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Biomedical subjects

J D Singer

Publications and source records attributed to J D Singer.

At least 19 recordsLinked to original sources
PubMed2001

The effect of medical education on primary care orientation: results of two national surveys of students' and residents' perspectives.

PURPOSE: To examine changes among a nationally representative sample of students and residents in their orientations toward primary care as reflected in their attitudes toward the psychosocial and technical aspects of medicine and their perceptions of the academic environment for primary care. METHOD: Confidential telephone interviews of stratified national probability samples of first- and fourth-year medical students and residents were conducted in 1994 and 1997. The 1997 survey included 219 students and 241 residents who had also been interviewed in 1994. Participants were asked about their attitudes toward addressing psychosocial issues in medicine and their perceptions of faculty and peer attitudes toward primary care. Responses were compared over time and across groups. RESULTS: Between the first and fourth years of medical school, there was a decline over time in students' reported orientations to socioemotional aspects of patient care (61.6% versus 42.7%, p =.001) and their perceptions that working with psychosocial issues of patients made primary care more attractive (56.3% versus 43.5%, p =.01). This pattern continued for 1997 residents (PGY-3), who were even less likely to say that addressing psychosocial issues made primary care more attractive (26.9%). For fourth-year students in 1994 who became PGY-3 residents in 1997, there was an increased perception that non-primary-care house officers and specialty faculty had positive attitudes toward primary care (20.8% versus 33.0%, p =.005; 28.3% versus 45.7%, p <.0001; respectively). CONCLUSIONS: Between 1994 and 1997 students and residents perceived a positive shift in the attitudes of peers and faculty toward primary care. During the course of their education and training, however, the students experienced an erosion of their orientations to primary care as they progressed through medical school into residency.

Adult↗
PubMed2000

Proteasomal turnover of p21Cip1 does not require p21Cip1 ubiquitination.

The Cdk inhibitor p21Cip1 is an unstable protein. Pharmacologic inhibition of the proteasome increases the half-life of p21 from less than 30 min to more than 2 hr and results in the accumulation of p21-ubiquitin conjugates. To determine whether ubiquitination was required for proteasomal degradation of p21, we constructed mutant versions of p21 that were not ubiquitinated in vivo. Remarkably, these mutants remained unstable and increased in abundance upon proteasome inhibition, indicating that direct ubiquitination of p21 is not necessary for its turnover by the proteasome. The frequently observed correlation between protein ubiquitination and proteasomal degradation is insufficient to conclude that ubiquitination is a prerequisite for degradation.

3T3 Cells↗
PubMed1999

Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells.

Cyclin E is an unstable protein that is degraded in a ubiquitin- and proteasome- dependent pathway. Two factors stimulate cyclin E ubiquitination in vivo: when it is free of its CDK partner, and when it is phosphorylated on threonine 380. We pursued the first of these pathways by using a two-hybrid screen to identify proteins that could bind only to free cyclin E. This resulted in the isolation of human Cul-3, a member of the cullin family of E3 ubiquitin-protein ligases. We found that Cul-3 was bound to cyclin E but not to cyclin E-Cdk2 complexes in mammalian cells, and that overexpression of Cul-3 increased ubiquitination of cyclin E but not other cyclins. Conversely, deletion of the Cul-3 gene in mice caused increased accumulation of cyclin E protein, and had cell-type-specific effects on S-phase regulation. In the extraembryonic ectoderm, in which cells undergo a standard mitotic cycle, there was a greatly increased number of cells in S phase. In the trophectoderm, in which cells go through endocycles, there was a block to entry into S phase. The SCF pathway, which targets cyclins for ubiquitination on the basis of their phosphorylation state, and the Cul-3 pathway, which selects cyclin E for ubiquitination on the basis of its assembly into CDK complexes, may be complementary ways to control cyclin abundance.

3T3 Cells↗
PubMed1999

Views of managed care--a survey of students, residents, faculty, and deans at medical schools in the United States.

BACKGROUND AND METHODS: Views of managed care among academic physicians and medical students in the United States are not well known. In 1997, we conducted a telephone survey of a national sample of medical students (506 respondents), residents (494), faculty members (728), department chairs (186), directors of residency training in internal medicine and pediatrics (143), and deans (105) at U.S. medical schools to determine their experiences in and perspectives on managed care. The overall rate of response was 80.1 percent. RESULTS: Respondents rated their attitudes toward managed care on a 0-to-10 scale, with 0 defined as "as negative as possible" and 10 as "as positive as possible." The expressed attitudes toward managed care were negative, ranging from a low mean (+/-SD) score of 3.9+/-1.7 for residents to a high of 5.0+/-1.3 for deans. When asked about specific aspects of care, fee-for-service medicine was rated better than managed care in terms of access (by 80.2 percent of respondents), minimizing ethical conflicts (74.8 percent), and the quality of the doctor-patient relationship (70.6 percent). With respect to the continuity of care, 52.0 percent of respondents preferred fee-for-service medicine, and 29.3 percent preferred managed care. For care at the end of life, 49.1 percent preferred fee-for-service medicine, and 20.5 percent preferred managed care. With respect to care for patients with chronic illness, 41.8 percent preferred fee-for-service care, and 30.8 percent preferred managed care. Faculty members, residency-training directors, and department chairs responded that managed care had reduced the time they had available for research (63.1 percent agreed) and teaching (58.9 percent) and had reduced their income (55.8 percent). Overall, 46.6 percent of faculty members, 26.7 percent of residency-training directors, and 42.7 percent of department chairs reported that the message they delivered to students about managed care was negative. CONCLUSIONS: Negative views of managed care are widespread among medical students, residents, faculty members, and medical school deans.

Administrative Personnel↗
PubMed1998

The design and analysis of longitudinal studies of development and psychopathology in context: statistical models and methodological recommendations.

The utility and flexibility of recent advances in statistical methods for the quantitative analysis of developmental data--in particular, the methods of individual growth modeling and survival analysis--are unquestioned by methodologists, but have yet to have a major impact on empirical research within the field of developmental psychopathology and elsewhere. In this paper, we show how these new methods provide developmental psychopathologists with powerful ways of answering their research questions about systematic changes over time in individual behavior and about the occurrence and timing of life events. In the first section, we present a descriptive overview of each method by illustrating the types of research questions that each method can address, introducing the statistical models, and commenting on methods of model fitting, estimation, and interpretation. In the following three sections, we offer six concrete recommendations for developmental psychopathologists hoping to use these methods. First, we recommend that when designing studies, investigators should increase the number of waves of data they collect and consider the use of accelerated longitudinal designs. Second, we recommend that when selecting measurement strategies, investigators should strive to collect equatable data prospectively on all time-varying measures and should never standardize their measures before analysis. Third, we recommend that when specifying statistical models, researchers should consider a variety of alternative specifications for the time predictor and should test for interactions among predictors, particularly interactions between substantive predictors and time. Our goal throughout is to show that these methods are essential tools for answering questions about life-span developmental processes in both normal and atypical populations and that their proper use will help developmental psychopathologists and others illuminate how important contextual variables contribute to various pathways of development.

Adolescent↗
PubMed1998

Early child-care selection: variation by geographic location, maternal characteristics, and family structure.

More than half of all U.S. infants and toddlers spend at least 20 hr per week in the care of a nonparent adult. This article uses survival analysis to identify which families are most likely to place their child in care and the ages when these choices are made, using data from a national probability sample of 2,614 households. Median age at first placement is 33 months, but age varies by geographic region, mother's employment status during pregnancy, mother's education level, and family structure (1 vs. 2 parents, mother's age at 1st birth, and number of siblings). Controlling for these effects, differences by race and ethnicity are small. Implications for studies of child-care selection and evaluations of early childhood programs are discussed.

Adolescent↗
PubMed1998

Mixed messages about primary care in the culture of U.S. medical schools.

PURPOSE: To examine the contributions of school-level variables associated with primary care career choice to students' enthusiasm for and perceived encouragement toward primary care. METHOD: Multilevel analysis of 264 fourth-year students and 500 clinical faculty members at 59 medical schools using data obtained in 1993 to 1994 from telephone interviews of a national stratified probability sample of students (response rate 90%) and faculty (response rate 81%). RESULTS: On average, students reported slightly positive regard for primary care and felt neither supported nor unsupported in their interests in primary care. Students' reports of encouragement toward primary care showed some consistency within schools (intraclass correlation = .08); their regard for primary care did not (intraclass correlation = .02). Regard for primary care was associated with students' intended specialty choices (p < .001), with students who planned to enter primary care careers reporting more positive attitudes. Students' perceptions of encouragement toward primary care careers were unrelated to their intended specialty choices, but significantly related to their schools' historical primary care production (p < .0001), federal research funding (p < .01), and school ownership (p < .01). CONCLUSION: Schools that have primary care missions and have historically produced more generalists transmit higher levels of encouragement to their students about primary care. However, even at schools with strong primary care missions, students hold unenthusiastic attitudes about primary care practice.

Attitude of Health Personnel↗
PubMed1998

Physician retention in community and migrant health centers: who stays and for how long?

OBJECTIVES: This study used discrete-time survival analysis to estimate the tenure of primary care physicians in Community Health Centers (CHCs), to identify the changing risk of leaving Community Health Center employment as time passes, and to identify factors associated with a physician's likelihood of remaining in a Community Health Center. Because of dramatic differences in physician career trajectories, much of the focus was on differences between physicians with and without National Health Service Corps obligations. METHODS: Beginning with an administrative dataset at the Bureau of Primary Health Care that listed primary care physicians for each Community Health Center, the completeness and accuracy of the information provided were verified and an analytic database of all physicians working in those centers during a 21-month measurement window from January 1, 1990 through September 30, 1992 was constructed. The data included start and end dates, percent full-time equivalent status, and certain demographic characteristics. In addition, several data elements describing the Community Health Center were merged onto each physician record. These included urban or rural location, expenditure level, productivity, and federal grade. Through the use of discrete-time survival analysis, it was possible to include in the analytic sample all 2,654 physicians who worked during the period, even those who started working before January 1, 1990 and those who were still working on September 30, 1992. Survivor functions were estimated showing the proportion of physicians remaining after each quarter of their tenure (ie, after the fourth quarter of work, after the 12th quarter of work, etc). In addition, hazard functions were estimated showing the risk that a physician who had worked through the end of one quarter would leave during the following quarter. Finally, multivariate analysis demonstrated the relation of certain physician and center characteristics to the likelihood of the physician's leaving the center during each quarter. RESULTS: The median tenure of primary care physicians in Community Health Centers was approximately 3 years regardless of whether or not the physician had a National Health Service Corps obligation. But the career trajectories for the two groups of physicians varied dramatically. Most physicians left on or about their anniversary date, probably because it coincided with the end of their contract, but the effect was much more pronounced for National Health Service Corps physicians than for non-National Health Service Corps physicians. By the end of 5 years, approximately 36% of physicians who started without an National Health Service Corps obligation were still working compared with only approximately 17% of those with an National Health Service Corps obligation. CONCLUSIONS: The study demonstrates the value of discrete-time survival analysis in addressing questions related to the tenure of primary care physicians in Community Health Centers, making it possible to use data from physicians whose Community Health Center careers began before or ended after a give measurement window. Second, the study measured primary care physician tenure, providing center directors with a yard-stick against which to compare their own center's performance. Finally, the data provided some help in trying to explain differences in the propensity to stay or leave employment in Community Health Centers.

Career Mobility↗
PubMed1996

Academia's chilly climate for primary care.

OBJECTIVE: To describe the attitudes toward and perceptions of primary care education and practice among academic health center constituents. DESIGN AND PARTICIPANTS: Descriptive study using confidential telephone interviews (October 1993 to March 1994) of national stratified probability samples of first- and fourth-year medical students, residents, clinical faculty, internal medicine and pediatrics residency training directors and chairs, and deans (N=2293). RESULTS: Five areas were examined: respondents' specialty orientation, attitudes toward the competence of primary care physicians, encouragement and positive regard for primary care, exposure to primary care-related educational experiences, and socioemotional orientation. The response rate was 84%. Respondents generally perceive primary care tasks as not requiring high levels of expertise; nearly half believe that generalists are not the best physicians to manage patients with serious illness and that the quality of primary care research is inferior to that in other fields. Attitudes are more positive toward the quality of primary care teaching. Learners perceive little encouragement for generalist careers and negative attitudes toward generalists among faculty, and view the quality of their primary care training as inferior to that for specialty practice. Those who have progressed further in the academic medicine hierarchy generally report lower levels of socioemotional orientation than individuals at earlier phases of career development. CONCLUSIONS: Despite changes in the health care system and in education, students and residents encounter an atmosphere that is chilly toward primary care. If medical educators seek to optimize enthusiasm and preparation for primary care careers, they must develop approaches to changing the attitudes, values and composition of their faculties.

Academic Medical Centers↗
PubMed1996

Coordinating DNA replication to produce one copy of the genome requires genes that act in ubiquitin metabolism.

We have developed a genetic screen of the yeast Saccharomyces cerevisiae to identify genes that act to coordinate DNA replication so that each part of the genome is copied exactly once per cell cycle. A mutant was recovered in this screen that accumulates aberrantly high DNA contents but does not complete a second round of synthesis. The mutation principally responsible for this phenotype is in the DOA4 gene, which encodes a ubiquitin hydrolase, one of several yeast genes that encode enzymes that can remove the signalling polypeptide ubiquitin hydrolase, one of several yeast genes that encode enzymes that can remove the signaling polypeptide ubiquitin from its covalently linked conjugated forms. DOA4 is nonessential, and deleting this gene causes uncoordinated replication. Overreplication does not occur in cells with limiting amounts of Cdc7 protein kinase, suggesting that entry into S phase is required for this phenotype. The DNA formed in doa4 mutants is not highly unusual in the sense that mitotic recombination rates are normal, implying that a high level of repair is not induced. The temperature sensitivity of doa4 mutations is partially suppressed by extra copies of the polyubiquitin gene UB14, but overreplication still occurs in the presence of this suppressor. Mutations in DOA4 cause loss of the free ubiquitin pool in cells under heat stress conditions, and extra copies of UB14 restore this pool without restoring coordination of replication. We conclude that a ubiquitin-mediated signaling event directly involving the ubiquitin hydrolase encoded by DOA4 is needed in S. cerevisiae to prevent uncoordinated DNA replication.

DNA Polymerase II↗
PubMed1994

Binding properties of newly identified Xenopus proteins containing dsRNA-binding motifs.

BACKGROUND: Although most RNA-binding proteins recognize a complex set of structural motifs in their RNA target, the double-stranded (ds) RNA-binding proteins are limited to interactions with double helices. Recently, it has been discovered that some dsRNA-binding proteins share regions of amino-acid similarity known as dsRNA-binding motifs. RESULTS: A Xenopus ovary cDNA expression library was screened with radiolabeled dsRNA to identify previously uncharacterized dsRNA-binding proteins. The analysis of an incomplete cDNA identified during the screen led to the discovery of two longer cDNAs of related sequence. The proteins encoded by these cDNAs each contained two dsRNA-binding motifs, in glycine. The nucleic-acid-binding properties of a fusion protein containing the two dsRNA-binding motifs and the auxiliary domain were analyzed using a gel mobility shift assay. The fusion protein bound dsRNA of a variety of different sequences, and exhibited a preference for binding to dsRNA and RNA-DNA hybrids over other nucleic acids. Appropriate mRNAs, corresponding to each cDNA, were detected in polyadenylated RNA isolated from Xenopus stage VI oocytes, but translation of one of the mRNAs appeared to be masked until meiotic maturation. CONCLUSION: dsRNA-binding motifs are often found in proteins that bind dsRNA, and our results show that they can be associated with auxiliary domains rich in arginine and glycine. These motifs can confer very tight binding to dsRNA. Binding can also occur to RNA-DNA hybrids, suggesting recognition of some aspect of the A-form helical structure that is adopted by both dsRNA and RNA-DNA hybrids.

Amino Acid Sequence↗
PubMed1994

Designing and analyzing studies of onset, cessation, and relapse: using survival analysis in drug abuse prevention research.

Many questions arising in drug abuse prevention and intervention studies focus on whether and, if so, when events occur. When do adolescents start using drugs? Does participation in a drug prevention program at school decrease the risk that high school students will initiate drug use? Does failure to participate in a relapse prevention program at a community health center increase the risk that newly abstinent ex-abusers will start using drugs again? Research questions about event occurrence present unique design and analytic difficulties. The fundamental problem is how to handle censored observations, observations of those people who do not experience the target event during data collection. The methods of survival analysis overcome these difficulties and allow prevention researchers to describe patterns of occurrence, compare these patterns among groups, and build statistical models of the risk of occurrence over time. In this chapter, the authors present a nonmathematical introduction to survival analysis for drug abuse prevention researchers. After developing the basic concepts, they focus on two topics-study design and data analysis-and identify for each the key issues researchers face and provide guidelines for making informed decisions about them. In the process, the authors review how prevention researchers have used the methods to date and point towards new directions for the application of these methods.

Data Collection↗
PubMed1993

Investigating onset, cessation, relapse, and recovery: why you should, and how you can, use discrete-time survival analysis to examine event occurrence.

In this article, we show how discrete-time survival analysis can address questions about onset, cessation, relapse, and recovery. Using data on the onset of suicide ideation and depression and relapse into cocaine use, we introduce key concepts underpinning the method, describe the action of the discrete-time hazard model, and discuss several types of main effects and interactions that can be included as predictors. We also comment on practical issues of data analysis and strategies for interpretation and presentation.

Adolescent↗
PubMed1992

Job experiences over time, multiple roles, and women's mental health: a longitudinal study.

Are changes over time in the quality of a woman's job associated with changes in her psychological distress? Do family roles moderate these relationships? We addressed these questions using longitudinal data from a 2-year 3-wave study of a stratified random sample of 403 employed women who varied in occupation, race, partnership, and parental status. After estimating individual rates of change for each woman on each of the predictors and the outcome, we modeled the relationships between family role occupancy and change in job-role quality on the one hand, and change in psychological distress on the other. Among single women and women without children, as job-role quality declined, levels of psychological distress increased. Among partnered women and women with children, change in job-role quality was unrelated to change in psychological distress.

Adaptation, Psychological↗
PubMed1991

Applications of survival analysis to aging research.

Many research questions in aging research treat time as the outcome variable. Researchers ask how much time must pass before a specific type of change or event occurs, and whether these times differ by characteristics of the subjects' background, training and treatment. Because of serious technical problems that arise when analyzing duration data, specially derived statistical methods--the methods of survival analysis--are required to answer the questions. In this paper, we introduce the conceptual framework of these new methodologies for analyzing duration data. We begin by identifying the types of research question that might appropriately treat time as an outcome. We then describe the new statistical methods for addressing such questions, provide a broad overview of their application, and identify relevant published sources containing additional background and technical information.

Aging↗
PubMed1991

Technology's children: report of a statewide census of children dependent on medical supports.

In April 1987, a census of children dependent on medical technology was carried out in Massachusetts to determine the one-month point prevalence. All medical and educational providers in the state who were likely to interact with such children were contacted and asked to complete a two-sided data form on youngsters (aged 3 months to 18 years) with tracheostomies, supplementary oxygen, respirators, suctioning, gastric feeding, central venous lines, ostomies, ureteral diversion, urethral catheterization and dialysis. Nearly 1250 children were found meeting these criteria. Capture-recapture analysis set the lower bound for technology dependence at 0.08% of the state's children. An analysis of the organ systems involved showed that 57% of the children had neurologic involvement--13% multisystem, 7% gastrointestinal-metabolic, 4% renal-genitourinary, and 3% musculoskeletal. Less than 1% of the children were reported as having immunologic or "other" disorders. Review of putative etiologies indicated that 45% of the children had congenital anomalies, 33% chronic medical diseases, 9% perinatal conditions, 7% hereditary-genetic disorders, 5% injuries, 2% infections, and 3% "other." The substantial prevalence of technology dependency among children creates challenges at the social, economic, and policy-making levels. It will be important to carry out systematic reporting and monitoring activities throughout time and across sites. This census is an example of one such statewide effort.

Adolescent↗
PubMed1990

In vivo analysis of the Saccharomyces cerevisiae HO nuclease recognition site by site-directed mutagenesis.

HO nuclease introduces a specific double-strand break in the mating-type locus (MAT) of Saccharomyces cerevisiae, initiating mating-type interconversion. To define the sequence recognized by HO nuclease, random mutations were produced in a 30-base-pair region homologous to either MAT alpha or MATa by a chemical synthesis procedure. The mutant sites were introduced into S. cerevisiae on a shuttle vector and tested for the ability to stimulate recombination in an assay that mimics mating-type interconversion. The results suggest that a core of 8 noncontiguous bases near the Y-Z junction of MAT is essential for HO nuclease to bind and cleave its recognition site. Other contacts must be required because substrates that contain several mutations outside an intact core reduce or eliminate cleavage in vivo. The results show that HO site recognition is a complex phenomenon, similar to promoter-polymerase interactions.

Base Sequence↗