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David Davis

Publications and source records attributed to David Davis.

At least 19 recordsLinked to original sources
PubMed2006

Research to practice in The Journal of Continuing Education in the Health Professions: a thematic analysis of volumes 1 through 24.

INTRODUCTION: Authors have stressed the importance of the broader contextual influences on practice improvement and learning and have expressed concern about gaps between research and practice. This implies a potential expansion of the knowledge base for continuing education in the health professions (CEHP) and an increased emphasis on research evidence for that knowledge. How has the content of The Journal of Continuing Education in the Health Professions (JCEHP) reflected those changes? What are the implications for CEHP practitioners? METHODS: Based on all abstracts, tables of contents, and editorials, a thematic analysis was completed for volumes 1 through 24 of JCEHP. All texts were downloaded into qualitative analysis software and coded. Main code categories included demographics of articles, concepts relating to CEHP as a discipline, knowledge translation and outcomes-oriented continuing education, and theories and frameworks. Key themes were identified. RESULTS: Key themes include categories of topics included in JCEHP over the years, the increased prominence of research in JCEHP, a dual research evidence-to-practice gap, the professionalization of continuing education providers, and interdisciplinarity and the links with broader frameworks that have been proposed for CEHP. DISCUSSION: Two sets of research-to-practice gaps are portrayed in the journal: the gap between clinical research and practice and the gap between research and practice in CEHP. To close the first gap, authors have asserted that the second gap must be addressed, ensuring that CEHP practices themselves are evidence based, driven by theory-based research. This is a variation on prior debates regarding the need to define CEHP as a discipline, which uses the language of professionalization. The increased focus of continuing education on the contexts of health care providers' practices has multiplied the topics that are potentially relevant to CEHP practice.

Education, Medical, Continuing↗
PubMed2006

Neutralization kinetics of sensitive and resistant subtype B primary human immunodeficiency virus type 1 isolates.

The aim of the study was to determine if sensitive and resistant human immunodeficiency virus type 1 (HIV-1) subtype B primary isolates have different neutralization kinetics. Neutralization assays were undertaken where either the time allowed for virus to react with antibodies or the subsequent period of this mixture's exposure to target cells were varied. The relative neutralization sensitivity/resistance is a reproducible property of the isolates. In a minority of combinations, the titre falls exponentially for as long as the free virions are exposed to antibody. In the remainder, neutralization kinetics shows deviations which may be attributed to events occurring after the virus-antibody mixture is added to the target cells: significant neutralization with minimal exposure of the free virions to antibody; a plot where reduction in virus titre is parallel to the duration of the incubation phase of the assay. Neutralization rate constants are similar for primary HIV-1 SF33, HIV-1 SF162, and HIV-1 89.6, reaching 5 x 10(5)-1 x 10(6)/M sec for the monoclonal antibody IgG1 b12. However, although increased antibody levels produced greater reductions in virus titre the rate of neutralization was not proportional to the antibody concentration. Neutralization of either the free virion or cell-associated virus does not correlate with the resistance/sensitivity of primary subtype B isolates. The target cells play an active role, so that in designing neutralization assays with primary isolates of HIV-1, events following the virus-antibody complex binding to the cell surface have to be taken into consideration.

Antibodies, Monoclonal↗
PubMed2006

Transmission of simian immunodeficiency virus SIVcpz and the evolution of infection in the presence and absence of concurrent human immunodeficiency virus type 1 infection in chimpanzees.

Current data suggest that the human immunodeficiency virus type 1 (HIV-1) epidemic arose by transmission of simian immunodeficiency virus (SIV) SIVcpz from a subspecies of common chimpanzees (Pan troglodytes troglodytes) to humans. SIVcpz of chimpanzees is itself a molecular chimera of SIVs from two or more different monkey species, suggesting that recombination was made possible by coinfection of one individual animal with different lentiviruses. However, very little is known about SIVcpz transmission and the susceptibility to lentivirus coinfection of its natural host, the chimpanzee. Here, it is revealed that either infected plasma or peripheral blood mononuclear cells readily confer infection when exposure occurs by the intravenous or mucosal route. Importantly, the presence of preexisting HIV-1 infection did not modify the kinetics of SIVcpz infection once it was established by different routes. Although humoral responses appeared as early as 4 weeks postinfection, neutralization to SIVcpz-ANT varied markedly between animals. Analysis of the SIVcpz env sequence over time revealed the emergence of genetic viral variants and persistent SIVcpz RNA levels of between 10(4) and 10(5) copies/ml plasma regardless of the presence or absence of concurrent HIV-1 infection. These unique data provide important insight into possible routes of transmission, the kinetics of acute SIVcpz infection, and how readily coinfection with SIVcpz and other lentiviruses may be established as necessary preconditions for potential recombination.

Animals↗
PubMed2004

Neutralization of primary HIV-1 SF13 can be detected in extended incubation phase assays with sera from monkeys immunized with recombinant HIV-1 SF2 gp120.

Phase III efficacy trials of recombinant human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins were postponed. In Phase I and II trials these candidate vaccines had failed to induce neutralizing antibodies against virus which had been isolated by co-culture with human peripheral blood mononuclear cells (PBMC). The aim of the present study was to determine assay conditions for detecting neutralization of primary HIV-1 isolates with sera from immunized individuals. We show that in two immunogenicity trials in rhesus macaques, recombinant HIV-1 SF2 gp120 induced antibodies which neutralized the primary HIV-1 SF13 isolate. Statistically significant in vitro neutralization required assays in which the incubation phase was extended. Sterile immunity was only seen with the highest level of neutralization, induced by a recombinant prime, peptide boost strategy. We recommend that neutralization assays with extended incubation phases should be used to monitor Phase III efficacy trials.

AIDS Vaccines↗
PubMed2004

Design and synthesis of hydroxyethylene-based peptidomimetic inhibitors of human beta-secretase.

The hydroxyethylene (HE) transition state isostere was developed as a scaffold to provide potent, small molecule inhibitors of human beta-secretase (BACE). The previous work on the statine series proved critical to the discovery of HE structure-activity relationships. Compound 20 with the N-terminal isophthalamide proved to be the most potent HE inhibitor (IC(50) = 30 nM) toward BACE. Unlike the statine series, we identified HE inhibitors without carboxylic acids on the C terminus, leading to enhanced cell penetration and making them attractive candidates for further drug development in Alzheimer's disease.

Amides↗
PubMed2004

Analysis of a database of materials for HIV prevention program evaluation.

Program evaluation technology transfer is the transfer of information on program evaluation from research to practitioners. There have been anecdotal reports of a lack of technology transfer materials related to HIV prevention program evaluation, especially materials usable by persons without extensive training in evaluation. The Centers for Disease Control and Prevention reviewed available program evaluation materials relevant to HIV prevention and developed a database of those materials. Materials were classified according to appropriate audience, level of evaluation expertise required, steps in the evaluation process addressed, and other criteria. The database was queried to determine the number of materials available for various combinations of search criteria. These queries revealed that for certain audiences and steps in the evaluation process there are few materials, especially usable by individuals without evaluation experience. The conclusion is that for certain areas of program evaluation, and for certain audiences, more evaluation technology transfer materials are needed.

Databases, Factual↗
PubMed2003

The first generation of candidate HIV-1 vaccines can induce antibodies able to neutralize primary isolates in assays with extended incubation phases.

Quantification of human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies is considered to be an important parameter in evaluating candidate vaccines. Most previous studies have failed to detect vaccine-induced antibodies against primary isolates, which are more resistant to antibody mediated neutralization compared with laboratory isolates, in neutralization assays. In this study, sera from a prime boost vaccination strategy of a phase I clinical trial were tested against six clade B primary HIV-1 isolates and single isolates of clades C and F. These sera produced statistically significant neutralization against primary isolates MN, SF13, SF162 and Han 2 but not the most resistant subtype B isolates (92US077 and 93US143) nor the subtype C and F isolates. These data suggest that the sera from vaccinated volunteers have subtype-specific neutralizing antibodies against primary HIV-1 isolates. We recommend using assays with extended incubation phases to monitor current HIV vaccine efficacy trials.

AIDS Vaccines↗
PubMed2003

Differential processing of stromal-derived factor-1alpha and stromal-derived factor-1beta explains functional diversity.

The chemokine stromal-derived factor-1 (SDF-1), which is constitutively expressed in most tissues as SDF-1alpha and SDF-1beta resulting from alternative gene splicing, regulates hematopoiesis, lymphocyte homing, B-lineage cell growth, and angiogenesis. Because SDF-1alpha and SDF-1beta are constitutively and ubiquitously expressed, their degradation must serve an important regulatory role. Here we show that SDF-1alpha and SDF-1beta are secreted as full-length molecules. When exposed to human serum, full-length SDF-1alpha (1-68) undergoes processing first at the COOH terminus to produce SDF-1alpha 1-67 and then at the NH2 terminus to produce SDF-1alpha 3-67. By contrast, full-length SDF-1beta (1-72) is processed only at the NH2 terminus to produce SDF-1beta 3-72. CD26/dipeptidyl peptidase is responsible for serum cleavage of SDF-1alpha and SDF-1beta at the NH2 terminus. Serum processing of SDF-1alpha at the COOH terminus, which has not been previously reported, reduces the ability of the polypeptide to bind to heparin and to cells and to stimulate B-cell proliferation and chemotaxis. The additional processing at the NH2 terminus renders both forms of SDF-1 unable to bind to heparin and to activate cells. The differential processing of SDF-1alpha and SDF-1beta provides biologic significance to the existence of 2 splice forms of the chemokine and adds a tool to precisely regulate SDF-1's biologic activity by changes in specific activity.

Alternative Splicing↗
PubMed2003

Serum inactivation contributes to the failure of stromal-derived factor-1 to block HIV-I infection in vivo.

The chemokine stromal-derived factor-1 (SDF-1) can block human immunodeficiency virus type 1 (HIV-1) infection in vitro by binding to the CXC chemokine receptor, CXCR-4, which serves as a coreceptor for T cell tropic HIV-1. In spite of being constitutively expressed in vivo, SDF-1 does not appear to block HIV-1 infection and spread in vivo. We report that SDF-1 is consistently measured in normal serum (15.4+/-3.0 ng/ml; mean+/-sd) and in serum from AIDS patients (16.6+/-3.7 ng/ml). However, we find that circulating SDF-1 is modified to an inactive form. When exposed to serum, recombinant SDF-1 is specifically and rapidly altered to yield an apparently smaller chemokine that does not bind to SDF-1 receptor-expressing cells, does not have chemoattractive or pre-B cell stimulatory activity, and does not block HIV-1 infection. Thus, serum modification and inactivation contribute to the failure of SDF-1 to block HIV-1 infection and spread in man. The inactivation of circulating SDF-1 may be critical in permitting local gradients to develop and direct cell trafficking.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Inter-subtype cross-neutralizing antibodies recognize epitopes on cell-associated HIV-1 virions.

HIV-1 infected individuals with cross-neutralizing antibodies against primary HIV-1 isolates belonging to Group M (envA-H) and O, are identified. To investigate the neutralization-kinetics of primary isolates with these antibodies, different neutralization assay conditions are compared. Each set is summarized as a/b/c where a is the time in hours for which antibody is incubated with virus, b is the time in hours allowed for virus to absorb to cells, c is the total culture period in days, from the cells' first exposure to virus, before antigen production (peripheral blood mononuclear cells) or number of fluorescent cells (GHOST) are measured. In HIV-infected individuals, neutralizing antibodies can be detected against a wide range of primary isolates (Group M; A-H and Group O) in PBMC-assays with short incubation phases (1/2/7 or 1/24/7). If cultures are extended (1/2/14 or 1/24/14), however, neutralization can be lost. In kinetic experiments, neutralization can even be seen without pre-incubation (a=0 hr). This study shows that neutralization of primary HIV isolates by cross-reactive antibodies can continue after the virus has bound to its target cell. This neutralization, however, is not an all or nothing loss in virus infectivity. Most often it leads only to a reduction in viral replication rates.

Cell Line↗
PubMed2003

Epitopes corresponding to the envelope genetic subtype are present on the surface of free virions of HIV-1 group M primary isolates and can be detected in neutralization assays with extended incubation phases.

The hypothesis is that there are neutralizing epitopes on the surface of free virions of human immunodeficiency virus type 1 (HIV-1) that correspond to the genetic subtype of the envelope glycoprotein. Assays with extended incubation and reduced absorption phases are required to demonstrate neutralization with antibodies to these epitopes. These assays quantify virus infectivity, rather than reductions in release of antigen into culture supernatants. Neutralizing antibodies reduce virus infectivity by at least 80%, as scored by the presence/absence of antigen released after 14 days in culture of mitogen-transformed peripheral blood mononuclear cells (PBMCs). The epitopes are shared within different subtypes of group M, but not group O, isolates. Individual plasma, selected from three, independent panels of seropositive individuals, cross-neutralize within each subtype as well as the combinations of A with C, B with D or G, and C with CRF01_AE. Isolates within subtype B show the greatest variation in their resistance to neutralization, ranging from highly sensitive to highly resistant. No highly sensitive subtype D isolates were identified. Isolates from subtypes A, C, and CRF01_AE were all resistant. The strategic implication for vaccine design is that antibodies to a limited number of epitopes can neutralize more than 90% of the HIV-1 isolates that are circulating currently in the world. Also, since only antibodies that produce an all-or-nothing loss in virus infectivity can reasonably be expected to prevent the viremic phase after in vivo infection, assays with extended incubation, and culture phases should be used to monitor current efficacy trials.

Cross Reactions↗
PubMed2002

In vitro susceptibility to infection with SIVcpz and HIV-1 is lower in chimpanzee than in human peripheral blood mononuclear cells.

This study was undertaken to evaluate and compare the susceptibility of chimpanzee versus human peripheral blood mononuclear cells (PBMCs) to infection with SIVcpz and HIV-1 non-syncitium inducing primary isolates. The results demonstrate clearly that chimpanzee PBMCs have a lower capacity to support viral replication as compared to human PBMCs. There was no experimental evidence that this difference was due to a lower availability of target cells for viral infection (PBMCs positive for CD4 and CCR5 molecules) or to a differential susceptibility to apoptosis (PBMCs positive for CD4 and CD95 molecules). A lower capacity of chimpanzee PBMCs to support SIVcpz and HIV-1 replication in vitro is related to a post-entry barrier to virus replication.

Animals↗
PubMed2002

Intravirion processing of the human immunodeficiency virus type 1 Vif protein by the viral protease may be correlated with Vif function.

The human immunodeficiency virus type 1 (HIV-1) Vif protein is specifically packaged into virus particles through an interaction with viral genomic RNA in which it associates with the viral nucleoprotein complex. We now demonstrate for the first time that virus-associated Vif is subject to proteolytic processing by the viral protease (Pr). Pr-dependent processing of Vif was observed both in vivo and in vitro. In vivo processing of Vif was cell type independent and evident by the appearance of a 7-kDa processing product, which was restricted to cell-free virus preparations. Processing of Vif required an active viral Pr and was sensitive to Pr inhibitors such as ritonavir. The processing site in Vif was characterized both in vivo and in vitro and mapped to Ala(150). Interestingly, the Vif processing site is located in a domain that is highly conserved among HIV-1, HIV-2, and simian immunodeficiency virus Vif isolates. Mutations at or near the processing site did not affect protein stability or packaging efficiency but had dramatic effects on Vif processing. In general, mutations that markedly increased or decreased the sensitivity of Vif to proteolytic processing severely impaired or completely abolished Vif function. In contrast, mutations at the same site that had little or no effect on processing efficiency also did not influence Vif function. None of the mutants affected the ability of the virus to replicate in permissive cell lines. Our data suggest that mutations in Vif that cause a profound change in the sensitivity to Pr-dependent processing also severely impaired Vif function, suggesting that intravirion processing of Vif is important for the production of infectious viruses.

Amino Acid Sequence↗
PubMed2002

The value of engaging stakeholders in planning and implementing evaluations.

Stakeholder participation in evaluation has surfaced as a major factor contributing to the effectiveness of HIV prevention programs. In recognition of the multiple benefits, the Centers for Disease Control and Prevention (CDC), has used a framework to involve stakeholders in the evaluation of its programs. This article describes the framework used by the CDC and provides examples of four studies that involved various stakeholders from health departments, community-based organizations, and community planning groups to national and regional organizations in designing and implementing evaluations that yielded results useful for program improvement. The participatory process involved stakeholders in each of the four phases of the framework: evaluation planning, implementation, development of action plans, and dissemination. Lessons learned include the importance of having a facilitator to coordinate activities and ongoing communication with those involved in the evaluation. Stakeholders shared that using the evaluation results for action planning was beneficial for improving their programs. Despite many challenges faced in the stakeholder evaluation process, most stakeholders agreed that many benefits grew out of the multiple perspectives presented and understanding of the service agencies.

Centers for Disease Control and Prevention, U.S.↗
PubMed2002

Use of the Internet as a research method in a study of the emotional effects of tooth loss in Poland.

The study explored the use of the Internet to investigate the emotional effects of tooth loss in a Polish population. The Internet was used as a novel method of recruiting study participants. The study was announced on Internet pages in the Polish language inviting anyone who had lost some natural teeth to respond. Respondents were sent a questionnaire by e-mail, which they completed and returned by the same means. Twenty nine completed questionnaires were received in a twelve month period. The respondents were predominantly males under the age of 50 years reflecting the profile of Internet users in Poland. Despite the sample bias, the results showed a trend similar to the findings of earlier studies into the emotional effects of tooth loss with many of the respondents reporting difficulty in coming to terms with the loss of some or all their natural teeth.

Anger↗