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Biomedical subjects

Mark A Hall

Publications and source records attributed to Mark A Hall.

At least 19 recordsLinked to original sources
PubMed2006

A critical role for the transcription factor Scl in platelet production during stress thrombopoiesis.

The generation of platelets from megakaryocytes in the steady state is regulated by a variety of cytokines and transcription factors, including thrombopoietin (TPO), GATA-1, and NF-E2. Less is known about platelet production in the setting of stress thrombopoiesis, a pivotal event in the context of cytotoxic chemotherapy. Here we show in mice that the transcription factor Scl is critical for platelet production after chemotherapy and in thrombopoiesis induced by administration of TPO. Megakaryocytes from these mice showed appropriate increases in number and ploidy but failed to shed platelets. Ultrastructural examination of Scl-null megakaryocytes revealed a disorganized demarcation membrane and reduction in platelet granules. Quantitative real-time polymerase chain reaction showed that Scl-null platelets lacked NF-E2, and chromatin immunoprecipitation analysis demonstrated Scl binding to the NF-E2 promoter in the human megakaryoblastic-cell line Meg-01, along with its binding partners E47, Lmo2, and the cofactors Ldb1 and GATA-2. These findings suggest that Scl acts up-stream of NF-E2 expression to control megakaryocyte development and platelet release in settings of thrombopoietic stress.

Animals↗
PubMed2006

Policies of academic medical centers for disclosing financial conflicts of interest to potential research participants.

PURPOSE: To document the current state of institutional review board (IRB) and conflict of interest committee policies regarding disclosures of financial conflicts of interest to potential research participants, and to use this information to identify and share models for effectively achieving disclosure. METHOD: The authors identified the 123 U.S. academic medical centers that have IRBs and sought their IRB and institutional policies regarding financial conflicts of interest. In February and March 2004, using manual and key word searches, each institution's Web site was searched to identify documents containing information regarding the disclosure of financial conflicts of interest. Letters were sent to 24 institutions that had either no information or incomplete information posted on their Web sites. To assess institutions' guidelines for disclosure, the authors extracted and content coded each institution's information on disclosure. RESULTS: Relevant information was obtained from 120 (98%) academic medical centers (AMCs), of which 57 (48%) mentioned disclosing financial conflicts to potential research participants. Of these 57, 33 (58%) included verbatim language that could be used in informed consent documents. AMCs' recommendations and requirements for disclosure included details of the financial arrangement, administrative management of conflicts of interest, and encouragement of dialogue between the investigator and the potential research participant. CONCLUSIONS: Considerable variability exists concerning the specific information that should be disclosed. Most of the AMCs' policies were consistent with the goal of protection from legal liability. Significant questions remain, however, concerning the goals of disclosure and the most effective methods for achieving those goals.

Academic Medical Centers↗
PubMed2006

Impact of hemochromatosis screening in patients with indeterminate results: the hemochromatosis and iron overload screening study.

PURPOSE: Assess the quality of life impact of receiving indeterminate test results for hemochromatosis, a disorder involving HFE genetic mutations and/or elevated serum transferrin saturation and ferritin. METHODS: The study sample was from the Hemochromatosis and Iron Overload Screening Study, a large observational study of hemochromatosis among primary care patients in the US and Canada using HFE genotype and serum transferrin saturation and ferritin screening. Study subjects included 2,304 patients found with hemochromatosis risk of uncertain clinical significance. Assessed was SF-36 general health and emotional well-being before screening and six weeks after participants received their test results. Health worries were assessed after screening. RESULTS: Of the study subjects, 1,268 participants (51.5%) completed both assessments. Compared to normal controls, those with HFE mutations or elevated serum transferrin saturation and ferritin levels of uncertain significance were more likely to report diminished general health and mental well-being, and more health worries. These effects were associated with participants' belief of having tested positive for hemochromatosis or iron overload. CONCLUSION: Notification of indeterminate results from screening may be associated with mild negative effects on well-being, and might be a potential participant risk in screening programs for disorders with uncertain genotype-phenotype.

Adult↗
PubMed2006

Measuring trust in medical researchers.

BACKGROUND: Concern is widespread that the public's and participants' trust in medical research is threatened, but few empirical measures of research trust exist. This project aims to enable more rigorous study of researcher trust by developing and testing appropriate survey measures. METHODS: Survey items were developed based on a conceptual model of the primary domains of researcher trust (safety, fidelity, honesty, global trust). Pilot testing was conducted on a regional convenience sample of adults (n = 124). Exploratory factor analyses of the data were performed, and an item selection procedure reduced the number of survey questions. A final set of 12 items was validated, and a 4-item short version of the researcher trust scale was selected and tested in a national web-based survey of asthma and diabetes patients (n = 3623). Further factor analysis and validation were performed on this larger sample. RESULTS: Both the full and short scales have a single-factor structure with acceptable internal reliability (alphas of 0.87 [12 items] and 0.72 [4 items]). Trust in physician researchers and trust in medical researchers generally were found not to be separate constructs. In the national sample, the short scale was positively associated with better health status, prior participation in medical research, and willingness to participate in a hypothetical medical research study, and negatively associated with African-American race and higher education. CONCLUSIONS: Trust in medical researchers is a measurable single-factor construct including trust in safety, researcher fidelity, and honesty. This new scale provides an empirical tool for informing the ethics and public policy of medical research.

Adult↗
PubMed2006

Researching medical trust in the United States.

PURPOSE: This article reviews research in the U.S.A. bearing on trust in physicians and medical institutions. DESIGN/METHODOLOGY/APPROACH: This article provides a conceptual analysis, and general review of the literature. FINDINGS: Empirical research of medical trust is burgeoning in the U.S.A., and a fairly clear conceptual model of interpersonal physician trust has emerged. However, most studies focus on individual patients and their physicians, due to the highly individualistic attitudes that prevail in the U.S.A. Lacking are studies of more social dimensions of trust in broader medical institutions. A conceptual model of trust is presented to help draw these relevant distinctions, and to review the US literature. Also presented are the full set of trust scales, developed at Wake Forest University, which follow this conceptual model. These conceptual categories may differ, however, in other languages and cultures. ORIGINALITY/VALUE: The considerable body of research in the USA on patients' trust in individual physicians should help inform and focus international efforts to study social trust in medical institutions.

Cross-Cultural Comparison↗
PubMed2006

The essential haematopoietic transcription factor Scl is also critical for neuronal development.

Abstract The basic helix-loop-helix (bHLH) transcription factor Scl displays tissue-restricted expression and is critical for the establishment of the haematopoietic system; loss of Scl results in embryonic death due to absolute anaemia. Scl is also expressed in neurons of the mouse diencephalon, mesencephalon and metencephalon; however, its requirement in those sites remains to be determined. Here we report conditional deletion of Scl in neuronal precursor cells using the Cre/LoxP system. Neuronal-Scl deleted mice died prematurely, were growth retarded and exhibited an altered motor phenotype characterized by hyperactivity and circling. Moreover, ablation of Scl in the nervous system affected brain morphology with abnormal neuronal development in brain regions known to express Scl under normal circumstances; there was an almost complete absence of Scl-null neurons in the hindbrain and partial loss of Scl-null neurons in the thalamus and midbrain from early neurogenesis onwards. Our results demonstrate a crucial role for Scl in the development of Scl-expressing neurons, including gamma-aminobutyric acid (GABA)ergic interneurons. Our study represents one of the first demonstrations of functional overlap of a single bHLH protein that regulates neural and haematopoietic cell development. This finding underlines Scl's critical function in cell fate determination of mesodermal as well as neuroectodermal tissues.

Acoustic Stimulation↗
PubMed2006

Views of potential research participants on financial conflicts of interest: barriers and opportunities for effective disclosure.

BACKGROUND: There is little guidance regarding how to disclose researchers' financial interests to potential research participants. OBJECTIVE: To determine what potential research participants want to know about financial interests, their capacity to understand disclosed information and its implications, and the reactions of potential research participants to a proposed disclosure statement. DESIGN AND PARTICIPANTS: Sixteen focus groups in 3 cities, including 6 groups of healthy adults, 6 groups of adults with mild chronic illness, 1 group of parents of healthy children, 1 group of parents of children with leukemia or brain tumor, 1 group of adults with heart failure, and 1 group of adults with cancer. APPROACH: Focus group discussions covered a range of topics including financial relationships in clinical research, whether people should be told about them, and how they should be told. Audio-recordings of focus groups were transcribed, verified, and coded for analysis. RESULTS: Participants wanted to know about financial interests, whether or not those interests would affect their participation. However, they varied in their desire and ability to understand the nature and implications of financial interests. Whether disclosure was deemed important depended upon the risk of the research. Trust in clinicians was also related to views regarding disclosure. If given the opportunity to ask questions during the consent process, some participants would not have known what to ask; however, after the focus group sessions, participants could identify information they would want to know. CONCLUSIONS: Financial interests are important to potential research participants, but obstacles to effective disclosure exist.

Adolescent↗
PubMed2006

Disclosing conflicts of interest in clinical research: views of institutional review boards, conflict of interest committees, and investigators.

Strategies for disclosing investigators' financial interests to potential research participants have been adopted by many research institutions. However, little is known about how decisions are made regarding disclosures of financial interests to potential research participants, including what is disclosed and the rationale for making these determinations. We sought to understand the attitudes, beliefs, and practices of institutional review board chairs, conflict of interest committee chairs, and investigators regarding disclosure of financial interests to potential research participants. Several themes emerged, including general attitudes toward conflicts of interest, circumstances in which financial interests should be disclosed, rationales and benefits of disclosure, what should be disclosed, negative effects of and barriers to disclosure, and timing and presentation of disclosure. Respondents cited several rationales for disclosure, including enabling informed decision making, promoting trust in researchers and research institutions, and reducing legal liability. There was general agreement that disclosure should happen early in the consent process. Respondents disagreed about whether to disclose the amounts of particular financial interests. Clarifying the goals of disclosure and understanding how potential research participants use the information will be critical in efforts to ensure the integrity of clinical research and to protect the rights and interests of participants.

Attitude of Health Personnel↗
PubMed2006

For-profit conversion of Blue Cross plans: public benefit or public harm?

Conversions of Blue Cross plans to for-profit status have the potential to remake the corporate landscape of health care finance. Absent regulatory intervention, current trends could easily result in more than half of Blue Cross subscribers being in for-profit plans, a phenomenon far more significant than the conversion of nonprofit hospitals. Therefore, regulators' deliberations over conversion proposals are beginning to focus on the health policy impacts. This chapter surveys the full range of health policy implications by analyzing all existing studies of Blue Cross conversions and reporting on the authors' own case studies of conversion impacts. These studies conclude that conversions have not caused major negative impacts on the availability or accessibility of health care in the states in which conversions have occurred so far. However, a great deal of uncertainty exists about the actual effects of previous conversions, and each state is unique; therefore, even if the historical record were clear, it is difficult to predict with great certainty what the actual effects will be in another state undergoing a Blue conversion.

Blue Cross Blue Shield Insurance Plans↗
PubMed2006

Employers' liability risk for managed care injuries.

Concerns about employer liability are a major public policy barrier to expanding tort liability for managed health care organizations. To evaluate the extent of these legal concerns, interviews were conducted with key informants, selected to represent a range of legal and demographic characteristics nationwide. These subjects reported a low level of existing concern about liability arising from managed health care, and few indicated that an increase in this threat would likely cause them to drop health benefits. Instead, most said employers would take a wait-and-see approach to theoretical liability threats and would consider responses short of dropping coverage, such as switching to fully insured health benefits, or from defined benefits to defined contributions.

Health Benefit Plans, Employee↗
PubMed2005

Development of abbreviated measures to assess patient trust in a physician, a health insurer, and the medical profession.

BACKGROUND: Despite the recent proliferation in research on patient trust, it is seldom a primary outcome, and is often a peripheral area of interest. The length of our original scales to measure trust may limit their use because of the practical needs to minimize both respondent burden and research cost. The objective of this study was to develop three abbreviated scales to measure trust in: (1) a physician, (2) a health insurer, and (3) the medical profession. METHODS: Data from two samples were used. The first was a telephone survey of English-speaking adults in the United States (N = 1117) and the second was a telephone survey of English-speaking adults residing in North Carolina who were members of a health maintenance organization (N = 1024). Data were analyzed to examine data completeness, scaling assumptions, internal consistency properties, and factor structure. RESULTS: Abbreviated measures (5-items) were developed for each of the three scales. Cronbach's alpha was 0.87 for trust in a physician (test-retest reliability = 0.71), 0.84 for trust in a health insurer (test-retest reliability = 0.73), and 0.77 for trust in the medical profession. CONCLUSION: Assessment of data completeness, scale score dispersion characteristics, reliability and validity test results all provide evidence for the soundness of the abbreviated 5-item scales.

Adult↗
PubMed2005

Gene selection from microarray data for cancer classification--a machine learning approach.

A DNA microarray can track the expression levels of thousands of genes simultaneously. Previous research has demonstrated that this technology can be useful in the classification of cancers. Cancer microarray data normally contains a small number of samples which have a large number of gene expression levels as features. To select relevant genes involved in different types of cancer remains a challenge. In order to extract useful gene information from cancer microarray data and reduce dimensionality, feature selection algorithms were systematically investigated in this study. Using a correlation-based feature selector combined with machine learning algorithms such as decision trees, naïve Bayes and support vector machines, we show that classification performance at least as good as published results can be obtained on acute leukemia and diffuse large B-cell lymphoma microarray data sets. We also demonstrate that a combined use of different classification and feature selection approaches makes it possible to select relevant genes with high confidence. This is also the first paper which discusses both computational and biological evidence for the involvement of zyxin in leukaemogenesis.

Algorithms↗
PubMed2005

Patient acceptability of genotypic testing for hemochromatosis in primary care.

PURPOSE: Genetic screening can enable timely detection and treatment of hereditary hemochromatosis (HH). Little is known about patient acceptability of DNA testing as compared to conventional phenotypic testing. METHODS: Within the HEIRS Study, a large primary-care screening study of HH and iron overload, we randomly assigned participants to receive brief information on either HH genotypic or phenotypic testing, and assessed the willingness to accept this test. The study was designed to recruit an equal number of African Americans and Caucasians. RESULTS: A total of 2500 participants were recruited from waiting rooms of primary care practices; 2165 participants who self-identified as African Americans and Caucasians were included in the analyses. Overall, 56% had accepted a genotypic test versus 58% for a phenotypic test. Adjusting for Field Center (FC), age, gender, race, educational attainment, global health rating, and knowledge of the test, the odds ratio of accepting a genotypic versus phenotypic test was 0.85 (95% CI: 0.71, 1.02; P = 0.078). Characteristics associated with test acceptance were age 45-64 years, female gender, Caucasian race, self-rated health less than ''very good'', and knowledge of the test. Test acceptance was associated with interest in knowing more about health (81%) and in helping family members (71%). Refusal reasons included a need to talk with a doctor (44%), concern about privacy (32%), and dislike of blood drawing (29%). CONCLUSION: In this diverse sample of primary care patients, stated acceptance of genotypic testing for HH mutations was similar to phenotypic testing for blood iron. Patient education regarding the nature of test, importance of disease detection, and privacy protection appear to be essential for achieving high rates of screening participation.

Adult↗
PubMed2005

Impacts of managed care patient protection laws on health services utilization and patient satisfaction with care.

OBJECTIVE: To assess effects of patient protection laws implemented by the vast majority of states during the 1990s on the public's satisfaction and trust relating to health care, and on key utilization measures. DATA SOURCES/STUDY SETTING: Measures of individuals' health care utilization and satisfaction, and control variables, came from three waves of the Community Tracking Study (CTS) Household Surveys conducted in 1996-1997, 1998-1999, and 2000-2001. The CTS was conducted in 60 randomly selected communities, throughout the U.S. In addition, a supplemental national sample of households from CTS was also included, resulting in a combined sample with cases from 48 states and the District of Columbia. After applying exclusion restrictions, the analysis sample was 149,688 adults. STUDY DESIGN: Using a fixed-effects methodology, we assessed the influence of patient protection laws on satisfaction with care and utilization of services for the entire sample and for subsamples of persons in poor health, with low income, and who were enrolled in HMOs. DATA COLLECTION/EXTRACTION METHODS: One of the authors (Hall) compiled relevant laws in all U.S. states through 2001 from primary legal sources, checking for accuracy by conducting independent research on statutory changes and by asking three to five regulators in each state to verify that the information was correct. PRINCIPAL FINDINGS: Overall, patient protection laws had little or no effect on either trust, satisfaction with care, or utilization. Significance was found postenactment of a state patient protection law only for emergency room visits in the general sample, and only for physician trust in the low-income sample. Because of the number of possible associations examined, occasional findings of significance could occur by chance. CONCLUSIONS: Enactment of managed care patient protection laws did not generally increase utilization of health services or improve patient satisfaction with care.

Adolescent↗
PubMed2005

Functional but abnormal adult erythropoiesis in the absence of the stem cell leukemia gene.

Previous studies have indicated that the stem cell leukemia gene (SCL) is essential for both embryonic and adult erythropoiesis. We have examined erythropoiesis in conditional SCL knockout mice for at least 6 months after loss of SCL function and report that SCL was important but not essential for the generation of mature red blood cells. Although SCL-deleted mice were mildly anemic with increased splenic erythropoiesis, they responded appropriately to endogenous erythropoietin and hemolytic stress, a measure of late erythroid progenitors. However, SCL was more important for the proliferation of early erythroid progenitors because the predominant defects in SCL-deleted erythropoiesis were loss of in vitro growth of the burst-forming erythroid unit and an in vivo growth defect revealed by transplant assays. With respect to erythroid maturation, SCL-deleted proerythroblasts could generate more mature erythroblasts and circulating red blood cells. However, SCL was required for normal expression of TER119, one of the few proposed target genes of SCL. The unexpected finding that SCL-independent erythropoiesis can proceed in the adult suggests that alternate factors can replace the essential functions of SCL and raises the possibility that similar mechanisms also explain the relatively minor defects previously observed in SCL-null hematopoietic stem cells.

Aging↗
PubMed2005

The death of managed care: a regulatory autopsy.

On the heels of widespread patient protection legislation in the states, the managed care industry abandoned or greatly scaled back the core elements of gate-keeping, utilization management, and financial incentives, which are the very targets of this legislation. This article explores whether, and to what extent, the industry's abrupt change in course can be attributed to these laws. Based on extensive interviews with key informants in six representative states, the article concludes that these laws were not the primary driver of changes in managed care practices. However, patient protection laws interacted with other social and market forces, through complex forms of feedback and reinforcement, to bring about more thoroughgoing change than would have otherwise occurred.

Gatekeeping↗