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The purpose of this study wa~ to deteraine the pharaacokinetics of calcium leucoYorin in nor•al subjects and in patients undergoing High-Dose methotrexa~e therapy for the treat•ent of neoplastic diseaseBy characterizing the disposition of leucovorin it was hoped that the the efficacy of the aethotrexate therapy might be i•proved, while at the sa•e time, the incidence of toxicity could be di•inished. An assay for the separation and quantification of leucovorin in serua was developed. The reduced folate vas extracted from seru• using re•erse-phase chromatographic •inicoluans and a paired-ion reagent. Leucovorin was eluted from this systea in methanol and e•aporated to dryness under nitrogen. The extracted samples were stable for 3 days vhen stored at -4oc. Bigh pressure liquid chroaatoqraphy vas used to separate leuco•orin from the extracted Rerua coaponents using a reverse-phase, paired-ion mode. Aamonium phosphate, dibasic, vas found to be a suitable pairing agent. The recently developed radially coapressed reverse-phase coluans vere found to provide superior resolution of serua components than vas possible with conventional stainless steel columns. The effects of flov rate, pH, column teaperature, and buffer concentration on the separation of leucoYorin vere investigated. Electrochemical detection vas used to quantify the reduced folate in the extracted serum samples. An applied potential of 0.8 volts vas used to produce a sensitive and selective aeans of detecting leucovorin. The apparent lover limit of sensitivity under the conditions employed vas 12 ng leuco•orin. The effects of pH, buffer concentration, methanol concentration, and mobile phase flow rate on detector response vere investigated. The protein binding of leucovorin and its major aetabolite 5-aethyltetrahydrofolate to hu•an serum albumin was determined. Over the concentration range of 5.0x10-78 to 1x10-•K neither folate saturated the available binding sites. Leucovorin binding was a constant 701, vhile aethyltetrahydrofolate decreased slightly over this range. When both folates vere present in the albumin solution, there was a significant decrease in the degree of binding of each. ftethotrexate did not affect the binding of leucovorin or its metabolite. The pharaacokinetics of leucovorin vas determined in 6 noraal subjects and in 5 cancer patient s. There were no siqnif icant differences in the kinetic parameters calculated fro• either group. The disposition of leucovorin is best characterized by a two coapartment open aodel. ln initial half-life of 8.79 ± 4.44 minutes and a second, slower elimination phase of 231.46 ± 31.76 minutes vas determined. The volume of the central compartment vas calculated as 5.49 ± 3.53 Liters. Leucovorin serum concentrations in 3 cancer patients receiving HighDose methotrexate vere deterained to be 3 to 11 times greater than vas predicted using methotrexate pharmacokinetic paraaeters. This study clearly deaonstrates that there are significant differences in the pharmacokinetics of leucovorin and methotrexate. The data presented in this study suggests that it aight be possible to reduce the aaount of leucovorin administered to patients being treated vith met.hotrexate. This may be expected to improve the efficacy of the antimetabolite therapy without additional risk of toxicity. ( ABSTRACT ACKNOilLEDGEftENT TABLE OF CONTENTS LIST OP TABLES LIST OP FIGURES

Additional file 1: Table S1. Core taxa within each lung disease category. Given is prevalence, the number of samples a given core taxon was detected in, and average relative abundance across those samples. Operational taxonomic unit (OTU) identifications have been used for bacterial taxon names. OTU numbers have been used to differentiate between taxa within the same genus. Given the length of the ribosomal sequences analysed, species identities should be considered putative.

Additional file 5: Table S4. PERMANOVA summary statistics from testing for significant differences in microbiota composition between lung function categories. Given in each instance are mean Bray-Curtis similarity within and between categories (± standard deviation of the mean), F-statistic, and significance (P). Asterisks denote significant differences in composition following one-way PERMANOVA tests with Bonferroni correction.

Additional file 2: Table S2. Kruskal-Wallis summary statistics for testing for significant differences in diversity between lung function categories. Given for each test is the mean Fisher's alpha diversity index, standard deviation of the mean, H-statistic, and significance (P), and mean of ranks values. Asterisks denote significant differences in diversity following Kruskal-Wallis with post-hoc Dunn test.

Excessive alcohol consumption can be associated with cognitive impairment not only in drinkers but also in their offspring. Studies of children of alcoholics (COA’s), and particularly of sons of male alcoholics (SOMA’s), have identified a characteristic cognitive profile. COA’s frequently have deficits in verbal skills, classification of verbal and visual stimuli, abstract thinking, and goal-directed planning. SOMA’s show additional deficits in visuospatial abilities, perceptual motor skills, and learning and memory. A model is described that explains how the observed cognitive deficits may contribute to the behavioral problems frequently observed in COA’s and to their risk of becoming alcoholic themselves. However, only some, but not all, COA’s exhibit a cognitive profile predictive of behavioral problems.

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A quality comparison of enlistees under the draft lottery system and enlistees under the all-volunteer force policy is made from data obtained in the Monterey Peninsula, California area of the Eighth Naval Recruiting District. The results indicate that no significant change in quality has occurred during the first four months of the All-Volunteer policy. The implications are that no reduction in the quality of new enlistees is a good indication that the Navy is maintaining a quality status quo, and no increasing trend in quality might reflect the effectiveness of the Navy's program to enlist the highest caliber of recruit needed to form a future smaller, but more professional, naval force. (Author)

This project sought to equip parents of teenagers at Westwood Baptist Church to disciple their teenagers. Chapter 1 introduces Westwood and the project strategy to equip parents. Chapter 2 explores the biblical and theological foundations for parents as the primary disciple-makers of their teenagers. Chapter 3 considers the theoretical, philosophical, and practical issues for parent's discipling their teenagers. Furthermore the chapter addresses how parents can disciple with competence and confidence, and how churches are to equip parents to disciple their teenagers. Chapter 4 discusses the details of the project and how three phases were executed at Westwood. Chapter 5 evaluates the results project and offers personal reflection on the project.