Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance.

Determinants of the recommended dietary allowance (RDA) for vitamin C include the relationship between vitamin C dose and steady-state plasma concentration, bioavailability, urinary excretion, cell concentration, and potential adverse effects. Because current data are inadequate, an in-hospital depletion-repletion study was conducted. Seven healthy volunteers were hospitalized for 4-6 months and consumed a diet containing <5 mg of vitamin C daily. Steady-state plasma and tissue concentrations were determined at seven daily doses of vitamin C from 30 to 2500 mg. Vitamin C steady-state plasma concentrations as a function of dose displayed sigmoid kinetics. The steep portion of the curve occurred between the 30- and 100-mg daily dose, the current RDA of 60 mg daily was on the lower third of the curve, the first dose beyond the sigmoid portion of the curve was 200 mg daily, and complete plasma saturation occurred at 1000 mg daily. Neutrophils, monocytes, and lymphocytes saturated at 100 mg daily and contained concentrations at least 14-fold higher than plasma. Bioavailability was complete for 200 mg of vitamin C as a single dose. No vitamin C was excreted in urine of six of seven volunteers until the 100-mg dose. At single doses of 500 mg and higher, bioavailability declined and the absorbed amount was excreted. Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses. Based on these data and Institute of Medicine criteria, the current RDA of 60 mg daily should be increased to 200 mg daily, which can be obtained from fruits and vegetables. Safe doses of vitamin C are less than 1000 mg daily, and vitamin C daily doses above 400 mg have no evident value.

Identification by representational difference analysis of a homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region.

Homozygous deletions have been central to the discovery of several tumor-suppressor genes, but their finding has often been either serendipitous or the result of a directed search. A recently described technique [Lisitsyn, N., Lisitsyn, N. & Wigler, M. (1993) Science 259, 946-951] held out the potential to efficiently discover such events in an unbiased manner. Here we present the application of the representational difference analysis (RDA) to the study of cancer. We cloned two DNA fragments that identified a homozygous deletion in a human pancreatic adenocarcinoma, mapping to a 1-centimorgan region at chromosome 13q12.3 flanked by the markers D13S171 and D13S260. Interestingly, this lies within the 6-centimorgan region recently identified as the BRCA2 locus of heritable breast cancer susceptibility. This suggests that the same gene may be involved in multiple tumor types and that its function is that of a tumor suppressor rather than that of a dominant oncogene.

Calcareous dinoflagellates in the eastern equatorial Atlantic

Sediments of the Equatorial Atlantic (core GeoB 1105-4) have been investigated for both calcareous dinoflagellates and organic-walled dinoflagellate cysts. In order to determine the ecological affinity of calcareous dinoflagellates the statistical methods of Detrended Correspondence Analysis (DCA) and Redundancy Analysis (RDA) were used. Utilising DCA, distribution patterns of calcareous dinoflagellates have been compared with those of the ecologically much better known organic-walled dinoflagellate cysts. This method was also used to determine which environmental gradients have a major influence on the species composition. By using existing environmental information based on benthic and planktic foraminifera, such as Sea Surface Temperature (SST) and stable oxygen and carbon isotopes, as well as information on the amount of Calcium Carbonate and Total Organic Carbon (TOC) in bottom sediments, these gradients could be interpreted in terms of productivity and glacial-interglacial trends. Using RDA, the direct relationships between the distribution patterns of calcareous dinoflagellates with the above mentioned external variables could be determined. For the studied region and time interval (141-6.7 ka) the calcareous dinoflagellates show enhanced abundances in periods with reduced productivity most probably related to decreased divergence and relatively stratified, oligotrophic oceanic conditions.

Army RD & A.

"Professional publication of the RD & A community."

Samlade skrifter /

Edited by John Lindquist.

Pedagogisk tidskrift.

"Förteckning öfver artiklar införda i Pedagogisk tidskrift årgångarna 1881-1889": v. 26, p. [500]-520.

Negotiating regional futures:the successes and failures of the West Midlands Regional Development Agency Network

The introduction of Regional Development Agencies (RDAs) in the English regions in 1999 presented a new set of collaborative challenges to existing local institutions. The key objectives of the new policy impetus emphasise increased joined-up thinking and holistic regional governance. Partners were enjoined to promote cross-sector collaboration and present a coherent regional voice. This study aims to evaluate the impact of an RDA on the partnership infrastructure of the West Midlands. The RDA network incorporates a wide spectrum of interest and organisations with diverse collaborative histories, competencies and capacities. The study has followed partners through the process over an eighteen-month period and has sought to explore the complexities and tensions of partnership working 'on the ground'. A strong qualitative methodology has been employed in generating 'thick descriptions' of the policy domain. The research has probed beyond the 'rhetoric' of partnerships and explores the sensitivities of the collaboration process. A number of theoretical frameworks have been employed, including policy network theory; partnership and collaboration theory; organisational learning; and trust and social capital. The structural components of the West Midlands RDA network are explored, including the structural configuration of the network and stocks of human and social capital assets. These combine to form the asset base of the network. Three sets of network behaviours are then explored, namely, strategy, the management of perceptions, and learning. The thesis explores how the combination of assets and behaviours affect, and in turn are affected by, each other. The findings contribute to the growing body of knowledge and understanding surrounding policy networks and collaborative governance.

Changing policies for the automotive industry in an 'old' industrial region:an open innovation model for the UK West Midlands?

Automobile manufacture in the UK West Midlands peaked during the 1950s and early 1960s but, with overseas competition, declined thereafter. Successive policies, such as government supported mergers to form the British Motor Corporation in the 1950s, green-field development away from the region in the 1960s, nationalisation of the (then) British Leyland in the 1970s, Japanese FDI in the 1980s and the Rover-centric Accelerate Project in the 1990s have failed to halt the decline. Since early 2000, regional policy has been the responsibility of the Regional Development Agency, Advantage West Midlands. The RDA has moved away from traditional support based on the needs of big companies or ‘champions’ and adopted an approach centred on a mix of small and large businesses and high level research, and – arguably – an ‘open innovation’ model. Here, we examine these new policies and their potential to create an innovative and competitive regional environment.

Representational difference analysis:Critical appraisal and method development for the identification of unique DNA sequences from prokaryotes

Representational difference analysis (RDA) has great potential for preferential amplification of unique but uncharacterised DNA sequences present in one source such as a whole genome, but absent from a related genome or other complex population of sequences. While a few examples of its successful exploitation have been published, the method has not been well dissected and robust, detailed published protocols are lacking. Here we examine the method in detail, suggest improvements and provide a protocol that has yielded key unique sequences from a pathogenic bacterial genome. © 2003 Elsevier Science B.V. All rights reserved.

Application of Regularized Discriminant Analysis

2000 Mathematics Subject Classification: 62H30, 62P99

The health and nutritional status of multiethnic perimenopausal women

An integrated, dual-phase study design assessed the health and nutritional status and practices of African-American (A-A), Caribbean (A-C), and white non-Hispanic (W-A) women during perimenopause (40–55 years). During Phase I, four focus groups (n = 37) of male and female participants discussed the health and social implications of perimenopause. A conceptual framework for the main study (Phase II) was developed from the focus groups' findings, in concert with the main study's specific aims and objectives. ^ The main study, a cross-sectional survey, quantitatively assessed the health and nutritional status of a convenience sample of 109 women (25 A-A, 31 A-C and 53 W-A), who met specific eligibility criteria. Using seven instruments, sociodemographic, dietary, medical, reproductive health, health practice and anthropometric data were collected. ^ The groups were of comparable age, education, and socioeconomic status (SES). Despite these similarities, statistically significant interethnic nutritional status differences were found. Significantly more total energy and energy from fat were consumed by A-A than W-A and A-C women. Also, significantly more A-A and A-C than W-A women were overweight or obese with android-type weight patterning. ^ Overall, iron and calcium Recommended Dietary Allowances (RDA's) were not met by 35% and 68% of participants, respectively. Iron deficiency anemia was reported by 29% of participants while 33% reported heavier menstrual bleeding. Coupled with suboptimal iron intakes, this is likely to present a serious public health problem. Similarly, increased bone demineralization characteristic of perimenopause, coupled with suboptimal calcium intakes could precipitate another public health problem, osteoporosis. ^ Participants had different expectations about the role of medical care during perimenopause. Significantly more white (57%) than black (38% [A-A and AC]) women sought medical attention for symptoms. Whereas Hormone Replacement Therapy (HRT) was prescribed for 25% of them, only 13% were compliant at enrollment. ^ The trends and statistically significant findings of this study have huge public health policy implications. It is imperative that appropriate policies are formulated to ensure that America's ethnically diverse perimenopausal women have ready access to culturally appropriate care. This would optimize their health outcomes, and enhance their quality of life and productive capacities at this critical juncture of their lives. ^

A developmental intervention science outreach research approach to promoting positive youth development

Recent intervention efforts in promoting positive identity in troubled adolescents have begun to draw on the potential for an integration of the self-construction and self-discovery perspectives in conceptualizing identity processes, as well as the integration of quantitative and qualitative data analytic strategies. This study reports an investigation of the Changing Lives Program (CLP), using an Outcome Mediation (OM) evaluation model, an integrated model for evaluating targets of intervention, while theoretically including a Self-Transformative Model of Identity Development (STM), a proposed integration of self-discovery and self-construction identity processes. This study also used a Relational Data Analysis (RDA) integration of quantitative and qualitative analysis strategies and a structural equation modeling approach (SEM), to construct and evaluate the hypothesized OM/STM model. The CLP is a community supported positive youth development intervention, targeting multi-problem youth in alternative high schools in the Miami Dade County Public Schools (M-DCPS). The 259 participants for this study were drawn from the CLP’s archival data file. The model evaluated in this study utilized three indices of core identity processes (1) personal expressiveness, (2) identity conflict resolution, and (3) informational identity style that were conceptualized as mediators of the effects of participation in the CLP on change in two qualitative outcome indices of participants’ sense of self and identity. Findings indicated the model fit the data (χ2 (10) = 3.638, p = .96; RMSEA = .00; CFI = 1.00; WRMR = .299). The pattern of findings supported the utilization of the STM in conceptualizing identity processes and provided support for the OM design. The findings also suggested the need for methods capable of detecting and rendering unique sample specific free response data to increase the likelihood of identifying emergent core developmental research concepts and constructs in studies of intervention/developmental change over time in ways not possible using fixed response methods alone.

Pattern of nutrient availability and plant community assemblage in Everglades Tree Islands, Florida, USA

We address the relative importance of nutrient availability in relation to other physical and biological factors in determining plant community assemblages around Everglades Tree Islands (Everglades National Park, Florida, USA). We carried out a one-time survey of elevation, soil, water level and vegetation structure and composition at 138 plots located along transects in three tree islands in the Park’s major drainage basin. We used an RDA variance partitioning technique to assess the relative importance of nutrient availability (soil N and P) and other factors in explaining herb and tree assemblages of tree island tail and surrounded marshes. The upland areas of the tree islands accumulate P and show low N concentration, producing a strong island-wide gradient in soil N:P ratio. While soil N:P ratio plays a significant role in determining herb layer and tree layer community assemblage in tree island tails, nevertheless part of its variance is shared with hydrology. The total species variance explained by the predictors is very low. We define a strong gradient in nutrient availability (soil N:P ratio) closely related to hydrology. Hydrology and nutrient availability are both factors influencing community assemblages around tree islands, nevertheless both seem to be acting together and in a complex mechanism. Future research should be focused on segregating these two factors in order to determine whether nutrient leaching from tree islands is a factor determining community assemblages and local landscape pattern in the Everglades, and how this process might be affected by water management.

Cognitive competence and life course change in multi-problem adolescents

The dissertation reports on two studies. The purpose of Study I was to develop and evaluate a measure of cognitive competence (the Critical Problem Solving Skills Scale – Qualitative Extension) using Relational Data Analysis (RDA) with a multi-ethnic, adolescent sample. My study builds on previous work that has been conducted to provide evidence for the reliability and validity of the RDA framework in evaluating youth development programs (Kurtines et al., 2008). Inter-coder percent agreement among the TOC and TCC coders for each of the category levels was moderate to high, with a range of .76 to .94. The Fleiss' kappa across all category levels was from substantial agreement to almost perfect agreement, with a range of .72 to .91. The correlation between the TOC and the TCC demonstrated medium to high correlation, with a range of r(40)=.68, p<.001 to r(40)=.79, p<.001. Study II reports an investigation of a positive youth development program using an Outcome Mediation Cascade (OMC) evaluation model, an integrated model for evaluating the empirical intersection between intervention and developmental processes. The Changing Lives Program (CLP) is a community supported positive youth development intervention implemented in a practice setting as a selective/indicated program for multi-ethnic, multi-problem at risk youth in urban alternative high schools in the Miami Dade County Public Schools (M-DCPS). The 259 participants for this study were drawn from the CLP's archival data file. The study used a structural equation modeling approach to construct and evaluate the hypothesized model. Findings indicated that the hypothesized model fit the data (χ2 (7) = 5.651, p = .83; RMSEA = .00; CFI = 1.00; WRMR = .319). My study built on previous research using the OMC evaluation model (Eichas, 2010), and the findings are consistent with the hypothesis that in addition to having effects on targeted positive outcomes, PYD interventions are likely to have progressive cascading effects on untargeted problem outcomes that operate through effects on positive outcomes.

Participation in a positive youth development program and multi -problem alternative high school students' transformative goals: An investigation of the theoretical and methodological utility and validity of the Transformative Goal Attainment (TGAS)

There is a growing body of literature that provides evidence for the efficacy of positive youth development programs in general and preliminary empirical support for the efficacy of the Changing Lives Program (CLP) in particular. This dissertation sought to extend previous efforts to develop and preliminarily examine the Transformative Goal Attainment Scale (TGAS) as a measure of participant empowerment in the promotion of positive development. Consistent with recent advances in the use of qualitative research methods, this dissertation sought to further investigate the utility of Relational Data Analysis (RDA) for providing categorizations of qualitative open-ended response data. In particular, a qualitative index of Transformative Goals, TG, was developed to complement the previously developed quantitative index of Transformative Goal Attainment (TGA), and RDA procedures for calculating reliability and content validity were refined. Second, as a Stage I pilot/feasibility study this study preliminarily examined the potentially mediating role of empowerment, as indexed by the TGAS, in the promotion of positive development. ^ Fifty-seven participants took part in this study, forty CLP intervention participants and seventeen control condition participants. All 57 participants were administered the study's measures just prior to and just following the fall 2003 semester. This study thus used a short-term longitudinal quasi-experimental research design with a comparison control group. ^ RDA procedures were refined and applied to the categorization of open-ended response data regarding participants' transformative goals (TG) and future possible selves (PSQ-QE). These analyses revealed relatively strong, indirect evidence for the construct validity of the categories as well as their theoretically meaningful structural organization, thereby providing sufficient support for the utility of RDA procedures in the categorization of qualitative open-ended response data. ^ In addition, transformative goals (TG) and future possible selves (PSQ-QE), and the quantitative index of perceived goal attainment (TGA) were evaluated as potential mediators of positive development by testing their relationships to other indices of positive intervention outcome within a four-step method involving both analysis of variance (ANOVA and RMANOVAs) and regression analysis. Though more limited in scope than the efforts at the development and refinement of the measures of these mediators, the results were also promising. ^