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Biomedical subjects

William A Knaus

Publications and source records attributed to William A Knaus.

8 recordsLinked to original sources

CXC chemokine receptor 3 expression by activated CD8+ T cells is associated with survival in melanoma patients with stage III disease.

Despite the presence of tumor Ag-specific CD8(+) T cells in the peripheral blood, metastatic melanoma often evades immune-mediated destruction. Even after therapeutic efforts to expand Ag-specific T-cell populations, the correlation between magnitude of response and clinical efficacy has been weak. Because the migratory phenotype of tumor Ag-specific effector T cells may determine their ability for tumor control, we hypothesized that the expression of CC or CXC chemokine receptor (CCR) molecules on activated CD8(+) T cells may define phenotypes associated with more effective control of melanoma progression and prolonged survival. In a retrospective evaluation of patient isolates, CCR expression was determined for activated CD8(+) T cells derived from the peripheral blood or tumor-involved lymph nodes of 52 patients with stage III or IV metastatic melanoma. In patients with stage III disease, expression of CXCR3 by CD8(+)CD45RO(+) cells was significantly associated with enhanced survival. This was a stage-specific effect, because it was not observed in patients with stage IV disease. In addition, CCR4 and CXCR3 were highly coexpressed and associated with enhanced survival in stage III patients; however, CXCR3 seems to be the dominant receptor associated with clinical outcome. These findings support the hypothesis that the host immune system affects cancer progression and control, and that measures of CCR status of circulating lymphocytes may have prognostic value.

CD8-Positive T-Lymphocytes↗

Outcomes up to 5 years after severe, acute respiratory failure.

STUDY OBJECTIVE: To use an existing database from a large cohort study with follow-up as long as 5.5 years to assess the extended prognosis of patients who survived their hospitalizations for severe acute respiratory failure (ARF). DESIGN, SETTING, AND PATIENTS: Secondary analysis of an inception cohort of 1,722 patients with ARF requiring mechanical ventilation from five major medical centers who were entered into the prospective Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment. The 1,075 patients (62.4%) who survived hospitalization had systematic follow-up of vital status for a median time of 662 days (interquartile range, 327 to 1,049 days; range, 2 to 2,014 days). Interviews performed a median of 5 months after hospital discharge assessed functional capacity and quality of life (QOL). The main outcome measure was survival after hospital discharge. Secondary measures were functional status and QOL. Cox proportional hazard regression identified factors influencing posthospital survival. RESULTS: The median survival time after hospital discharge for ARF was > 5.3 years. The posthospital survival time was shorter for those with older age, male gender, several preexisting comorbid conditions, worse prehospital functional status, greater acute physiologic derangement, and a do-not-resuscitate order while in the hospital, and for those discharged to a location other than home. Five months after hospital discharge, 48% of survivors needed help with at least one activity of daily living, and 27% rated their QOL as poor or fair. However, most of these impairments were present before respiratory failure occurred. CONCLUSIONS: Extended survival is common among patients with ARF who require mechanical ventilation and who survive hospitalization. Among these patients, only a small fraction of the impairment in activity and QOL can be considered to be a sequela of the respiratory failure or its therapy. These findings are relevant to the care decisions for such critically ill patients.

Activities of Daily Living↗

GeneX Va: VBC open source microarray database and analysis software.

Developed by the Virginia Bioinformatics Consortium (VBC), GeneX Va is an open source, freeware database and bioinformatics analysis software for archiving and analyzing Affymetrix GeneChip data. It provides an integrated framework for management, documentation, and analysis of microarray experiments and data to support a range of users, from individual research laboratories to institutional microarray facilities. GeneX Va also provides web-based access to a PostgreSQL relational database system with a comprehensive security system. Data can be extracted from the database and delivered to interactive or scriptable statistical analysis protocols. The security system allows each investigator to manage their own array data and analysis output files and also provides custom access privileges for other users, groups, and internal/external collaborators. The analysis interface uses "Analysis Trees," an innovative user interface that allows researchers to interactively create a tree-structured flow chart of analysis routines. The latest GeneX Va software is available from and can be freely downloaded at the Sourceforge web site http://va-genex.sourceforge.net. To allow researchers to access the database and analysis capabilities of the GeneX Va system, microarray data from many VBC GeneChip experiments have been deposited into a public section of the GeneX Va system at the University of Virginia. The VBC GeneX Va sites, which include documentation, are at http://genes.med.virginia.edu/ of the University of Virginia and at http://genex.csbc.vcu.edu/ of the Virginia Commonwealth University.

Computer Security↗

A user-centered model for web site design: needs assessment, user interface design, and rapid prototyping.

As the Internet continues to grow as a delivery medium for health information, the design of effective Web sites becomes increasingly important. In this paper, the authors provide an overview of one effective model for Web site design, a user-centered process that includes techniques for needs assessment, goal/task analysis, user interface design, and rapid prototyping. They detail how this approach was employed to design a family health history Web site, Health Heritage . This Web site helps patients record and maintain their family health histories in a secure, confidential manner. It also supports primary care physicians through analysis of health histories, identification of potential risks, and provision of health care recommendations. Visual examples of the design process are provided to show how the use of this model resulted in an easy-to-use Web site that is likely to meet user needs. The model is effective across diverse content arenas and is appropriate for applications in varied media.

Family Health↗