for the detection of environmental carcinogens, in which the test compound is administered during the promotion phase after initiation with diethylnitrosamine. In experiment I, repeated intraperitoneal administration of SS concomitantly with the hepatopromoting agent deoxycholic acid (DCA) or phenobarbital (PB) resulted in a cirrhotic state and a significant increase in the number or size of preneoplastic glutathione S-transferase placental form (GST-P)-positive liver cell foci as compared to the corresponding DCA or PB alone groups. In experiment II, SS was given prior to commencement of the same medium-term bioassay system, in which a known hepatopromoting agent, DCA, 17-alpha-ethynylestradiol, or 2-acetylaminofluorene, was applied. In this case, the liver did not show obvious cirrhotic change and, rather than any enhancement, slight inhibition of promotion occurred. The results indicate that a coexisting, but not a pre-existing, cirrhotic condition acts to increase growth pressure on GST-P+ preneoplastic foci, and suggest that concomitant administration of SS with the promoting agent could be applied to improve the sensitivity of the assay protocol.

An Agent-Based Model for Analyzing Control Policies and the Dynamic Service-Time Performance of a Capacity-Constrained Air Traffic Management Facility

NASA Technical Reports Server (NTRS)

Conway, Sheila R.

2006-01-01

Simple agent-based models may be useful for investigating air traffic control strategies as a precursory screening for more costly, higher fidelity simulation. Of concern is the ability of the models to capture the essence of the system and provide insight into system behavior in a timely manner and without breaking the bank. The method is put to the test with the development of a model to address situations where capacity is overburdened and potential for propagation of the resultant delay though later flights is possible via flight dependencies. The resultant model includes primitive representations of principal air traffic system attributes, namely system capacity, demand, airline schedules and strategy, and aircraft capability. It affords a venue to explore their interdependence in a time-dependent, dynamic system simulation. The scope of the research question and the carefully-chosen modeling fidelity did allow for the development of an agent-based model in short order. The model predicted non-linear behavior given certain initial conditions and system control strategies. Additionally, a combination of the model and dimensionless techniques borrowed from fluid systems was demonstrated that can predict the system s dynamic behavior across a wide range of parametric settings.

Design and Simulation of Material-Integrated Distributed Sensor Processing with a Code-Based Agent Platform and Mobile Multi-Agent Systems

PubMed Central

Bosse, Stefan

2015-01-01

Multi-agent systems (MAS) can be used for decentralized and self-organizing data processing in a distributed system, like a resource-constrained sensor network, enabling distributed information extraction, for example, based on pattern recognition and self-organization, by decomposing complex tasks in simpler cooperative agents. Reliable MAS-based data processing approaches can aid the material-integration of structural-monitoring applications, with agent processing platforms scaled to the microchip level. The agent behavior, based on a dynamic activity-transition graph (ATG) model, is implemented with program code storing the control and the data state of an agent, which is novel. The program code can be modified by the agent itself using code morphing techniques and is capable of migrating in the network between nodes. The program code is a self-contained unit (a container) and embeds the agent data, the initialization instructions and the ATG behavior implementation. The microchip agent processing platform used for the execution of the agent code is a standalone multi-core stack machine with a zero-operand instruction format, leading to a small-sized agent program code, low system complexity and high system performance. The agent processing is token-queue-based, similar to Petri-nets. The agent platform can be implemented in software, too, offering compatibility at the operational and code level, supporting agent processing in strong heterogeneous networks. In this work, the agent platform embedded in a large-scale distributed sensor network is simulated at the architectural level by using agent-based simulation techniques. PMID:25690550

Design and simulation of material-integrated distributed sensor processing with a code-based agent platform and mobile multi-agent systems.

PubMed

Bosse, Stefan

2015-02-16

Multi-agent systems (MAS) can be used for decentralized and self-organizing data processing in a distributed system, like a resource-constrained sensor network, enabling distributed information extraction, for example, based on pattern recognition and self-organization, by decomposing complex tasks in simpler cooperative agents. Reliable MAS-based data processing approaches can aid the material-integration of structural-monitoring applications, with agent processing platforms scaled to the microchip level. The agent behavior, based on a dynamic activity-transition graph (ATG) model, is implemented with program code storing the control and the data state of an agent, which is novel. The program code can be modified by the agent itself using code morphing techniques and is capable of migrating in the network between nodes. The program code is a self-contained unit (a container) and embeds the agent data, the initialization instructions and the ATG behavior implementation. The microchip agent processing platform used for the execution of the agent code is a standalone multi-core stack machine with a zero-operand instruction format, leading to a small-sized agent program code, low system complexity and high system performance. The agent processing is token-queue-based, similar to Petri-nets. The agent platform can be implemented in software, too, offering compatibility at the operational and code level, supporting agent processing in strong heterogeneous networks. In this work, the agent platform embedded in a large-scale distributed sensor network is simulated at the architectural level by using agent-based simulation techniques.

A Survey of Pre-Service Teachers' Acceptance of Technology in Thailand

ERIC Educational Resources Information Center

Teo, Timothy; Khlaisang, Jintavee; Thammetar, Thapanee; Ruangrit, Nammon; Satiman, Anirut; Sunphakitjumnong, Kobkul

2014-01-01

In the recent decade, Thailand has launched many initiatives to ensure that technology is integrated into the school curriculum. Despite the investment and efforts of the government, few studies have been conducted to examine users' acceptance of technology. Given that educators are the change agents in many educational initiatives, it is…

Tumor-Initiating Cells and Methods of Use

NASA Technical Reports Server (NTRS)

Hlatky, Lynn (Inventor)

2014-01-01

Provided herein are an isolated or enriched population of tumor initiating cells derived from normal cells, cells susceptible to neoplasia, or neoplastic cells. Methods of use of the cells for screening for anti-hyperproliferative agents, and use of the cells for animal models of hyperproliferative disorders including metastatic cancer, diagnostic methods, and therapeutic methods are provided.

Colon Cancer Chemoprevention by Flavonoid Silibinin | Division of Cancer Prevention

Cancer.gov

DESCRIPTION (provided by applicant): Cancer stem cells (CSC) are now recognized as the main cause for initiation, promotion and progression of most of the cancers, including colorectal cancer (CRC). Despite this fact, efficacy of chemopreventive agents towards CSC generation leading to cancer initiation and tumorigenesis has not yet been well- defined. |

Formal and Informal Structures for Collaboration on a Campus-Wide Information Literacy Program

ERIC Educational Resources Information Center

Shane, Jordana M. Y.

2004-01-01

Information literacy initiatives provide a vehicle for academic librarians to become agents of positive change. A campus-wide Information Literacy Initiative can improve teaching and learning, and further the mission of the institution. The Instruction Librarian may travel across literal and figurative boundaries. Librarians charged with designing…

Strategy selection in the minority game

NASA Astrophysics Data System (ADS)

D'hulst, R.; Rodgers, G. J.

2000-04-01

We investigate the dynamics of the choice of an active strategy in the minority game. A history distribution is introduced as an analytical tool to study the asymmetry between the two choices offered to the agents. Its properties are studied numerically. It allows us to show that the departure from uniformity in the initial attribution of strategies to the agents is important even in the efficient market. Also, an approximate expression for the variance of the number of agents at one side in the efficient phase is proposed. All the analytical propositions are supported by numerical simulations of the system.

Personalized E- learning System Based on Intelligent Agent

NASA Astrophysics Data System (ADS)

Duo, Sun; Ying, Zhou Cai

Lack of personalized learning is the key shortcoming of traditional e-Learning system. This paper analyzes the personal characters in e-Learning activity. In order to meet the personalized e-learning, a personalized e-learning system based on intelligent agent was proposed and realized in the paper. The structure of system, work process, the design of intelligent agent and the realization of intelligent agent were introduced in the paper. After the test use of the system by certain network school, we found that the system could improve the learner's initiative participation, which can provide learners with personalized knowledge service. Thus, we thought it might be a practical solution to realize self- learning and self-promotion in the lifelong education age.

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

Rose, Steven C., E-mail: scrose@ucsd.edu; Kikolski, Steven G.; Chomas, James E.

Purpose: The purpose of this work was to evaluate blood pressure changes caused by deployment of the Surefire antireflux expandable tip. The pressure measurements are relevant because they imply changes in hepatoenteric arterial blood flow within this liver compartment during hepatic artery delivery of cytotoxic agents. Methods: After positioning the Surefire antireflux system in the targeted hepatic artery, blood pressure was obtained initially with the tip collapsed (or through a femoral artery sheath), then again after the tip was expanded before chemoembolization or yttrium 90 ({sup 90}Y) radioembolization. Results: Eighteen patients with liver malignancy underwent 29 procedures in 29 hepaticmore » arteries (3 common hepatic, 22 lobar, 4 segmental). Systolic, diastolic, and mean blood pressure were all decreased by a mean of 29 mm Hg (p = 0.000004), 14 mm Hg (p = 0.0000004), and 22 mm Hg (p = 0.00000001), respectively. Conclusion: When the Surefire expandable tip is deployed to prevent retrograde reflux of agents, it also results in a significant decrease in blood pressure in the antegrade distribution, potentially resulting in hepatopedal blood flow in vessels that are difficult to embolize, such as the supraduodenal arteries.« less

A computational model for the flow of resin in self-healing composites

NASA Astrophysics Data System (ADS)

Hall, J.; Qamar, I. P. S.; Rendall, T. C. S.; Trask, R. S.

2015-03-01

To explore the flow characteristics of healing agent leaving a vascular network and infusing a damage site within a fibre reinforced polymer composite, a numerical model of healing agent flow from an orifice has been developed using smoothed particle hydrodynamics. As an initial validation the discharge coefficient for low Reynolds number flow from a cylindrical tank is calculated numerically, using two different viscosity formulations, and compared to existing experimental data. Results of this comparison are very favourable; the model is able to reproduce experimental results for the discharge coefficient in the high Reynolds number limit, together with the power-law behaviour for low Reynolds numbers. Results are also presented for a representative delamination geometry showing healing fluid behaviour and fraction filled inside the delamination for a variety of fluid viscosities. This work provides the foundations for the vascular self-healing community in calculating not only the flow rate through the network, but also, by simulating a representative damage site, the final location of the healing fluid within the damage site in order to assess the improvement in local and global mechanical properties and thus healing efficiency.

An innovative chairside bleaching protocol for treating stained dentition: initial results.

PubMed

Miara, P

2000-09-01

For years, investigators have attempted to develop a predictable means of bleaching pathologically and nonpathologically stained dentition. While previous efforts have modified the concentration of the bleaching material, the duration of the procedure, and the manner by which the bleaching agent is activated, the ability to affect a significant shade improvement remains an elusive objective. This article demonstrates an innovative technique used to influence the penetration of oxygen ions into the tooth enamel, which may resolve this clinical dilemma.

Epoxy Nanocomposites Containing Zeolitic Imidazolate Framework-8.

PubMed

Liu, Cong; Mullins, Michael; Hawkins, Spencer; Kotaki, Masaya; Sue, Hung-Jue

2018-01-10

Zeolitic imidazole framework-8 (ZIF-8) is utilized as a functional filler and a curing agent in the preparation of epoxy nanocomposites. The imidazole group on the surface of the ZIF-8 initiates epoxy curing, resulting in covalent bonding between the ZIF-8 crystals and epoxy matrix. A substantial reduction in dielectric constant and increase in tensile modulus were observed. The implication of the present study for utilization of metal-organic framework to improve physical and mechanical properties of polymeric matrixes is discussed.

Concentration of extracellular superoxide radical as a function of time during lignin degradation by the fungus Coriolus versicolor

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

Amer, G.I.; Drew, S.W.

1981-01-01

During a 9 day fermentation of lignin by C. versicolor, the concentration of superoxide radical in the extracellular medium of the submerged culture rose and fell, reaching a maximum after 2 and 6 days of incubation, and a minimum at 3 and 8 days. The results indicate that the extracellular superoxide radical is involved in lignin degradation, but there was no evidence that it is an initial attacking agent. (Refs. 9).

Clinical experience with iodine-123-iodophenylpentadecanoic acid.

PubMed

Corbett, J

1994-04-01

Initial research in dogs and later research in normal volunteers and patients with coronary artery disease indicated that 123I-iodophenylpentadecanoic acid (IPPA) can provide valuable diagnostic information. This agent compared favorably to 201Tl in detecting stenosed coronary arteries and identified reversible lesions with greater frequency. Testing with both 201Tl and IPPA before and after percutaneous transluminal coronary angioplasty produced similar results, supporting the notion that IPPA deserves inclusion among the diagnostic tools used to evaluate coronary heart disease.

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research HIV Working Group

PubMed Central

Uldrick, Thomas S.; Ison, Gwynn; Rudek, Michelle A.; Noy, Ariela; Schwartz, Karl; Bruinooge, Suanna; Schenkel, Caroline; Miller, Barry; Dunleavy, Kieron; Wang, Judy; Zeldis, Jerome; Little, Richard F.

2018-01-01

Purpose People with HIV are living longer as a result of effective antiretroviral therapy. Cancer has become a leading cause of morbidity and mortality in this patient population. However, studies of novel cancer therapeutics have historically excluded patients with HIV. Critical review of eligibility criteria related to HIV is required to accelerate development of and access to effective therapeutics for HIV-infected patients with cancer and make studies more generalizable to this patient population. Methods From January through April 2016, the HIV Working Group conducted a series of teleconferences; a review of 46 New Drug Applications from registration studies of unique agents studied in adults with cancer that led to the initial US Food and Drug Administration approval of that agent from 2011 to 2015; and a review of HIV-related eligibility criteria from National Cancer Institute–sponsored studies. Results were discussed and refined at a multistakeholder workshop held May 12, 2016. The HIV Working Group developed recommendations for eligibility criteria that focus on pharmacologic and immunologic considerations in this patient population and that balance patient safety, access to appropriate investigational agents, and study integrity. Results Exclusion of patients with HIV remains common in most studies of novel cancer agents. Models for HIV-related eligibility criteria in National Cancer Institute–sponsored studies are instructive. HIV infection itself should no longer be an exclusion criterion for most studies. Eligibility criteria related to HIV infection that address concurrent antiretroviral therapy and immune status should be designed in a manner that is appropriate for a given cancer. Conclusion Expanding clinical trial eligibility to be more inclusive of patients with HIV is justified in most cases and may accelerate the development of effective therapies in this area of unmet clinical need. PMID:28968173

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology-Friends of Cancer Research HIV Working Group.

PubMed

Uldrick, Thomas S; Ison, Gwynn; Rudek, Michelle A; Noy, Ariela; Schwartz, Karl; Bruinooge, Suanna; Schenkel, Caroline; Miller, Barry; Dunleavy, Kieron; Wang, Judy; Zeldis, Jerome; Little, Richard F

2017-11-20

Purpose People with HIV are living longer as a result of effective antiretroviral therapy. Cancer has become a leading cause of morbidity and mortality in this patient population. However, studies of novel cancer therapeutics have historically excluded patients with HIV. Critical review of eligibility criteria related to HIV is required to accelerate development of and access to effective therapeutics for HIV-infected patients with cancer and make studies more generalizable to this patient population. Methods From January through April 2016, the HIV Working Group conducted a series of teleconferences; a review of 46 New Drug Applications from registration studies of unique agents studied in adults with cancer that led to the initial US Food and Drug Administration approval of that agent from 2011 to 2015; and a review of HIV-related eligibility criteria from National Cancer Institute-sponsored studies. Results were discussed and refined at a multistakeholder workshop held May 12, 2016. The HIV Working Group developed recommendations for eligibility criteria that focus on pharmacologic and immunologic considerations in this patient population and that balance patient safety, access to appropriate investigational agents, and study integrity. Results Exclusion of patients with HIV remains common in most studies of novel cancer agents. Models for HIV-related eligibility criteria in National Cancer Institute-sponsored studies are instructive. HIV infection itself should no longer be an exclusion criterion for most studies. Eligibility criteria related to HIV infection that address concurrent antiretroviral therapy and immune status should be designed in a manner that is appropriate for a given cancer. Conclusion Expanding clinical trial eligibility to be more inclusive of patients with HIV is justified in most cases and may accelerate the development of effective therapies in this area of unmet clinical need.

Approach for Autonomous Control of Unmanned Aerial Vehicle Using Intelligent Agents for Knowledge Creation

NASA Technical Reports Server (NTRS)

Dufrene, Warren R., Jr.

2004-01-01

This paper describes the development of a planned approach for Autonomous operation of an Unmanned Aerial Vehicle (UAV). A Hybrid approach will seek to provide Knowledge Generation thru the application of Artificial Intelligence (AI) and Intelligent Agents (IA) for UAV control. The application of many different types of AI techniques for flight will be explored during this research effort. The research concentration will be directed to the application of different AI methods within the UAV arena. By evaluating AI approaches, which will include Expert Systems, Neural Networks, Intelligent Agents, Fuzzy Logic, and Complex Adaptive Systems, a new insight may be gained into the benefits of AI techniques applied to achieving true autonomous operation of these systems thus providing new intellectual merit to this research field. The major area of discussion will be limited to the UAV. The systems of interest include small aircraft, insects, and miniature aircraft. Although flight systems will be explored, the benefits should apply to many Unmanned Vehicles such as: Rovers, Ocean Explorers, Robots, and autonomous operation systems. The flight system will be broken down into control agents that will represent the intelligent agent approach used in AI. After the completion of a successful approach, a framework of applying a Security Overseer will be added in an attempt to address errors, emergencies, failures, damage, or over dynamic environment. The chosen control problem was the landing phase of UAV operation. The initial results from simulation in FlightGear are presented.

Pharmacotherapy for obesity: novel agents and paradigms

PubMed Central

Manning, Sean; Pucci, Andrea

2014-01-01

Public health initiatives focused on obesity prevention and lifestyle intervention programmes for patients with obesity have struggled to contain the obesity epidemic to date. In recent years, antiobesity drug therapies have had a limited role in clinical treatment algorithms for patients with obesity. Indeed, a number of high-profile antiobesity drug suspensions have markedly impacted upon the landscape of obesity pharmacotherapy. In this review, we discuss the advent of an increasing array of pharmacotherapeutic agents, which are effective both in inducing weight loss and in maintaining weight loss achieved by lifestyle measures. The development of these drugs as antiobesity agents has followed varying paths, ranging from lorcaserin, a selective serotonin agent, exploiting the beneficial central actions of fenfluramine but without the associated systemic side effects, to liraglutide, a gut hormone already used as a glucose-lowering drug but with appetite-suppressant properties, or the novel drug combination of phentermine/topiramate, two ‘old’ drugs used in lower doses than with previous therapeutic uses, resulting in an additive effect on weight loss and fewer side effects. We summarize the key findings from recent randomized controlled trials of these three drugs. Although these agents lead to clinically important weight loss when used as monotherapy, the use of antiobesity drugs as adjunctive therapy post intensive lifestyle intervention could prove to be the most successful strategy. Moreover, a progressive approach to obesity pharmacotherapy perhaps offers the best opportunity to finally address the obesity crisis on a mass scale. PMID:24790728

Event-Triggered Distributed Average Consensus Over Directed Digital Networks With Limited Communication Bandwidth.

PubMed

Li, Huaqing; Chen, Guo; Huang, Tingwen; Dong, Zhaoyang; Zhu, Wei; Gao, Lan

2016-12-01

In this paper, we consider the event-triggered distributed average-consensus of discrete-time first-order multiagent systems with limited communication data rate and general directed network topology. In the framework of digital communication network, each agent has a real-valued state but can only exchange finite-bit binary symbolic data sequence with its neighborhood agents at each time step due to the digital communication channels with energy constraints. Novel event-triggered dynamic encoder and decoder for each agent are designed, based on which a distributed control algorithm is proposed. A scheme that selects the number of channel quantization level (number of bits) at each time step is developed, under which all the quantizers in the network are never saturated. The convergence rate of consensus is explicitly characterized, which is related to the scale of network, the maximum degree of nodes, the network structure, the scaling function, the quantization interval, the initial states of agents, the control gain and the event gain. It is also found that under the designed event-triggered protocol, by selecting suitable parameters, for any directed digital network containing a spanning tree, the distributed average consensus can be always achieved with an exponential convergence rate based on merely one bit information exchange between each pair of adjacent agents at each time step. Two simulation examples are provided to illustrate the feasibility of presented protocol and the correctness of the theoretical results.

Unbinding of targeted ultrasound contrast agent microbubbles by secondary acoustic forces.

PubMed

Garbin, Valeria; Overvelde, Marlies; Dollet, Benjamin; de Jong, Nico; Lohse, Detlef; Versluis, Michel

2011-10-07

Targeted molecular imaging with ultrasound contrast agent microbubbles is achieved by incorporating targeting ligands on the bubble coating and allows for specific imaging of tissues affected by diseases. Improved understanding of the interplay between the acoustic forces acting on the bubbles during insonation with ultrasound and other forces (e.g. shear due to blood flow, binding of targeting ligands to receptors on cell membranes) can help improve the efficacy of this technique. This work focuses on the effects of the secondary acoustic radiation force, which causes bubbles to attract each other and may affect the adhesion of targeted bubbles. First, we examine the translational dynamics of ultrasound contrast agent microbubbles in contact with (but not adherent to) a semi-rigid membrane due to the secondary acoustic radiation force. An equation of motion that effectively accounts for the proximity of the membrane is developed, and the predictions of the model are compared with experimental data extracted from optical recordings at 15 million frames per second. A time-averaged model is also proposed and validated. In the second part of the paper, initial results on the translation due to the secondary acoustic radiation force of targeted, adherent bubbles are presented. Adherent bubbles are also found to move due to secondary acoustic radiation force, and a restoring force is observed that brings them back to their initial positions. For increasing magnitude of the secondary acoustic radiation force, a threshold is reached above which the adhesion of targeted microbubbles is disrupted. This points to the fact that secondary acoustic radiation forces can cause adherent bubbles to detach and alter the spatial distribution of targeted contrast agents bound to tissues during activation with ultrasound. While the details of the rupture of intermolecular bonds remain elusive, this work motivates the use of the secondary acoustic radiation force to measure the strength of adhesion of targeted microbubbles.

Functional copolymer/organo-MMT nanoarchitectures. VI. Synthesis and characterization of novel nanocomposites by interlamellar controlled/living radical copolymerization via preintercalated RAFT-agent/organoclay complexes.

PubMed

Rzayev, Zakir M O; Söylemez, A Ernur

2011-04-01

We have developed a new approach for the synthesis of polymer nanocomposites using a bifunctional reversible addition-fragmentation chain transfer (RAFT) agent, two types of organo-montmorillonites, such as a non-reactive dimethyldodecyl ammonium (DMDA)-MMT and a reactive octadecylamine (ODA)-MMT organoclays, and a radical initiator. The method includes the following stages: (1) synthesis of RAFT intercalated O-MMTs by a physical or chemical interaction of the RAFT agent having two pendant carboxylic groups [S,S-bis(alpha,alpha'-dimethyl-alpha"-acetic acid)trithiocarbonate] with surface alkyl amines of O-MMT containing tertiary ammonium cation or primary amine groups through strong H-bonding and complexing/amidization reactions, respectively, and (2) utilization of these well-dispersed and intercalated RAFT ... O-MMT complexes and their amide derivatives as new modified RAFT agents in radical-initiated interlamellar controlled/living copolymerization of itaconic acid (IA)-n-butylmethacrylate (BMA) monomer pair. The structure and compositions of the synthesized RAFT ... O-MMT complexes and functional copolymer/O-MMT hybrids were confirmed by FTIR, XRD, thermal (DSC-TGA), SEM and TEM morphology analyses. It was demonstrated that the degree of interaction/exfoliation, morphology and thermal behavior of nanocomposites significantly depended on the type of organoclay and in situ interaction, as well as on the content of flexible butyl-ester linkages as a internal plasticizer. The results of the comparative analysis of the nanocomposites structure-composition-property relations show that the functional copolymer-organoclay hybrids prepared with reactive RAFT ... ODA-MMT complex and containing a combination of partially intercalated and predominantly exfoliated nano-structures exhibit relatively higher thermal stability and fine dispersed morphology. These effects were explained by in situ interfacial chemical reactions through amidization of RAFT with surface alkyl amine of MMT clay in interlamellar copolymerization. This simple and versatile method can be applied to a wide range of functional monomer/comonomer systems and mono- and bifunctional RAFT compounds for preparation new generation of nanomaterials.

Nondestructive Intervention to Multi-Agent Systems through an Intelligent Agent

PubMed Central

Han, Jing; Wang, Lin

2013-01-01

For a given multi-agent system where the local interaction rule of the existing agents can not be re-designed, one way to intervene the collective behavior of the system is to add one or a few special agents into the group which are still treated as normal agents by the existing ones. We study how to lead a Vicsek-like flocking model to reach synchronization by adding special agents. A popular method is to add some simple leaders (fixed-headings agents). However, we add one intelligent agent, called ‘shill’, which uses online feedback information of the group to decide the shill's moving direction at each step. A novel strategy for the shill to coordinate the group is proposed. It is strictly proved that a shill with this strategy and a limited speed can synchronize every agent in the group. The computer simulations show the effectiveness of this strategy in different scenarios, including different group sizes, shill speed, and with or without noise. Compared to the method of adding some fixed-heading leaders, our method can guarantee synchronization for any initial configuration in the deterministic scenario and improve the synchronization level significantly in low density groups, or model with noise. This suggests the advantage and power of feedback information in intervention of collective behavior. PMID:23658695

Time-Extended Payoffs for Collectives of Autonomous Agents

NASA Technical Reports Server (NTRS)

Tumer, Kagan; Agogino, Adrian K.

2002-01-01

A collective is a set of self-interested agents which try to maximize their own utilities, along with a a well-defined, time-extended world utility function which rates the performance of the entire system. In this paper, we use theory of collectives to design time-extended payoff utilities for agents that are both aligned with the world utility, and are "learnable", i.e., the agents can readily see how their behavior affects their utility. We show that in systems where each agent aims to optimize such payoff functions, coordination arises as a byproduct of the agents selfishly pursuing their own goals. A game theoretic analysis shows that such payoff functions have the net effect of aligning the Nash equilibrium, Pareto optimal solution and world utility optimum, thus eliminating undesirable behavior such as agents working at cross-purposes. We then apply collective-based payoff functions to the token collection in a gridworld problem where agents need to optimize the aggregate value of tokens collected across an episode of finite duration (i.e., an abstracted version of rovers on Mars collecting scientifically interesting rock samples, subject to power limitations). We show that, regardless of the initial token distribution, reinforcement learning agents using collective-based payoff functions significantly outperform both natural extensions of single agent algorithms and global reinforcement learning solutions based on "team games".

Comparing large-scale computational approaches to epidemic modeling: agent-based versus structured metapopulation models.

PubMed

Ajelli, Marco; Gonçalves, Bruno; Balcan, Duygu; Colizza, Vittoria; Hu, Hao; Ramasco, José J; Merler, Stefano; Vespignani, Alessandro

2010-06-29

In recent years large-scale computational models for the realistic simulation of epidemic outbreaks have been used with increased frequency. Methodologies adapt to the scale of interest and range from very detailed agent-based models to spatially-structured metapopulation models. One major issue thus concerns to what extent the geotemporal spreading pattern found by different modeling approaches may differ and depend on the different approximations and assumptions used. We provide for the first time a side-by-side comparison of the results obtained with a stochastic agent-based model and a structured metapopulation stochastic model for the progression of a baseline pandemic event in Italy, a large and geographically heterogeneous European country. The agent-based model is based on the explicit representation of the Italian population through highly detailed data on the socio-demographic structure. The metapopulation simulations use the GLobal Epidemic and Mobility (GLEaM) model, based on high-resolution census data worldwide, and integrating airline travel flow data with short-range human mobility patterns at the global scale. The model also considers age structure data for Italy. GLEaM and the agent-based models are synchronized in their initial conditions by using the same disease parameterization, and by defining the same importation of infected cases from international travels. The results obtained show that both models provide epidemic patterns that are in very good agreement at the granularity levels accessible by both approaches, with differences in peak timing on the order of a few days. The relative difference of the epidemic size depends on the basic reproductive ratio, R0, and on the fact that the metapopulation model consistently yields a larger incidence than the agent-based model, as expected due to the differences in the structure in the intra-population contact pattern of the approaches. The age breakdown analysis shows that similar attack rates are obtained for the younger age classes. The good agreement between the two modeling approaches is very important for defining the tradeoff between data availability and the information provided by the models. The results we present define the possibility of hybrid models combining the agent-based and the metapopulation approaches according to the available data and computational resources.

Practical aspects of treatment with target specific anticoagulants: initiation, payment and current market, transitions, and venous thromboembolism treatment.

PubMed

Mahan, Charles E

2015-04-01

Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.

Information flow in a network of dispersed signalers-receivers

NASA Astrophysics Data System (ADS)

Halupka, Konrad

2017-11-01

I consider a stochastic model of multi-agent communication in regular network. The model describes how dispersed animals exchange information. Each agent can initiate and transfer the signal to its nearest neighbors, who may pass it farther. For an external observer of busy networks, signaling activity may appear random, even though information flow actually thrives. Only when signal initiation and transfer are at low levels do spatiotemporal autocorrelations emerge as clumping signaling activity in space and pink noise time series. Under such conditions, the costs of signaling are moderate, but the signaler can reach a large audience. I propose that real-world networks of dispersed signalers-receivers may self-organize into this state and the flow of information maintains their integrity.

Passive Antibody Administration (Immediate Immunity) as a Specific Defense Against Biological Weapons

PubMed Central

2002-01-01

The potential threat of biological warfare with a specific agent is proportional to the susceptibility of the population to that agent. Preventing disease after exposure to a biological agent is partially a function of the immunity of the exposed individual. The only available countermeasure that can provide immediate immunity against a biological agent is passive antibody. Unlike vaccines, which require time to induce protective immunity and depend on the host’s ability to mount an immune response, passive antibody can theoretically confer protection regardless of the immune status of the host. Passive antibody therapy has substantial advantages over antimicrobial agents and other measures for postexposure prophylaxis, including low toxicity and high specific activity. Specific antibodies are active against the major agents of bioterrorism, including anthrax, smallpox, botulinum toxin, tularemia, and plague. This article proposes a biological defense initiative based on developing, producing, and stockpiling specific antibody reagents that can be used to protect the population against biological warfare threats. PMID:12141970

Method for producing and treating coal gases

DOEpatents

Calderon, Albert

1990-01-01

A method of generating a de-sulphurized volatile matter and a relatively low Btu gas includes the initial step of pyrolyzing coal to produce volatile matter and a char. The volatile matter is fed to a first de-sulphurizer containing a de-sulphurizing agent to remove sulphur therefrom. At the same time, the char is gasified to produce a relatively low Btu gas. The low Btu gas is fed to a second de-sulphurizer containing the de-sulphurizing agent to remove sulphur therefrom. A regenerator is provided for removing sulphur from the de-sulphurizing agent. Portions of the de-sulphurizing agent are moved among the first de-sulphurizer, the second de-sulphurizer, and the regenerator such that the regenerator regenerates the de-sulphurizing agent. Preferably, the portions of the de-sulphurizing agent are moved from the second de-sulphurizer to the first de-sulphurizer, from the first de-sulphurizer to the regenerator, and from the regenerator to the second de-sulphurizer.

A Review of Antibacterial Agents in Endodontic Treatment

PubMed Central

Rahimi, Saeed; Janani, Maryam; Lotfi, Mehrdad; Shahi, Shahriar; Aghbali, Amirala; Vahid Pakdel, Mahdi; Salem Milani, Amin; Ghasemi, Negin

2014-01-01

Microorganisms play a major role in initiation and perpetuation of pulpal and periapical diseases. Therefore, elimination of the microorganisms present in the root canal system is the fundamental objective of endodontic treatment. The use of mechanical debridement, chemical irrigation or other antimicrobial protocols and intra-canal medicaments are critical to attain this goal. The aim of this article was to review the antimicrobial agents and their properties in endodontics. PMID:25031587

[Formation of endogenous pyrogen by mononuclear phagocytes].

PubMed

Agasarov, L G; Sorokin, A V; Ukhanova, I K

1984-07-01

Production of endogenous pyrogen by human and rabbit blood monocytes in response to stimulation with agents of different origin was studied by inhibitory analysis under comparable conditions. Actinomycin D and cytochalasin B were applied. New evidence was obtained about an important role in the mechanism of activation of mononuclear phagocytes of initial interaction between a stimulating agent and the leukocyte membrane and of the biphasic process of endogenous pyrogen production.

The Human Dimension of Systemic Department-Level Change: A Change Agent's Retrospective on a Case of Reform

ERIC Educational Resources Information Center

Vanasupa, Linda

2011-01-01

This paper represents a narrative of the process of department-level reform through the eyes of the initiating agent of change. Over the course of reform, our program has grown by 40%, primarily through retaining students. We exhibit a 10% net important rate of engineering students in the first two years of the curriculum relative to the college's…

Method for the decontamination of metallic surfaces

DOEpatents

Purohit, Ankur; Kaminski, Michael D.; Nunez, Luis

2003-01-01

A method of decontaminating a radioactively contaminated oxide on a surface. The radioactively contaminated oxide is contacted with a diphosphonic acid solution for a time sufficient to dissolve the oxide and subsequently produce a precipitate containing most of the radioactive values. Thereafter, the diphosphonic solution is separated from the precipitate. HEDPA is the preferred diphosphonic acid and oxidizing and reducing agents are used to initiate precipitation. SFS is the preferred reducing agent.

Model-based Utility Functions

NASA Astrophysics Data System (ADS)

Hibbard, Bill

2012-05-01

Orseau and Ring, as well as Dewey, have recently described problems, including self-delusion, with the behavior of agents using various definitions of utility functions. An agent's utility function is defined in terms of the agent's history of interactions with its environment. This paper argues, via two examples, that the behavior problems can be avoided by formulating the utility function in two steps: 1) inferring a model of the environment from interactions, and 2) computing utility as a function of the environment model. Basing a utility function on a model that the agent must learn implies that the utility function must initially be expressed in terms of specifications to be matched to structures in the learned model. These specifications constitute prior assumptions about the environment so this approach will not work with arbitrary environments. But the approach should work for agents designed by humans to act in the physical world. The paper also addresses the issue of self-modifying agents and shows that if provided with the possibility to modify their utility functions agents will not choose to do so, under some usual assumptions.

Many-Agent Controlled Teleportation of Multi-qubit Quantum Information via Quantum Entanglement Swapping

NASA Astrophysics Data System (ADS)

Zhang, Zhan-Jun; Liu, Yi-Min; Man, Zhong-Xiao

2005-11-01

We present a method to teleport multi-qubit quantum information in an easy way from a sender to a receiver via the control of many agents in a network. Only when all the agents collaborate with the quantum information receiver can the unknown states in the sender's qubits be fully reconstructed in the receiver's qubits. In our method, agents's control parameters are obtained via quantum entanglement swapping. As the realization of the many-agent controlled teleportation is concerned, compared to the recent method [C.P. Yang, et al., Phys. Rev. A 70 (2004) 022329], our present method considerably reduces the preparation difficulty of initial states and the identification difficulty of entangled states, moreover, it does not need local Hadamard operations and it is more feasible in technology. The project supported by National Natural Science Foundation of China under Grant No. 10304022

Dispensing patterns for antidiabetic agents in New Zealand: are the guidelines being followed?

PubMed

Murray, Peter; Norris, Hew; Metcalfe, Scott; Betty, Bryan; Young, Vanessa; Locke, Bronwyn

2017-11-10

Type 2 diabetes mellitus (T2DM) is a significant public health issue in New Zealand. Effective management and glycaemic control is critical for reducing diabetes-related complications. Treatment guidelines are well established in New Zealand. Using dispensing data as a proxy for prescribing data, this paper aims to describe the pattern of first- and second-line antidiabetic agent (AA) dispensing for T2DM in New Zealand and assess adherence with treatment guidelines. Analysis of national dispensing data for AA medications using the Pharmaceutical Collection database from 2007/08 to 2015/16. Metformin monotherapy remains the most commonly prescribed first-line T2DM medication prescribed, accounting for 85% of initial agents prescribed. Sulfonylureas are the most common second-line agents used, accounting for 70% of all second-line agents. There is a high degree of adherence with the T2DM treatment guidelines in New Zealand.

Biocompatible blood pool MRI contrast agents based on hyaluronan

PubMed Central

Zhu, Wenlian; Artemov, Dmitri

2010-01-01

Biocompatible gadolinium blood pool contrast agents based on a biopolymer, hyaluronan, were investigated for magnetic resonance angiography application. Hyaluronan, a non-sulfated linear glucosaminoglycan composed of 2000–25,000 repeating disaccharide subunits of D-glucuronic acid and N-acetylglucosamine with molecular weight up to 20 MDa, is a major component of the extracellular matrix. Two gadolinium contrast agents based on 16 and 74 kDa hyaluronan were synthesized, both with R1 relaxivity around 5 mM−1 s−1 per gadolinium at 9.4 T at 25°C. These two hyaluronan based agents show significant enhancement of the vasculature for an extended period of time. Initial excretion was primarily through the renal system. Later uptake was observed in the stomach and lower gastrointestinal tract. Macromolecular hyaluronan-based gadolinium agents have a high clinical translation potential as hyaluronan is already approved by FDA for a variety of medical applications. PMID:21504061

Bioterrorism for the respiratory physician.

PubMed

Waterer, Grant W; Robertson, Hannah

2009-01-01

Terrorist attacks by definition are designed to cause fear and panic. There is no question that a terrorist attack using biological agents would present a grave threat to stability of the society in which they were released. Early recognition of such a bioterrorist attack is crucial to containing the damage they could cause. As many of the most likely bioterrorism agents present with pulmonary disease, respiratory physicians may be crucial in the initial recognition and diagnosis phase, and certainly would be drawn into treatment of affected individuals. This review focuses on the biological agents thought most likely to be used by terrorists that have predominantly respiratory presentations. The primary focus of this review is on anthrax, plague, tularaemia, ricin, and Staphylococcal enterotoxin B. The pathogenesis, clinical manifestations and treatment of these agents will be discussed as well as historical examples of their use. Other potential bioterrorism agents with respiratory manifestations will also be discussed briefly.

Treatment Patterns Associated with ACR-Recommended Medications in the Management of Fibromyalgia in the United States.

PubMed

Liu, Yifei; Qian, Chunlin; Yang, Mei

2016-03-01

Fibromyalgia (FM) affects up to 6% of U.S. adults, resulting in a significant burden on the health care system and poor quality of life for patients. Duloxetine, pregabalin, and milnacipran are approved for management of FM; however, consensus is lacking regarding optimal therapy. Patients with FM taking approved medications often do not experience meaningful symptom relief, and many experience intolerable adverse events. To assess treatment patterns associated with available and commonly used medications for the management of FM using U.S. health insurance claims. This retrospective analysis used the MarketScan claims database to identify adults with a first diagnosis of FM (ICD-9-CM code 729.1) between 2009 and 2011 with continuous health plan enrollment for 12 months pre- and post-index. Medications of interest were pregabalin, gabapentin, duloxetine, milnacipran, cyclobenzaprine, and tramadol. These are 6 of the 8 medications recommended by the American College of Rheumatology (ACR) for treating FM; the other 2 (amitriptyline and venlafaxine) were only included in some initial assessments. The Charlson Comorbidity Index (CCI) was used to assess overall comorbidity burden. Endpoints included proportion of patients treated within 1 year after first diagnosis; initial treatment pattern; adherence over the first-year follow-up period for the medications of interest; and discontinuation, switching, and combination therapy patterns among pain medications of interest at different time points. Proportion of days covered (PDC; defined as number of days in the period when the patient had drug supply divided by the number of days in the period) was used to define adherence, which was categorized as low (PDC < 50%), medium (PDC 50% to < 80%), or high (PDC ≥ 80%). The time to discontinuation (defined as the first drug supply gap ≥ 90 days) was estimated using Kaplan-Meier analysis. Overall, 240,144 patients met the inclusion criteria. Patients were predominantly women (68%), had preferred provider organization insurance coverage (68%), and had a CCI score < 1 at baseline (69%). Only 31% (n = 74,738) initiated a treatment with a prescription medication listed in the ACR guidelines, and many patients received less than the recommended dose. Most (n = 70,919) patients initially received monotherapy with one of the 8 prescription medications. Of those who started with ≥ 2 medications (n = 3,819), cyclobenzaprine plus tramadol was the most frequent combination. Adherence was suboptimal for all 6 medications of interest. Duloxetine had the highest mean PDC (59%); for all other agents, mean PDC was < 50%. With the exception of duloxetine, discontinuation rates at 6 months were > 50% for all agents. Alterations in therapy were common. Among patients who discontinued their initial treatment of duloxetine, pregabalin, or milnacipran, approximately one-third had switched treatments within 90 days after their first prescription. For those who maintained their initial treatment agent, approximately 50% of patients added a second pain medication within 1 year of treatment initiation. The evidence suggests that patients with FM often do not receive 1 of the prescription medications recommended by ACR guidelines, and those who do are commonly prescribed lower-than-recommended doses, potentially resulting in poor effectiveness and tolerability. Discontinuation, switching, and addition of new pain medications are common, which may indicate low levels of satisfaction with initial treatment. New therapies with improved effectiveness and better tolerability are urgently needed for patients with FM.

Non-Steroidal Anti-Inflammatory Drugs and Cardiovascular Outcomes in Women: Results from the Women’s Health Initiative

PubMed Central

Bavry, Anthony A.; Thomas, Fridtjof; Allison, Matthew; Johnson, Karen C.; Howard, Barbara V.; Hlatky, Mark; Manson, JoAnn E.; Limacher, Marian C.

2014-01-01

Background Conclusive data regarding cardiovascular (CV) toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) are sparse. We hypothesized that regular NSAID use is associated with increased risk for CV events in post-menopausal women, and that this association is stronger with greater cyclooxygenase (cox)-2 compared with cox-1 inhibition. Methods and Results Post-menopausal women enrolled in the Women’s Health Initiative (WHI) were classified as regular users or non-users of non-aspirin NSAIDs. Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total CV disease defined as CV death, nonfatal myocardial infarction, or nonfatal stroke. Secondary analyses considered the association of selective cox-2 inhibitors (e.g., celecoxib), non-selective agents with cox-2>cox-1 inhibition (e.g., naproxen), and non-selective agents with cox-1>cox-2 inhibition (e.g., ibuprofen) with the primary outcome. Overall, 160,801 participants were available for analysis (mean follow-up 11.2 years). Regular NSAID use at some point in time was reported by 53,142 participants. Regular NSAID use was associated with an increased hazard for CV events versus no NSAID use (HR=1.10[95% CI 1.06–1.15], Pitalic>0.001). Selective cox-2 inhibitors were associated with a modest increased hazard for CV events (HR=1.13[1.04–1.23], P=0.004; celecoxib only HR=1.13[1.01–1.27], P=0.031). Among aspirin users, concomitant selective cox-2 inhibitor use was no longer associated with increased hazard for CV events. There was an increased risk for agents with cox-2>cox-1 inhibition (HR=1.17[1.10–1.24], Pbold>0.001; naproxen only HR=1.22[1.12–1.34], P<0.001). This harmful association remained among concomitant aspirin users. We did not observe a risk elevation for agents with cox-1>cox-2 inhibition (HR=1.01[0.95–1.07], P=0.884; ibuprofen only HR=1.00[0.93–1.07], P=0.996). Conclusions Regular use of selective cox-2 inhibitors and non-selective NSAIDs with cox-2>cox-1 inhibition showed a modestly increased hazard for CV events. Non-selective agents with cox-1>cox-2 inhibition were not associated with increased CV risk. Clinical Trial Registration www.clinicaltrials.gov NCT00000611 PMID:25006185

Adhesion strength of norbornene-based self-healing agents to an amine-cured epoxy

NASA Astrophysics Data System (ADS)

Huang, Guang Chun; Lee, Jong Keun; Kessler, Michael R.; Yoon, Sungho

2009-07-01

Self-healing is triggered by crack propagation through embedded microcapsules in an epoxy matrix, which then release the liquid healing agent into the crack plane. Subsequent exposure of the healing agent to the chemical catalyst initiates ring-opening metathesis polymerization (ROMP) and bonding of the crack faces. In order to improve self-healing functionality, it is necessary to enhance adhesion of polymerized healing agent within the crack to the matrix resin. In this study, shear bond strength between different norbornene-based healing agents and an amine-cured epoxy resin was evaluated using the single lap shear test method (ASTM D3163, modified). The healing agents tested include endodicyclopentadiene (endo-DCPD), 5-ethylidene-2-norbornene (ENB) and DCPD/ENB blends. 5-Norbornene-2-methanol (NBM) was used as an adhesion promoter, containing hydroxyl groups to form hydrogen bonds with the amine-cured epoxy. A custom synthesized norbornene-based crosslinking agent was also added to improve adhesion for ENB by increasing the crosslinking density of the adhesive after ROMP. The healing agents were polymerized with varying loadings of the 1st generation Grubbs' catalyst at different reaction times and temperatures.

Optimal Routing and Control of Multiple Agents Moving in a Transportation Network and Subject to an Arrival Schedule and Separation Constraints

NASA Technical Reports Server (NTRS)

Sadovsky, A. V.; Davis, D.; Isaacson, D. R.

2012-01-01

We address the problem of navigating a set of moving agents, e.g. automated guided vehicles, through a transportation network so as to bring each agent to its destination at a specified time. Each pair of agents is required to be separated by a minimal distance, generally agent-dependent, at all times. The speed range, initial position, required destination, and required time of arrival at destination for each agent are assumed provided. The movement of each agent is governed by a controlled differential equation (state equation). The problem consists in choosing for each agent a path and a control strategy so as to meet the constraints and reach the destination at the required time. This problem arises in various fields of transportation, including Air Traffic Management and train coordination, and in robotics. The main contribution of the paper is a model that allows to recast this problem as a decoupled collection of problems in classical optimal control and is easily generalized to the case when inertia cannot be neglected. Some qualitative insight into solution behavior is obtained using the Pontryagin Maximum Principle. Sample numerical solutions are computed using a numerical optimal control solver.

Initial English Language Teacher Education: Processes and Tensions towards a Unifying Curriculum in an Argentinian Province

ERIC Educational Resources Information Center

Banegas, Dario Luis

2014-01-01

In this reflective piece I discuss the process of developing a new unifying initial English language teacher education curriculum in the province of Chubut (Argentina). Trainers and trainees from different institutions were called to work on it with the aim of democratising curriculum development and enhancing involvement among agents. In the…

Variations in Health Insurance Policies Regarding Biologic Therapy Use in Inflammatory Bowel Disease.

PubMed

Yadav, Abhijeet; Foromera, Joshua; Feuerstein, Ilana; Falchuk, Kenneth R; Feuerstein, Joseph D

2017-06-01

The American Gastroenterological Association (AGA) has developed guidelines for the management of ulcerative colitis and Crohn's disease (CD) recommending anti-TNF therapy in moderate-severe disease. However, which drug is used is often dictated by insurance company policies. We sought to determine the insurance policy requirements prior to approval of biologic therapies. Using the National Association of Insurance Commissioners report of the top 125 insurance companies by market share in 2014, we reviewed the first 50 that had online policies regarding anti-TNF and vedolizumab available. Policies were reviewed for criteria needed for approval of anti-TNF or vedolizumab therapy, and for compliance with the current AGA clinical pathway recommendations. Ninety-eight percent of policies are inconsistent with the AGA ulcerative colitis pathway and require step-wise drug failure before approval of an anti-TNF. Only 11% of the policies allowed starting vedolizumab without initial failures of an anti-TNF agent, and 21% required the failure of two or more anti-TNF agents. Ninety percent of the policies are inconsistent with AGA CD pathway and require step-wise drug failure before approval of an anti-TNF. Seventy-four percent allowed for initiating infliximab specifically for fistulizing CD. Twenty-eight percent required failing of at least two or more drugs before starting anti-TNF. Only 8% policies allowed starting vedolizumab without initial failures of an anti-TNF agent, and 28% required the failure of two anti-TNF agents. The majority of the policies reviewed fail to adhere to the current AGA pathway recommendations for ulcerative colitis and CD. Further interventions are needed to better align policies with optimal evidence-based drug therapy.

Use of autologous hematopoietic cell transplantation as initial therapy in multiple myeloma and the impact of socio-geo-demographic factors in the era of novel agents.

PubMed

Al-Hamadani, Mohammed; Hashmi, Shahrukh K; Go, Ronald S

2014-08-01

Very effective combination chemotherapy using novel agents has become available in multiple myeloma (MM). Its impact on the use of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHCT) as part of initial therapy is unknown. Using the National Cancer Data Base, we studied the rate of upfront AHCT use among 137,409 newly diagnosed MM patients from 1998 to 2010 in the United States and determined whether disparity exists among various sociodemographic as well as geographic subgroups. Overall, 12,378 (9.0%) patients received AHCT as part of initial treatment. The use of upfront AHCT increased steadily from 5.2% in 1998 to 12.1% in 2010 (trend test, P < 0.001), with no sign of plateau. This was seen across all socio-geo-demographic subgroups except among patients treated in the Northeast where the rate fell from 8.7% in 1998 to 6.6% in 2010. In multivariable analysis, patients with the following characteristics were the least likely to receive AHCT (odds ratio): year of diagnosis from 1998 to 2003 before the era of novel agents (0.67), older age (0.35), Black race (0.58), Hispanic ethnicity (0.78), low level of education or annual household income (0.55), residence in a metro area (0.66), no or unknown medical insurance (0.30), treatment at a community cancer center (0.16), and treatment facility located in the Northeast region (0.54). Even after the introduction of novel agents, the rate of upfront AHCT in MM continues to increase annually. Significant disparities exist dependent on demographic, social, and geographic factors. © 2014 Wiley Periodicals, Inc.

Adverse Effects (AEs) of Topical NSAIDs in Older Adults with Osteoarthritis (OA): a Systematic Review of the Literature

PubMed Central

Makris, UE.; Kohler, MJ.; Fraenkel, L.

2010-01-01

Objective To systematically review the literature on reported adverse effects (AEs) associated with topical NSAID use in older adults with osteoarthritis (OA). Methods A systematic search of Medline (1950 to November 2009), Scopus, Embase, Web of Science, Cochrane databases, Dissertation and American College of Rheumatology Meeting Abstracts was performed to identify original randomized controlled trials, case reports, observational studies, editorials or dissertations reporting AEs from topical NSAIDs in older adults with OA. Information was sought on study and participant characteristics, detailed recording of application site and systemic AEs as well as withdrawals due to AEs. Results The initial search yielded 953 articles of which 19 met eligibility criteria. Subjects receiving topical NSAIDs reported up to 39.3% application site AEs, and up to 17.5% systemic AEs. Five cases of warfarin potentiation with topical agents were reported; 1 resulting in gastrointestinal bleeding. In formal trials, the withdrawal rate from AEs ranged from 0-21% in the topical agents, 0-25% in the oral NSAIDs, and 0-16% in the placebo group. Conclusion In summary, although topical NSAIDs are safer than oral NSAIDs (fewer severe gastrointestinal AEs), a substantial proportion of older adults report systemic AEs with topical agents. Moreover, the withdrawal rate due to AEs with topical agents is comparable to that of oral NSAIDs. Given the safety profile and withdrawal rates described in this study, further data are needed to determine the incremental benefits of topical NSAIDs compared to other treatment modalities in older adults with OA. PMID:20360183

Role of β-Interferon Inducer (DEAE-Dextran) in Tumorigenesis by VEGF and NOTCH1 Inhibition along with Apoptosis Induction.

PubMed

Bakrania, Anita K; Variya, Bhavesh C; Patel, Snehal S

2017-01-01

As a novel target for breast cancer, interferon inducers have found its role as anti-angiogenic agents with diethylaminoethyl dextran (DEAE-Dextran) being a molecule used for centuries as a transfection agent. Our results herein offer an explanation for the emergence of DEAE-Dextran as an anti-tumor agent for TNBC with in-depth mechanistic approach as an anti-angiogenic molecule. DEAE-Dextran has found to possess cytotoxic activity demonstrated during the various in vitro cytotoxicity assays; moreover, as an anti-oxidant, DEAE-Dextran has shown to possess excellent reactive oxygen species scavenging activity. The interferon inducing capacity of DEAE-Dextran was determined qualitatively as well as quantitatively specifically demonstrating overexpression of β-interferon. As a measure of anti-proliferative activity, DEAE-Dextran exhibited reduced ki67, p53, and PCNA levels. Also, overexpression of CK5/6 and p63 in DEAE-Dextran treated animals indicated improvement in breast cell morphology along with an improvement in cell-cell adhesion by virtue of upregulation of β-catenin and E-cadherin. Anti-angiogenic property of DEAE-Dextran was concluded by the downregulation of CD31, VEGF, and NOTCH1 both in vivo and in vitro . Further, apoptosis due to DEAE-Dextran, initially determined by downregulation of Bcl2, was confirmed with flow cytometry. Overall, results are defensive of DEAE-Dextran as an emerging anti-tumor agent with mechanisms pertaining to β-interferon induction with probable VEGF and NOTCH1 inhibition as well as apoptosis which still needs to be studied in further depth.

Role of β-Interferon Inducer (DEAE-Dextran) in Tumorigenesis by VEGF and NOTCH1 Inhibition along with Apoptosis Induction

PubMed Central

Bakrania, Anita K.; Variya, Bhavesh C.; Patel, Snehal S.

2017-01-01

As a novel target for breast cancer, interferon inducers have found its role as anti-angiogenic agents with diethylaminoethyl dextran (DEAE-Dextran) being a molecule used for centuries as a transfection agent. Our results herein offer an explanation for the emergence of DEAE-Dextran as an anti-tumor agent for TNBC with in-depth mechanistic approach as an anti-angiogenic molecule. DEAE-Dextran has found to possess cytotoxic activity demonstrated during the various in vitro cytotoxicity assays; moreover, as an anti-oxidant, DEAE-Dextran has shown to possess excellent reactive oxygen species scavenging activity. The interferon inducing capacity of DEAE-Dextran was determined qualitatively as well as quantitatively specifically demonstrating overexpression of β-interferon. As a measure of anti-proliferative activity, DEAE-Dextran exhibited reduced ki67, p53, and PCNA levels. Also, overexpression of CK5/6 and p63 in DEAE-Dextran treated animals indicated improvement in breast cell morphology along with an improvement in cell–cell adhesion by virtue of upregulation of β-catenin and E-cadherin. Anti-angiogenic property of DEAE-Dextran was concluded by the downregulation of CD31, VEGF, and NOTCH1 both in vivo and in vitro. Further, apoptosis due to DEAE-Dextran, initially determined by downregulation of Bcl2, was confirmed with flow cytometry. Overall, results are defensive of DEAE-Dextran as an emerging anti-tumor agent with mechanisms pertaining to β-interferon induction with probable VEGF and NOTCH1 inhibition as well as apoptosis which still needs to be studied in further depth. PMID:29311933

Minimally invasive convection-enhanced delivery of biologics into dorsal root ganglia: validation in the pig model and prospective modeling in humans. Technical note.

PubMed

Pleticha, Josef; Maus, Timothy P; Christner, Jodie A; Marsh, Michael P; Lee, Kendall H; Hooten, W Michael; Beutler, Andreas S

2014-10-01

Dorsal root ganglia (DRG) are critical anatomical structures involved in nociception. Intraganglionic (IG) drug delivery is therefore an important route of administration for novel analgesic therapies. Although IG injection in large animal models is highly desirable for preclinical biodistribution and toxicology studies of new drugs, no method to deliver pharmaceutical agents into the DRG has been reported in any large species. The present study describes a minimally invasive technique of IG agent delivery in domestic swine, one of the most common large animal models. The technique utilizes CT guidance for DRG targeting and a custom-made injection assembly for convection enhanced delivery (CED) of therapeutic agents directly into DRG parenchyma. The DRG were initially visualized by CT myelography to determine the optimal access route to the DRG. The subsequent IG injection consisted of 3 steps. First, a commercially available guide needle was advanced to a position dorsolateral to the DRG, and the dural root sleeve was punctured, leaving the guide needle contiguous with, but not penetrating, the DRG. Second, the custom-made stepped stylet was inserted through the guide needle into the DRG parenchyma. Third, the stepped stylet was replaced by the custom-made stepped needle, which was used for the IG CED. Initial dye injections performed in pig cadavers confirmed the accuracy of DRG targeting under CT guidance. Intraganglionic administration of adeno-associated virus in vivo resulted in a unilateral transduction of the injected DRG, with 33.5% DRG neurons transduced. Transgene expression was also found in the dorsal root entry zones at the corresponding spinal levels. The results thereby confirm the efficacy of CED by the stepped needle and a selectivity of DRG targeting. Imaging-based modeling of the procedure in humans suggests that IG CED may be translatable to the clinical setting.

Biological therapy of hematologic malignancies: toward a chemotherapy-free era.

PubMed

Klener, Pavel; Etrych, Tomas; Klener, Pavel

2017-10-06

Less than 70 years ago, the vast majority of hematologic malignancies were untreatable diseases with fatal prognoses. The development of modern chemotherapy agents, which had begun after the Second World War, was markedly accelerated by the discovery of the structure of DNA and its role in cancer biology and tumor cell division. The path travelled from the first temporary remissions observed in children with acute lymphoblastic leukemia treated with single-agent antimetabolites until the first cures achieved by multi-agent chemotherapy regimens was incredibly short. Despite great successes, however, conventional genotoxic cytostatics suffered from an inherently narrow therapeutic index and extensive toxicity, which in many instances limited their clinical utilization. In the last decade of the 20th century, increasing knowledge on the biology of certain malignancies resulted in the conception and development of first molecularly targeted agents designed to inhibit specific druggable molecules involved in the survival of cancer cells. Advances in technology and genetic engineering enabled the production of structurally complex anticancer macromolecules called biologicals, including therapeutic monoclonal antibodies, antibody-drug conjugates and antibody fragments. The development of drug delivery systems (DDSs), in which conventional drugs were attached to various types of carriers including nanoparticles, liposomes or biodegradable polymers, represented an alternative approach to the development of new anticancer agents. Despite the fact that the antitumor activity of drugs attached to DDSs was not fundamentally different, the improved pharmacokinetic profiles, decreased toxic side effects and significantly increased therapeutic indexes resulted in their enhanced antitumor efficacy compared to conventional (unbound) drugs. Approval of the first immune checkpoint inhibitor for the treatment of cancer in 2011 initiated the era of cancer immunotherapy. Checkpoint inhibitors, bispecific T-cell engagers, adoptive T-cell approaches and cancer vaccines have joined the platform so far, represented mainly by recombinant cytokines, therapeutic monoclonal antibodies and immunomodulatory agents. In specific clinical indications, conventional drugs have already been supplanted by multi-agent, chemotherapy-free regimens comprising diverse immunotherapy and/or targeted agents. The very distinct mechanisms of the anticancer activity of new immunotherapy approaches not only call for novel response criteria, but also might fundamental change treatment paradigms of certain types of hematologic malignancies in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

An evolutionary model of cooperation, fairness and altruistic punishment in public good games.

PubMed

Hetzer, Moritz; Sornette, Didier

2013-01-01

We identify and explain the mechanisms that account for the emergence of fairness preferences and altruistic punishment in voluntary contribution mechanisms by combining an evolutionary perspective together with an expected utility model. We aim at filling a gap between the literature on the theory of evolution applied to cooperation and punishment, and the empirical findings from experimental economics. The approach is motivated by previous findings on other-regarding behavior, the co-evolution of culture, genes and social norms, as well as bounded rationality. Our first result reveals the emergence of two distinct evolutionary regimes that force agents to converge either to a defection state or to a state of coordination, depending on the predominant set of self- or other-regarding preferences. Our second result indicates that subjects in laboratory experiments of public goods games with punishment coordinate and punish defectors as a result of an aversion against disadvantageous inequitable outcomes. Our third finding identifies disadvantageous inequity aversion as evolutionary dominant and stable in a heterogeneous population of agents endowed initially only with purely self-regarding preferences. We validate our model using previously obtained results from three independently conducted experiments of public goods games with punishment.

An Evolutionary Model of Cooperation, Fairness and Altruistic Punishment in Public Good Games

PubMed Central

Hetzer, Moritz; Sornette, Didier

2013-01-01

We identify and explain the mechanisms that account for the emergence of fairness preferences and altruistic punishment in voluntary contribution mechanisms by combining an evolutionary perspective together with an expected utility model. We aim at filling a gap between the literature on the theory of evolution applied to cooperation and punishment, and the empirical findings from experimental economics. The approach is motivated by previous findings on other-regarding behavior, the co-evolution of culture, genes and social norms, as well as bounded rationality. Our first result reveals the emergence of two distinct evolutionary regimes that force agents to converge either to a defection state or to a state of coordination, depending on the predominant set of self- or other-regarding preferences. Our second result indicates that subjects in laboratory experiments of public goods games with punishment coordinate and punish defectors as a result of an aversion against disadvantageous inequitable outcomes. Our third finding identifies disadvantageous inequity aversion as evolutionary dominant and stable in a heterogeneous population of agents endowed initially only with purely self-regarding preferences. We validate our model using previously obtained results from three independently conducted experiments of public goods games with punishment. PMID:24260101

Leukocyte Anti-Trafficking Strategies: Current Status and Future Directions.

PubMed

Sands, Bruce E

2017-01-01

In inflammatory bowel diseases (IBD), a pivotal step in the initiation and perpetuation of mucosal inflammation entails the recruitment of inflammatory leukocytes to the gut. Understanding the carefully coordinated series of molecular events that culminate in the recruitment of leukocytes to the gut has resulted in novel interventions with new capabilities in treating both Crohn's disease and ulcerative colitis. Key Messages: Natalizumab, an anti-α4 integrin antibody, was the first agent to demonstrate the efficacy of this approach for the induction and maintenance of response and remission in Crohn's disease. Widespread adoption was mitigated by the previously unknown risk of progressive multifocal leukoencephalopathy (PML) with this approach. Current approaches employ a more selective inhibition of adhesion molecules targeting the gut to avoid broad suppression of surveillance for JC virus, the causal pathogen of PML. Subsequently, vedolizumab, a humanized anti-α4β7 integrin antibody, has demonstrated efficacy in patients with IBD and has an excellent safety profile. To date, there have been no cases of PML in patients treated with vedolizumab, suggesting that this more selective agent does not have the same risk for PML as natalizumab. Other agents target β7 integrin (etrolizumab) and mucosal addressin cellular adhesion molecule-1, the endothelial ligand of α4β7 integrin. Efforts to inhibit the chemokine receptor CCR9 using the agent CCX282-B in Crohn's disease were not successful. An orally administered anti-α4 integrin compound showed some promise in a phase 2 trial but raises concern for PML. Finally, the S1P1 receptor agonist ozanimod showed promise in early trials in ulcerative colitis. In summary, anti-trafficking agents have the potential to provide safe and effective therapy for IBD, and are a burgeoning class of novel agents. © 2017 S. Karger AG, Basel.

Colon targeted delivery systems of metronidazole based on osmotic technology: development and evaluation.

PubMed

Kumar, Pramod; Singh, Sanjay; Mishra, Brahmeshwar

2008-09-01

Colon targeted delivery systems of metronidazole (MTZ) based on osmotic technology were developed. The developed systems consisted of osmotic core (drug, osmotic agent and wicking agent), coated with semipermeable membrane (SPM) containing guar gum as pore former, coated core were then further coated with enteric coating to protect the system from acidic environment of stomach. The effect of various formulation variables namely the level of wicking agent (sodium lauryl sulphate), osmotic agent in the osmotic core, the level of pore former (guar gum) in SPM, and the thickness of SPM, were studied on physical parameters and drug release characteristics of developed formulations. MTZ release was inversely proportional to SPM thickness, but directly related to the level of pore former, wicking agent and osmotic agent. On the other hand burst strength of the exhausted shells was decreased with the increase in level of pore former in the membrane but increased with the increase in the thickness of SPM. The drug release from the developed formulations was independent of pH, and agitation intensity, but dependent on the osmotic pressure of the release media. The thickness of enteric coating could prevent formation of delivery pores before contact with simulated colonic fluid, but had no effect on drug release. Result of SEM studies showed the formation of in-situ delivery pores in the membrane from where the drug release occurred, and the number of pores formed were directly related to the initial level of pore former (guar gum) in SPM. The manufacturing procedure was found to be reproducible and formulations were found to be stable during 3 months of accelerated stability studies.

Clostridium difficile infection: current, forgotten and emerging treatment options.

PubMed

Drekonja, Dimitri M

2014-09-01

Clostridium difficile infection (CDI) has increased in incidence and severity, and is now among the most common nosocomial infections. Several agents are available for the initial treatment of CDI, some of which are rarely used, and none of which is clearly superior for initial clinical cure. Fidaxomicin appears to offer a benefit in terms of preventing recurrent disease, although the cost-benefit ratio is debated. Recurrent CDI is a major challenge, occurring after 15-30% of initial episodes. The treatment of recurrent CDI is difficult, with sparse evidence available to support any particular agent. Fecal microbiota therapy, also known as 'stool transplantation', appears to be highly effective, although availability is currently limited, and the regulatory environment is in flux. Synthetic stool products and an orally available fecal microbiota therapy product are both under investigation, which may address the problem of availability. As with most infectious diseases, an effective vaccine would be a welcome addition to our armamentarium, but none is currently available.

Nursing Home Medication Reconciliation: A Quality Improvement Initiative.

PubMed

Tong, Monica; Oh, Hye Young; Thomas, Jennifer; Patel, Sheila; Hardesty, Jennifer L; Brandt, Nicole J

2017-04-01

The current quality improvement initiative evaluated the medication reconciliation process within select nursing homes in Washington, DC. The identification of common types of medication discrepancies through monthly retrospective chart reviews of newly admitted patients in two different nursing homes were described. The use of high-risk medications, namely antidiabetic, anticoagulant, and opioid agents, was also recorded. A standardized spreadsheet tool based on multiple medication reconciliation implementation tool kits was created to record the information. The five most common medication discrepancies were incorrect indication (21%), no monitoring parameters (17%), medication name omitted (11%), incorrect dose (10%), and incorrect frequency (8%). Antidiabetic agents in both sites were the most used high-risk medication. This initiative highlights that medication discrepancies on admission are common in nursing homes and may be clinically impactful. More attention needs to be given to work flow processes to improve medication reconciliation considering the increased risk for adverse drug events and hospitalizations. [Journal of Gerontological Nursing and Mental Health Services, 43(4), 9-14.]. Copyright 2017, SLACK Incorporated.

Effect of anticholinesterase agents on airway epithelial function. Annual report, 15 July 1888-14 August 1989

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

Marin, M.G.

1989-09-15

Irreversible anticholinesterase compounds have potential serious health effects when employed as chemical warfare agents. Intoxication with these agents will cause an accumulation of acetylcholine at nerve muscle and nerve-gland junctions. Because tracheal glands have rich cholinergic innervation, we hypothesized that exposure to anticholinesterase agents, such as soman, would stimulate glandular secretion. This would cause pathological changes in the important lung defense mechanism of mucociliary clearance. Initial work on this contract revealed a dose-related increase in mucociliary transport in the ferret in response to soman. This effect could be inhibited by atropine but not by pralidoxime. The investigation described in thismore » report relates to the effects of soman and its antidotes on glycoconjugate secretion of ferret trachea in vitro.« less

High-performance super capacitors based on activated anthracite with controlled porosity

NASA Astrophysics Data System (ADS)

Lee, Hyun-Chul; Byamba-Ochir, Narandalai; Shim, Wang-Geun; Balathanigaimani, M. S.; Moon, Hee

2015-02-01

Mongolian anthracite is chemically activated using potassium hydroxide as an activation agent to make activated carbon materials. Prior to the chemical activation, the chemical agent is introduced by two different methods as follows, (1) simple physical mixing, (2) impregnation. The physical properties such as specific surface area, pore volume, pore size distribution, and adsorption energy distribution are measured to assess them as carbon electrode materials for electric double-layer capacitors (EDLC). The surface functional groups and morphology are also characterized by X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) analyses respectively. The electrochemical results for the activated carbon electrodes in 3 M sulfuric acid electrolyte solution indicate that the activated Mongolian anthracite has relatively large specific capacitances in the range of 120-238 F g-1 and very high electrochemical stability, as they keep more than 98% of initial capacitances until 1000 charge/discharge cycles.

Solving Assembly Sequence Planning using Angle Modulated Simulated Kalman Filter

NASA Astrophysics Data System (ADS)

Mustapa, Ainizar; Yusof, Zulkifli Md.; Adam, Asrul; Muhammad, Badaruddin; Ibrahim, Zuwairie

2018-03-01

This paper presents an implementation of Simulated Kalman Filter (SKF) algorithm for optimizing an Assembly Sequence Planning (ASP) problem. The SKF search strategy contains three simple steps; predict-measure-estimate. The main objective of the ASP is to determine the sequence of component installation to shorten assembly time or save assembly costs. Initially, permutation sequence is generated to represent each agent. Each agent is then subjected to a precedence matrix constraint to produce feasible assembly sequence. Next, the Angle Modulated SKF (AMSKF) is proposed for solving ASP problem. The main idea of the angle modulated approach in solving combinatorial optimization problem is to use a function, g(x), to create a continuous signal. The performance of the proposed AMSKF is compared against previous works in solving ASP by applying BGSA, BPSO, and MSPSO. Using a case study of ASP, the results show that AMSKF outperformed all the algorithms in obtaining the best solution.

'Click'-xylosides as initiators of the biosynthesis of glycosaminoglycans: Comparison of mono-xylosides with xylobiosides.

PubMed

Chatron-Colliet, Aurore; Brusa, Charlotte; Bertin-Jung, Isabelle; Gulberti, Sandrine; Ramalanjaona, Nick; Fournel-Gigleux, Sylvie; Brézillon, Stéphane; Muzard, Murielle; Plantier-Royon, Richard; Rémond, Caroline; Wegrowski, Yanusz

2017-03-01

Different mono-xylosides and their corresponding xylobiosides obtained by a chemo-enzymatic approach featuring various substituents attached to a triazole ring were probed as priming agents for glycosaminoglycan (GAG) biosynthesis in the xylosyltransferase-deficient pgsA-745 Chinese hamster ovary cell line. Xylosides containing a hydrophobic aglycone moiety were the most efficient priming agents. Mono-xylosides induced higher GAG biosynthesis in comparison with their corresponding xylobiosides. The influence of the degree of polymerization of the carbohydrate part on the priming activity was investigated through different experiments. We demonstrated that in case of mono-xylosides, the cellular uptake as well as the affinity and the catalytic efficiency of β-1,4-galactosyltransferase 7 were higher than for xylobiosides. Altogether, these results indicate that hydrophobicity of the aglycone and degree of polymerization of glycone moiety were critical factors for an optimal priming activity for GAG biosynthesis. © 2016 John Wiley & Sons A/S.

Biological Control Potential of Bacillus amyloliquefaciens KB3 Isolated from the Feces of Allomyrina dichotoma Larvae

PubMed Central

Nam, Hyo-Song; Yang, Hyun-Ju; Oh, Byung Jun; Anderson, Anne J.; Kim, Young Cheol

2016-01-01

Most biocontrol agents for plant diseases have been isolated from sources such as soils and plants. As an alternative source, we examined the feces of tertiary larvae of the herbivorous rhino beetle, Allomyrina dichotoma for presence of biocontrol-active microbes. The initial screen was performed to detect antifungal activity against two common fungal plant pathogens. The strain with strongest antifungal activity was identified as Bacillus amyloliquefaciens KB3. The inhibitory activity of this strain correlated with lipopeptide productions, including iturin A and surfactin. Production of these surfactants in the KB3 isolate varied with the culture phase and growth medium used. In planta biocontrol activities of cell-free culture filtrates of KB3 were similar to those of the commercial biocontrol agent, B. subtilis QST-713. These results support the presence of microbes with the potential to inhibit fungal growth, such as plant pathogens, in diverse ecological niches. PMID:27298603

Hydrogels in a historical perspective: from simple networks to smart materials.

PubMed

Buwalda, Sytze J; Boere, Kristel W M; Dijkstra, Pieter J; Feijen, Jan; Vermonden, Tina; Hennink, Wim E

2014-09-28

Over the past decades, significant progress has been made in the field of hydrogels as functional biomaterials. Biomedical application of hydrogels was initially hindered by the toxicity of crosslinking agents and limitations of hydrogel formation under physiological conditions. Emerging knowledge in polymer chemistry and increased understanding of biological processes resulted in the design of versatile materials and minimally invasive therapies. Hydrogel matrices comprise a wide range of natural and synthetic polymers held together by a variety of physical or chemical crosslinks. With their capacity to embed pharmaceutical agents in their hydrophilic crosslinked network, hydrogels form promising materials for controlled drug release and tissue engineering. Despite all their beneficial properties, there are still several challenges to overcome for clinical translation. In this review, we provide a historical overview of the developments in hydrogel research from simple networks to smart materials. Copyright © 2014 Elsevier B.V. All rights reserved.

The limitations of opportunistic epidemiology, pseudopod epidemiology.

PubMed

Kuller, Lewis H

2016-10-01

Epidemiology has been remarkably successful in the past in identifying the important agents of disease, the impact of the environment, both physical and social, and interrelationship with host susceptibility (genomics). Many of the advances in improving the health of individuals and populations have been the result of epidemiology studies that have identified the specific "agents" of disease and application of public health and preventive medicine. In recent years, large longitudinal studies have dominated epidemiology research, especially long incubation period chronic diseases. The initial hypotheses in these studies have been expanded by vertical extension studies using newer technologies to measure independent variables, vertical pseudopods, and additional studies of other diseases, horizontal pseudopods, of the original longitudinal study. Host susceptibility, i.e. genomics, has also become a prominent component of these longitudinal studies. The critical question addressed in this paper is whether these "pseudopod" epidemiology approaches have enhanced public health or generated a large number of studies of little impact.

Phosphate binder usage in kidney failure patients.

PubMed

Bleyer, Anthony J

2003-06-01

Phosphorus binders are used in patients with kidney failure because of the incomplete removal of phosphorus with dialysis and the inability to exclude phosphorus from the diet. Aluminium was the initial phosphorus binder used, but was replaced by calcium-containing binders because of the development of aluminium toxicity. Calcium-based binders have been the mainstay of therapy for many years, but recent investigations have pointed to increased rates of vascular calcification in patients taking calcium-containing binders. For this reason, alternative agents have been developed. Sevelamer (Renagel), GelTex Pharmaceuticals Inc.) is a polymer which has been found to effectively bind phosphorus. It has resulted in a decreased rate of vascular calcification compared to calcium-containing binders. Other agents under development include lanthanum carbonate and iron-complex preparations. Further research will likely concentrate on identifying binders that bind phosphate more efficiently, have minimal gastrointestinal side effects and provide other benefits to dialysis patients.

Current application and future perspectives of PSMA PET imaging in prostate cancer.

PubMed

Ceci, Francesco; Castellucci, Paolo; Fanti, Stefano

2018-03-08

As precision medicine evolves, the contribution of molecular imaging to the management of prostate cancer (PCa) patients, especially for Positron Emission Tomography (PET) imaging, is gaining importance. Highly successful approaches to measure the expression of the prostate specific membrane antigen (PSMA) have been introduced recently. PSMA, the glutamate carboxypeptidase II (GCP-II), is a membrane bound metallo-peptidase that is overexpressed in 90-100% of PCa cells. Due to its selective over-expression, PSMA is a reliable tissue marker for prostate cancer and is considered an ideal target for tumor specific imaging and therapy. A variety of PET and SPECT probes targeting this peptide receptor have been introduced. These are undergoing extensive clinical evaluations. Initial results attest to a high accuracy for disease detection compared conventional radiology (CT or MRI) and other nuclear medicine procedure (choline PET or fluciclovine PET). However, prospective evaluation of the impact on patient management for PSMA-ligand PET and its impact on patient outcome is currently missing. Finally, PSMA inhibitors can be radio-labeled with diagnostic (68Ga-PSMA-11), or therapeutic nuclides (177Lu/225Ac PSMA-617) to be used as theranostic agent. Initial results showed that PSMA-targeted radioligand therapy (RLT) can potentially delay disease progression in metastatic castrate-resistant PCa. This review aims to explore the current application of PSMA based imaging in prostate cancer, reporting about main advantages and limitations of this new theranostic procedure. The future perspectives and potential the applications of this agent will be also discussed.

Women's Health Leadership to Enhance Community Health Workers as Change Agents.

PubMed

Ingram, Maia; Chang, Jean; Kunz, Susan; Piper, Rosie; de Zapien, Jill Guernsey; Strawder, Kay

2016-05-01

Objectives A community health worker (CHW) is a frontline public health worker who is a trusted member of and/or has an unusually close understanding of the community served. While natural leadership may incline individuals to the CHW profession, they do not always have skills to address broad social issues. We describe evaluation of the Women's Health Leadership Institute (WHLI), a 3-year training initiative to increase the capacity of CHWs as change agents. Methods Pre-/postquestionnaires measured the confidence of 254 participants in mastering WHLI leadership competencies. In-depth interviews with CHW participants 6 to 9 months after the training documented application of WHLI competencies in the community. A national CHW survey measured the extent to which WHLI graduates used leadership skills that resulted in concrete changes to benefit community members. Multivariate logistic regressions controlling for covariates compared WHLI graduates' leadership skills to the national sample. Results Participants reported statistically significant pre-/postimprovements in all competencies. Interviewees credited WHLI with increasing their capacity to listen to others, create partnerships, and initiate efforts to address community needs. Compared to a national CHW sample, WHLI participants were more likely to engage community members in attending public meetings and organizing events. These activities led to community members taking action on an issue and a concrete policy change. Conclusions Leadership training can increase the ability of experienced CHWs to address underlying issues related to community health across different types of organizational affiliations and job responsibilities. © 2016 Society for Public Health Education.

Tumor suppressor Lzap regulates cell cycle progression, doming and zebrafish epiboly

PubMed Central

Liu, Dan; Wang, Wen-Der; Melville, David B.; Cha, Yong I.; Yin, Zhirong; Issaeva, Natalia; Knapik, Ela W.; Yarbrough, Wendell G.

2012-01-01

Initial stages of embryonic development rely on rapid, synchronized cell divisions of the fertilized egg followed by a set of morphogenetic movements collectively called epiboly and gastrulation. Lzap is a putative tumor suppressor whose expression is lost in 30% of head and neck squamous cell carcinomas. Lzap activities include regulation of cell cycle progression and response to therapeutic agents. Here we explore developmental roles of the lzap gene during zebrafish morphogenesis. Lzap is highly conserved among vertebrates and is maternally deposited. Expression is initially ubiquitous during gastrulation, and later becomes more prominent in the pharyngeal arches, digestive tract and brain. Antisense morpholino-mediated depletion of Lzap resulted in delayed cell divisions and apoptosis during blastomere formation, resulting in fewer, larger cells. Cell cycle analysis suggested that Lzap loss in early embryonic cells resulted in a G2/M arrest. Furthermore, the Lzap-deficient embryos failed to initiate epiboly – the earliest morphogenetic movement in animal development – which has been shown to be dependent on cell adhesion and migration of epithelial sheets. Our results strongly implicate Lzap in regulation of cell cycle progression, adhesion and migratory activity of epithelial cell sheets during early development. These functions provide further insight into Lzap activity that may contribute not only to development, but also to tumor formation. PMID:21523853

Breast Cancer Resistance to Cyclophosphamide and Other Oxazaphosphorines

DTIC Science & Technology

1996-10-01

therapeutic potential of gossypol as a male contraceptive agent and in gynaecological disease. Drugs, 38:333-341, 1989. Wu, Y.-W., Chik, C. L. and Knazek, R. A...Olgiati and Toscano, 1983; Olgiati et al., 1984). Initially, gossypol was of investigative interest mainly because of its male contraceptive properties...clinical pharmacology and therapeutic potential of gossypol as a male contraceptive agent and in gynaecological disease. Drugs 38 (1989) 333-341. Wu, D.-F

Screening for Cerebroprotective Agents Using an In Vivo Model of Cerebral Reversible Depolarization in Awake Rats

DTIC Science & Technology

2001-01-01

next millennium. Roach RC, Wagner pathophysiology and therapy . Neurosci Biobehav Res 1987; 11: PD, Hackett PH, eds. New York: Kluwer Academic/Plenum 287...Medical 43. Anonymous. Neuroprotection as initial therapy in acute Publishers, 1989. stroke. Third report of an ad hoc consensus group meeting. The 19...metabolism during electroconvulsive treatment in relaxation. rotoxicity risk assessment. In: Neuroprotective agents, vol. 825. EEG-EMG Zeitschrift fur

The Limitations of Diazepam as a Treatment for Nerve Agent-Induced Seizures and Neuropathology in Rats: Comparison with UBP302

DTIC Science & Technology

2014-11-01

to nerve agents induces prolonged status epilepticus (SE), causing brain damage or death. Diazepam (DZP) is the cur- rent US Food and Drug... status epilepticus (SE), which are initiated by the excessive stimulation of cholinergic receptors. If immediate death is prevented by adequate...5-yl)ethyl] decahydroisoquinoline-3-carboxylic acid; PBS, phosphate-buffered saline; SE, status epilepticus ; UBP302, (S)-3-(2-carboxybenzyl

Comparison of Aflibercept, Bevacizumab, and Ranibizumab for Treatment of Diabetic Macular Edema: Extrapolation of Data to Clinical Practice.

PubMed

Heier, Jeffrey S; Bressler, Neil M; Avery, Robert L; Bakri, Sophie J; Boyer, David S; Brown, David M; Dugel, Pravin U; Freund, K Bailey; Glassman, Adam R; Kim, Judy E; Martin, Daniel F; Pollack, John S; Regillo, Carl D; Rosenfeld, Philip J; Schachat, Andrew P; Wells, John A

2016-01-01

The Diabetic Retinopathy Clinical Research Network (DRCR Network), sponsored by the National Eye Institute, reported the results of a comparative effectiveness randomized clinical trial (RCT) evaluating the 3 anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept (2.0 mg), bevacizumab (1.25 mg), and ranibizumab (0.3 mg) for treatment of diabetic macular edema (DME) involving the center of the retina and associated with visual acuity loss. The many important findings of the RCT prompted the American Society of Retina Specialists to convene a group of experts to provide their perspective regarding clinically relevant findings of the study. To describe specific outcomes of the RCT judged worthy of highlighting, to discuss how these and other clinically relevant results should be considered by specialists treating DME, and to identify unanswered questions that merit consideration before treatment. The DRCR Network-authored publication on primary outcomes of the comparative effectiveness RCT at 89 sites in the United States. The study period of the RCT was August 22, 2012, to August 28, 2013. On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and with visual acuity impairment, including mean (SD) improvements by +13.3 (11.1) letters with aflibercept vs +9.7 (10.1) letters with bevacizumab (P < .001) and +11.2 (9.4) letters with ranibizumab (P = .03). Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept (+18.9 [11.5]) over bevacizumab (+11.8 [12.0]) or ranibizumab (14.2 [10.6]) 1 year later (P < .001 for interaction with visual acuity as a continuous variable, and P = .002 for interaction with visual acuity as a categorical variable). It is unknown whether different visual acuity outcomes associated with the use of the 3 anti-VEGF agents would be noted with other treatment regimens or with adequately repackaged bevacizumab, as well as in patients with criteria that excluded them from the RCT, such as persistent DME despite recent anti-VEGF treatment. On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and visual acuity impairment. Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept over bevacizumab or ranibizumab 1 year later. Care needs to be taken when attempting to extrapolate outcomes of this RCT to differing treatment regimens. With access to adequately repackaged bevacizumab, many specialists might initiate therapy with bevacizumab when visual acuity is good (ie, 20/32 to 20/40 as measured in the DRCR Network), recognizing that the cost-effectiveness of bevacizumab outweighs that of aflibercept or ranibizumab.

Chemical warfare agents. Classes and targets.

PubMed

Schwenk, Michael

2018-09-01

Synthetic toxic chemicals (toxicants) and biological poisons (toxins) have been developed as chemical warfare agents in the last century. At the time of their initial consideration as chemical weapon, only restricted knowledge existed about their mechanisms of action. There exist two different types of acute toxic action: nonspecific cytotoxic mechanisms with multiple chemo-biological interactions versus specific mechanisms that tend to have just a single or a few target biomolecules. TRPV1- and TRPA-receptors are often involved as chemosensors that induce neurogenic inflammation. The present work briefly surveys classes and toxicologically relevant features of chemical warfare agents and describes mechanisms of toxic action. Copyright © 2017 Elsevier B.V. All rights reserved.

ANTIBIOTIC THERAPY OF ABSCESS OF THE LUNG AND BRONCHIECTASIS

PubMed Central

Hewitt, William L.

1952-01-01

Since the fusospirochetal group of bacteria are the commonest etiologic agents in abscess of the lung, aqueous crystalline penicillin is the agent of first choice in the majority of cases. Streptomycin is indicated for a small group of cases in which Klebsiella is the etiologic agent. Aureomycin, chloramphenicol or terramycin may produce an excellent therapeutic response either initially or after therapeutic failure with penicillin. Administration of antibiotics by inhalation should be carried out in conjunction with systemic forms of treatment. In the treatment of bronchiectasis, the antibiotics are most useful in the control of acute exacerbations of pulmonary infection which punctuate the course of this disease. PMID:14935877

Current state of immunotherapy for bladder cancer.

PubMed

Kassouf, Wassim; Kamat, Ashish M

2004-12-01

Bacillus Calmette-Guerin (BCG) has been shown to be the most effective agent for the treatment of superficial bladder cancer since its approval by the US Food and Drug Administration for the treatment of carcinoma in situ of the bladder in 1990. Recently, augmentation of BCG immunotherapy with interferon-alpha2b and other agents is emerging as salvage therapy for those patients who fail initial treatment. This review summarizes the role of various immunotherapeutic agents in the treatment of bladder cancer, with special emphasis on the appropriate administration and schedule of BCG therapy as well as salvage with the combination of BCG with interferon-alpha2b.

Seventeen years of subcutaneous infection by Aspergillus flavus; eumycetoma confirmed by immunohistochemistry.

PubMed

Ahmed, Sarah A; Abbas, Manal A; Jouvion, Gregory; Al-Hatmi, Abdullah M S; de Hoog, G Sybren; Kolecka, Anna; Mahgoub, El Sheikh

2015-12-01

Chronic subcutaneous infections caused by Aspergillus species are considered to be extremely rare. Because these fungi are among the most common laboratory contaminants, their role as eumycetoma causative agents is difficult to ascertain. Here, we report the first case of A. flavus eumycetoma confirmed by isolation, molecular identification and immunohistochemical analysis. Patient was a 55-year-old male from Sudan suffering from eumycetoma on his left foot for a period of 17 years. He developed swelling, sinuses and white grain discharge was observed. He has been operated nine times and was treated with several regimens of ketoconazole and itraconazole without improvement. Initial diagnosis based on histology and radiology was Scedosporium eumycetoma. However, examination of the biopsy revealed A. flavus, which was identified by molecular analysis and MALDI-TOF MS. Immunohistochemistry using antibody directed against Aspergillus species was positive. Because of the earlier treatment failures with ketoconazole and itraconazole, therapy with voriconazole was initiated. However, in vitro susceptibility testing yielded a lower Minimum Inhibitory Concentration (MIC) value for itraconazole (0.25 μg ml(-1) ) than for voriconazole (1 μg ml(-1) ). Based on the presented results, A. flavus can be considered as one of the agents of white-grain eumycetoma. © 2015 Blackwell Verlag GmbH.

Epigenetic regulation of miRNA-Cancer Stem Cells nexus by Nutraceuticals

PubMed Central

Ahmad, Aamir; Li, Yiwei; Bao, Bin; Kong, Dejuan; Sarkar, Fazlul H.

2014-01-01

Nutraceuticals, the bioactive food components represented by many naturally occurring dietary compounds, have been investigated for a few decades for their numerous beneficial effects, including their anticancer properties. The initial interest in the cancer-preventing/therapeutic ability of these agents was based on their ability to affect multiple signaling pathways that are deregulated in cancer cells. With a shift in the focus of cancer research to the emerging areas such as epigenetic regulation, microRNAs (miRNAs) and the cancer stem cells (CSCs), nutraceuticals initially appeared out of place. However, research investigations over the last several years have slowly but firmly presented evidence that supports a relevance of these agents in modern day research. While nutraceuticals are increasingly being realized to alter miRNA/CSCs expression and function, the molecular mechanism(s) are not very clearly understood. Epigenetic regulation is one mechanism by which these agents exert their anticancer effects. In this focused mini review, we summarize our current understanding of epigenetic regulation of miRNAs and CSCs by nutraceuticals. We discuss both direct and indirect evidences that support such an activity of these compounds. PMID:24272883

The Key Events Dose-Response Framework: a cross-disciplinary mode-of-action based approach to examining dose-response and thresholds.

PubMed

Julien, Elizabeth; Boobis, Alan R; Olin, Stephen S

2009-09-01

The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents-food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework-the Key Events Dose-Response Framework (KEDRF)-for systematically examining key events that occur between the initial dose of a bioactive agent and the effect of concern. Individual key events are considered with regard to factors that influence the dose-response relationship and factors that underlie variability in that relationship. This approach illuminates the connection between the processes occurring at the level of fundamental biology and the outcomes observed at the individual and population levels. Thus, it promotes an evidence-based approach for using mechanistic data to reduce reliance on default assumptions, to quantify variability, and to better characterize biological thresholds. This paper provides an overview of the KEDRF and introduces a series of four companion papers that illustrate initial application of the approach to a range of bioactive agents.

Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents.

PubMed

Runge, Val M

2017-06-01

For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was convincing evidence of gadolinium deposition in the brain months after injection of these linear agents. Primovist/Eovist (gadoxetic acid disodium) will remain available, being used at a lower dose for liver imaging, because it meets an important diagnostic need. In addition, a formulation of Magnevist for intra-articular injection will remain available because of its very low gadolinium concentration.

DNA condensation and size effects of DNA condensation agent

NASA Astrophysics Data System (ADS)

Liu, Yan-Hui; Jiang, Chong-Ming; Guo, Xin-Miao; Tang, Yan-Lin; Hu, Lin

2013-08-01

Based on the model of the strong correlation of counterions condensed on DNA molecule, by tailoring interaction potential, interduplex spacing and correlation spacing between condensed counterions on DNA molecule and interduplex spacing fluctuation strength, toroidal configuration, rod-like configuration and two-hole configurations are possible. The size effects of counterion structure on the toroidal structure can be detected by this model. The autocorrelation function of the tangent vectors is found as an effective way to detect the structure of toroidal conformations and the generic pathway of the process of DNA condensation. The generic pathway of all of the configurations involves an initial nucleation loop, and the next part of the DNA chain is folded on the top of the initial nucleation loop with different manners, in agreement with the recent experimental results.

Microvascular dysfunction with increased vascular leakage response in mice systemically exposed to arsenic.

PubMed

Chen, Shih-Chieh; Huang, Shin-Yin; Lu, Chi-Yu; Hsu, Ya-Hung; Wang, Dean-Chuan

2014-09-01

The mechanisms underlying cardiovascular disease induced by arsenic exposure are not completely understood. The objectives of this study were to investigate whether arsenic-fed mice have an increased vascular leakage response to vasoactive agents and whether enhanced type-2 protein phosphatase (PP2A) activity is involved in mustard oil-induced leakage. ICR mice were fed water or sodium arsenite (20 mg/kg) for 4 or 8 weeks. The leakage response to vasoactive agents was quantified using the Evans blue (EB) technique or vascular labeling with carbon particles. Increased EB leakage and high density of carbon-labeled microvessels were detected in arsenic-fed mice treated with mustard oil. Histamine induced significantly higher vascular leakage in arsenic-fed mice than in water-fed mice. Pretreatment with the PP2A inhibitor okadaic acid or the neurokinin 1 receptor (NK1R) blocker RP67580 significantly reduced mustard oil-induced vascular leakage in arsenic-fed mice. The protein levels of PP2Ac and NK1R were similar in both groups. PP2A activity was significantly higher in the arsenic-fed mice compared with the control group. These findings indicate that microvessels generally respond to vasoactive agents, and that the increased PP2A activity is involved in mustard oil-induced vascular leakage in arsenic-fed mice. Arsenic may initiate endothelial dysfunction, resulting in vascular leakage in response to vasoactive agents.

Reinforcement Learning in a Nonstationary Environment: The El Farol Problem

NASA Technical Reports Server (NTRS)

Bell, Ann Maria

1999-01-01

This paper examines the performance of simple learning rules in a complex adaptive system based on a coordination problem modeled on the El Farol problem. The key features of the El Farol problem are that it typically involves a medium number of agents and that agents' pay-off functions have a discontinuous response to increased congestion. First we consider a single adaptive agent facing a stationary environment. We demonstrate that the simple learning rules proposed by Roth and Er'ev can be extremely sensitive to small changes in the initial conditions and that events early in a simulation can affect the performance of the rule over a relatively long time horizon. In contrast, a reinforcement learning rule based on standard practice in the computer science literature converges rapidly and robustly. The situation is reversed when multiple adaptive agents interact: the RE algorithms often converge rapidly to a stable average aggregate attendance despite the slow and erratic behavior of individual learners, while the CS based learners frequently over-attend in the early and intermediate terms. The symmetric mixed strategy equilibria is unstable: all three learning rules ultimately tend towards pure strategies or stabilize in the medium term at non-equilibrium probabilities of attendance. The brittleness of the algorithms in different contexts emphasize the importance of thorough and thoughtful examination of simulation-based results.

New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo?

PubMed

Oder, Esther; Safo, Martin K; Abdulmalik, Osheiza; Kato, Gregory J

2016-10-01

The hallmark of sickle cell disease is the polymerization of sickle haemoglobin due to a point mutation in the β-globin gene (HBB). Under low oxygen saturation, sickle haemoglobin assumes the tense (T-state) deoxygenated conformation that can form polymers, leading to rigid erythrocytes with impaired blood vessel transit, compounded or initiated by adhesion of erythrocytes to endothelium, neutrophils and platelets. This process results in vessel occlusion and ischaemia, with consequent acute pain, chronic organ damage, morbidity and mortality. Pharmacological agents that stabilize the higher oxygen affinity relaxed state (R-state) and/or destabilize the lower oxygen affinity T-state of haemoglobin have the potential to delay the sickling of circulating red cells by slowing polymerization kinetics. Relevant classes of agents include aromatic aldehydes, thiol derivatives, isothiocyanates and acyl salicylates derivatives. The aromatic aldehyde, 5-hydroxymethylfurfural (5-HMF) increases oxygen affinity of sickle haemoglobin and reduces hypoxia-induced sickling in vitro and protects sickle cell mice from effects of hypoxia. It has completed pre-clinical testing and has entered clinical trials as treatment for sickle cell disease. A related molecule, GBT440, has shown R-state stabilization and increased oxygen affinity in preclinical testing. Allosteric modifiers of haemoglobin as direct anti-sickling agents target the fundamental pathophysiological mechanism of sickle cell disease. © 2016 John Wiley & Sons Ltd.

Novel Agents for Multiple Myeloma to Overcome Resistance in Phase III Clinical Trials

PubMed Central

Orlowski, Robert Z.

2013-01-01

The incorporation of novel agents such as bortezomib and lenalidomide into initial therapy for multiple myeloma has improved the response rate of induction regimens. Also, these drugs are being increasingly used in the peri-transplant setting for transplant-eligible patients, and as part of consolidation and/or maintenance after front-line treatment, including in transplant-ineligible patients. Together, these and other strategies have contributed to a prolongation of progression-free and overall survival in myeloma patients, and an increasing proportion are able to sustain a remission for many years. Despite these improvements, however, the vast majority of patients continue to suffer relapses, which suggests a prominent role for either primary, innate drug resistance, or secondary, acquired drug resistance. As a result, there remains a strong need to develop new proteasome inhibitors and immunomodulatory agents, as well as new drug classes, which would be effective in the relapsed and/or refractory setting, and overcome drug resistance. This review will focus on novel drugs that have reached phase III trials, including carfilzomib and pomalidomide, which have recently garnered regulatory approvals. In addition, agents that are in phase II or III, potentially registration-enabling trials will be described as well, to provide an overview of the possible landscape in the relapsed and/or refractory arena over the next five years. PMID:24135408

Fitness voter model: Damped oscillations and anomalous consensus.

PubMed

Woolcock, Anthony; Connaughton, Colm; Merali, Yasmin; Vazquez, Federico

2017-09-01

We study the dynamics of opinion formation in a heterogeneous voter model on a complete graph, in which each agent is endowed with an integer fitness parameter k≥0, in addition to its + or - opinion state. The evolution of the distribution of k-values and the opinion dynamics are coupled together, so as to allow the system to dynamically develop heterogeneity and memory in a simple way. When two agents with different opinions interact, their k-values are compared, and with probability p the agent with the lower value adopts the opinion of the one with the higher value, while with probability 1-p the opposite happens. The agent that keeps its opinion (winning agent) increments its k-value by one. We study the dynamics of the system in the entire 0≤p≤1 range and compare with the case p=1/2, in which opinions are decoupled from the k-values and the dynamics is equivalent to that of the standard voter model. When 0≤p<1/2, agents with higher k-values are less persuasive, and the system approaches exponentially fast to the consensus state of the initial majority opinion. The mean consensus time τ appears to grow logarithmically with the number of agents N, and it is greatly decreased relative to the linear behavior τ∼N found in the standard voter model. When 1/2

What Impact Does a Change-Agent Have on Faculty Use of Technology?

ERIC Educational Resources Information Center

Stanley, Iain

2015-01-01

This study was undertaken to examine the influence that a set of Professional Development (PD) initiatives had on faculty use of Moodle, a well-known Course Management System. The context of the study was a private university in Japan that specializes in languages. Specifically, it aimed to identify the way in which the PD initiatives adhered to…

System for forming janus particles

DOEpatents

Hong, Liang [Midland, MI; Jiang, Shan [Champaign, IL; Granick, Steve [Champaign, IL

2011-01-25

The invention is a method of forming Janus particles, that includes forming an emulsion that contains initial particles, a first liquid, and a second liquid; solidifying the first liquid to form a solid that contains at least a portion of the initial particles on a surface of the solid; and treating the exposed particle sides with a first surface modifying agent, to form the Janus particles. Each of the initial particles on the surface has an exposed particle side and a blocked particle side.

Combinatorial Effects of Lapatinib and Rapamycin in Triple-Negative Breast Cancer Cells

PubMed Central

Liu, Tongrui; Yacoub, Rami; Taliaferro-Smith, LaTonia D.; Sun, Shi-Yong; Graham, Tisheeka R.; Dolan, Ryan; Lobo, Christine; Tighiouart, Mourad; Yang, Lily; Adams, Amy; O'Regan, Ruth M.

2016-01-01

Triple-negative breast cancers, which lack estrogen receptor, progesterone receptor, and HER2/neu overexpression, account for approximately 15% of breast cancers, but occur more commonly in African Americans. The poor survival outcomes seen with triple-negative breast cancers patients are, in part, due to a lack of therapeutic targets. Epidermal growth factor receptor (EGFR) is overexpressed in 50% of triple-negative breast cancers, but EGFR inhibitors have not been effective in patients with metastatic breast cancers. However, mTOR inhibition has been shown to reverse resistance to EGFR inhibitors. We examined the combination effects of mTOR inhibition with EGFR inhibition in triple-negative breast cancer in vitro and in vivo. The combination of EGFR inhibition by using lapatinib and mTOR inhibition with rapamycin resulted in significantly greater cytotoxicity than the single agents alone and these effects were synergistic in vitro. The combination of rapamycin and lapatinib significantly decreased growth of triple-negative breast cancers in vivo compared with either agent alone. EGFR inhibition abrogated the expression of rapamycin-induced activated Akt in triple-negative breast cancer cells in vitro. The combination of EGFR and mTOR inhibition resulted in increased apoptosis in some, but not all, triple-negative cell lines, and these apoptotic effects correlated with a decrease in activated eukaryotic translation initiation factor (eIF4E). These results suggest that mTOR inhibitors could sensitize a subset of triple-negative breast cancers to EGFR inhibitors. Given the paucity of effective targeted agents in triple-negative breast cancers, these results warrant further evaluation. PMID:21690228

Advancing molecular-guided surgery through probe development and testing in a moderate cost evaluation pipeline

NASA Astrophysics Data System (ADS)

Pogue, Brian W.; Paulsen, Keith D.; Hull, Sally M.; Samkoe, Kimberley S.; Gunn, Jason; Hoopes, Jack; Roberts, David W.; Strong, Theresa V.; Draney, Daniel; Feldwisch, Joachim

2015-03-01

Molecular guided oncology surgery has the potential to transform the way decisions about resection are done, and can be critically important in areas such as neurosurgery where the margins of tumor relative to critical normal tissues are not readily apparent from visual or palpable guidance. Yet there are major financial barriers to advancing agents into clinical trials with commercial backing. We observe that development of these agents in the standard biological therapeutic paradigm is not viable, due to the high up front financial investment needed and the limitations in the revenue models of contrast agents for imaging. The hypothesized solution to this problem is to develop small molecular biologicals tagged with an established fluorescent reporter, through the chemical agent approval pathway, targeting a phase 0 trials initially, such that the initial startup phase can be completely funded by a single NIH grant. In this way, fast trials can be completed to de-risk the development pipeline, and advance the idea of fluorescence-guided surgery (FGS) reporters into human testing. As with biological therapies the potential successes of each agent are still moderate, but this process will allow the field to advance in a more stable and productive manner, rather than relying upon isolated molecules developed at high cost and risk. The pathway proposed and tested here uses peptide synthesis of an epidermal growth factor receptor (EGFR)-binding Affibody molecules, uniquely conjugated to IRDye 800CW, developed and tested in academic and industrial laboratories with well-established records for GMP production, fill and finish, toxicity testing, and early phase clinical trials with image guidance.

Emerging collective behavior and local properties of financial dynamics in a public investment game

NASA Astrophysics Data System (ADS)

da Silva, Roberto; Bazzan, Ana L. C.; Baraviera, Alexandre T.; Dahmen, Sílvio R.

2006-11-01

In this paper we consider a simple model of a society of economic agents, namely a variation of the well known “public investment game”, where each agent can contribute with a discrete quantity, i.e., cooperate to increase the benefits of the group. Interactions take place among nearest neighbors and depend on the motivation level (insider information, economy prospects). The profit is used to update individual motivations. We first explore a deterministic scenario and the existence of fixed points and attractors. We also consider the presence of noise, where profits fluctuate stochastically. In this scenario we analyze the global persistence as a function of time-a measure of the probability that the amount of money of the entire group remains at least equal to its initial value. Our simulations show that this quantity has a power law behavior. We have also performed simulations with a population of heterogeneous agents, including deceivers and conservatives. We show that, although there is no regular pattern regarding the average wealth, robust power laws for persistence do exist and argue that this can be used to characterize the emerging collective behavior. The influence of the motivation updating and the presence of conservatives and deceivers on persistence is also studied. Simulations for the local persistence exploring two different versions of this concept: the probability of a particular agent not going bankrupt (i.e., remaining wealth ⩾0 up to time t) and the probability of a particular agent making more money than he initially had. Different power law behaviors are also observed in these situations.

Land Use Change on Household Farms in the Ecuadorian Amazon: Design and Implementation of an Agent-Based Model.

PubMed

Mena, Carlos F; Walsh, Stephen J; Frizzelle, Brian G; Xiaozheng, Yao; Malanson, George P

2011-01-01

This paper describes the design and implementation of an Agent-Based Model (ABM) used to simulate land use change on household farms in the Northern Ecuadorian Amazon (NEA). The ABM simulates decision-making processes at the household level that is examined through a longitudinal, socio-economic and demographic survey that was conducted in 1990 and 1999. Geographic Information Systems (GIS) are used to establish spatial relationships between farms and their environment, while classified Landsat Thematic Mapper (TM) imagery is used to set initial land use/land cover conditions for the spatial simulation, assess from-to land use/land cover change patterns, and describe trajectories of land use change at the farm and landscape levels. Results from prior studies in the NEA provide insights into the key social and ecological variables, describe human behavioral functions, and examine population-environment interactions that are linked to deforestation and agricultural extensification, population migration, and demographic change. Within the architecture of the model, agents are classified as active or passive. The model comprises four modules, i.e., initialization, demography, agriculture, and migration that operate individually, but are linked through key household processes. The main outputs of the model include a spatially-explicit representation of the land use/land cover on survey and non-survey farms and at the landscape level for each annual time-step, as well as simulated socio-economic and demographic characteristics of households and communities. The work describes the design and implementation of the model and how population-environment interactions can be addressed in a frontier setting. The paper contributes to land change science by examining important pattern-process relations, advocating a spatial modeling approach that is capable of synthesizing fundamental relationships at the farm level, and links people and environment in complex ways.

Therapist strategies early in therapy associated with good or poor outcomes among clients with low proactive agency.

PubMed

von der Lippe, Anna Louise; Oddli, Hanne Weie; Halvorsen, Margrethe Seeger

2017-09-10

Within a mixed methods program of research the present study aimed at expanding knowledge about interactions in the initial therapeutic collaboration by combining focus on client interpersonal style and therapist contribution. The study involves in-depth analyses of therapist-client interactions in the initial two sessions of good and poor outcome therapies. Based on interpersonal theory and previous research, the Inventory of Interpersonal Problems (IIP-64-C) was used to define poor outcome cases, that is, low proactive agency cases. To compare good and poor outcome cases matched on this interpersonal pattern, cases were drawn from two different samples; nine poor outcome cases from a large multi-site outpatient clinic study and nine good outcome cases from a process-outcome study of highly experienced therapists. Qualitative analysis of therapist behaviors resulted in 2 main categories, fostering client's proactive agentic involvement in change work and discouraging client's proactive agentic involvement in change work, 8 categories and 22 sub-categories. The findings revealed distinct and cohesive differences in therapist behaviors between the two outcome groups, and point to the particular therapist role of fostering client agency through engagement in a shared work on change when clients display strong unassertiveness and low readiness for change. Clinical or Methodological Significance Summary: The present analysis combines focus on client interpersonal style, therapist strategies/process and outcome. The categories generated from the present grounded theory analysis may serve as a foundation for identifying interactions that are associated with agentic involvement in future process research and practice, and hence we have formulated principles/strategies that were identified by the analysis.