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Biomedical subjects

D Harris

Publications and source records attributed to D Harris.

At least 343 records · Page 19Linked to original sources
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Distributed situation awareness in dynamic systems: theoretical development and application of an ergonomics methodology.

The purpose of this paper is to propose foundations for a theory of situation awareness based on the analysis of interactions between agents (i.e. both human and non-human) in subsystems. This approach may help to promote a better understanding of technology-mediated interaction in systems, as well as helping in the formulation of hypotheses and predictions concerning distributed situation awareness. It is proposed that agents within a system each hold their own situation awareness, which may be very different from (although compatible with) that of other agents. It is argued that we should not always hope for, or indeed want, sharing of this awareness, as different system agents have different purposes. This view marks situation awareness as a dynamic and collaborative process binding agents together on tasks on a moment-by-moment basis. Implications of this viewpoint for the development of a new theory of, and accompanying methodology for, distributed situation awareness are offered.

Awareness↗
PubMedDate not supplied

Sexuality and the adolescent with a physical disability: understandings and misunderstandings.

The purpose of this descriptive study was to examine the areas of sexual knowledge, sexual behavior, and beliefs about sexuality among adolescents with congenital physical disabilities. The sample consisted of 15 males and 14 females, ranging in age from 12 to 22 years. The Sexual Knowledge Interview Schedule (SKIS) was administered to all participants during face-to-face interviews. In addition, the participants were asked questions regarding their ability to engage in intimate relationships and their future childbearing potential. Overall, the findings suggested that these adolescents are uninformed or misinformed about general sexual knowledge, have many misconceptions about sexuality and their disability, and depend on health care professionals and parents for sex education. Implications of this research are discussed.

Adolescent↗
PubMedDate not supplied

Heat-inducible vectors for use in gene therapy.

The objectives of this study were to quantity and compare the activities of a minimal heat shock (HS) promoter and other promoters used in gene therapy applications, and to identify strategies to amplify the heat inducibility of therapeutic genes. Human tumour cells were transiently or stably transfected with the HS promoter driving expression of reporter genes. HS promoter activity was induced transiently, with maximum activity 16-24 h after HS, and was dependent on temperature. The activity of the minimal HS promoter was similar, after 42 degrees C HS for 1 h, to that of the cytomegalovirus (CMV) promoter. To determine if the HS promoter could be used to activate a second conditional promoter, cells were transiently transfected with vectors containing both the HS and human immunodeficiency virus type 1 (HIV1) promoters. When the IL-2 gene was placed downstream of the HIV1 promoter. IL-2 production was temperature-independent. The addition of the HIV tat gene downstream of the HS promoter caused IL-2 to be induced more than 3 fold after a single 42 degrees C HS. These data indicate that the minimal HS promoter, following activation by clinically attainable temperatures (< or = 42 degrees C), can drive expression of therapeutic genes at levels comparable to the CMV promoter and be used in conjunction with a second conditional promoter to drive temperature-dependent, gene expression.

Genes, tat↗
PubMedDate not supplied

Sympathoadrenal and renin-angiotensin systems in the development of two-kidney, one clip renal hypertension in rats.

The relative roles of the sympathetic nervous system and renin-angiotensin system in the development of two-kidney renal hypertension were studied using four groups of rats: Group I = vehicle control; Group II = 6-OH-dopamine (2 weeks prior to renal clipping then weekly throughout the study); Group III = adrenal medullectomy plus vehicle; Group IV = 6-OH-dopamine plus adrenal medullectomy. Six weeks after clipping of a single renal artery, plasma renin activity (PRA) was comparably elevated in all groups. However, mean blood pressure (MBP) of Group II was lower than that of Group I controls (154.7 +/- 6.8 vs 197.3 +/- 6.6 mm Hg respectively). The MBP of Group III (207.0 +/- 5.2 mm Hg) was not different from that of Group I whereas in Group IV (134.2 +/- 18.0 mm Hg) it was markedly lower. All groups of rats were given a single dose of captopril (30 mg/kg p.o.) to inhibit the renin-angiotensin system. Despite differences in starting MBP, captopril caused similar reductions (38-50%) of MBP and increases in PRA in all groups. Similar results were obtained in two-kidney renal hypertensive rats with hypertension of 12 weeks' duration. It is concluded that the sympathetic nervous system does not contribute to the elevated PRA in two-kidney renal hypertensive rats but does contribute significantly to the development of hypertension in this model.

Adrenal Glands↗
PubMedDate not supplied

Comparison between flow cytometric and cytogenetic tumor cell DNA content using a simple flow sample preparation method: ploidy comparison of 86 fresh pediatric tumors.

A comparison of tumor ploidy by flow cytometry (FL) and cytogenetics (CYG) was made in 86 fresh pediatric solid (n = 47) and hematopoietic (n = 39) tumors using simple sampling and semiautomated proprietary FL preparation methods and defined histogram interpretive criteria. Tumor karyotypes with 44-48 chromosomes were regarded as CYG diploid and other chromosomal complements CYG aneuploid for comparison purposes. Five histograms were uninterpretable and nine cases failed to produce 15 or more metaphases for karyotyping. Mean G0/G1 peak coefficients of variation of all 86 cases were 2.7 and 3.0 for the diploid and aneuploid populations, respectively. Of the 72 eligible cases, 41 were concordant diploid and 16 concordant aneuploid with an overall concordance of 79%. The DNA index and karyotypic index correlation coefficient was 0.92 for the 16 concordant aneuploid cases. Analysis of the 15 discordant cases highlights the limitations of both methods and of the histogram interpretive criteria and indicates that FL is probably more sensitive for detection of tumor aneuploidy as defined and detected by these methods.

Aneuploidy↗
PubMedDate not supplied

WP744, a novel anthracycline with enhanced proapoptotic and antileukemic activity.

BACKGROUND: MDR1 or MRP1 drug resistance mechanisms seriously limit the efficacy of anthracyclines such as doxorubicin, in the treatment of acute myeloid leukemia (AML). Our studies indicated that reducing basicity, increasing steric hindrance at C-4', and/or lipophilicity may help circumvent P-glycoprotein (P-gp)-mediated anthracycline efflux and thus increase drug retention in MDR-positive cells. From a series of 4'-substituted analogs, 4'-O-benzylated doxorubicin (WP744) was selected for a comparison with the classic anthracycline doxorubicin for their cytotoxic and pro-apoptotic properties. WP744 retains cytotoxic activity against P-gp and MRP-positive cells. METHODS AND RESULTS: In three AML cell lines (K562, KBM-3, and OCIM2) WP744 was markedly more potent (IC50 values of 0.18, <0.05, and <0.05 microg/ml, respectively) than doxorubicin (IC50 values of >0.5, 0.07, and 0.09 microg/ml, respectively). Likewise, WP744 inhibited the colony formation by AML-CFU cells from fresh bone marrow of three AML patients more strongly than doxorubicin. Cell growth inhibition by WP744 is accompanied by apoptosis induction as shown by TUNEL assay in OCIM2 cells. WP744-induced apoptosis appears to be mediated by caspase-3 as apoptotic changes were abrogated in the presence of the caspase 3 inhibitor Z-DEVD-FMK. Accordingly, caspase 3 activity was elevated in the lysates from drug-treated cells. WP744 induced also cleavage of apoptotic marker poly(ADP-ribose)polymerase (PARP). Finally, WP744 at 0.05 microM and greater was a potent inducer of apoptosis (by quantitative DNA fragmentation) in cultured human acute lymphoblastic leukemia (ALL) CEM cells, compared to 0.5 microM doxorubicin needed for a similar effect. CONCLUSION: The novel anthracycline WP744 was found to be an antileukemic agent with proapoptotic activity superior to that of doxorubicin.

Adult↗
PubMedDate not supplied

Assessment of students.

Assessment can use the written word, the spoken word or practical activity. Often the learner has little idea of the purpose of the assessment or the expectations. Here I present a brief outline for designing assessments and balancing assessment techniques in relation to the purposes and content of the learning experience.

Clinical Competence↗