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Veritti, Daniele, Paolo Lanzetta, Francesco Bandello, and Raffaella Gortana Chiodini. "VISCOELASTIC AGENT RETENTION AND FAILED MACULAR HOLE SURGERY." Retinal Cases & Brief Reports 3, no. 1 (2009): 77–79. http://dx.doi.org/10.1097/icb.0b013e318158de4f.
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Kumar, Anurup. "Capnocytophaga canimorsus Meningitis – Diagnosis with 16S rDNA PCR when Conventional Methods Failed to Identify the Causative Agent." Clinical Research and Clinical Trials 3, no. 4 (2021): 01–06. http://dx.doi.org/10.31579/2693-4779/025.
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Meningitis whether bacterial or viral, poses many challenges to clinicians as the causative agent is often not found. According to guidelines, it is standard to start empiric treatment before a Cerebrospinal Fluid (CSF) sample is obtained. Meningitis, if not diagnosed and treated early, can lead to high morbidity and mortality rates with serious neurological sequelae. While the most common cases of bacterial meningitis are related to Streptococcus pneumoniae and Neisseria meningitidis, this clinical case report found a rare case of meningitis caused by a zoonotic pathogen, Capnocytophaga canimorsus; a commensal found as part of the normal flora of dogs and cats. This rare organism was identified with the help of broad range 16S ribosomal DNA Polymerase Chain Reaction (rDNA PCR), an emerging technique that is now increasingly useful in rapid diagnosis especially if the offending agent is not timely identified and conventional methods have failed, making diagnosis and management difficult for physicians.
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Agostino, Nicole M., Rebecca Gingrich, and Joseph J. Drabick. "Bevacizumab Demonstrates Prolonged Disease Stabilization in Patients with Heavily Pretreated Metastatic Renal Cell Carcinoma: A Case Series and Review of the Literature." Advances in Urology 2010 (2010): 1–4. http://dx.doi.org/10.1155/2010/687043.
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There are now a variety of therapies approved for the treatment of metastatic renal cell carcinoma (RCC). These include the immunotherapeutics, alfa-interferon, and interleukin-2, and agents that target the vascular endothelial growth factor receptor (VEGFR) via its tyrosine kinase, such as sorafenib, sunitinib, and pazopanib, or the mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus. Bevacizumab, a monoclonal antibody directed against the ligand, VEGF, has shown activity against RCC as a single agent in patients who had failed prior cytokine therapy and as first line therapy in combination with interferon. The activity of bevacizumab in patients who had received and failed prior therapy has not been described. We report our experience in 4 patients with metastatic RCC who had failed prior cytokine, TKI, and mTOR inhibitors who were treated with bevacizumab as single agent therapy. These heavily pretreated patients sustained very prolonged periods of stable disease (median of 12 months) with very little toxicity and excellent quality of life. The activity of this agent in patients who had failed prior therapies directed against the VEGFR and mTOR suggests that therapy targeting the ligand, VEGF, is still a viable approach in these patients and deserves further study.
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Peacock, David, and Ian Abbott. "The mongoose in Australia: failed introduction of a biological control agent." Australian Journal of Zoology 58, no. 4 (2010): 205. http://dx.doi.org/10.1071/zo10043.
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We reviewed historical literature and obtained nearly 200 records of the mongoose in Australia up to 1942. Although the earliest importations (from 1855) were for its snake-killing prowess, often as entertainment, its perceived potential as a control agent for the European rabbit (Oryctolagus cuniculus) plague saw concerted introductions made in New South Wales, Victoria and South Australia, primarily in 1883 and 1884. At least 1000 mongoose were released to control rabbits at 14 reported release locations in these states. As many as 700 of these mongoose were reported released in one New South Wales rabbit-control trial. These numbers indicate that insufficient propagule pressure does not explain why Australia escaped the additional devastation of an established mongoose population. The only reason stated for the failure of the mongoose releases to control rabbits is destruction of the mongoose by rabbit trappers, both inadvertently and in seeking to protect their employment. Unfavourable climate was implicated by CLIMATCH modelling in the failure of all releases, especially those into semiarid areas such as western New South Wales. No contemporary detail could be located of the reported 1884 failed introduction of ‘numbers’ of mongoose into North Queensland to control rats in sugarcane plantations.
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Hartline, Jason D. "Approximation in Mechanism Design." American Economic Review 102, no. 3 (2012): 330–36. http://dx.doi.org/10.1257/aer.102.3.330.
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This paper considers three challenge areas for mechanism design and describes the role approximation plays in resolving them. Challenge 1: optimal mechanisms are finely tuned to precise details of the distribution on agent preferences. Challenge 2: in environments with multi-dimensional agent preferences economic analysis has failed to provide general characterizations optimal mechanisms. Challenge 3: optimal mechanisms are parameterized by unrealistic knowledge of the distribution of agents' private preferences. This paper surveys positive resolutions to these challenges with emphasis on basic techniques and their relevance to theory and practice.
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Okun, Ilya, Sergei Malarchuk, Elena Dubrovskaya, et al. "Screening for Caspase-3 Inhibitors: Effect of a Reducing Agent on Identified Hit Chemotypes." Journal of Biomolecular Screening 11, no. 6 (2006): 694–703. http://dx.doi.org/10.1177/1087057106289231.
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When studying cysteinyl proteases in general and caspases in particular, it is generally accepted that a reaction buffer must contain a reducing agent to prevent essential cysteinyl groups from spontaneous oxidation. Dithiothreitol (DTT) and β-mercaptoethanol (β-MCE) are 2 of the most broadly used reducing agents. While screening a library of small molecules against caspase-3, the authors have found that the nature of the reducing agent used, DTT or β-MCE, dramatically affects screening results and leads to identification of nonoverlapping hits. Screening in DTT-containing buffer revealed few novel classes of small molecules that selectively and reversibly inhibit caspase-3 but failed to identify isatin sulfonamides recently found to be potent and selective caspase-3 inhibitors (false negatives). On the other hand, screening in the presence of β-MCE failed to identify a series of hit compounds, 1,3-dioxo-2,3-dichloro-1 H-pyrrolo[3,4- c]quinolines, discovered with DTT, whereas isatin sulphonamides in these conditions exhibited strong caspase-3 inhibition. In this work, the authors show that thiol-containing reducing agents can affect catalytic activity of caspase-3 and modify its thermostability in a redox-potential-independent manner. The authors speculate that the differential structural modifications of caspase-3 seen with different reducing agents represent structurally different caspase-3 conformations and are responsible for its differential sensitivity to small molecules of different chemotypes. Hence, selection of the reducing agent may dramatically affect the quality of high-throughput screening campaigns.
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Honda, Yuko, Taketoshi Furugohri, and Yoshiyuki Morishima. "Tranexamic Acid Failed to Reverse the Anticoagulant Effect and Bleeding by an Oral Direct Factor Xa Inhibitor Edoxaban." Pharmacology 101, no. 1-2 (2017): 92–95. http://dx.doi.org/10.1159/000484172.
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Background/Aims: Agents to reverse the anticoagulant effect of edoxaban, an oral direct factor Xa inhibitor, would be desirable in emergency situations. The aim of this study is to determine the effect of tranexamic acid, an antifibrinolytic agent, on the anticoagulant activity and bleeding by edoxaban in rats. Methods: A supratherapeutic dose of edoxaban (3 mg/kg) was intravenously administered to rats. Three minutes after dosing, tranexamic acid (100 mg/kg) was given intravenously. Bleeding was induced by making an incision with a blade on the planta 8 min after edoxaban injection and bleeding time was measured. Prothrombin time (PT) and clot lysis were examined. Results: A supratherapeutic dose of edoxaban significantly prolonged PT and bleeding time. Tranexamic acid did not affect PT or bleeding time prolonged by edoxaban, although tranexamic acid significantly inhibited clot lysis in rat plasma. Conclusion: An antifibrinolytic agent tranexamic acid failed to reverse the anticoagulant effect and bleeding by edoxaban in rats.
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Nguyen, Duc Thien, William Yeoh, Hoong Chuin Lau, and Roie Zivan. "Distributed Gibbs: A Linear-Space Sampling-Based DCOP Algorithm." Journal of Artificial Intelligence Research 64 (March 14, 2019): 705–48. http://dx.doi.org/10.1613/jair.1.11400.
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 Researchers have used distributed constraint optimization problems (DCOPs) to model various multi-agent coordination and resource allocation problems. Very recently, Ottens et al. proposed a promising new approach to solve DCOPs that is based on confidence bounds via their Distributed UCT (DUCT) sampling-based algorithm. Unfortunately, its memory requirement per agent is exponential in the number of agents in the problem, which prohibits it from scaling up to large problems. Thus, in this article, we introduce two new sampling-based DCOP algorithms called Sequential Distributed Gibbs (SD-Gibbs) and Parallel Distributed Gibbs (PD-Gibbs). Both algorithms have memory requirements per agent that is linear in the number of agents in the problem. Our empirical results show that our algorithms can find solutions that are better than DUCT, run faster than DUCT, and solve some large problems that DUCT failed to solve due to memory limitations.
 
 
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Serudji, Joserizal, Rika Effendy, and Hafni Bachtiar. "PERBEDAAN RERATA KADAR IL-6 SERUM MATERNAL BERDASARKAN KEBERHASILAN PEMBERIAN TOKOLITIK PADA PARTUS PREMATURUS IMMINENS." JOURNAL OBGIN EMAS 1, no. 1 (2019): 15–21. http://dx.doi.org/10.25077/aoj.1.1.15-21.2017.
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Preterm labor needs to be prevented, one of the prevention methods is by tocolytic administration which could prevent labor thus providing a chance for lung maturation. Preterm Pregnancy is associated with increased concentrations of cytokines such as Interleukin (IL). The increasing concentration of maternal serum IL-6 can be used to predict preterm labor. This research uses the design Cross-Sectional Comparative to determine differences in means of maternal serum levels of IL-6 based on the success of the administration of a tocolytic agent on preterm labor. This study was performed on pregnant women who come to the obstetric emergency room of DR. MA. Hanafiah Batusangkar Hospital within August-November 2015. The total number which was included in statistical analysis was 34 pregnant women which were divided into 2 groups, 17 people in the group of patients who failed in tocolytic agent administration, and 17 people in the group who success in managed with a tocolytic agent. Statistical analysis was performed to analyze the validity using the T-test. There are significant differences in the average rate of maternal serum IL-6 in patients who failed to treat with a tocolytic agent and successful to treat with a tocolytic agent. Seen from the p-value 0.000. Levels of maternal serum IL-6 in patients who failed to treat with a tocolytic agent were higher than successful to treat with a tocolytic agent.Keywords: IL-6, Tocolytic, Preterm labor
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Lee, Ha Na, Young-Suk Lee, Ji-Yeon Han, Jae Yong Jeong, Myung-Soo Choo, and Kyu-Sung Lee. "Transurethral injection of bulking agent for treatment of failed mid-urethral sling procedures." International Urogynecology Journal 21, no. 12 (2010): 1479–83. http://dx.doi.org/10.1007/s00192-010-1224-z.
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Oliva, Brunello, Keith Miller, Nico Caggiano, et al. "Biological Properties of Novel Antistaphylococcal Quinoline-Indole Agents." Antimicrobial Agents and Chemotherapy 47, no. 2 (2003): 458–66. http://dx.doi.org/10.1128/aac.47.2.458-466.2003.
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ABSTRACT The antibacterial properties of novel quinoline-indole (QI) agents were examined. QI agents demonstrated potent bactericidal activities against Staphylococcus aureus, killing by lytic and nonlytic mechanisms. S. aureus mutants resistant to a lytic QI agent (SEP 155342) and a nonlytic QI agent (SEP 118843) arose at frequencies of 1.4 × 10−9 and 1.2 × 10−8, respectively, by selection at four times the MICs. Mutants resistant to QI agent SEP 155342 were unstable, but mutants resistant to QI agent SEP 118843 displayed stable resistance. Mutants resistant to QI agent SEP 118843 were not cross resistant to other inhibitors, including QI agent SEP 155342. Addition of QI agents SEP 118843 and SEP 155342 at four times the MIC caused nonspecific inhibition of several macromolecular biosynthetic pathways in S. aureus. Within 10 min, QI agents SEP 118843 and SEP 155342 both interfered with bacterial membrane integrity, as measured by uptake of propidium iodide. Agents from the two classes of the QI agents probably kill staphylococci by separate mechanisms which, nevertheless, both involve interference with cytoplasmic membrane function. Precise structure-activity relationships for the division of QI agents into two classes could not be determined. However, lytic activity was often associated with substitution of a basic amine at position 4 of the quinoline nucleus, whereas compounds with nonlytic activity usually contained an aromatic ring with or without a methoxy substituent at position 4. Nonlytic QI agents such as SEP 118843 may possess selective activity against the prokaryotic membrane since this compound failed to lyse mouse erythrocytes when it was added at a concentration equivalent to four times the MIC for S. aureus.
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Zhu, Jiacheng, Jiahao Lin, Meng Wang, et al. "Generative Adversarial Imitation Learning from Failed Experiences (Student Abstract)." Proceedings of the AAAI Conference on Artificial Intelligence 34, no. 10 (2020): 13997–98. http://dx.doi.org/10.1609/aaai.v34i10.7271.
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Imitation learning provides a family of promising methods that learn policies from expert demonstrations directly. As a model-free and on-line imitation learning method, generative adversarial imitation learning (GAIL) generalizes well to unseen situations and can handle complex problems. In this paper, we propose a novel variant of GAIL called GAIL from failed experiences (GAILFE). GAILFE allows an agent to utilize failed experiences in the training process. Moreover, a constrained optimization objective is formalized in GAILFE to balance learning from given demonstrations and from self-generated failed experiences. Empirically, compared with GAIL, GAILFE can improve sample efficiency and learning speed over different tasks.
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Leyon, Joe J., Swarupsinh Chavda, Allan Thomas, and Saleh Lamin. "Preliminary experience with the liquid embolic material agent PHIL (Precipitating Hydrophobic Injectable Liquid) in treating cranial and spinal dural arteriovenous fistulas: technical note." Journal of NeuroInterventional Surgery 8, no. 6 (2015): 596–602. http://dx.doi.org/10.1136/neurintsurg-2015-011684.
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BackgroundLiquid embolic agents are the preferred embolic material in endovascular treatment of pial and brain arteriovenous malformations and dural arteriovenous fistulas (DAVFs). There is little choice available in interventional neuroradiology practice other than two of the most commonly used liquid embolic agents—n-butyl cyanoacrylate and the Onyx liquid embolic system (ev3 Neurovascular, Irvine, California, USA). PHIL (Precipitating Hydrophobic Injectable Liquid) (Microvention, Inc California, USA) is a new liquid embolic agent, CE marked and available for clinical use in Europe.ObjectiveTo present our preliminary experience using PHIL in treating cranial and spinal DAVFs.MethodsBetween September 2014 and January 2015, eight patients, with five cranial DAVFs and three spinal DAVFs were treated with PHIL as the sole embolic agent used with intent to cure. Clinical presentation, location of DAVF, Borden type, fluoroscopic time, radiation dose, procedural time, injecting microcatheter used, volume of PHIL injected, complications, immediate angiographic data, premorbid and discharge modified Rankin Scale score, and any neurologic deficits were included in the analysis.ResultsSeven patients were successfully treated with complete angiographic exclusion of the fistula in a single sitting. Treatment failed in one patient where only suboptimal microcatheter positioning could be achieved and PHIL failed to penetrate the fistula's nidus. Venous penetration was achieved in all other patients except one with a small fistula, but with adequate fistula penetration by the embolic material. No other technical complication or neurologic deterioration occurred in any of the patients.ConclusionsPHIL liquid embolic agent appears to be an excellent alternative embolic material with certain advantages compared with other available liquid embolic agents. Further studies are required to fully evaluate its safety and efficacy.
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Eng, J., A. Gomez, and S. Mink. "Insensitivity of maximum expiratory flow to bronchodilation in normal dogs." Journal of Applied Physiology 68, no. 5 (1990): 2006–12. http://dx.doi.org/10.1152/jappl.1990.68.5.2006.
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We examined the effects of the inhaled parasympatholytic agent atropine and the sympathomimetic agent salbutamol on partitioned frictional pressure (Pfr) losses to the site of flow limitation (choke point, CP) in dogs to see how changes brought about by these agents would affect maximum expiratory flow (Vmax) and response to breathing 80% He-20% O2 (delta Vmax) in terms of wave-speed theory of flow limitation. In open-chest dogs, a Pitot-static tube was advanced down the right lower lobe to locate CP, to determine CP lateral and end-on pressures (PE), and to partition the airway into peripheral (alveoli to sublobar) and central (sublobar to CP) segments. Measurements were obtained at approximately 50% vital capacity. After inhalation, CP locations were unchanged with both bronchodilating agents. After atropine inhalation, Pfr central was decreased by one-half compared with base line. Despite the decrease in Pfr central, however, Vmax failed to increase after atropine because of altered bronchial area pressure (BAP) behavior at the CP site. After salbutamol inhalation, Pfr peripheral was reduced by about one-half compared with base line. However, Vmax failed to increase, because this reduction was too small to significantly increase the CP pressure head (i.e., PE). delta Vmax was also insensitive to these agents. Our results show mechanisms by which small changes in Pfr, as well as the complex interaction of changes in Pfr and BAP, may limit the use of Vmax in detecting bronchodilation at different airway sites.
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Lumbroso, Darren, Mark Davison, Richard Body, and Gregor Petkovšek. "Modelling the Brumadinho tailings dam failure, the subsequent loss of life and how it could have been reduced." Natural Hazards and Earth System Sciences 21, no. 1 (2021): 21–37. http://dx.doi.org/10.5194/nhess-21-21-2021.
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Abstract. In recent years the number of tailings dams failures has increased. On 25 January 2019, the Brumadinho tailings dam in Brazil suddenly failed, releasing a mudflow over 10 m deep comprising some 107 m3 of mining waste which killed between 270 and 320 people. This paper details the use of an agent-based model, known as the Life Safety Model (LSM), to estimate the risk to people downstream of the Brumadinho tailings dam and to assess if the number of fatalities could have been reduced if a warning had been received prior to or at time the dam failed. The LSM modelling indicates that even if a warning had been issued as the dam failed, the number of fatalities could have been reduced. Agent-based modelling tools such as the LSM can help to inform and improve emergency plans for tailings dams, which will help to reduce the risks posed by them in the future.
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Saffra, Norman A., and Benjamin J. Reinherz. "Peripapillary Choroidal Neovascularization Associated with Optic Nerve Head Drusen Treated with Anti-VEGF Agents." Case Reports in Ophthalmology 6, no. 1 (2015): 51–55. http://dx.doi.org/10.1159/000375480.
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Optic nerve head drusen can be associated with peripapillary choroidal neovascularization, in both the pediatric and adult population. These membranes can involve the macula, causing significant visual loss. Herein, we present a case that required treatment with an anti-VEGF agent. The patient failed to respond to the initial agent, but subsequently responded to a change of agent. Adult patients with macular degeneration involving peripapillary choroidal neovascularization associated with optic nerve head drusen may require individualized treatment plans.
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Marquis, Jean-Philippe, Sonia Goulet, and François Y. Doré. "Schizophrenia-like syndrome inducing agent phencyclidine failed to impair memory for temporal order in rats." Neurobiology of Learning and Memory 80, no. 2 (2003): 158–67. http://dx.doi.org/10.1016/s1074-7427(03)00067-4.
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MORI, Takashi, Kazuya NAGATA, Takuo ISHIDA, et al. "FK-506: A New Immunosuppressive Agent, Failed to Reduce Cerebral Vasospasm after Experimental Subarachnoid Hemorrhage." Journal of Veterinary Medical Science 55, no. 4 (1993): 581–86. http://dx.doi.org/10.1292/jvms.55.581.
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Ramchurn, S. D., C. Mezzetti, A. Giovannucci, J. A. Rodriguez-Aguilar, R. K. Dash, and N. R. Jennings. "Trust-Based Mechanisms for Robust and Efficient Task Allocation in the Presence of Execution Uncertainty." Journal of Artificial Intelligence Research 35 (June 16, 2009): 119–59. http://dx.doi.org/10.1613/jair.2751.
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Vickrey-Clarke-Groves (VCG) mechanisms are often used to allocate tasks to selfish and rational agents. VCG mechanisms are incentive compatible, direct mechanisms that are efficient (i.e., maximise social utility) and individually rational (i.e., agents prefer to join rather than opt out). However, an important assumption of these mechanisms is that the agents will "always" successfully complete their allocated tasks. Clearly, this assumption is unrealistic in many real-world applications, where agents can, and often do, fail in their endeavours. Moreover, whether an agent is deemed to have failed may be perceived differently by different agents. Such subjective perceptions about an agent's probability of succeeding at a given task are often captured and reasoned about using the notion of "trust". Given this background, in this paper we investigate the design of novel mechanisms that take into account the trust between agents when allocating tasks. Specifically, we develop a new class of mechanisms, called "trust-based mechanisms", that can take into account multiple subjective measures of the probability of an agent succeeding at a given task and produce allocations that maximise social utility, whilst ensuring that no agent obtains a negative utility. We then show that such mechanisms pose a challenging new combinatorial optimisation problem (that is NP-complete), devise a novel representation for solving the problem, and develop an effective integer programming solution (that can solve instances with about 2x10^5 possible allocations in 40 seconds).
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Sanna, Alessandro, Antonella Gozzini, Francesca Sassolini, Alberto Bosi, and Valeria Santini. "Decitabine Treatment in Higher Risk MDS, CMML and AML Post-MDS Who Failed Azacitidine." Blood 118, no. 21 (2011): 5052. http://dx.doi.org/10.1182/blood.v118.21.5052.5052.
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Abstract Abstract 5052 Background: 5-azacytidine (Vidaza, AZA) and 5-aza-2'-deoxycytidine (Decitabine, DAC) are active in therapy of myelodysplastic syndromes (MDS) probably with different mechanisms of action. Azacitidine is approved by FDA and EMEA and is routinely used in therapy of higher risk MDS in Europe and in the US. Decitabine is a demethylating agent approved for treatment of IPSS INT-2 and high risk MDS by FDA but not yet from EMEA and it seems particularly active in Chronic myelomonocytic leukemia (CMML) and AML of the elderly. Difference in mechanisms of action of these 2 agents have been determined in vitro, involving nuclear acid incorporation, cell cycle and apoptosis, gene and protein expression. Patients: Nine patients (4 RAEB 2, 4 AML, 1 CMML-1) were treated with decitabine 20mg/m2 × 5 days every 28 days as single agent or in association with Gemtuzumab ozogamicin 3 mg/m2 in day 5 and 9. IPSS score at diagnosis was: 1 low, 4 intermediate 1, 4 intermediate 2. All patients received at least 4 cycles of azacitidine 75 mg/mq per seven days every 28, 44% of them reached at least Hematological improvement and received DAC as second line after relapse. Median age was 70 (62–84) and 8/9 were male. Methods: Medical records of 14 patients who received decitabine treatment were reviewed and survival was calculated by the Kaplan Meier method and differences in survival calculated by the log-rank test using SPSS software. Complete remission was defined by normo-cellular bone marrow with <5% blasts and normal Hgb, WBC, and platelet counts, and PR required 50% decrease in blast count, increases in Hgb by >1.5 mmol/L, WBC count by >1000, and platelet count by >50,000. Results: Median overall survival (OS) was 121 days, range 27–586 days. Overall response rate (CR+PR+HI) was 33.3% with mean duration of response was 3.33 months. Mean number of cycles was 4 (range 1–20). Median OS of responder patients was 12 months vs 1 month of non responder patients. OS of patients treated with DAC after AZA-resistance was 2 months vs 4 months of patients relapsed, but who reached at least HI with AZA (p>0.05). Longer history of MDS disease seemed not relevant for outcome. Therapy was well tolerated and only two patients required a long hospitalization (42 and 77 days) for sepsis due to relevant myelosuppression. Conclusions: Decitabine treatment has some activity in MDS, CMML and AML patients refractory to AZA or who relapsed after initial response to AZA, suggesting that the two supposed hypomethylating agents act via partially different molecular mechanisms. Disclosures: No relevant conflicts of interest to declare.
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Sadilek, A., and H. Kautz. "Location-Based Reasoning about Complex Multi-Agent Behavior." Journal of Artificial Intelligence Research 43 (January 31, 2012): 87–133. http://dx.doi.org/10.1613/jair.3421.
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Recent research has shown that surprisingly rich models of human activity can be learned from GPS (positional) data. However, most effort to date has concentrated on modeling single individuals or statistical properties of groups of people. Moreover, prior work focused solely on modeling actual successful executions (and not failed or attempted executions) of the activities of interest. We, in contrast, take on the task of understanding human interactions, attempted interactions, and intentions from noisy sensor data in a fully relational multi-agent setting. We use a real-world game of capture the flag to illustrate our approach in a well-defined domain that involves many distinct cooperative and competitive joint activities. We model the domain using Markov logic, a statistical-relational language, and learn a theory that jointly denoises the data and infers occurrences of high-level activities, such as a player capturing an enemy. Our unified model combines constraints imposed by the geometry of the game area, the motion model of the players, and by the rules and dynamics of the game in a probabilistically and logically sound fashion. We show that while it may be impossible to directly detect a multi-agent activity due to sensor noise or malfunction, the occurrence of the activity can still be inferred by considering both its impact on the future behaviors of the people involved as well as the events that could have preceded it. Further, we show that given a model of successfully performed multi-agent activities, along with a set of examples of failed attempts at the same activities, our system automatically learns an augmented model that is capable of recognizing success and failure, as well as goals of people's actions with high accuracy. We compare our approach with other alternatives and show that our unified model, which takes into account not only relationships among individual players, but also relationships among activities over the entire length of a game, although more computationally costly, is significantly more accurate. Finally, we demonstrate that explicitly modeling unsuccessful attempts boosts performance on other important recognition tasks.
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Burnakis, Thomas G. "Inaccurate Assessment of Drug-Induced Thrombocytopenia: Reason for Concern." Annals of Pharmacotherapy 28, no. 6 (1994): 726–29. http://dx.doi.org/10.1177/106002809402800608.
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OBJECTIVE: To report two cases in which patients were reputed to have exhibited thrombocytopenia secondary to the histamine-receptor blocking agent ranitidine. Evaluation and the associated time frame of events failed to confirm these observations. DESIGN: Two case studies. RESULTS: Ranitidine was ordered as part of the therapeutic course of two patients admitted to the medicine service. The development of thrombocytopenia in both patients was attributed to this agent and it was discontinued. In addition to ranitidine, both patients received several other agents with greater potential to cause thrombocytopenia, and had a time course of development of the adverse effect that would not support ranitidine as the offending agent. Both patients required histamine-receptor antagonists at some point following their discontinuation and, based on the available evidence, the pharmacy suggested that these agents be restarted. In neither case did restarting the histamine-receptor antagonist lead to recurrence of thrombocytopenia. CONCLUSIONS: Although ranitidine can cause thrombocytopenia, the reported incidence is very low. Spontaneous reporting of adverse effects is essential in establishing a true pattern of safety for a drug. However, reports need to be scrutinized before they are rolled into the collective intelligence. Overzealous or incomplete reporting will lead to cautions that are either unnecessary or, because they deny people necessary treatment, dangerous.
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Dada, Reyad, and Fawwaz Yassin. "Everolimus Is Active in Pretreated Hodgkin Lymphoma after Failure of Brentuximab Vedotin: Single Institute Experience." Blood 128, no. 22 (2016): 5368. http://dx.doi.org/10.1182/blood.v128.22.5368.5368.
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Abstract Introduction: Patients with Hodgkin lymphoma (HL) relapsing after ASCT and those not eligible for myeloablative therapy can be salvaged with conventional chemotherapy or new novel agents such the immunotoxin brentuximab vedotin and the recently FDA approved anti-PD-1 inhibitor nivolumab. Other options include the mTOR inhibitor everolimus (1) for which, the data in literature is scarce. Moreover, there is no data on the efficacy of everolimus after failure of brentuximab vedotin. Patients and methods: In this study, we retrospectively analyzed the outcome of patients with relapsed/ refractory HL treated with single agent everolimus at our center between July 2015 and July 2016. All patients were started on everolimus 10 mg daily. Response to treatment was assessed every 2 months. Primary endpoint was the response rate of everolimus as single agent in patients with relapsed/refractory HL. Results: We identified 5 patients with heavily pretreated HL who received single agent everolimus. Mean age was 24.4 years (range, 20-30). Mean lines of previous treatment was 6.4 (range, 5-8). All patients failed brentuximab vedotin. Two patients failed previous autologous stem cell transplantation. Prior treatments included ABVD, radiation, ICE, ESHAP, miniBEAM, GVD, brentuximab vedotin, gemzar plus brentuximab vedotin, bendamustine, and ASCT. Mean duration of everolimus treatment was 5 months (range 4-7). One patient showed complete metabolic remission after 5 months of treatment. This remarkable response was achieved after failure of 6 lines. Partial remission and stable disease each were documented in 40%. Grade 1 neutropenia was reported in 80%. Grade 2 anemia, thrombocytopenia, fatigue and stomatitis were observed in 60%, 80%, 20% and 20% respectively. Everolimus dose reduction (5 mg) was required in two cases (one patient had grade 2 thrombocytopenia and other one had grade 3 fatigue). The latter discontinued the treatment after 4 months and is still in complete remission 5 months after discontinuation. No pulmonary toxicity was observed. Conclusion:The presented data suggest that everolimus is effective in heavily pretreated HL patients who failed conventional treatment including ASCT and new novel agents with 60% ORR. This result is the first of its kind showing efficacy of everolimus after failure of brentuximab vedotin. Literature: Johnston PB et al. A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. Am J Hematol. 2010 May;85(5):320-4. Disclosures No relevant conflicts of interest to declare.
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Moore, T. D., P. H. Phillips, S. R. Nerenstone, and B. D. Cheson. "Systemic treatment of advanced and recurrent endometrial carcinoma: current status and future directions." Journal of Clinical Oncology 9, no. 6 (1991): 1071–88. http://dx.doi.org/10.1200/jco.1991.9.6.1071.
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Multiple systemic therapies have been used to treat patients with endometrial cancer. Although progestins have been the standard initial treatment for metastatic disease for the past 30 years, they are effective in only 20% of patients, and several large randomized trials have failed to demonstrate any benefit in the adjuvant setting. Alternative agents such as tamoxifen have shown modest activity. Few studies have investigated combinations of hormonally active drugs. Doxorubicin and cisplatin are the most active cytotoxic agents; a current randomized study is comparing the combination of these drugs with single-agent doxorubicin. Maximizing the effectiveness of established drugs, possibly with hematopoietic growth factors, and identifying alternative hormonal and cytotoxic agents with a sound scientific rationale will hopefully increase the effective treatment options for these patients.
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Popugaeva, Elena. "Fine Tuning of Intracellular Ca2+ Content by Pharmacological Agents – A Strategy to Prevent Synapse Loss in Alzheimer Disease Hippocampal Neurons." Current Alzheimer Research 17, no. 12 (2021): 1065–71. http://dx.doi.org/10.2174/1567205018666210119145735.
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: Alzheimer disease is the dominant form of elderly dementia. Today all clinical trials that target β-amyloid have failed to indicate that β-amyloid may not be a causative agent in AD pathogenesis. Thus there is a need to search for alternative ways to treat AD patients. : Neuronal store-operated calcium entry is a fine-tuning mechanism that regulates intracellular Ca2+ content. Recent evidence suggests that store-operated calcium channels may be targeted with pharmacological agents in order to prevent synapse loss, recover long-term potentiation and change behavior. : Current mini-review discusses basic chemical structures that modulate intracellular calcium dysbalance via targeting store-operated calcium channels and their applicability as anti-AD pharmacological agents.
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Gregorini, Luisa, Jean Marco, Monique Bernies, et al. "The Alpha-1 Adrenergic Blocking Agent Urapidil Counteracts Postrotational Atherectomy “Elastic Recoil” Where Nitrates Have Failed." American Journal of Cardiology 79, no. 8 (1997): 1100–1103. http://dx.doi.org/10.1016/s0002-9149(97)00053-2.
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Pellegrin, F., N. Duran-Vila, M. Van Munster, and D. Nandris. "Rubber tree (Hevea brasiliensis) trunk phloem necrosis: aetiological investigations failed to confirm any biotic causal agent." Forest Pathology 37, no. 1 (2007): 9–21. http://dx.doi.org/10.1111/j.1439-0329.2007.00471.x.
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AlDhaheri, Fahmi, Talal Almteri, Naji Dwid, Ahd Majdali, Nahed Janoudi та Hani Almoallim. "Rituximab Can Induce Remission in a Patient with Ankylosing Spondylitis Who Failed Anti-TNF-α Agent". American Journal of Case Reports 18 (9 лютого 2017): 143–47. http://dx.doi.org/10.12659/ajcr.900563.
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Lee, Sung-Eun, Jae-Ho Yoon, Seung-Hwan Shin, et al. "Impact of failed response to novel agent induction in autologous stem cell transplantation for multiple myeloma." Annals of Hematology 93, no. 4 (2013): 627–34. http://dx.doi.org/10.1007/s00277-013-1911-1.
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Nabhan, Chadi, and Neil E. Kay. "The Emerging Role of Ofatumumab in the Treatment of Chronic Lymphocytic Leukemia." Clinical Medicine Insights: Oncology 5 (January 2011): CMO.S4087. http://dx.doi.org/10.4137/cmo.s4087.
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The treatment of chronic lymphocytic leukemia (CLL) has evolved over the past decade. Our better understanding of disease biology and risk stratification has allowed delivering more effective therapies. In fact, front-line chemoimmunotherapy has demonstrated improvement in overall survival when compared to chemotherapy in randomized studies. Yet, treatment of relapsed CLL remains challenging and few agents are effective in that setting. Ofatumumab (Ofa) is a humanized monoclonal antibody targeted against CD20 with demonstrable activity in rituximab-resistant CLL cell lines. This agent was recently approved for the treatment of relapsed/refractory CLL patients who have failed fludarabine and alemtuzumab. In this review, we provide a historical perspective on approaches to CLL as front-line and in the relapsed setting. We further summarize novel anti-CD20 antibodies with specific emphasis on ofa. We review studies that led to ofatumumab's approval including pre-clinical data, trials using ofa in combination therapies, and adverse events/toxicities reported with this agent.
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Loraine, Jessica, Feifei Pu, Obolbek Turapov, and Galina V. Mukamolova. "Development of anIn VitroAssay for Detection of Drug-Induced Resuscitation-Promoting-Factor-Dependent Mycobacteria." Antimicrobial Agents and Chemotherapy 60, no. 10 (2016): 6227–33. http://dx.doi.org/10.1128/aac.00518-16.
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ABSTRACTTuberculosis is a major infectious disease that requires prolonged chemotherapy with a combination of four drugs. Here we present data suggesting that treatment ofMycobacterium tuberculosis, the causative agent of tuberculosis, andMycobacterium smegmatis, a model organism widely used for the screening of antituberculosis agents, with first-line drugs resulted in the generation of substantial populations that could be recovered only by the addition of a culture supernatant from growing mycobacteria. These bacilli failed to grow in standard media, resulting in significant underestimation of the numbers of viable mycobacteria in treated samples. We generatedM. smegmatisstrains overexpressingM. tuberculosisresuscitation-promoting factors (Rpfs) and demonstrated their application for the detection of Rpf-dependent mycobacteria generated after drug exposure. Our data offer novel opportunities for validation of the sterilizing activity of antituberculosis agents.
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Marik, Paul. "Hydrocortisone, Ascorbic Acid and Thiamine (HAT Therapy) for the Treatment of Sepsis. Focus on Ascorbic Acid." Nutrients 10, no. 11 (2018): 1762. http://dx.doi.org/10.3390/nu10111762.
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Sepsis is a devastating disease that carries an enormous toll in terms of human suffering and lives lost. Over 100 novel pharmacologic agents that targeted specific molecules or pathways have failed to improve the outcome of sepsis. Preliminary data suggests that the combination of Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) may reduce organ failure and mortality in patients with sepsis and septic shock. HAT therapy is based on the concept that a combination of readily available, safe and cheap agents, which target multiple components of the host’s response to an infectious agent, will synergistically restore the dysregulated immune response and thereby prevent organ failure and death. This paper reviews the rationale for HAT therapy with a focus on vitamin C.
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Riganti, Chiara, Roberta Giampietro, Joanna Kopecka, et al. "MRP1-Collateral Sensitizers as a Novel Therapeutic Approach in Resistant Cancer Therapy: An In Vitro and In Vivo Study in Lung Resistant Tumor." International Journal of Molecular Sciences 21, no. 9 (2020): 3333. http://dx.doi.org/10.3390/ijms21093333.
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Multidrug resistance (MDR) is the main obstacle to current chemotherapy and it is mainly due to the overexpression of some efflux transporters such as MRP1. One of the most studied strategies to overcome MDR has been the inhibition of MDR pumps through small molecules, but its translation into the clinic unfortunately failed. Recently, a phenomenon called collateral sensitivity (CS) emerged as a new strategy to hamper MDR acting as a synthetic lethality, where the genetic changes developed upon the acquisition of resistance towards a specific agent are followed by the development of hypersensitivity towards a second agent. Among our library of sigma ligands acting as MDR modulators, we identified three compounds, F397, F400, and F421, acting as CS-promoting agents. We deepened their CS mechanisms in the “pure” model of MRP1-expressing cells (MDCK-MRP1) and in MRP1-expressing/drug resistant non-small cell lung cancer cells (A549/DX). The in vitro results demonstrated that (i) the three ligands are highly cytotoxic for MRP1-expressing cells; (ii) their effect is MRP1-mediated; (iii) they increase the cytotoxicity induced by cis-Pt, the therapeutic agent commonly used in the treatment of lung tumors; and (iv) their effect is ROS-mediated. Moreover, a preclinical in vivo study performed in lung tumor xenografts confirms the in vitro findings, making the three CS-promoting agents candidates for a novel therapeutic approach in lung resistant tumors.
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Liu, G., M. Crump, P. E. Goss, J. Dancey, and F. A. Shepherd. "Prospective comparison of the sclerosing agents doxycycline and bleomycin for the primary management of malignant pericardial effusion and cardiac tamponade." Journal of Clinical Oncology 14, no. 12 (1996): 3141–47. http://dx.doi.org/10.1200/jco.1996.14.12.3141.
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PURPOSE To compare the clinical efficacy and toxicity of doxycycline and bleomycin as sclerosing agents in the primary management of malignant pericardial effusion (MPE). METHODS Twenty-seven consecutive adult patients referred to a tertiary-care institution for the management of cardiac tamponade and malignancy underwent pericardial drainage through a percutaneously placed pigtail catheter. They were then alternately assigned to undergo bleomycin or doxycycline pericardial sclerosis. RESULTS There were 13 men and 14 women, with a median age of 59 years. They mainly had lung (70%) and breast cancers (11%), and all had clinical and echocardiographic evidence of cardiac tamponade. Although all patients had successfully placed catheters, six were inadvertently dislodged before sclerosis; 11 underwent bleomycin sclerosis and 10 doxycycline sclerosis. Twenty patients (one early death) were assessable. One patient in each group failed to respond to sclerosis with the initial agent, but both were sclerosed successfully with the other agent. Sclerosis was achieved with a median of two instillations for each agent and total median doses of bleomycin 20 mg and doxycycline 1,250 mg. Seventy percent of doxycycline patients developed significant retrosternal pain, compared with no bleomycin patients (P = .04). Doxycycline patients required a median of 3.5 more days of hospitalization (8.5 v 5) and 2 more days of pericardial catheterization (7 v 5) compared with bleomycin patients. Tamponade recurred in one bleomycin patient at 253 days, and in no doxycycline patient. CONCLUSION Although bleomycin and doxycycline are equally effective sclerosing agents, bleomycin is associated with significantly less morbidity and should be the first-line chemical sclerosing agent for malignant pericardial effusions.
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Newaz, Mohammad Tanvi, Peter Rex Davis, Marcus Jefferies, and Manikam Pillay. "Validation of an agent-specific safety climate model for construction." Engineering, Construction and Architectural Management 26, no. 3 (2019): 462–78. http://dx.doi.org/10.1108/ecam-01-2018-0003.
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Purpose Safety climate (SC) is considered a leading indicator of safety performance, but scholars suggest that a common SC assessment framework is yet to be developed. Following the debate between the importance of facet analysis and agent analysis, the purpose of this paper is to test a factor structure, developed by the authors in previous work and arising from their systematic literature review, highlighting the role of safety agents in a construction site setting. Design/methodology/approach Multi-level SC surveys were conducted at five construction sites in Sydney, Australia, collecting data from of 352 workers associated with a mega-construction project. While examining the factor analysis of different studies, data reliability and data validity of the survey findings were ensured and a goodness-of-fit of SC model was examined through structural equation modelling. Findings The systematic literature review of Newaz et al. (2018) suggested a five-factor model of: management commitment, safety system, role of the supervisor, workers’ involvement and group SC. However, empirical data indicated that the questionnaire used to measure “safety system” failed to pass scale reliability; thus, a four-factor model was proposed to develop an agent-specific SC factor structure in the construction industry. Originality/value The four-factor model indicates the role and level of influence of different safety agents to improve safety perceptions on construction sites. The findings of this study will encourage researchers in construction safety to use the simplified four-factor SC (agent-specific) model presented and test it to further develop a common factor structure for the construction industry. The fact that the model is comprised of four factors makes further implementation somewhat easier in the development of safety plans, and when considering the role of safety agents, therefore enhancing its potential value.
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Nieva, Jorge, Kelly Bethel, and Alan Saven. "Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia." Blood 102, no. 3 (2003): 810–13. http://dx.doi.org/10.1182/blood-2003-01-0014.
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Abstract Hairy cell leukemia (HCL) is an indolent B-cell neoplasm, strongly expressing CD20. Despite initial very high response rates following cladribine, many patients (pts) ultimately relapse. Having relapsed after prior treatment with cladribine, 24 HCL pts (21 male, 3 female) with a median age of 53.5 years were treated with rituximab at 375 mg/m2 intravenously weekly for 4 weeks. Of the pts, 3 (13%) achieved complete remissions and 3 (13%), partial responses. Thus, 6 (25%) of 24 pts achieved a response following rituximab. At a median follow-up of 14.6 months, 2 responders have relapsed; median time to relapse was not yet reached. The only grade III or IV toxicities demonstrated were culture-negative febrile neutropenia, transient and reversible disseminated intravascular coagulation related to rituximab administration, and a diverticular abscess, each in single patients. Of 18 nonresponders, 9 pts subsequently received other treatments; 5 pts were retreated with cladribine, 3 underwent splenectomy, and 1 received pentostatin. Follow-up data are available on 7 of these 9 patients; all 7 patients achieved improvements in hematologic parameters. Rituximab, administered at this dose and schedule, has only modest single-agent activity in cladribine-failed HCL patients when compared with other agents active in this disease.
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Das, Satya, and Michael K. Gibson. "Evolving Management Strategies for Metastatic Esophageal and Gastroesophageal Junction Adenocarcinoma." Oncology & Hematology Review (US) 14, no. 2 (2018): 82. http://dx.doi.org/10.17925/ohr.2018.14.2.82.
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Metastatic or unresectable esophageal and gastroesophageal junction adenocarcinoma represent a devastating disease with 5-year survival rate of <5%. Although cytotoxic chemotherapy with platinum doublet based regimens is initially effective, patients inevitably progress. Patients often decline rapidly after this initial progression, making later lines of therapy a challenge to successfully administer. There have been multiple efforts to incorporate biologic agents, targeting pathways known to be dysregulated in esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, into existing chemotherapy backbones. Other than therapeutics targeting human epidermal growth factor receptor-2 (HER2) and vascular endothelial growth factor receptor (VEGFR), other strategies have failed. Given the mixed success of biologic agents, along with the promise of immunotherapy to generate durable and sometimes complete responses, immune-agent based trials are a major area of interest for patients with this disease. Checkpoint inhibitors blocking programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) have demonstrated modest single-agent efficacy in patients with progressive esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma. However, other approaches such as novel checkpoint combinations, vaccine-based approaches and autologous T cells hold more promise to change the trajectory of disease.
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Zhamanova, Amina A. "Dream Collaborations: From the History of Eugene O’Neill’s Failed Projects." Literature of the Americas, no. 10 (2021): 25–45. http://dx.doi.org/10.22455/2541-7894-2021-10-25-45.
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This article is focused on Eugene O’Neill’s failed artistic collaborations with outstanding directors, actors and singers. It is the first attempt, in the Russian theatre studies, to get to the truth behind the playwright’s unrealized tandem with the legendary opera singer Feodor Chaliapin. The creative destiny of O’Neill’s play Lazarus Laughed (1927) is tracked from the attempts to stage it in New York, Chicago, Berlin and Moscow, all the way to the long-anticipated premiere at the Pasadena Playhouse in Pasadena, California. Special attention is paid to the Kamerny Theatre shows in Paris and Buenos Aires. Also under scrutiny is the American playwright’s private correspondence — in particular, with literary agent Richard Madden, translator Alexander Berkman and theatre producer Kenneth Macgowan. Particular emphasis is put on the playwright’s work behind the scenes and his active contribution to the translation of his ideas to the stage. The article reflects O’Neill’s approach to picking actors for lead roles in the stage productions of his plays, and also gives a logical conclusion to his failed meeting with two-time Academy Award winner Spencer Tracy at the Tao House in Danville, California. The paper provides a review of Ingrid Bergman’s acting performance in the Anna Christie production (Lobero Theatre, Santa Barbara, 1941) and in Jose Quintero’s Broadway production More Stately Mansions (Broadhurst Theatre, New York, 1967) based on Eugene O’Neill’s late unfinished play.
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Hotta, Katsuyuki, Keitaro Matsuo, Hiroshi Ueoka, Katsuyuki Kiura, Masahiro Tabata, and Mitsune Tanimoto. "Meta-Analysis of Randomized Clinical Trials Comparing Cisplatin to Carboplatin in Patients With Advanced Non–Small-Cell Lung Cancer." Journal of Clinical Oncology 22, no. 19 (2004): 3852–59. http://dx.doi.org/10.1200/jco.2004.02.109.
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Purpose It remains undetermined whether cisplatin and carboplatin are equally effective for advanced non–small-cell lung cancer (NSCLC). We therefore did a meta-analysis of trials that compared cisplatin-based chemotherapy with carboplatin-based chemotherapy. Methods We performed a literature search to identify trials that had investigated the substitution of carboplatin for cisplatin in the treatment of advanced NSCLC. We evaluated these trials for inclusion, rated methodologic quality, and abstracted relevant data. Results Of 1,191 reports, eight trials (2,948 patients) were identified, five of which investigated drug regimens containing platinum plus a new agent. Cisplatin-based chemotherapy produced a higher response rate, but the survival advantage was not significant (hazard ratio = 1.050; 95% CI, 0.907 to 1.216; P = .515). Subgroup analysis revealed that combination chemotherapy consisting of cisplatin plus a new agent yields 11% longer survival than carboplatin plus the same new agent (hazard ratio = 1.106; 95% CI, 1.005 to 1.218; P = .039). Patients on cisplatin-based chemotherapy frequently developed nausea and vomiting; thrombocytopenia was more frequent during carboplatin-based chemotherapy. No significant difference in treatment-related mortality was observed. Conclusion We found that combination chemotherapy consisting of cisplatin plus a new agent yields a substantial survival advantage compared with carboplatin plus a new agent in patients with advanced NSCLC, although we failed to find any survival difference in an analysis that included both new and old agents. The strength of our conclusion is limited because we used abstracted data, and careful interpretation is thus required. Nevertheless, our results raise a critical point that needs to be evaluated in future studies.
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English, Brett A., Daniel J. Still, John Harper, and Steven R. Saklad. "Failure of Tolterodine to Treat Clozapine-Induced Nocturnal Enuresis." Annals of Pharmacotherapy 35, no. 7-8 (2001): 867–69. http://dx.doi.org/10.1345/aph.10304.
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OBJECTIVE: To report the use and subsequent failure of the bladder-selective agent tolterodine, to treat clozapine-induced nocturnal enuresis in an adolescent patient with psychotic illness. CASE SUMMARY: A 16-year-old Hispanic girl was admitted to the state psychiatric hospital with a diagnosis of bipolar disorder with psychotic features. Clozapine therapy was initiated, and after three months of treatment the patient began experiencing episodes of nocturnal enuresis. The bladder-selective agent tolterodine was tried and subsequently failed to resolve the enuresis episodes. Desmopressin was initiated, which resulted in amelioration of symptoms. DISCUSSION: This is the first published report of using tolterodine to treat clozapine-induced nocturnal enuresis. Several methods to decrease clozapine-induced urinary incontinence have been used and typically include the addition of agents with high anticholinergic properties. Tolterodine is a bladder-selective anticholinergic agent indicated for the treatment of urinary urge incontinence and may be employed as a treatment for antipsychotic-induced incontinence. CONCLUSIONS: Nocturnal enuresis is an adverse effect that infrequently occurs with use of clozapine therapy. Although tolterodine was ineffective in our patient to treat clozapine-induced nocturnal enuresis, further trials are required to appropriately evaluate the effectiveness of tolterodine to treat this adverse drug reaction.
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Dessler, David. "What's at stake in the agent-structure debate?" International Organization 43, no. 3 (1989): 441–73. http://dx.doi.org/10.1017/s0020818300032999.
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Recent developments in the philosophy of science, particularly those falling under the rubric of “scientific realism,” have earned growing recognition among theorists of international relations but have failed to generate substantive programs of research. Consequently, the empirical relevance of much philosophical discourse, such as that centering on the agent-structure problem in social theory, remains unestablished. This article attempts to bridge the gap between the philosophy and practice of science by outlining a model of international structure based on the principles of scientific realism and by considering its implications for a structural research program in international relations theory. Appealing to Imre Lakatos's methodology of theorychoice, the article presents an ontological case for adopting a “transformational” model of structure over the “positional” model developed in the work of Kenneth Waltz. The article demonstrates that the positional approach offers no conceptual or explanatory hold on those features of the international structure that are the intended products of state action. In conclusion, the article argues that the stakes in the agent-structure debate include the capacity to generate integrative structural theory and the ability to theorize the possibilities for peaceful change in the international system.
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Townsley, Danielle M., and Thomas Winkler. "Nontransplant therapy for bone marrow failure." Hematology 2016, no. 1 (2016): 83–89. http://dx.doi.org/10.1182/asheducation-2016.1.83.
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Abstract Nontransplant therapeutic options for acquired and constitutional aplastic anemia have significantly expanded during the last 5 years. In the future, transplant may be required less frequently. That trilineage hematologic responses could be achieved with the single agent eltrombopag in refractory aplastic anemia promotes new interest in growth factors after years of failed trials using other growth factor agents. Preliminary results adding eltrombopag to immunosuppressive therapy are promising, but long-term follow-up data evaluating clonal evolution rates are required before promoting its standard use in treatment-naive disease. Danazol, which is traditionally less preferred for treating cytopenias, is capable of preventing telomere attrition associated with hematologic responses in constitutional bone marrow failure resulting from telomere disease.
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Chen, Can, Wenwei Zuo, Pan Yang, and Yanling Zhang. "Anti-PD-1, anti-VEGF, and temozolomide therapy in a patient with recurrent glioblastoma: a case report." Journal of International Medical Research 48, no. 9 (2020): 030006052095139. http://dx.doi.org/10.1177/0300060520951395.
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Background Patients suffering from postoperative recurrent glioblastoma have an extremely unfavorable outcome because there are no proven therapeutic options. The median overall survival for those with relapsed glioblastoma after surgery is only 7.5 months. Case presentation: Between March 2015 and October 2019, a 44-year-old female patient with recurrent glioblastoma was treated by our medical team. After several failed rounds of therapy, the patient was subsequently treated with the anti-programmed death (PD)-1 antibody nivolumab, anti-vascular endothelial growth factor (VEGF) antibody bevacizumab, and cytotoxic agent temozolomide. Results The patient showed a sustainable complete response to the regimen. To date, there have been no serious toxic side effects. As of October 2019 (the last follow-up), the patient has been in complete remission for 17 months since recurrence. Conclusion The experience of this complicated case indicates the possible application of immune checkpoint inhibitors, anti-angiogenesis agents, and cytotoxic reagents for recurrent glioblastoma. The administration of this three-agent regimen appears safe and effective. However, further clinical trials are warranted.
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Friend, Keith E. "Acromegaly: A New Therapy." Cancer Control 9, no. 3 (2002): 232–35. http://dx.doi.org/10.1177/107327480200900306.
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Background The treatment of acromegaly can be challenging. Despite a multimodality approach (surgery, radiation, dopamine agonists, somatostatin analogs), many patients do not achieve normalization of serum insulin-like growth factor I (IGF-I) concentrations. Methods The author discusses the characteristics and indications of pegvisomant therapy for patients with acromegaly and compares the use of this newly developed GH receptor antagonist with other pharmacological agents such as somatostatin and dopamine agonists. Results Therapy with pegvisomant allows serum IGF-I concentrations to be normalized in up to 97% of patients with acromegaly, including those who have failed other treatment modalities. With this agent, circulating GH levels increase as a result of the drop in IGF-I levels. The rise is rapid (within 2 weeks) and does not appear to be progressive over time. Conclusions Published studies have shown pegvisomant to have efficacy in the treatment of acromegaly. As it appears to be well tolerated and safe, this novel compound may be an important therapeutic option for patients with acromegaly. Additional study of this novel agent and its mode of action is warranted.
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Si, Mei. "Should I Stop Thinking About It: A Computational Exploration of Reappraisal Based Emotion Regulation." Advances in Human-Computer Interaction 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/856726.
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Agent-based simulation of people’s behaviors and minds has become increasingly popular in recent years. It provides a research platform to simulate and compare alternative psychological and social theories, as well as to create virtual characters that can interact with people or among each other to provide pedagogical or entertainment effects. In this paper, we investigate computationally modeling people’s coping behaviors and in particular in relation to depression, in decision-theoretic agents. Recent studies have suggested that depression can result from failed emotion regulation under limited cognitive resources. In this work, we demonstrate how reappraisal can fail under high levels of stress and limited cognitive resources using an agent-based simulation. Further, we explored the effectiveness of reappraisal under different conditions. Our experiments suggest that for people who are more likely to recall positive memories, it is more beneficial to think about the recalled events from multiple perspectives. However, for people who are more likely to recall negative memories, the better strategy is to not evaluate the recalled events against multiple goals.
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Mukhopadhyay, Srirupa, Sandip Bhattacharyya, Ramdhan Majhi, et al. "Use of an Attenuated Leishmanial Parasite as an Immunoprophylactic and Immunotherapeutic Agent against Murine Visceral Leishmaniasis." Clinical Diagnostic Laboratory Immunology 7, no. 2 (2000): 233–40. http://dx.doi.org/10.1128/cdli.7.2.233-240.2000.
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ABSTRACT The ability of the leishmanial parasite UR6 to act as an immunoprophylactic and immunotherapeutic agent against Leishmania donovani infection in BALB/c mice was investigated. Unlike the virulent L. donovani AG83 (MOHOM/IN/1983/AG83), UR6 given through intracardiac route failed to induce visceral infection, but when it was injected subcutaneously, UR6 induced a short-lived and localized self-healing skin lesion. Priming of peritoneal macrophages with UR6 in vitro induced superoxide (O2 −) generation, whereas similar experiments with virulent AG83 inhibited O2 − generation. It was observed that priming of mice with either live or sonicated UR6 in the absence of any adjuvant provided strong protection against subsequent virulent challenge. Further, UR6-primed infected mice not only displayed a strong antileishmanial delayed-type hypersensitivity (DTH) response but also showed an elevated level of the serum antileishmanial immunoglobulin G2a (IgG2a) isotype, whereas infected mice failed to mount any antileishmanial DTH response and showed an elevated level of IgG1. This indicates that UR6 priming and subsequent L. donovani infection allowed the expansion of Th1 cells. Our studies indicate that UR6 has potential to be used as an immunoprophylactic and immunotherapeutic agent against experimental visceral leishmaniasis.
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BLOM, MARLIES, WIETSKE KIEVIT, JAAP FRANSEN, et al. "The Reason for Discontinuation of the First Tumor Necrosis Factor (TNF) Blocking Agent Does Not Influence the Effect of a Second TNF Blocking Agent in Patients with Rheumatoid Arthritis." Journal of Rheumatology 36, no. 10 (2009): 2171–77. http://dx.doi.org/10.3899/jrheum.090054.
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Objective.To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent.Methods.Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking agents. Patients were divided into 3 groups based on reason for discontinuation of the first: nonresponse, loss of response, or adverse events. The primary outcome was the change from baseline of the disease activity (by DAS28) at 6 months, corrected for the baseline DAS28 score. Secondary outcomes were the change from baseline at 3 months, EULAR response rates, and the percentages of patients who reached a DAS28 score ≤ 3.2 at 3 and at 6 months.Results.In total, 49 patients who failed due to nonresponse, 75 due to loss of response, and 73 due to adverse events were included. At 6 months, the change of DAS28 score from baseline did not differ significantly between the groups (−0.6 to −1.3; p ≥ 0.173) and similar good and moderate response rates were found (12% to 18%, p ≥ 0.523, and 34% to 55%, p ≥ 0.078, respectively). The secondary outcomes were also comparable between the 3 groups.Conclusion.The results of our observational study suggest that a second TNF blocking agent may be effective after failure of the first, regardless of the reason for discontinuation of the first TNF blocking agent.
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Surian, Luca, Stefania Caldi, and Dan Sperber. "Attribution of Beliefs by 13-Month-Old Infants." Psychological Science 18, no. 7 (2007): 580–86. http://dx.doi.org/10.1111/j.1467-9280.2007.01943.x.
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In two experiments, we investigated whether 13-month-old infants expect agents to behave in a way that is consistent with information to which they have been exposed. Infants watched animations in which an animal was either provided information or prevented from gathering information about the actual location of an object. The animal then searched successfully or failed to retrieve the object. Infants' looking times suggest that they expected searches to be effective when—and only when—the agent had had access to the relevant information. This result supports the view that infants possess an incipient meta-representational ability that permits them to attribute beliefs to agents. We discuss the viability of more conservative explanations and the relation between this early ability and later forms of theory of mind that appear only after children have become experienced verbal communicators.
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Freeman, Hugh J., Jennifer E. Davis, Marcia E. Prest, and Edward J. Lawson. "Granulomatous Bronchiolitis with Necrobiotic Pulmonary Nodules in Chrohn's Disease." Canadian Journal of Gastroenterology 18, no. 11 (2004): 687–90. http://dx.doi.org/10.1155/2004/729689.
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A 37-year-old man with extensive Crohn's disease of the stomach, small and large intestine for almost a decade developed respiratory symptoms and radiological findings suggestive of pneumonia that failed to resolve with antibiotic treatment. Computed tomography scanning of his lungs showed extensive changes with cavitated parenchymal nodules. Histological evaluation of an open lung biopsy showed granulomatous bronchiolitis and pulmonary necrobiosis. Treatment with steroids and immunosuppression resulted in complete resolution of his clinical symptoms of pneumonia and abnormal computed tomography imaging changes. Granulomatous bronchiolitis and necrobiotic nodules may be a manifestation of Crohn's disease in the absence of microbial agents, including mycobacteria or fungal agents. While a multiplicity of complex pulmonary changes may occur in Crohn's disease, their clinical recognition and precise pathological definition may be particularly important if treatment with a biological agent, such as infliximab, is being considered.
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Menna, Cecilia, Claudio Andreetti, Mohsen Ibrahim, et al. "The Effect of Silver Nitrate Pleurodesis after a Failed Thoracoscopic Talc Poudrage." BioMed Research International 2013 (2013): 1–5. http://dx.doi.org/10.1155/2013/295890.
Full textAbstract:
Background. Chemical pleurodesis is the procedure of choice in the management of recurrent malignant pleural effusions (MPE). Talc is probably the most effective sclerosant, with a success rate of 80%. The aim of this study is to demonstrate the effectiveness of silver nitrate solution (SNS) pleurodesis after an unsuccessful thoracoscopic talc poudrage.Methods. Between 2011 and 2013 one hundred and nine patients with unilateral MPE underwent thoracoscopic talc poudrage. Seventeen patients who did not obtain a successful pleurodesis via thoracoscopic procedure were considered for an SNS slurry. The pleural injectate consisted of 100 mL 1% SNS with 10 mL of lidocaine (100 mg/5 mL). The SNS procedure was undertaken once and repeated with the same dose in 5 patients.Results. The duration of follow-up period was 30 days. Subjective pain was low and the same before and after SNS procedure ( value = NS). The mean daily fluid drainage was statistically different () comparing values before ( mL) and after SNS procedure ( mL). After 30 days from SNS procedure recurrence of pleural effusion was observed in 2 patients (11%).Conclusions. The present study demonstrates that SNS is an effective agent for producing pleurodesis after a failed thoracoscopic talc poudrage.