Development and validation of an HPLC method for the rapid and simultaneous determination of 6-mercaptopurine and four of its metabolites in plasma and red blood cells

An HPLC method has been developed and validated for the rapid determination of mercaptopurine and four of its metabolites; thioguanine, thiouric acid, thioxanthine and methylmercaptopurine in plasma and red blood cells. The method involves a simple treatment procedure based on deproteinisation by perchloric acid followed by acid hydrolysis and heating for 45min at 100 degrees C. The developed method was linear over the concentration range studied with a correlation coefficient >0.994 for all compounds in both plasma and erythrocytes. The lower limits of quantification were 13, 14, 3, 2, 95pmol/8 x 10(8) RBCs and 2, 5, 2, 3, 20ng/ml plasma for thioguanine, thiouric acid, mercaptopurine, thioxanthine and methylmercaptopurine, respectively. The method described is selective and sensitive enough to analyse the different metabolites in a single run under isocratic conditions. Furthermore, it has been shown to be applicable for monitoring these metabolites in paediatric patients due to the low volume requirement (200microl of plasma or erythrocytes) and has been successfully applied for investigating population pharmacokinetics, pharmacogenetics and non-adherence to therapy in these patients.

Exploring oxidative modifications of tyrosine:an update on mechanisms of formation, advances in analysis and biological consequences

Protein oxidation is increasingly recognised as an important modulator of biochemical pathways controlling both physiological and pathological processes. While much attention has focused on cysteine modifications in reversible redox signalling, there is increasing evidence that other protein residues are oxidised in vivo with impact on cellular homeostasis and redox signalling pathways. A notable example is tyrosine, which can undergo a number of oxidative post-translational modifications to form 3-hydroxy-tyrosine, tyrosine crosslinks, 3-nitrotyrosine and halogenated tyrosine, with different effects on cellular functions. Tyrosine oxidation has been studied extensively in vitro, and this has generated detailed information about the molecular mechanisms that may occur in vivo. An important aspect of studying tyrosine oxidation both in vitro and in biological systems is the ability to monitor the formation of oxidised derivatives, which depends on a variety of analytical techniques. While antibody-dependent techniques such as ELISAs are commonly used, these have limitations, and more specific assays based on spectroscopic or spectrometric techniques are required to provide information on the exact residues modified and the nature of the modification. These approaches have helped understanding of the consequences of tyrosine oxidation in biological systems, especially its effects on cell signalling and cell dysfunction, linking to roles in disease. There is mounting evidence that tyrosine oxidation processes are important in vivo and can contribute to cellular pathology.

An extension of Lorentz's almost convergence and applications in Banach spaces

2000 Mathematics Subject Classification: Primary 40C99, 46B99.

State legislative term limits and the law of unintended consequences: An examination of member behavior, power structures, and legislative organization in Florida

The implementation of term limits on state legislators has provided a wealth of data for study. Florida, the second largest state in the Union with term limits, has not been comprehensively studied. This research examines the effects of term limits on electoral competition, member composition, legislator career paths, legislative leadership, and intra- and inter-governmental influences on Florida's legislature. This study looks at the Florida legislature from 1992 when term limits were enacted through 2004, three electoral cycles in which term limits have been in effect. This study uses both quantitative and qualitative data where appropriate. Electoral data is used to assess electoral and demographic effects, as well as member career trajectories. Interview data with current and former legislators, lobbyists, and executive branch officials is used to analyze both changes in legislative organization and intra- and inter-governmental influences on the legislative process. Term limits has only created greater competition when a legislative seat opens and has actually created a greater advantage for incumbents. Women and minorities have only made minimal gains in winning seats post-term limits. Newly elected legislators are not political novices with a vast majority having previous elective experience. Leadership is more centralized under term limits and the Senate has gained an advantage over the more inexperienced House. Lastly, the influence of staff, lobbyists, and most importantly, the governor has greatly increased under term limits. This research finds that term limits have not produced the consequences that proponents had envisioned.^

Adaptation in knowledge-based teams: An examination of team composition, leader sensegiving, and cognitive, behavioral, and motivational mechanisms

Organizations are increasingly relying on teams to do the work that has traditionally been done by individuals. At the same time, the environments in which these organizations and teams operate have been becoming progressively more complex and uncertain. These trends raise important questions about the factors that enable teams to adapt. In response to these questions, the current study sought to identify the cognitive, behavioral, and motivational processes and emergent states that promote a team's adaptation to unforeseen changes and novel events, and the team compositional characteristics and leadership processes that enabled these processes and emergent states. Two hundred twenty two undergraduate students from a large Southeastern University composed 74 3-person teams, and participated in a computerized decision-making simulation where each team formed the governing body (i.e., Mayor's cabinet) for two separate simulated cities, and made strategic decisions about city operations. Participants were randomly assigned to one of three roles, distributing expertise and creating mutual interdependence. External team leader sensegiving was manipulated through video recorded communications from an external team leader. Results indicate that team cognitive ability, achievement striving, and psychological collectivism, as well as external team leader sensegiving, were all related to the similarity and quality of team members' strategy-focused mental models (cognitive emergent states), and to the amount of information sharing among members (behavioral process). In turn, teams with more similar and higher quality mental models, and who shared greater levels of information, were found to have a greater ability to react and adapt to environmental changes, and to have greater levels of decision-making effectiveness. Results indicate a pattern of relationships consistent with hypotheses, and have important implications for organizations and knowledge-based teams charged with management responsibilities. Organizations should staff teams with the compositional characteristics that enable the development of similar and high quality mental models, and that promote information sharing among teammates. Similarly, organizations which train and develop leaders to engage in sensegiving behaviors enable team adaptability and promote enhanced decision-making effectiveness when faced with unforeseen changes and novel situations.

An investigation of the relationship between antemortem and postmortem drug concentrations in blood

In the field of postmortem toxicology, principles from pharmacology and toxicology are combined in order to determine if exogenous substances contributed to ones death. In order to make this determination postmortem and (whenever available) antemortem blood samples may be analyzed. This project focused on evaluating the relationship between postmortem and antemortem blood drug levels, in order to better define an interpretive framework for postmortem toxicology. To do this, it was imperative to evaluate the differences in antemortem and postmortem drug concentrations, determine the role microbial activity and evaluate drug stability. Microbial studies determined that the bacteria Escherichia coli and Pseudomonas aeruginosa could use the carbon structures of drugs as a source of food. This would suggest prior to sample collection, microbial activity could potentially affect drug levels. This process however would stop before toxicologic evaluation, as at autopsy blood samples are stored in tubes containing the antimicrobial agent sodium fluoride. Analysis of preserved blood determined that under the current storage conditions sodium fluoride effectively inhibited microbial growth. Nonetheless, in many instances inconsistent drug concentrations were identified. When comparing antemortem to postmortem results, diphenhydramine, morphine, codeine and methadone, all showed significantly increased postmortem drug levels. In many instances, increased postmortem concentrations correlated with extended postmortem intervals. Other drugs, such as alprazolam, were likely to have concentration discrepancies when short antemortem to death intervals were coupled with extended postmortem intervals. While still others, such as midazolam followed the expected pattern of metabolism and elimination, which often resulted in decreased postmortem concentrations. The importance of drug stability was displayed when reviewing the clonazepam/ 7-aminoclonazepam data, as the parent drug commonly converted to its metabolite even when stored in the presence of a preservative. In instances of decreasing postmortem drug concentrations the effect of refrigerated storage could not be ruled out. A stability experiment, which contained codeine, produced data that indicated concentrations could continue to decline under the current storage conditions. The cumulative data gathered for this experiment was used to identify concentration trends, which subsequently aided in the development of interpretive considerations for the specific analytes examined in the study.

An Analysis of the Proposition Density, Sentence and Clause Types, and Non-Finite Verbal Usage in Two College Textbooks

This study investigated the proposition density, sentence and clause type usage and non-finite verbal usage in two college textbooks. The teaching implications are presented.

An investigation of the relationship between maltreatment and alcohol and other drug (AOD) problems in African -American and Hispanic adolescent girls

Maltreatment experienced in childhood or adolescence is a known risk factor for later problem alcohol and/or other drug (AOD) use (Bailey & McCloskey, 2005; Shin, Edwards, Heeren, 2009). A growing body of empirical work has found significant associations between adolescent girls’ AOD use and maltreatment experiences. However, questions remain as to how this relation unfolds with African-American and Hispanic adolescent girls. Guided by four relational models that have been proposed in the literature, this study examined the links between maltreatment, trauma symptoms, and alcohol and/or other drug (AOD) problems in a sample of 170 African-American and Hispanic adolescent girls who were participants in a school-based AOD use intervention. Results of this study revealed that maltreatment experiences (physical and emotional abuse) were positively related to trauma symptoms, which were positively related to AOD problem severity, alcohol abuse, alcohol dependency, drug abuse, and drug dependency. Perceived discrimination moderated this relation between sexual abuse and trauma symptoms, such that more perceived discrimination resulted in a stronger effect of sexual abuse on trauma symptoms. Ethnic identity moderated the relation between sexual abuse and AOD problem severity, such that ethnic identity demonstrated protective properties in the relation between sexual abuse and AOD problem severity. My research adds to extant knowledge on the relation between maltreatment and AOD use in adolescent girls and suggests the importance of developing interventions targeting maltreatment and AOD use concurrently.

Improving magnetic resonance imaging (MRI) examinations : Development and evaluation of an intervention to reduce movement in scanners and facilitate scan completion

© 2015 The British Psychological Society.

Improving magnetic resonance imaging (MRI) examinations : Development and evaluation of an intervention to reduce movement in scanners and facilitate scan completion

© 2015 The British Psychological Society.

"Sexism in the Schools" conference at P.S. 41 about the changing roles of women in Africa and America

General note: Title and date provided by Bettye Lane.

"Sexism in the Schools" conference at P.S. 41 about the changing roles of women in Africa and America

General note: Title and date provided by Bettye Lane.

"Sexism in the Schools" conference at P.S. 41 about the changing roles of women in Africa and America

General note: Title and date provided by Bettye Lane.

An Examination of Lotka’s law in the Field of Library and Information Studies

The purpose of this study was to test Lotka’s law of scientific publication productivity using the methodology outlined by Pao (1985), in the field of Library and Information Studies (LIS). Lotka’s law has been sporadically tested in the field over the past 30+ years, but the results of these studies are inconclusive due to the varying methods employed by the researchers. A data set of 1,856 citations that were found using the ISI Web of Knowledge databases were studied. The values of n and c were calculated to be 2.1 and 0.6418 (64.18%) respectively. The Kolmogorov-Smirnov (K-S) one sample goodness-of-fit test was conducted at the 0.10 level of significance. The Dmax value is 0.022758 and the calculated critical value is 0.026562. It was determined that the null hypothesis stating that there is no difference in the observed distribution of publications and the distribution obtained using Lotka’s and Pao’s procedure could not be rejected. This study finds that literature in the field of library and Information Studies does conform to Lotka’s law with reliable results. As result, Lotka’s law can be used in LIS as a standardized means of measuring author publication productivity which will lead to findings that are comparable on many levels (e.g., department, institution, national). Lotka’s law can be employed as an empirically proven analytical tool to establish publication productivity benchmarks for faculty and faculty librarians. Recommendations for further study include (a) exploring the characteristics of the high and low producers; (b) finding a way to successfully account for collaborative contributions in the formula; and, (c) a detailed study of institutional policies concerning publication productivity and its impact on the appointment, tenure and promotion process of academic librarians.

(Table 4) Distribution of bacterial populations in sediments of ODP Hole 128-798B

Sediment whole-round cores from a dedicated hole (798B) were obtained for detailed microbiological analysis, down to 518 m below the seafloor (mbsf). These sediments have characteristic bacterial profiles in the top 6 mbsf, with high but rapidly decreasing bacterial populations (total and dividing bacteria, and concentrations of different types of viable heterotrophic bacteria) and potential bacterial activities. Rates of thymidine incorporation into bacterial DNA and anaerobic sulfate reduction are high in the surface sediments and decrease rapidly down to 3 mbsf. Methanogenesis from CO2/H2 peaks below the maximum in sulfate reduction and although it decreases markedly down the core, is present at low rates at all but one depth. Consistent with these activities is the removal of pore-water sulfate, methane gas production, and accumulation of reduced sulfide species. Rates of decrease in bacterial populations slow down below 6 mbsf, and there are some distinct increases in bacterial populations and activities that continue over considerable depth intervals. These include a large and significant increase in total heterotrophic bacteria below 375 mbsf, which corresponds to an increase in the total bacterial population, bacterial viability, a small increase in potential rates of sulfate reduction, and the presence of thermogenic methane and other gases. Bacterial distributions seem to be controlled by the availability of terminal electron acceptors (e.g., sulfate), the bioavailability of organic carbon (which may be related to the dark/light bands within the sediment), and biological and geothermal methane production. Significant bacterial populations are present even in the deepest samples (518 mbsf) and hence it seems likely that bacteria may continue to be present and active much deeper than the sediments studied here. These results confirm and extend our previous results of bacterial activity within deep sediments of the Peru Margin from Leg 112, and to our knowledge this is the first comprehensive report of the presence of active bacterial populations from the sediment surface to in excess of 500 mbsf and sediments > 4 m.y. old.