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Biomedical subjects

J R Harris

Publications and source records attributed to J R Harris.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cancer incidence for Swedish twins studied by means of bivariate frailty models.

Cancer incidence rates for Swedish twins born between 1928 and 1965 and who both were alive at age 30 are studied by means of bivariate frailty models. Altogether, 7,280 fraternal (DZ) and 4,699 identical (MZ) twin pairs were followed up through December 31, 1995, for cancer status. The association between cancer incidence rates was statistically greater among the MZ than among the DZ pairs and stronger between women than between men; however, the magnitude of this association is relatively small and decreases over time. The relative decrease in dependency (association) is most easily detected using shared frailty models but may also be demonstrated, at least for women, using correlated frailty models. We also demonstrate that estimates of the correlation coefficient are similar when using any correlated frailty models derived from the power variance family but that these estimates disagree regarding the age at which the dependence is most important. The relative importance of dependence across age may sometimes be more interesting than the correlation coefficient itself. The latter may usually be estimated using alternative methods. Furthermore, when estimating correlation coefficients close to the boundary of the parameter space, simulation studies indicate that the correlated inverse Gaussian frailty model is more robust than the gamma frailty model.

Adult↗
PubMed2000

Developing an evidence-based Guide to Community Preventive Services--methods. The Task Force on Community Preventive Services.

Systematic reviews and evidence-based recommendations are increasingly important for decision making in health and medicine. Over the past 20 years, information on the science of synthesizing research results has exploded. However, some approaches to systematic reviews of the effectiveness of clinical preventive services and medical care may be less appropriate for evaluating population-based interventions. Furthermore, methods for linking evidence to recommendations are less well developed than methods for synthesizing evidence. The Guide to Community Preventive Services: Systematic Reviews and Evidence-Based Recommendations (the Guide) will evaluate and make recommendations on population-based and public health interventions. This paper provides an overview of the Guide's process to systematically review evidence and translate that evidence into recommendations. The Guide reviews evidence on effectiveness, the applicability of effectiveness data, (i.e., the extent to which available effectiveness data is thought to apply to additional populations and settings), the intervention's other effects (i.e., important side effects), economic impact, and barriers to implementation of interventions. The steps for obtaining and evaluating evidence into recommendations involve: (1) forming multidisciplinary chapter development teams, (2) developing a conceptual approach to organizing, grouping, selecting and evaluating the interventions in each chapter; (3) selecting interventions to be evaluated; (4) searching for and retrieving evidence; (5) assessing the quality of and summarizing the body of evidence of effectiveness; (6) translating the body of evidence of effectiveness into recommendations; (7) considering information on evidence other than effectiveness; and (8) identifying and summarizing research gaps. Systematic reviews of and evidence-based recommendations for population-health interventions are challenging and methods will continue to evolve. However, using an evidence-based approach to identify and recommend effective interventions directed at specific public health goals may reduce errors in how information is collected and interpreted, identify important gaps in current knowledge thus guiding further research, and enhance the Guide users' ability to assess whether recommendations are valid and prudent from their own perspectives. Over time, all of these advantages could help to increase agreement regarding appropriate community health strategies and help to increase their implementation.

Decision Making↗
PubMed2000

Methods for systematic reviews of economic evaluations for the Guide to Community Preventive Services. Task Force on Community Preventive Services.

OBJECTIVES: This paper describes the methods used in the Guide to Community Preventive Services: Systematic Reviews and Evidence-Based Recommendations (the Guide) for conducting systematic reviews of economic evaluations across community health-promotion and disease-prevention interventions. The lack of standardized methods to improve the comparability of results from economic evaluations has hampered the use of data on costs and financial benefits in evidence-based reviews of effectiveness. The methods and instruments developed for the Guide provide an explicit and systematic approach for abstracting economic evaluation data and increase the usefulness of economic information for policy making in health care and public health. METHODS: The following steps were taken for systematic reviews of economic evaluations: (1) systematic searches were conducted; (2) studies using economic analytic methods, such as cost analysis or cost-effectiveness, cost-benefit or cost-utility analysis, were selected according to explicit inclusion criteria; (3) economic data were abstracted and adjusted using a standardized abstraction form; and (4) adjusted summary measures were listed in summary tables. RESULTS: These methods were used in a review of 10 interventions designed to improve vaccination coverage in children, adolescents and adults. Ten average costs and 14 cost-effectiveness ratios were abstracted or calculated from data reported in 24 studies and expressed in 1997 USD. The types of costs included in the analysis and intervention definitions varied extensively. Gaps in data were found for many interventions.

Abstracting and Indexing↗
PubMed2000

Haliotis tuberculata hemocyanin (HtH): analysis of oligomeric stability of HtH1 and HtH2, and comparison with keyhole limpet hemocyanin KLH1 and KLH2.

The multimeric/higher oligomeric states of the two isoforms of Haliotis tuberculata hemocyanin (HtH1 and HtH2) have been assessed by transmission electron microscopy (TEM) of negatively stained specimens, for comparison with previously published structural data from keyhole limpet hemocyanin (KLH1 and KLH2) [see Harris, J.R., Gebauer, W., Guderian, F.U., Markl, J., 1997a. Keyhole limpet hemocyanin (KLH), I: Reassociation from Immucothel followed by separation of KLH1 and KLH2. Micron, 28, 31-41; Harris, J.R., Gebauer, W., Söhngen, S.M., Nermut, M.V., Markl, J., 1997b. Keyhole limpet hemocyanin (KLH). II: Characteristic reassociation properties of purified KLH1 and KLH2. Micron, 28, 43-56; Harris, J.R., Gebauer, W., Adrian, M., Markl, J., 1998. Keyhole limpet hemocyanin (KLH): Slow in vitro reassociation of KLH1 and KLH2 from Immucothel. Micron, 29, 329-339]. In purified samples of both HtH isoforms, the hollow cylindrical ca 8MDa didecamer predominates together with a small number of decamers, but tri- and longer multidecamers are detectable only in the HtH2. The stability of the two HtH isoforms under varying ionic conditions have been monitored, thereby enabling conditions for the production of stable decamers to be established. The ability of these decamers to reform multimers in the presence of 10 and 100mM concentrations of calcium and magnesium ions in Tris-HCl buffer (pH 7.4), and also of individual HtH1 and HtH2 subunits (produced by pH 9.6 dissociation in glycine-NaOH buffer), to reassociate in the presence of calcium and magnesium ions, has been assessed. For the HtH1 decamers, the predominant multimeric product is the didecamer at 10 and 100mM calcium and magnesium concentrations, whereas for the HtH2 decamers, large numbers of multidecamers are produced, with the reaction proceeding more completely at the higher calcium and magnesium concentration. With the HtH1 subunit, reassociation in the presence of 10 and 100mM calcium and magnesium ions yielded an almost 100% conversion into didecamers, whereas the HtH2 subunit produced a mixture containing large numbers of short multidecamers and relatively few didecamers, together with a considerable number of smaller diameter helical/tubular polymers. The association properties of the HtH1 and HtH2 decamers, and the subunit reassociation, firmly indicate the integrity and structural competency of the protein under the experimental conditions used. Data on the association of KLH2 decamers is also presented, which together with previously published data on the association KLH1 decamers and the reassociation of KLH1 and KLH2 subunits, enables a detailed comparison of the two hemocyanin isoforms from both molluscan species to be made. Biochemical manipulation of the oligomer states and the subunit reassociation of molluscan hemocyanins can usefully be assessed by the study of negatively stained TEM specimens.

Animals↗
PubMed2000

The influence of infiltrating lobular carcinoma on the outcome of patients treated with breast-conserving surgery and radiation therapy.

BACKGROUND: The role of conservative surgery and radiation therapy (CS and RT) in the treatment of patients with infiltrating ductal carcinoma is well established. However, the efficacy of CS and RT for patients with infiltrating lobular carcinoma is less well documented. The goal of this study was to examine treatment outcome after CS and RT for patients with infiltrating lobular carcinoma and to compare the results to those of patients with infiltrating ductal carcinoma and patients with mixed ductal-lobular histology. METHODS: Between 1970 and 1986, 1624 patients with Stage I or II invasive breast cancer were treated with CS and RT consisting of a complete gross excision of the tumor and > or = 6000 cGy to the primary site. Slides were available for review for 1337 of these patients (82%). Of these, 93 had infiltrating lobular carcinoma, 1089 had infiltrating ductal carcinoma, and 59 had tumors with mixed ductal and lobular features; these patients constitute the study population. The median follow-up time for surviving patients was 133 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. Additional histologic features assessed for patients with infiltrating lobular carcinoma included histologic subtype, multifocal invasion, stromal desmoplasia, and the presence of signet ring cells. RESULTS: Five and 10-year crude results by site of first failure were similar for patients with infiltrating lobular, infiltrating ductal, and mixed histology. In particular, the 10-year crude local recurrence rates were 15%, 13%, and 13% for patients with infiltrating lobular, infiltrating ductal, and mixed histology, respectively. Ten-year distant/regional recurrence rates were 22%, 23%, and 20% for the three groups, respectively. In addition, the 10-year crude contralateral breast cancer rates were 4%, 13% and 6% for patients with infiltrating lobular, infiltrating ductal and mixed histology, respectively. In a multiple regression analysis which included established prognostic factors, histologic type was not significantly associated with either survival or time to recurrence. CONCLUSIONS: Patients with infiltrating lobular carcinoma have a similar outcome following CS and RT to patients with infiltrating ductal carcinoma and to patients with tumors that have mixed ductal and lobular features. We conclude that the presence of infiltrating lobular histology should not influence decisions regarding local therapy in patients with Stage I and II breast cancer.

Aged↗
PubMed2000

Socialization, personality development, and the child's environments: comment on Vandell (2000).

Although many socialization agents influence children's behavior (D. L. Vandell, 2000), the evidence (e.g., from intervention studies) indicates that each exerts its influence only within its own domain. Context effects and genetic effects are among the confounding factors that make it impossible, given current data, to reject the null hypothesis of zero long-term effects of parenting on child outcomes. Problems with the prevailing view of development cannot be solved by invoking within-home environmental differences or gene- environment interactions. Group socialization theory can account for findings that do not fit the prevailing view. The theory attributes outside-the-home socialization to identification with a peer group and assimilation of group norms, but attributes nongenetic variation in personality to differentiation within the group. The latter proposition is still largely untested but other aspects of the theory are well supported by evidence.

Child↗
PubMed2000

Tracking clinical preventive service use: a comparison of the health plan employer data and information set with the behavioral risk factor surveillance system.

BACKGROUND: There is a need for meaningful and accurate ways of tracking preventive service delivery among different sectors of the US population. OBJECTIVES: To compare methodologies of and clinical preventive service use estimates obtained from 2 data sets: the Health Plan Employer Data and Information Set (HEDIS 3.0) and the Behavioral Risk Factor Surveillance System (BRFSS). METHODS: HEDIS used a combination of mailed-survey, administrative, and medical-record data to measure preventive service use among commercial enrollees of 320 HMOs in 42 states during 1996. BRFSS data are from insured respondents (excluding those reporting Medicare or Medicaid coverage) to a random-digit-dialed telephone survey conducted in the same 42 states during 1996. RESULTS: The median state-specific mammography, Papanicolaou smear, and retinal examination rates reported by HEDIS were consistently and substantially lower than those reported by BRFSS. For mammography, the median HEDIS rate was 72.4%, compared with 81.1% for BRFSS. For Papanicolaou smear and retinal examinations, HEDIS rates were 72.7% and 40.8%, respectively, compared with 91.2% and 61.6% for BRFSS. The median state rates of advice to quit smoking reported by HEDIS were similar to those for BRFSS: 62.1% versus 62.2%, respectively. For each measure, the absolute difference between HEDIS and BRFSS rates varied substantially both within a state and between states. CONCLUSIONS: It does not appear that the BRFSS and HEDIS data can be compared directly to accurately track progress toward national preventive health objectives. This study highlights some of the problems with comparing these data and possible means for addressing the discrepancies.

Adult↗
PubMed2000

Risk factors for nosocomial pneumonia in critically ill trauma patients.

Nosocomial pneumonia is the most common pulmonary complication in trauma patients and the leading cause of death in nosocomial infections. A comprehensive review of pneumonia studies is provided. The Centers for Disease Control's nosocomial pneumonia pathogenesis model is reviewed and was used to guide the selection of risk factors evaluated in this study. The purposes of this research were to identify underlying dimensions (factors) of variables that increase the risk of nosocomial pneumonia and to identify predictors of nosocomial pneumonia in critically ill trauma patients.

Adult↗
PubMed2000

The outcome of parenting: what do we really know?

Lykken's proposal that people should be required to apply for a license before they can become parents is based on his belief that the increase in crime over the past 40 years is due largely to the increase in the number of children reared in fatherless homes. I argue that the absence of a father is a correlate of criminal behavior in the offspring but not its cause. Other correlations that are usually interpreted as the effects of good or bad child-rearing practices are similarly ambiguous and subject to other explanations. I conclude that the increase in crime over the past 40 years cannot be blamed on the absence of fathers or inept child rearing, and offer two alternative hypotheses.

Child↗
PubMed2000

Dense bodies of human cytomegalovirus induce both humoral and cellular immune responses in the absence of viral gene expression.

Infection of fibroblast cell cultures with human cytomegalovirus (HCMV) leads to the production of significant amounts of defective enveloped particles, termed dense bodies (DB). These noninfectious structures contain major antigenic determinants which are responsible for induction of both the humoral and the cellular immune response against HCMV. We tested the hypothesis that, by virtue of their unique antigenic and structural properties, DB could induce a significant immune response in the absence of infectious virus. Mice were immunized with gradient-purified DB, which were either left untreated or subjected to sequential rounds of sonication and freeze-thawing to prevent cellular entry. Titers of neutralizing antibodies induced by DB were in a range comparable to levels present in convalescent human sera. The virus-neutralizing antibody response was surprisingly durable, with neutralizing antibodies detected 12 months following primary immunization. The HCMV-specific major histocompatibility complex class I-restricted cytolytic T-cell (CTL) response was assayed using mice transgenic for the human HLA-A2 molecule. Immunization with DB led to high levels of HCMV-specific CTL in the absence of de novo viral protein synthesis. Maximal total cytolytic activity in mice immunized with DB was nearly as efficient as the cytolytic activity induced by a standard immunization with murine cytomegalovirus. Furthermore, DB induced a typical T-helper 1 (Th1)-dominated immune response in mice, as determined by cytokine and immunoglobulin G isotype analysis. Induction of humoral and cellular immune responses was achieved without the concomitant use of adjuvant. We thus propose that DB can serve as a basis for the future development of a recombinant nonreplicating vaccine against HCMV. Finally, such particles could be engineered for efficient delivery of antigens from other pathogens to the immune system.

3T3 Cells↗
PubMed2000

Keyhole limpet hemocyanin: molecular structure of a potent marine immunoactivator. A review.

OBJECTIVES: In this short review we present a survey of the available biochemical and electron microscopic data on keyhole limpet hemocyanin (KLH). RESULTS: The biosynthesis of KLH and its biological role are discussed and the purification of the two isoforms of KLH (KLH1 and KLH2) presented in some detail. The determination of the molecular mass of KLH, its functional unit structure, carbohydrate content, immunological analysis and aspects of the molecular biology of KLH are all dealt with. Transmission electron microscopy (TEM) and crossed immunoelectrophoresis have played a significant part in the understanding of KLH structure. We present a summary of TEM studies on the native oligomers of KLH, the experimental manipulation of the different oligomeric states, immunological analysis and subunit reassociation. CONCLUSION: This fundamental structural information provides the scientific background upon which the understanding of the in vivo immunostimulatory function of KLH can be based.

Adjuvants, Immunologic↗
PubMed2000

Cost-effectiveness of adding an electron-beam boost to tangential radiation therapy in patients with negative margins after conservative surgery for early-stage breast cancer.

PURPOSE: Electron-beam boosts (EBB) are routinely added after conservative surgery and tangential radiation therapy (TRT) for early-stage breast cancer. We performed an incremental cost-utility analysis to evaluate their cost-effectiveness. METHODS: A Markov model examined the impact of adding an EBB to TRT from a societal perspective. Outcomes were measured in quality-adjusted life years (QALYs). On the basis of the Lyon trial, the EBB was assumed to reduce local recurrences by approximately 2% at 10 years but to have no impact on survival. Patients' utilities were used to adjust for quality of life. Given the small absolute benefit of the EBB, baseline utilities were assumed to be the same with or without it, an assumption evaluated by Monte Carlo simulation. Direct medical, time, and travel costs were considered. RESULTS: Adding the EBB led to an additional cost of $2,008, an increase of 0.0065 QALYs and, therefore, an incremental cost-effectiveness ratio of over $300,000/QALY. In a sensitivity analysis, the ratio was moderately sensitive to the efficacy and cost of the EBB and highly sensitive to patients' utilities for treatment without it. Even if patients do value a small risk reduction, the mean cost-effectiveness ratio estimated by the Monte Carlo simulation remains high, at $70,859/QALY (95% confidence interval, $53,141 to $105,182/QALY). CONCLUSION: On the basis of currently available data, the cost-effectiveness ratio for the EBB is well above the commonly cited threshold for cost-effective care ($50,000/QALY). The EBB becomes cost-effective only if patients place an unexpectedly high value on the small absolute reduction in local recurrences achievable with it.

Adult↗
PubMed2000

Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence.

PURPOSE: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. PATIENTS AND METHODS: The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. RESULTS: At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). CONCLUSION: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.

Adult↗
PubMed2000

Finite element modeling of ROPS in static testing and rear overturns.

Even with the technological advances of the last several decades, agricultural production remains one of the most hazardous occupations in the United States. Death due to tractor rollover is a prime contributor to this hazard. Standards for rollover protective structures (ROPS) performance and certification have been developed by groups such as the Society of Automotive Engineers (SAE) and the American Society of Agricultural Engineers (ASAE) to combat these problems. The current ROPS certification standard, SAE J2194, requires either a dynamic or static testing sequence or both. Although some ROPS manufacturers perform both the dynamic and static phases of SAE J2194 testing, it is possible for a ROPS to be certified for field operation using static testing alone. This research compared ROPS deformation response from a simulated SAE J2194 static loading sequence to ROPS deformation response as a result of a simulated rearward tractor rollover. Finite element analysis techniques for plastic deformation were used to simulate both the static and dynamic rear rollover scenarios. Stress results from the rear rollover model were compared to results from simulated static testing per SAE J2194. Maximum stress values from simulated rear rollovers exceeded maximum stress values recorded during simulated static testing for half of the elements comprising the uprights. In the worst case, the static model underpredicts dynamic model results by approximately 7%. In the best case, the static model overpredicts dynamic model results by approximately 32%. These results suggest the need for additional experimental work to characterize ROPS stress levels during staged overturns and during testing according to the SAE standard.

Accidents, Occupational↗
PubMed2000

Prevalence of germline truncating mutations in ATM in women with a second breast cancer after radiation therapy for a contralateral tumor.

Patients treated with conservative surgery and radiation therapy for early-stage breast cancer develop a contralateral breast cancer at a rate of approximately 0.75% per year. Ataxia-telangiectasia (AT) is an autosomal recessive disease that is characterized by increased sensitivity to ionizing radiation (IR) and cancer susceptibility. Epidemiologic studies have suggested that AT carriers, who comprise 1% of the population, may be at an increased risk for developing breast cancer, particularly after exposure to IR. To test this hypothesis, we analyzed blood samples from 57 patients who developed a contralateral breast cancer at least 6 months after completion of radiation therapy for an initial breast tumor. A cDNA-based truncation assay in yeast was used to test for heterozygous mutations in the ATM gene, which is responsible for AT. No mutations were detected. Our findings fail to support the hypothesis that AT carriers account for a significant fraction of breast cancer cases arising in women after exposure to radiation. Genes Chromosomes Cancer 27:124-129, 2000.

Adult↗