An Analysis of Factors Influencing ITC Decisions in Antidumoing, Countervailing Duty and Safeguard Cases

This paper attempts to determine the economic factors that best explain the decisions of the International Trade Commission in antidumping, countervailing duty and safeguard cases, utilizing the economic data collected by the Commission for each investigation. We also consider the extent to which these factors measure the injury conditions and causation relationships specified in U.S. trade laws. Our analyses yield mixed results. For example, while the Commission tends to require declining profits and employment in an industry before recommending import protection in safeguard cases -- as specified in the law, it is not clear that it delineates between serious injury caused by increased imports and serious injury due to other factors. Similarly, in countervailing duty and antidumping cases, economic conditions, such as changes in industry shipments and the degree of capacity utilization, are taken into consideration in material injury decisions, but other factors one would expect to be associated with affirmative decisions, e.g., the ratio of unfair imports to consumption, do not seem to playa significant role. Some variables also enter significantly in the regressions that do not seem to be indicators of material injury.

Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats

The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats

Characterization of Heat Shock Protein A12B as a Novel Angiogenesis Regulator.

Previously, we cloned Heat shock protein A12B (HspA12B), the newest member of a recently defined subfamily of proteins distantly related to the Hsp70 family that are enriched in atherosclerotic lesions. We have found that HspA12B is predominantly expressed in vascular endothelium, and that it is involved in angiogenesis which we probed by in vitro angiogenesis assays (Matrigel), migration assays and Directed In Vivo Angiogenesis Assay (DIVAA). Hsp70s are molecular chaperones that are inducible by stress and have been found to be anti-apoptotic (Li et al. 2000; Nylandsted et al. 2000; Garrido et al. 2001). Because of its homology to Hsp70, we propose that it is the first endothelial-specific chaperone that is required for angiogenesis and interacts with known angiogenesis regulators. To begin to understand the molecular mechanisms underlying the role of HspA12B in angiogenesis, we turned our attention to identifying proteins that are involved in angiogenesis and also interact with HspA12B. Through the use of a yeast two-hybrid (Y2H) system HspA12B was found to interact with a known angiogenesis regulator, A Kinase Anchoring Protein 12 (AKAP12). This interaction was confirmed by co-immunoprecipitation and by colocalization. In primary human umbilical vein endothelial cells (HUVECs), shRNA mediated HspA12B knockdown increased AKAP12 levels and decreased VEGF by more than 75%, whereas HspA12B over-expression decreased AKAP12 and more than doubled VEGF levels. We further identified a 32-Amino Acid (32-AA) domain in AKAP12 that mediates interaction with HspA12B. Over-expression of this 32-AA domain in HUVECs disrupted the HspA12B-AKAP12 interaction and decreased VEGF expression suggesting the importance of the HspA12B-AKAP12 interaction in regulating VEGF. This is the first evidence that HspA12B promotes angiogenesis resulting in up-regulation of VEGF by suppressing AKAP12. Consistent with the proposed role in angiogenesis, HspA12B was also found to be increased in endothelial cells (ECs) by angiogenic stresses including hypoxia and shearing stress while knockdown of HspA12B abolished hypoxia-induced tubule formation. This work provides new insight into the mechanisms controlling angiogenesis by providing the first example of an EC-specific molecular chaperone that acts as a regulator of angiogenesis and lays the foundation for future studies of HspA12B-derived therapeutics for angiogenesis related diseases

Preserving the lost cause through "Dixie's football pride" : the Birmingham News' coverage of the Alabama crimson tide during the core of the civil rights movement, 1961-1966

This study examines college football's role in redefining the American South's regional identity in the century following the Civil War. During this time, southern college football began to resonate in many respects with the Lost Cause -- a set of exaggerated beliefs memorializing the Confederacy's defeat -- due to the sport's shared traditions with the Old South's values of masculinity, honor, and chivalry. Growing tired of national media's backward stereotypes, the University of Alabama's victory over the University of Washington in the 1926 Rose Bowl presented much of the South with the illusion that "northern values" were nonessential components in keeping pace with the rest of America's progress. The reviewed literature provides a historic account of the Deep South and the evolution of southern college football in the nineteenth and twentieth centuries in order to place the state of Alabama and its Crimson Tide football program within the proper sociocultural context for this study. Guided by framing theory, a textual analysis was conducted on 1,407 articles written by the Birmingham News Crimson Tide sportswriters during each college football season between 1961 and 1966. The analysis reveals how the News framed its coverage of arguably the greatest college football dynasty of all time, while the rest of Alabama faced more national scrutiny than any other state for such violent responses to the "threat" of racial equalit

Assessment of chronic pain in companion animals : development and concurrent validation of neurophysiological methods

La douleur est une expérience complexe impliquant des composantes sensorielles et de perception (émotionnelle, affective, cognitive). Elle est associée au stress, de la souffrance et une dégradation de la qualité de la vie. Les affections douloureuses chroniques telles que l'arthrose et le cancer des os touchent les chats et les chiens. La douleur dans ces conditions implique de nombreux mécanismes affectant les systèmes nerveux périphérique et central, qui génèrent et entretiennent une douleur pathologique. Les tests sensoriels quantitatifs (TSQ) sont des outils pour quantifier la composante sensorielle de la douleur, qui peuvent aussi être utilisés pour éluder les mécanismes de la douleur impliquée. Les travaux initiaux sur les chats et les chiens souffrant d'arthrose ont permis de développer et de valider certaines méthodes de TSQ; cependant, quelques questions sont restées sans réponse chez les chats souffrant de l'arthrose, et cette méthodologie n'a pas été encore explorée chez les chiens atteints d’ostéosarcome. Nos hypothèses de recherche étaient: 1) les chats arthrosiques sont affectés par des modifications neurophysiologiques caractéristiques de la sensibilisation centrale, pouvant être détectées par les TSQ et répondant à l'administration d'analgésiques à action centrale; et 2) l’ostéosarcome provoque une sensibilisation périphérique et centrale avec des mécanismes descendants d’inhibition de la douleur déficients chez le chien. Nos objectifs étaient : 1) chez les chats souffrant d'arthrose, de fournir des évidences sur la thérapie basée sur les mécanismes neurophysiologiques à l'aide de TSQ; et 2) de tester la capacité d'un protocole TSQ à démontrer la sensibilisation périphérique et centrale chez les chiens atteints de cancer des os, y compris un test de modulation de la douleur conditionnée, et de tester l’efficacité d’un protocole d’analgésique palliatif par paliers chez ces patients. En utilisant les TSQ statiques et dynamiques chez les chats arthrosiques, nous avons démontré que les analgésiques à action centrale tels que le tramadol peuvent renverser la sensibilisation centrale mesurée par la sommation temporelle de la douleur. Cet effet n’a pas été observé après l’administration d’analgésique à action périphérique tel que les antiinflammatoires non stéroïdiens comme le meloxicam. Ces résultats 3 soulignent l’importance d’une approche de traitement fondée sur les mécanismes de la douleur chronique. Le protocole TSQ développé pour les chiens a révélé que ceux atteints de cancer des os manifestaient de l'hyperalgésie primaire et secondaire et de l’allodynie dynamique au brossage par rapport aux chiens en bonne santé. Un test de modulation de la douleur conditionnée pouvant être facilement appliqué a été mis au point et a démontré la capacité de différencier les chiens sains des chiens cancéreux. En utilisant cette méthodologie, il s’est avéré que cette dernière population démontrait un système descendant d’inhibition de la douleur déficient. Ces études ont fourni des preuves des similitudes dans le profil sensoriel entre les malades humains et les animaux de compagnie affectés par l'arthrose, ainsi que les ostéosarcomiques. Les TSQ sont utiles dans la recherche vétérinaire sur la douleur et doivent être accompagnés des normes les plus strictes en matière de soins des animaux et de conception, de conduite et de compte-rendu des études.Pain is a complex experience involving sensory and perceptual components. It causes stress, suffering and decreased quality of life. Chronic painful conditions such as osteoarthritis (OA) and bone cancer affect cats and dogs. Pain in these conditions results from numerous mechanisms affecting the peripheral and central nervous systems which generate and maintain pathological pain in affected individuals. Quantitative sensory testing (QST) are means to quantify the sensory component of pain. In combination with observed analgesic efficacy, they can be used to study mechanisms of pain. Initial work on cats and dogs with OA has helped to develop and validate some QST methods; however, questions remained unanswered in cats with OA, and this methodology was not yet explored in dogs with bone cancer. Our main hypotheses were: 1) osteoarthritic cats are affected by neurophysiological changes characteristic of central sensitization which can be detected by QST and the concomitant administration of centrally-acting analgesics; and 2) bone cancer in dogs causes peripheral and central sensitization with deficient descending modulating mechanisms. Our main objectives were: 1) to provide evidence of mechanism-based therapy in cats with OA using QST; and 2) to test the ability of a QST protocol to provide evidence of peripheral and central sensitization in dogs with bone cancer including the development and validation of a conditioned pain modulation test, and to test the efficacy of a step-wise palliative analgesic protocol in these patients. Using static and dynamic QST in osteoarthritic cats, we demonstrated that centrally-acting analgesics such as tramadol can reverse central sensitization as measured by facilitated temporal summation of pain, while the same is not observed when a peripherally-acting analgesic such as non-steroidal anti-inflammatory drug, meloxicam, is administered. These findings highlight the importance of mechanism-based approach for the treatment of chronic pain. The QST protocol developed for use in dogs revealed that dogs with bone cancer are affected by primary and secondary hyperalgesia and brush allodynia when compared 5 with healthy dogs. A conditioned pain modulation test which can be easily applied into clinical practice was developed and demonstrated ability to differentiate between healthy and cancerous dogs. Using this methodology, the latter population was found to be affected by deficient descending modulating systems. These studies provided evidence of the similarities in sensory profile between people and companion animals affected by OA- and bone cancer-related pain. The use of QST is valuable in veterinary pain research and should be accompanied by the highest standards of animal care and study design, conduct and reporting

Assessment of a carbon dioxide laser for the measurement of thermal nociceptive thresholds following intramuscular administration of analgesic drugs in pain-free female cats

Objective: To assess the potential for using a thermal carbon dioxide (CO2) laser to 8 assess anti-nociception in pain-free cats. Animals: Sixty healthy adult female cats with a mean weight (± SD) of 3.3 k g (± 0. 6 11 kg). Methods: This is a prospective, blinded and randomised study. Cats were systematically allocated to one of six treatments 1) saline 0.2 ml/cat; 2) morphine 0.5 mg/kg; 3) buprenorphine 20 μg/kg; 4) medetomidine 2 μg/kg; 5) tramadol 2mg/kg; 6) ketoprofen 2 mg/kg. Latency to respond to thermal stimulation was assessed prior to intramuscular injection and at 6 time periods following injection (15-30; 30-45; 45- 18 60; 60-75; 90-105; 120-135 min). Thermal thresholds were assessed using time to respond behaviourally to stimulation with a 500 mW CO2 laser with maximum latency to respond set at 60 seconds. Differences in response latency for each treatment across the duration of the experiment were assessed using a Friedman's test. Differences between treatments at any given time were assessed using an independent Kruskal-Wallis test. Where significant effects were identified, pair-wise comparisons were conducted at 30-45, 60-75 and 120-135 min to further explain the direction of the effect. Results: Cats treated with morphine (χ2 = 12.90; df = 6; P = 0.045) and tramadol (χ2 = 20.28; df = 6; P = 0.002) showed significant increases in latency to respond over the duration of the test period. However, subsequent pairwise comparisons indicated that latencies at specific time points were only significantly different (P < 0.05) for tramadol at 60-75 and 90-105 min after administration. No significant pairwise comparisons were found within the morphine treatment group. Injection of saline, ketoprofen, medetomidine or buprenorphine showed no significant effect on latency to respond. Conclusions: This project further validates the CO 2 laser technique for use in cats. It can be used for assessment of thermal nociceptive thresholds in pain-free cats after analgesic administration and shows some promise in differentiating amongst analgesic treatments. It may provide a simpler alternative to existing systems although further exploration is required both in terms of its sensitivity and comparative utility (i.e. relative to other thermal threshold systems). Future experiments should seek to quantify the effects of skin temperature and sedation on latency to respond. Given that this technique was found to cause minor skin blistering in individuals that reached the 60 s exposure limit, a cut off time of <45 s is recommended

Assessment of Tandem Mass Spectrometry and High Resolution Mass Spectrometry for the Analysis of Bupivacaine in Plasma

Triple quadrupole mass spectrometers coupled with high performance liquid chromatography are workhorses in quantitative bioanalyses. It provides substantial benefits including reproducibility, sensitivity and selectivity for trace analysis. Selected Reaction Monitoring allows targeted assay development but data sets generated contain very limited information. Data mining and analysis of non-targeted high-resolution mass spectrometry profiles of biological samples offer the opportunity to perform more exhaustive assessments, including quantitative and qualitative analysis. The objectives of this study was to test method precision and accuracy, statistically compare bupivacaine drug concentration in real study samples and verify if high resolution and accurate mass data collected in scan mode can actually permit retrospective data analysis, more specifically, extract metabolite related information. The precision and accuracy data presented using both instruments provided equivalent results. Overall, the accuracy was ranging from 106.2 to 113.2% and the precision observed was from 1.0 to 3.7%. Statistical comparisons using a linear regression between both methods reveal a coefficient of determination (R2) of 0.9996 and a slope of 1.02 demonstrating a very strong correlation between both methods. Individual sample comparison showed differences from -4.5% to 1.6% well within the accepted analytical error. Moreover, post acquisition extracted ion chromatograms at m/z 233.1648 ± 5 ppm (M-56) and m/z 305.2224 ± 5 ppm (M+16) revealed the presence of desbutyl-bupivacaine and three distinct hydroxylated bupivacaine metabolites. Post acquisition analysis allowed us to produce semiquantitative evaluations of the concentration-time profiles for bupicavaine metabolites

Caenorhabditis elegans as a model system to identify therapeutics for alcohol use disorders

Alcohol use disorders (AUDs) cause serious problems in society and few effective treatments are available. Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study the neurobiological basis of human behavior with a conserved, fully tractable genome, and a short generation time for fast generation of data at a fraction of the cost of other organisms. C. elegans demonstrate movement toward, and concentration-dependent self-exposure to various psychoactive drugs. The discovery of opioid receptors in C. elegans provided the impetus to test the hypothesis that C. elegans may be used as a medications screen to identify new AUD treatments. We tested the effects of naltrexone, an opioid antagonist and effective treatment for AUDs, on EtOH preference in C. elegans. Six-well agar test plates were prepared with EtOH placed in a target zone on one side and water in the opposite target zone of each well. Worms were treated with naltrexone before EtOH preference testing and then placed in the center of each well. Wild-type worms exhibited a concentration-dependent preference for 50, 70 and 95% EtOH. Naltrexone blocked acute EtOH preference, but had no effect on attraction to food or benzaldehyde in wild-type worms. Npr-17 opioid receptor knockout mutants did not display a preference for EtOH. In contrast, npr-17 opioid receptor rescue mutants exhibited significant EtOH preference behavior, which was attenuated by naltrexone. Chronic EtOH exposure induced treatment resistance and compulsive-like behavior. These data indicate that C. elegans can serve as a model system to identify compounds to treat AUDs

A epidemiologia para o enfermeiro

The subject of this paper emphasizes the uses of Epidemiology to nurses like an essential tool to afford health service assistance and his application in practice. Equally it evidences that epidemiology offers important support to the planning, administration, execution and evaluation of the health service and in addition an extremely useful and essential investigation instrument to his professional formation.Este trabajo resalta la utilización de la epidemiología por el enfermero como un instrumento indispensable a la prestación de servicios de asistencia a la salud u su aplicación en la práctica profesional. Evidencia similarmente que la disciplina ofrece subsídios importantes para el planeamiento, administración, ejecución y avaluación de la prestación de servicios a la salud, siendo todavía un procedimiento extremamente útil en la investigación, lo que torna obligatória en la formación de esse profesional.Este trabalho destaca o uso da epidemiologia pelo enfermeiro com um instrumento indispensável à prestação de serviços de assistência à saúde e sua aplicação na prática profissional. Evidencia igualmente que a disciplina oferece subsídios importantes para o planejamento, administração, execução e avaliação da prestação de serviços à saúde, sendo ainda um instrumento extremamente útil na investigação, o que a torna obrigatória na formação desse profissional