Home About us Contact
|
Home About us Contact | ||
|
|
||
Target
Kinds of Target Terms modified by Target Selected AbstractsINSULIN-LIKE GROWTH FACTOR-I RECEPTOR AS A CANDIDATE FOR A NOVEL MOLECULAR TARGET IN GASTROINTESTINAL CANCERSDIGESTIVE ENDOSCOPY, Issue 4 2006Yasushi Adachi Abnormal activation of growth factor receptors and their signal pathways are required for neoplastic transformation and tumor progression. The concept of targeting specific tumorigenic receptors has been validated by successful clinical application of multiple new drugs, such as those acting against HER2/neu, epidermal growth factor receptor 1, and c-Kit. In this review, we focus on the next promising therapeutic molecular target of insulin-like growth factor (IGF)-I receptor (IGF-Ir). The IGF/IGF-Ir system is an important modifier of cancer cell proliferation, survival, growth, and treatment sensitivity in a number of neoplastic diseases, including human gastrointestinal carcinomas. Preclinical studies demonstrated that downregulation of IGF-Ir signals reversed the neoplastic phenotype and sensitized cells to antitumor treatments. We summarize a variety of ways to disrupt IGF-Ir function. Then, we introduce our strategy of adenoviruses expressing dominant negative of IGF-Ir (IGF-Ir/dn) against gastrointestinal cancers, including stomach, colon, and pancreas. IGF-Ir/dn suppresses tumorigenicity both in vitro and in vivo and increases stressor-induced apoptosis. IGF-Ir/dn expression upregulates chemotherapy-induced apoptosis and these combination therapies with chemotherapy are very effective against tumors in mice. Some drugs blocking IGF-Ir function are now entering clinical trial, thus IGF-Ir might be a candidate for a therapeutic target in several gastrointestinal malignancies. [source] Payments Settlement: Tiering in Private and Public SystemsJOURNAL OF MONEY, CREDIT AND BANKING, Issue 5 2009CHARLES M. KAHN payment systems; limited enforcement; settlement risk; tiering What are the benefits provided by a payment system? What are the trade-offs in public versus private payment systems and in restricted versus open payments arrangements? Modern payment systems encompass a variety of institutional designs with varying degrees of counterparty protection. We develop a framework that allows for an examination and comparison of payment systems, and specification of conditions leading to their adoption. We relate these conditions to the design of present large-value payment systems (Fedwire, CHIPS, TARGET, etc.). [source] Latest news and product developmentsPRESCRIBER, Issue 9 2007Article first published online: 3 SEP 200 Clinical trials flatter anti-TNFs in RA The efficacy of anti-TNF agents in clinical trials is not matched by experience in daily practice in patients with rheumatoid arthritis, say Dutch investigators (Ann Rheum Dis online: 10 April 2007; doi:10.1136/ard.2007.072447). They compared outcomes from a systematic review of trials of etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) and a national postmarketing surveillance scheme (DREAM). In 5 of 11 comparisons, the response rate in DREAM was significantly lower than that in RCTs. Responses among DREAM patients who met the inclusion criteria for clinical trials were significantly greater than among noneligible patients and comparable with those of patients participating in the trials. The authors conclude that patients in trials have more severe disease and therefore a response to treatment that is not matched in daily practice. Methadone prescriptions double in 10 years Methadone treatment for opiate addicts has more than doubled in the past 10 years, according to an audit of opiate substitution in England by the National Treatment Agency for Substance Misuse (www.nta.nhs.uk). The total number of methadone prescriptions increased from 970 900 in 1995 to over 1.8 million in 2004. The introduction of buprenorphine (Subutex) has not reduced methadone prescribing , 96 per cent of responding centres prescribed methadone and 88 per cent prescribed buprenorphine. Seventy-two per cent of centres prescribe benzodiazepines to opiate addicts, causing the NTA some concern. GPs were involved in prescribing management in about 60 per cent of centres. Next NICE guidelines The Department of Health has referred eight topics to NICE for the development of clinical guidelines: preventing venous thromboembolism, acute coronary syndromes, chest pain, social complications during pregnancy (eg drug misuse), benign prostatic hyperplasia, constipation in children, neonatal jaundice and metastatic disease of unknown primary origin. Errors with children , Every step of drug treatment for children, from prescribing to writing notes, is associated with a substantial level of error, say US investigators (Quality and Safety in Health Care 2007;16:116-26). Their systematic review of 31 studies reporting medication errors in paediatrics found that 3-37 per cent were associated with prescribing errors, 5-58 per cent with dispensing errors, 72-75 per cent with errors of administration, and 17-21 per cent with documentation errors. Suggestions for remedial strategies were not evidence based, the authors found. , and transplant patients Errors in medication are common among outpatients who have received liver, kidney or pancreas transplants, a second US study has found (Arch Surg 2007;142:278-83). Twelve months' follow-up of 93 patients revealed a total of 149 errors of drug treatment, with a frequency of 15 in 219 visits over a four-week period. One-third of errors were associated with adverse events including hospital admission and graft rejection. Patients were taking an average of 11 medicines; analysis showed that over half of errors originated with the patients and 13 per cent were associated with prescribing. Paracetamol pack benefit challenged A new study has challenged accepted wisdom that reducing the OTC pack size of paracetamol cut the suicide rate (PLoS Medicine 2007;4:e105). In 1998, pack sizes of paracetamol were limited to 16 in general sale outlets and 32 in pharmacies. Suicide rates subsequently decreased but, though widely assumed, a causal link has not been established. Researchers from London and the Office of National Statistics have now examined mortality trends from suicide associated with antidepressants, aspirin, compound paracetamol preparations and nondrug poisoning. They found that all fatal suicides declined at similar rates after the pack size reductions. While not excluding the possibility that restricting easy access to paracetamol may have helped, these data suggest that other factors were also important. CV risk with ibuprofen among aspirin users Ibuprofen, but not naproxen, is associated with a higher risk of cardiovascular events and heart failure than lumiracoxib (Prexige) in high-risk patients, according to a new analysis of the TARGET trial (Ann Rheum Dis online: 5 April 2007; doi:10.1136/ard.2006.066001). TARGET comprised two studies comparing naproxen or ibuprofen with lumiracoxib in a total of 18 325 patients with OA. This post-hoc analysis stratified patients by their cardiovascular risk; the primary end-point was a composite of cardiovascular mortality, nonfatal myocardial infarction and stroke at one year. Among those at high risk who were taking aspirin, ibuprofen was associated with an increased risk of the composite end-point compared with lumiracoxib (2.14 vs 0.25 per cent). The risk was similar for naproxen and lumiracoxib (1.58 vs 1.48 per cent). In high-risk patients not taking aspirin, the risk was similar for ibuprofen and lumiracoxib, but lower for naproxen than lumiracoxib. Congestive heart failure was more common in patients taking ibuprofen than lumiracoxib (1.28 vs 0.14 per cent); the risk was similar with naproxen and lumiracoxib. The authors emphasise that their findings should be considered hypothesis-generating. CVD guidelines criticised The second edition of the guidelines of the Joint British Societies on preventing cardiovascular disease have been harshly criticised for failing to meet international quality standards (Int J Clin Pract online doi: 10.1111/j.1742-1241.2007.01310.x). Kent GP Dr Rubin Minhas evaluated the guidelines against the criteria of the Appraisal of Guidelines and Research (AGREE) Collaboration. He identified areas of weakness including stakeholder involvement, rigour of development, applicability (by not considering cost) and editorial independence from the pharmaceutical industry. The guidelines should not be recommended for clinical practice, he concludes. OTC naproxen? The MHRA is consulting on switching naproxen 250mg to pharmacy-only status for the treatment of period pain in women aged 15-50. The change would offer an alternative to ibuprofen, currently the only other OTC medicine with this indication. Responses should be submitted by 23 May. The Agency is currently considering responses to its consultation on switching tranexamic acid to OTC status for heavy menstrual bleeding. Diabetes costs The total cost of prescribing for diabetes in England has doubled in only five years, official statistics show. The NHS Information Centre (www.ic.nhs.uk) report shows that spending in primary and secondary care in 2006 was £561 million, up 14 per cent on 2005. Growth was due to increased prescribing of oral hypoglycaemic agents (notably the glitazones , up by one-third over 2005) and the higher costs of insulins. Pharmacists may give flu jabs PCTs may consider using pharmacists to administer flu vaccines to some at-risk groups in the 2007/08 season, according to Department of Health plans. Flu vaccination payment for patients with diabetes, coronary heart disease, and stroke and TIA is provided under the Quality Outcomes Framework. The Department suggests that PCTs consider contracting a local enhanced service from pharmacists to reach other patients at increased risk, such as those with chronic liver disease, multiple sclerosis and related conditions, hereditary and degenerative disease of the CNS and carers. Copyright © 2007 Wiley Interface Ltd [source] EMERGENCY CORONARY ARTERY BYPASS GRAFTING: A MOVING TARGETANZ JOURNAL OF SURGERY, Issue 9 2006Brian F. Buxton No abstract is available for this article. [source] TISSUE HYPOXIA AS A THERAPEUTIC TARGET IN ACUTE KIDNEY INJURYCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2009Roger G Evans No abstract is available for this article. [source] ANGIOTENSIN AT2 RECEPTOR AS A POTENTIAL THERAPEUTIC TARGET IN HYPERTENSIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1 2009Wing Tak Wong No abstract is available for this article. [source] The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes , results of the randomized, controlled PREDICTIVEÔ 303 studyDIABETES OBESITY & METABOLISM, Issue 6 2007L. Meneghini The Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation 303 (PREDICTIVEÔ 303) Study (n = 5604) evaluated the effectiveness of insulin detemir, a long-acting basal insulin analogue, using a simplified patient self-adjusted dosing algorithm (303 Algorithm group) compared with standard-of-care physician-driven adjustments (Standard-of-care group) in a predominantly primary care setting, over a period of 6 months. Insulin detemir was to be started once-daily as add-on therapy to any other glucose-lowering regimens or as a replacement of prestudy basal insulin in patients with type 2 diabetes. Investigator sites rather than individual patients were randomized to either the 303 Algorithm group or the Standard-of-care group. Patients from the 303 Algorithm group sites were instructed to adjust their insulin detemir dose every 3 days based on the mean of three ,adjusted' fasting plasma glucose (aFPG) values (capillary blood glucose calibrated to equivalent plasma glucose values) using a simple algorithm: mean aFPG < 80 mg/dl (<4.4 mmol/l), reduce dose by 3 U; aFPG between 80 and 110 mg/dl (4.4,6.1 mmol/l), no change; and aFPG > 110 mg/dl (>1.1 mmol/l), increase dose by 3 U. The insulin detemir dose for patients in the Standard-of-care group was adjusted by the investigator according to the standard of care. Mean A1C decreased from 8.5% at baseline to 7.9% at 26 weeks for the 303 Algorithm group and from 8.5 to 8.0% for the Standard-of-care group (p = 0.0106 for difference in A1C reduction between the two groups). Mean FPG values decreased from 175 mg/dl (9.7 mmol/l) at baseline to 141 mg/dl (7.8 mmol/l) for the 303 Algorithm group and decreased from 174 mg/dl (9.7 mmol/l) to 152 mg/dl (8.4 mmol/l) for the Standard-of-care group (p < 0.0001 for difference in FPG reduction between the two groups). Mean body weight remained the same at 26 weeks in both groups (change from baseline 0.1 and ,0.2 kg for the 303 Algorithm group and the Standard-of-care group respectively). At 26 weeks, 91% of the patients in the 303 Algorithm group and 85% of the patients in the Standard-of-care group remained on once-daily insulin detemir administration. The rates of overall hypoglycaemia (events/patient/year) decreased significantly from baseline in both groups [from 9.05 to 6.44 for the 303 Algorithm group (p = 0.0039) and from 9.53 to 4.95 for the Standard-of-care group (p < 0.0001)]. Major hypoglycaemic events were rare in both groups (0.26 events/patient/year for the 303 Algorithm group and 0.20 events/patient/year for the Standard-of-care group; p = 0.2395). In conclusion, patients in the 303 Algorithm group achieved comparable glycaemic control with higher rate of hypoglycaemia as compared with patients in the Standard-of-care group, possibly because of more aggressive insulin dose adjustments. The vast majority of the patients in both groups were effectively treated with once-daily insulin detemir therapy. The use of insulin detemir in this predominantly primary care setting achieved significant improvements in glycaemic control with minimal risk of hypoglycaemia and no weight gain. [source] Identifying Essential Topics in General and Special Education Introductory Assessment TextbooksEDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 1 2007Cynthia Campbell We reviewed the five top-selling introductory assessment textbooks in both general and special education to identify topics contained in textbooks and to determine the extent of agreement among authors regarding the essentialness of topics within and across discipline. Content analysis across the 10 assessment textbooks yielded 73 topics related to 13 categories: Decisions, Law, Technical Adequacy, Plan Assessment, Create Assessment, Score Assessment, Assessment Target, Assessment Type, Assessment Method, Interpret Assessment, Communicate Assessment Results, Assessment Population, and Computer-Assisted Assessment. Many of the topics identified were consistent with traditional assessment expectations of general and special education environments, while other, arguably important, topics were not identified as essential. The idea of core assessment topics for all teachers is introduced. [source] Policy interventions to reduce the harm from smokingADDICTION, Issue 1s1 2000Peter Anderson The other papers in this series on reduced smoking discuss interventions focused on individuals. This paper illustrates possible smoking reduction interventions focused on policies rather than individuals. Target 12 of the new WHO Health For All Policy aims to significantly reduce the harm from addictive substances, including tobacco, in all member states by 2015, and the WHO Third Action Plan for Tobacco-Free Europe focuses on reducing the harm from tobacco. These documents recommend five key policy strategies: market regulation, product liability, smoke-free environments, support for smoking cessation and education, public information and public opinion. Interventions such as price increases, restricting availability, advertising bans and product control could all be used to achieve harm reduction. Research on reducing the harm of smoking needs to include policy as well as treatment research. [source] Secreted TARSH regulates olfactory mitral cell dendritic complexityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2009Ting-Wen Cheng Abstract Olfactory sensory neurons synapse with mitral cells to form stereotyped connections in the olfactory bulb (OB). Mitral cell apical dendrites receive input from olfactory sensory neurons expressing the same odorant receptor. During development, this restricted dendritic targeting of mitral cells is achieved through eliminating elaborated dendritic trees to a single apical dendrite. Through a genome-wide microarray screen, we identified TARSH (Target of NESH SH3) as a transiently expressed molecule in mitral cells during the dendritic refinement period. TARSH expression is restricted to pyramidal neurons along the main olfactory pathway, including the anterior olfactory nucleus and piriform cortex. The dynamic TARSH expression is not altered when odor-evoked activity is blocked by naris closure or in AC3 knockout mice. We also demonstrate that TARSH is a secreted protein. In dissociated OB cultures, secreted TARSH promotes the reduction of mitral cell dendritic complexity and restricts dendritic branching and outgrowth of interneurons. Dendritic morphological changes were also observed in mitral cells overexpressing TARSH themselves. We propose that TARSH is part of the genetic program that regulates mitral cell dendritic refinement. [source] Metal-Assisted Hybridization of Oligonucleotides, Evaluation of Circular 2,- O -Me RNA as Ligands for the TAR RNA TargetEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2003Laurence Zapata Abstract Two complementary oligonucleotides were conjugated with terpyridine ligands at their nearby 5,- and 3,-ends. Addition of a stoichiometric amount of a transition metal (Zn2+, Fe2+) resulted in a large increase in the melting temperature of the duplex. The conjugation of TPY to stem-loop oligomers provided an efficient procedure for the cyclisation of the oligomer after the addition of metal ions. Such a short stem-loop oligomer was designed to target the HIV-1 TAR RNA through loop,loop interactions. The addition of Zn2+ ions yielded a good ligand (Kd = 30 nM) for this RNA structural element. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Nitrided Amorphous Stainless Steel Coatings Deposited by Reactive Magnetron Sputtering from an Austenitic Stainless Steel TargetADVANCED ENGINEERING MATERIALS, Issue 1-2 2009Salvatore Cusenza Abstract Stainless steel films were reactively magnetron sputtered in argon/nitrogen gas flow onto oxidized silicon wafers using austenitic AISI 316 stainless-steel targets. The deposited films of about 300,nm thickness were characterized by conversion electron Mö-i;ssbauer spectroscopy, magneto-optical Kerr-effect, X-ray diffraction, Rutherford backscattering spectrometry, and resonant nuclear reaction analysis. These complementary methods were used for a detailed examination of the nitriding effects for the sputtered stainless-steel films. The formation of an amorphous and soft ferromagnetic phase in a wide range of the processing parameters was found. Further, the influence of postvacuum-annealing was examined by perturbed angular correlation to achieve a comprehensive understanding of the nitriding process and phase formation. The amorphous phase is not very stable and crystallization can be observed at 973,K. [source] Explicit Input Enhancement: Effects on Target and Non-Target Aspects of Second Language AcquisitionFOREIGN LANGUAGE ANNALS, Issue 4 2006Article first published online: 31 DEC 200, Carolyn Gascoigne Many recent studies have examined the effectiveness of various types of input enhancement. The following study expands this line of inquivy to include tech nological applications of language learning by comparing the effectiveness of the com puter application of diacritics to a traditional pen-and-paper process among beginning students of French and Spanish. In addition to studying the effect of computer-mediated input enhancement on the recall of accents, this study also questions the incidental effects of input enhancement on non-target aspects of the second language acquisition (SLA) process. Results support the effectiveness of explicit and computer-mediated input enhancement. [source] Soft Decision with Soft Target for Car-like Mobile Vehicle in Dynamic EnvironmentIEEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING, Issue 4 2009Yougen Chen Non-member Abstract Online flexible operation of a car-like mobile vehicle with non-holonomic constraints in dynamic environment is still a very challenging problem because the surrounding situations are not qualified in static, knowledge is only partial and the execution is often associated with uncertainty. The difficulty lies in the setting of appropriate moving sub-targets in real-time to obtain a collision-free and low-cost path. In this paper, we present a new approach for the autonomous motion control of mobile vehicle in a narrow area with static and dynamic obstacles. It is based on the selection of sub-target points of vehicle's movement called ,soft target' which is a target set defined as all possible and reachable via-points in a navigation space. The soft target is acquired by online learning based on the final target and environment information. Each element of it has its membership value in [0, 1] denoting its evaluation degree. With the acquired soft target, soft decision is made like human's decision process by predictive fuzzy control (PFC) to achieve final target safely and economically. The simulation results show the effectiveness and flexibility of the proposed vehicle motion control method. © 2009 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [source] "Don't Ask, Don't Tell": The Influence of Stigma Concealing and Perceived Threat on Perceivers' Reactions to a Gay TargetJOURNAL OF APPLIED SOCIAL PSYCHOLOGY, Issue 5 2007Debra L. Oswald This research examined reactions to a gay target who was either concealing or not concealing his sexual orientation under conditions of threat (HIV-positive) or no threat (healthy). When the target concealed his sexual orientation, participants were more willing to interact socially with him, but rated him as having more negative characteristics than when he was open about his sexual orientation. Participants rated a threatening target more negatively on a thermometer evaluation, perceived him to be more immoral, had more negative affective reactions, and desired more social distance than when the target was nonthreatening. The results are integrated with previous theoretical discussions and are considered in terms of the conflicting motivations of perceivers and targets. [source] Cyclin D1 as a Target for the Proliferative Effects of PTH and PTHrP in Early Osteoblastic CellsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2007Nabanita S Datta MS Abstract PTHrP induced a proliferative cyclin D1 activation in low-density osteoblastic cells. The process was PKA and MAPK dependent and involved both AP-1 and CRE sites. In ectopic ossicles generated from implanted bone marrow stromal cells, PTH upregulated cyclin D1 after acute or intermittent anabolic treatment. These data suggest a positive role of PTH and PTHrP in the cell cycle of early osteoblasts. Introduction: The mechanisms underlying the actions of PTH and its related protein (PTHrP) in osteoblast proliferation, differentiation, and bone remodeling remain unclear. The action of PTH or PTHrP on the cell cycle during osteoblast proliferation was studied. Materials and Methods: Mouse calvarial MC3T3-E1 clone 4 cells were synchronized by serum starvation and induced with 100 nM PTHrP for 2,24 h under defined low serum conditions. Western blot, real-time PCR, EMSAs, and promoter/luciferase assays were performed to evaluate cyclin D1 expression. Pharmacological inhibitors were used to determine the relevant signaling pathways. Ectopic ossicles generated from implanted bone marrow stromal cells were treated with acute (a single 8- or 12-h injection) or intermittent anabolic PTH treatment for 7 days, and RNA and histologic analysis were performed. Results: PTHrP upregulated cyclin D1 and CDK1 and decreased p27 expression. Cyclin D1 promoter/luciferase assays showed that the PTHrP regulation involved both activator protein-1 (AP-1) and cyclic AMP response element binding protein (CRE) sites. AP-1 and CRE double mutants completely abolished the PTHrP effect of cyclin D1 transcription. Upregulation of cyclin D1 was found to be protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) dependent in proliferating MC3T3-E1 cells. In vivo expression of cyclin D1 in ectopic ossicles was upregulated after a single 12-h PTH injection or intermittent anabolic PTH treatment for 7 days in early developing ossicles. Conclusions: These data indicate that PTH and PTHrP induce cyclin D1 expression in early osteoblastic cells and their action is developmental stage specific. [source] Is Atrial Remodeling a Viable Target for Prevention of Atrial Fibrillation Recurrence?JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2004STANLEY NATTEL M.D. [source] Personality Judgments in Adolescents' Families: The Perceiver, the Target, Their Relationship, and the FamilyJOURNAL OF PERSONALITY, Issue 1 2003Susan J. T. Branje The present study investigated whether personality judgments involve different processes in a family setting than in a nonfamily setting. We used the Social Relations Model to distinguish the effects of perceiver, target, perceiver-target relationship, and family on personality judgments. Family members of families with adolescents judged their own and the other members' Big Five factors. Judgments were found to depend on the relevance of personality factors within the family setting: Agreeableness and Conscientiousness were judged most consistently. Large relationship variance indicated that parents adjust their judgments to the target family member; large perceiver variance indicated that adolescents judge family members' personalities rather similarly. However, a comparison of self- and other-judgments showed adolescents' judgments to be no more related to their self-perceptions than parents' judgments. We concluded that the relevance of personality factors may differ on specific tasks within a setting. [source] Multiresidue HPLC analysis of ten quinolones in milk after solid phase extraction: Validation according to the European Union Decision 2002/657/ECJOURNAL OF SEPARATION SCIENCE, JSS, Issue 15 2007Eleni A. Christodoulou Abstract A rapid and sensitive analytical method was developed for the residue analysis of ten quinolones (enoxacin (ENO), ofloxacin (OFL), norfloxacin (NOR), ciprofloxacin (CIP), danofloxacin (DAN), enrofloxacin (ENR), sarafloxacin (SAR), oxolinic acid (OXO), nalidixic acid (NAL), and flumequine (FLU)) in cow's milk. The analytes were extracted from milk by a deproteinization step followed by a simple SPE cleanup procedure using LiChrolut RP-18 Merck cartridges. Recoveries varied between 75 and 92%. HPLC separation was performed at 25°C using an ODS-3 PerfectSil® Target (250×4 mm2) 5 ,m analytical column (MZ-Analysentechnik, Germany). The mobile phase consisted of a mixture of TFA 0.1%,CH3CN,CH3OH, delivered by a gradient program at the flow rate of 1.2 mL/min. Elution of the ten analytes and the internal standard (caffeine, 7.5 ng/,L) was completed within 27 min. Column effluent was monitored using a photodiode array detector, set at 275 and 255 nm. The developed method was validated according to the criteria of Commission Decision 2002/657/EC. The LODs of the specific method of quinolones' determination in milk varied between 1.5 and 6.8 ng/,L. [source] Propofol formulated with long-/medium-chain triglycerides reduces the pain of injection by target controlled infusionACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2006H. Suzuki Background:, Propofol is a widely used intravenous anesthetic although its injection pain is a common and unpleasant problem. Long-/medium-chain triglyceride (LCT/MCT) propofol has been introduced, as its low free propofol content is expected to reduce injection pain compared with LCT propofol. Target controlled infusion (TCI) differs from conventional induction in the initial infusion pattern. During induction using TCI, we investigated injection pain caused by two propofol solutions with different triglyceride compositions. Methods:, Fifty patients, ASA I,II, with adequate communicative ability, were randomly assigned to two groups. TCI was conducted with Diprifusor for LCT and with BeComSim (custom-made software) for LCT/MCT. The target blood concentration was set at 4 ,g/ml for both groups. At 30, 60, and 120 s after the infusion, patients were asked questions regarding the severity of pain on a 0,10 pain score. The total dose of propofol and the time required to induce anesthesia were also investigated. Results:, The LCT/MCT propofol group had a larger number of pain-free patients and showed lower severity of pain than the LCT group [the number of pain-free patients being 11 and 3, respectively (P < 0.05), and median maximum pain being 0 and 4.5, respectively (P < 0.01)]. The dose and time required for induction were not significantly different between the groups (dose of 84 ± 27 and 80 ± 24 mg, respectively, and time of 119 ± 60 and 107 ± 55 s, respectively). Conclusion:, Our study showed that the frequency and severity of pain during TCI induction with propofol could be significantly reduced using LCT/MCT propofol rather than LCT propofol. [source] Editorial: Proteinuria in Chronic Kidney Disease in Cats,Prognostic Marker or Therapeutic Target?JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2006Jonathan Elliott No abstract is available for this article. [source] Target Costing für Werkstoffe , Potenziale und MethodikMATERIALWISSENSCHAFT UND WERKSTOFFTECHNIK, Issue 7 2009U. Götze Target Costing; Materials; Cost Management Abstract Das Target Costing , in der Betriebswirtschaftslehre ein Standardinstrument des Kostenmanagement , findet in der wirtschaftlich orientierten Literatur zu den Werkstoffwissenschaften bisher kaum Erwähnung. Dabei bestehen auch für die Entwickler, Hersteller oder Verwender von Werkstoffen große Potentiale im Hinblick auf die Sicherung bzw. Verbesserung der Wirtschaftlichkeit. Daran setzt der vorliegende Beitrag an. In diesem werden zunächst diese Potentiale eines werkstoffbezogenen Target Costing herausgearbeitet. Dann wird aufgezeigt, wie die allgemeine Methodik des Target Costing aus der Sicht von Werkstoffverwendern einerseits und Werkstoffentwicklern/-herstellern andererseits zu modifizieren ist, um den Besonderheiten von Werkstoffen gerecht zu werden. Target Costing for Materials , Potentialities and Methodology Target Costing is a standard instrument of cost management in business administration, but hardly mentioned in the economic oriented literature on material sciences. Nevertheless there are high potentialities for developers, producers, or users of materials regarding the improvement of efficiency. Therefore, this article will present these potentialities of a material oriented Target Costing. Besides, the general methodology of Target Costing will be modified to meet the specifics of materials from the perspectives of users of materials on the one hand and developers respectively producers of materials on the other. [source] Meeting the Johannesburg TargetNATURAL RESOURCES FORUM, Issue 2 2006JoAnne DiSano Director No abstract is available for this article. [source] Target setting in intensive insulin management is associated with metabolic control: the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005PEDIATRIC DIABETES, Issue 4 2010PGF Swift Swift PGF, Skinner TC, de Beaufort CE, Cameron FJ, Åman J, Aanstoot H-J, Castaño L, Chiarelli F, Daneman D, Danne T, Dorchy H, Hoey H, Kaprio EA, Kaufman F, Kocova M, Mortensen HB, Njølstad PR, Phillip M, Robertson KJ, Schoenle EJ, Urakami T, Vanelli M, Ackermann RW, Skovlund SE for the Hvidoere Study Group on Childhood Diabetes. Target setting in intensive insulin management is associated with metabolic control: the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005. Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. Methods: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. Results: A total of 2062 adolescents completed questionnaires (age 14.4 ± 2.3 yr; diabetes duration 6.1 ± 3.5 yr). Mean HbA 1c = 8.2 ± 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). Conclusions: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres. [source] Evidence that bcl-2 is the Target of Three Photosensitizers that Induce a Rapid Apoptotic Response,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2001David Kessel ABSTRACT We originally proposed that the subcellular target for one class of photosensitizing agents was the mitochondrion. This classification was based on effects that occur within minutes of irradiation of photosensitized cells: rapid loss of the mitochondrial membrane potential (,,m), release of cytochrome c into the cytosol and activation of caspase-3. These effects were followed by the appearance of an apoptotic morphology within 30,90 min. Fluorescence localization studies on three sensitizers initially classified as ,mitochondrial' revealed that these agents bind to a variety of intracellular membranes. The earliest detectable effect of photodamage is the selective loss of the antiapoptotic protein bcl-2 leaving the proapoptotic protein bax undamaged. Bcl-2 photodamage can be detected directly after irradiation of cells at 10°C. Subsequent warming of cultures to 37°C results in loss of ,,m, release of cytochrome c and activation of caspase-3. The latter appears to amplify the other two effects. Based on results reported here we propose that the apoptotic response to these photosensitizers is derived from selective photodamage to the antiapoptotic protein bcl-2 while leaving the proapoptotic protein bax unaffected. [source] Melanin as a Target for Melanoma Chemotherapy: Pro-oxidant Effect of Oxygen and Metals on Melanoma ViabilityPIGMENT CELL & MELANOMA RESEARCH, Issue 3 2003Patrick J. Farmer Melanoma cells have a poor ability to mediate oxidative stress, which may be attributed to constitutive abnormalities in their melanosomes. We hypothesize that disorganization of the melanosomes will allow chemical targeting of the melanin within. Chemical studies show that under oxidative conditions, synthetic melanins demonstrate increased metal affinity and a susceptibility to redox cycling with oxygen to form reactive oxygen species. The electron paramagnetic resonance (EPR)-active 5,5,-dimethyl-pyrollidine N-oxide spin adduct was used to show that binding of divalent Zn or Cu to melanin induces a pro-oxidant response under oxygen, generating superoxide and hydroxyl radicals. A similar pro-oxidant behaviour is seen in melanoma cell lines under external peroxide stress. Melanoma cultures grown under 95% O2/5% CO2 atmospheres show markedly reduced viability as compared with normal melanocytes. Cu- and Zn-dithiocarbamate complexes, which induce passive uptake of the metal ions into cells, show significant antimelanoma activity. The antimelanoma effect of metal- and oxygen-induced stress appears additive rather than synergistic; both treatments are shown to be significantly less toxic to melanocytes. [source] Study of the Cathode Potential in a Sputtering Discharge by Pulsing the Reactive Gas: Case of a W Target in an Ar-O2 AtmospherePLASMA PROCESSES AND POLYMERS, Issue 1 2007Nuno M.G. Parreira Abstract The process we used was d.c. magnetron sputtering, and we studied both the conventional process, using a constant flow of oxygen, and the process in which we pulsed the reactive gas. Square regulation signal with different pulsing periods (T) and oxygen injection time (ton) was used in the reactive gas pulsing (RGP), while the partial argon pressure was kept constant for all depositions. The oxygen flow rate during the injection time was sufficient to switch the process to compound sputtering mode, while the oxygen flow was stopped in the rest of period to allow cleaning of target. Sputtering experiments have shown that the instability phenomena, typical of the reactive sputtering process and known as the "hysteresis effect", are relatively weak due to the small reactivity of tungsten. The influence of the pulsing period and of the oxygen injection time on the deposition parameters is discussed in relation to the poisoning effect. It has been shown that d.c. magnetron sputtering with the oxygen pulsing is a suitable method to prepare tungsten oxide films. This process is very stable, leads to multilayered W-O coatings, and the deposition rates are slightly lower than those of obtained during the conventional process. [source] Positive reinforcement training in rhesus macaques,training progress as a result of training frequencyAMERICAN JOURNAL OF PRIMATOLOGY, Issue 5 2009A.-L. Fernström Abstract Positive reinforcement training (PRT) efficiency was examined as a function of training frequency in 33 pair- or triple-housed female rhesus macaques. The animals were trained three times a week, once a day or twice a day, using PRT and a clicker as a secondary reinforcer. All animals were trained on 30 sessions, with an average of 5,min per training session per animal. The behaviors, trained in succession, were Targeting (reliably touching and following a Target); Collaborating (dominant animals allowing subordinates to train while stationing); Box-training (accepting being enclosed in a small compartment while responding to Target training) and initial Injection training. Fulfilled criteria for Targeting were obtained in 32/33 animals in a median of nine training sessions. Collaboration was obtained in 27/33 animals in a median of 15 training sessions. However, only four animals completed Box-training during the 30 training sessions and started Injection training. When comparing training success in terms of number of training sessions, training twice a day was less efficient than the other two treatments. In terms of daily progress, our results suggest that from a management perspective, daily training is more conducive to quick training success than thrice weekly training. In addition, in this study no further advantages could be gained from training twice a day. Am. J. Primatol. 71:373,379, 2009. © 2009 Wiley-Liss, Inc. [source] Incentive Effects of Stock and Option Holdings of Target and Acquirer CEOsTHE JOURNAL OF FINANCE, Issue 4 2007JIE CAI ABSTRACT Acquisitions enable target chief executive officers (CEOs) to remove liquidity restrictions on stock and option holdings and diminish the illiquidity discount. Acquisitions also enable acquirer CEOs to improve the long-term value of overvalued holdings. Examining all firms during 1993 to 2001, we show that CEOs with higher holdings (illiquidity discount) are more likely to make acquisitions (get acquired). Further, in 250 completed acquisitions, target CEOs with a higher illiquidity discount accept a lower premium, offer less resistance, and more often leave after acquisition. Similarly, acquirer CEOs with higher holdings pay a higher premium, expedite the process, and make diversifying acquisitions using stock payment. [source] Potential Role of NKG2D and Its Ligands in Organ Transplantation: New Target for ImmunointerventionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009B. Suárez-Álvarez NKG2D is one of the best characterized activating receptors on Natural Killer (NK) and CD8+ T cells. This receptor recognizes several different ligands (MICA/MICB and ULBPs) induced by cellular stress and infection. In addition to the role described in cancer surveillance, recent data highlight the importance of NKG2D and its ligands in organ transplantation. Allografts show evidence of MICA and MICB expression in both acute and chronic rejection. The presence of anti-MICA antibodies has been correlated with incidence of graft rejection. Furthermore, NKG2D-ligand engagement activates NK cells, which provides T-cell costimulation, and enhances antigen specific CTL-mediated cytotoxicity. Activated NK cells may function as a bridge between innate and adaptive immunity associated with transplantation. Activated NK cells in response to IL-15 can also trigger organ rejection through NKG2D and affect the maturation of both donor and recipient antigen presenting cells (APCs) and ultimately the T-cell allogeneic response. Regulatory T cells, which modulate T-cell responses in organ transplantation and infections, were reduced in numbers by NK cells exposed to intracellular pathogens, possibly via interaction with one NK2GD receptor. Blockage of NKG2D-NKG2D-L interactions provides a novel pathway for development of inhibitors. These studies have important clinical and therapeutic implications in solid organ transplantation. [source] | ||||||||||||||||||||||||||||||||||||||||||||||||||||