The sisterhood method for estimating the level of maternal mortality. Seven years' experience.
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Subgroup analyses remain a popular and necessary component of controlled clinical trials. However, lack of prospective specification, inadequate sample size, inability to maintain power, and the cumulative effect of sampling error can complicate their interpretation. This article demonstrates that clinical trial design tools that would allow the medical community to draw confirmatory and not just exploratory conclusions from specific subgroup evaluations are available to methodologists. Distinct from the use of a treatment by subgroup interaction term, this methodology provides an evaluation of the effect of an intervention within a particular subgroup stratum prospectively declared to be of interest to the investigators. The necessary prespecification of stratum-specific type I error rates, when combined with (1) a stratum-specific event rate in the subgroup, (2) a stratum-specific primary endpoint, (3) a stratum-specific endpoint precision, and/or (4) a stratum-specific efficacy, satisfies the requirements for a subgroup stratum's "stand-alone" interpretation at the trial's conclusion.
Using a qualitative focus-group methodology, this study investigated risk-taking behaviors and AIDS knowledge among minority pregnant and parenting adolescents at risk for heterosexual and perinatal transmission of HIV. Seven focus groups were conducted with a total of 48 young women recruited from alternative schools and residential facilities for pregnant adolescents and young mothers in Southern California. Participants also completed a background questionnaire soliciting sociodemographic information and an AIDS knowledge test. The sample included 33 Latinas and 15 African-Americans, ranging in age from 12 to 19 years. There were bipolar findings regarding risk-taking behaviors. At one end of the continuum were young women with a history of one of more of the following behaviors: multiple sex partners, drug and alcohol use, carrying weapons, and participating in gang-related activities. Contrasting with these, were those who had one or two sex partners and no history of alcohol or drug abuse. A majority of the participants were having unprotected sex. A variety of factors affected condom use, including gender inequality, embarrassment, and personal preferences and values. Risk-taking was also influenced by lack of security and safety in daily living, emotion-focused coping and peer pressure.
Functional magnetic resonance imaging (fMRI) is now a well-established technique for directly identifying adult brain activity. This study builds on earlier pilot work that showed that fMRI could provide direct evidence of fetal brain cortical activation in response to an auditory stimulus. The new work presented here aims to assess the sensitivity of this technique in a larger sample group. This article includes a specific discussion of the methodology required for fetal fMRI. Sixteen pregnant subjects were scanned between 37 and 41 weeks gestation, 12 had an auditory stimulus applied to the maternal abdomen (study group) and 4 had an auditory stimulus applied to the mother's ears (control group). Two of twelve (2/12) study-group patients experienced back pain so that the experiment was abandoned; 4/12 showed significant activation (P < 0.005) in one or both of the temporal lobes; 1/12 showed significant activation in the frontal lobe. A susceptibility artifact at the interface between the maternal bowel and the fetus affected 3/12 data sets. No significant activation was found in 3/4 of the control cases, and 1/4 could not be analyzed due to a susceptibility artifact.
High density oligonucleotide arrays have been used extensively for expression studies of eukaryotic organisms. We have designed a prokaryotic high density oligonucleotide array using the complete Escherichia coli genome sequence to monitor expression levels of all genes and intergenic regions in the genome. Because previously described methods for preparing labeled target nucleic acids are not useful for prokaryotic cell analysis using such arrays, a mRNA enrichment and direct labeling protocol was developed together with a cDNA synthesis protocol. The reproducibility of each labeling method was determined using high density oligonucleotide probe arrays as a read-out methodology and the expression results from direct labeling were compared to the expression results from the cDNA synthesis. About 50% of all annotated E.coli open reading frames are observed to be transcribed, as measured by both protocols, when the cells were grown in rich LB medium. Each labeling method individually showed a high degree of concordance in replica experiments (95 and 99%, respectively), but when each sample preparation method was compared to the other, approximately 32% of the genes observed to be expressed were discordant. However, both labeling methods can detect the same relative gene expression changes when RNA from IPTG-induced cells was labeled and compared to RNA from uninduced E.coli cells.
During the Pleistocene pygmy elephantids, some only a quarter of their ancestors' size, were present on Mediterranean islands until about 10,000 years ago (y.a.). Using a new methodology for ancient DNA (aDNA) studies, the whole genomic multiple displacement amplification method, we were able to retrieve cytochrome b (cytb) DNA fragments from 4200 to 800,000 y.a. specimens from island and mainland samples, including pygmy and normal-sized forms. The short DNA sequence (43 bp) retrieved from the 800,000 y.a. sample is one of the oldest DNA fragment ever retrieved. Duplication of the experiments in two laboratories, the occurrence of three diagnostic sites and the results of the phylogenetic analyses strongly support its authenticity. Our results challenge the prevailing view that pygmy elephantids of the eastern Mediterranean originated exclusively from Elephas, suggesting independent histories of dwarfism and the presence of both pygmy mammoths and elephant-like taxa on these islands. Based on our molecular data, the origin of the Tilos and Cyprus elephantids from a lineage within the genus Elephas is confirmed, while the DNA sequence from the Cretan sample falls clearly within the mammoth clade. Thus, the name Mammuthus creticus rather than Elephas creticus, seems to be justified for this form. Our findings also suggest a need to re-evaluate the evolutionary history of the Sicilian/Maltese species, traditionally included in the genus Elephas.
A small linear peptide in solution may populate several stable states (called here microstates) in thermodynamic equilibrium; elucidating its dynamic three dimensional structure by multi- dimensional nmr is complex since the experimentally measured nuclear Overhauser effect intensities (NOEs) represent averages over the individual contributions. We propose a new methodology based on statistical mechanical considerations for analyzing nmr data of such peptides. In a previous paper (called paper I, H. Meirovitch et al. (1995) Journal of Physical Chemistry, 99, 4847-4854] we have developed theoretical methods for determining the contribution to the partition function Z of the most stable microstates, i.e. those that pertain to a given energy range above the global energy minimum (GEM). This relatively small set of dominant microstates provides the main contribution to medium- and long-range NOE intensities. In this work the individual populations and NOEs of the dominant microstates are determined, and then weighted averages are calculated and compared with experiment. Our methodology is applied to the pentapeptide Leu-enkephalin H-Tyr-Gly-Gly-Phe-Leu-OH, described by the potential energy function ECEPP. Twenty one significantly different energy minimized structures are first identified within the range of 2 kcal/mol above the GEM by an extensive conformational search; this range has been found in paper I to contribute 0.6 of Z. These structures then become "seeds" for Monte Carlo (MC) simulations designed to keep the molecule relatively close to its seed. Indeed, the MC samples (called MC microstates) illustrate what we define as intermediate chain flexibility; some dihedral angles remain in the vicinity of their seed value, while others visit the full range of [-180 degrees, 180 degrees]. The free energies of the MC microstates (which lead to the populations) are calculated by the local states method, which (unlike other techniques) can handle any chain flexibility. The NOE of MC microstate i is calculated as the average <1/r(3)>i(2), and an effective interatomic distance ri(eff) is defined as ri(eff) = i(-1/3), where r is the distance between two protons. Under "initial rate approximation," and neglecting angular modulations, the overall I is the average over ri(eff-6), weighted by the populations of the MC microstates. This treatment is justified under the assumption that the rates at which conformations interconvert within, and among, microstates are faster and slower, respectively, than the rotational reorientation of the molecule. I(-6) leads to the virtual theoretical distances, compared to the corresponding virtual experimental distances, which were obtained previously from a cryoprotective solution of Leu-enkephalin at 280 K. A reasonable fit is found between theory and experiment. Future research directions are outlined.
PURPOSE: This research reviewed studies that compare two or more racial, ethnic, national, or cultural groups on aspects of the dementia caregiving experience. DESIGN AND METHODS: Electronic databases were searched to find studies published between 1996 and 2000 in peer-reviewed journals that met the above criteria. RESULTS: Twenty-one studies based on 18 samples were identified. These articles included comparisons involving the following groups of caregivers: African Americans, Chinese, Chinese Americans, Koreans, Korean Americans, Latinos, Whites, and residents of 14 European Union countries. Consistent with previous research, White caregivers were more likely to be spouses when compared to other groups. White caregivers tended to report greater depression and appraised caregiving as more stressful than African American caregivers. Findings were mixed regarding differences in coping and social support, but suggested that minority groups may not have more available support than Whites. Common methodological limitations were a lack of noncaregiving control groups and failure to test specific pathways by which the grouping variable (e.g., race) exerts its impact on outcome variables. IMPLICATIONS: Future studies in this area should use both quantitative and qualitative research methods to specify the pathways by which race, ethnicity, and culture affect the caregiving experience, and should expand their focus beyond the primary caregiver to include the effects of caregiving on families and networks.
The purpose of this study was to determine the effect of coronary artery bypass graft (CABG) surgery on the quality of life of women. Wilson and Cleary's conceptual model of health-related quality of life, which examines five major outcomes (biological variables, symptom status, functional status, general health perceptions, perceived quality of life), was used. Participants included 61 women who provided information by self-report questionnaires before and three months after surgery. The major findings of the study are that women had significantly improved quality of life (p = .004) due to increased satisfaction with health and functioning (p < .001) at three months following CABG surgery. They experienced less angina (p < .001) and shortness of breath (p = .014), although fatigue was unrelieved for the majority of women. Psychological well being improved after surgery for most women (p < .001), with lower anxiety levels (p < .001), greater levels of well being (p = .021), feelings of health (p < .001) and vitality (p = .023). Women reported less use of emotive coping (p = .043), indicating less emotional distress. Nevertheless, 25% of the sample continued to experience severe psychological distress three months after surgery, indicating the need for continued follow-up.
Capture-recapture methodology, originally developed for estimating demographic parameters of animal populations, has been applied to human populations. This tutorial reviews various closed capture-recapture models which are applicable to ascertainment data for estimating the size of a target population based on several incomplete lists of individuals. Most epidemiological approaches merging different lists and eliminating duplicate cases are likely to be biased downwards. That is, the final merged list misses those who are in the population but were not ascertained in any of the lists. If there are no matching errors, then the duplicate information collected from a capture-recapture experiment can be used to estimate the number of missed under proper assumptions. Three approaches and their associated estimation procedures are introduced: ecological models; log-linear models, and the sample coverage approach. Each approach has its unique way of incorporating two types of source dependencies: local (list) dependence and dependence due to heterogeneity. An interactive program, CARE (for capture-recapture) developed by the authors is demonstrated using four real data sets. One set of data deals with infection by the acute hepatitis A virus in an outbreak in Taiwan; the other three sets are ascertainment data on diabetes, spina bifida and infants' congenital anomaly discussed in the literature. These data sets provide examples to show the usefulness of the capture-recapture method in correcting for under-ascertainment. The limitations of the methodology and some cautionary remarks are also discussed.
PURPOSE: To describe the stressful experiences of Chinese-American parents who have an infant in the intensive care unit (ICU), and to assess the influence of acculturation, parents' characteristics, and social supports on parental stress. DESIGN: A cross-sectional, descriptive, correlational study. SAMPLE/SETTING: A convenience sample of 30 Chinese-American families (30 mothers, 25 fathers) who had an infant hospitalized in 3 ICU sites in the San Francisco area. METHODOLOGY: Measures included: (1) Infant's health data from the medical records and parents' demographic data, and (2) Parental Stressor Scale: Infant Hospitalization, Suinn-Lew Asian Self-Identity Acculturation Scale, and Family Support Scale. MAIN OUTCOME MEASURE: The dependent variable was mothers' and fathers' stress levels. Independent variables included personal/family characteristics, acculturation, uncertainty regarding infants' illness, and social supports. PRINCIPAL RESULTS: The ICU stressors were ranked by both mothers and fathers in the following order: infant's appearance, parental role alteration, staff communication and behaviors, and ICU environment. The combined effects of uncertainty about their infant's illness and its future impact, a strong belief in Asian family values, and lack of support from healthcare providers accounted for 26% and 55% of the variance in parental stress for mothers and fathers, respectively. CONCLUSIONS: Findings from this study suggest implications for the education of both families and the ICU staffs.
We argue that the current literature on prosopagnosia fails to demonstrate unequivocal evidence for a disproportionate impairment for faces as compared to nonface objects. Two prosopagnosic subjects were tested for the discrimination of objects from several categories (face as well as nonface) at different levels of categorization (basic, subordinate, and exemplar levels). Several dependent measures were obtained including accuracy, signal detection measures, and response times. The results from Experiments 1 to 4 demonstrate that, in simultaneous-matching tasks, response times may reveal impairments with nonface objects in subjects whose error rates only indicate a face deficit. The results from Experiments 5 and 6 show that, given limited stimulus presentation times for face and nonface objects, the same subjects may demonstrate a deficit for both stimulus categories in sensitivity. In Experiments 7, 8 and 9, a match-to-sample task that places greater demands on memory led to comparable recognition sensitivity with both face and nonface objects. Regardless of object category, the prosopagnosic subjects were more affected by manipulations of the level of categorization than normal controls. This result raises questions regarding neuropsychological evidence for the modularity of face recognition, as well as its theoretical and methodological foundations.
BACKGROUND: The Self-Perception and Relationships Tool (S-PRT) is intended to be a clinically responsive and holistic assessment of patients' experience of illness and subjective Health Related Quality of Life (HRQL). METHODS: A diversity of patients were involved in two phases of this study. Patient samples included individuals involved with renal, cardiology, psychiatric, cancer, chronic pelvic pain, and sleep services. In Phase I, five patient focus groups generated 128 perceptual rating scales. These scales described important characteristics of illness-related experience within six life domains (i.e., Physical, Mental-Emotional, Interpersonal Receptiveness, Interpersonal Contribution, Transpersonal Receptiveness and Transpersonal Orientation). Item reduction was accomplished using Importance Q-sort and Importance Checklist methodologies with 150 patients across the participating services. In Phase II, a refined item pool (88 items) was administered along with measures of health status (SF-36) and spiritual beliefs (Spiritual Involvements and Beliefs Scale--SIBS) to 160 patients, of these 136 patients returned complete response sets. RESULTS: Factor analysis of S-PRT results produced a surprisingly clean five-factor solution (Eigen values> 2.0 explaining 73.5% of the pooled variance). Items with weaker or split loadings were removed leaving 36 items to form the final S-PRT rating scales; Intrapersonal Well-being (physical, mental & emotional items), Interpersonal Receptivity, Interpersonal Contribution, Transpersonal Receptivity and Transpersonal Orientation (Eigen values> 5.4 explaining 83.5% of the pooled variance). The internal consistency (Cronbach's Alpha) of these scales was very high (0.82-0.97). Good convergent correlations (0.40 to 0.67) were observed between the S-PRT scales and the Mental Health scales of the SF-36. Correlations between the S-PRT Intrapersonal Well-being scale and three of SF-36 Physical Health scales were moderate (0.30 to 0.46). The criterion-related validity of the S-PRT spiritual scales was supported by moderate convergence (0.40-0.49) with three SIBS scales. CONCLUSION: Evidence supports the validity of the S-PRT as a generally applicable measure of perceived health status and HRQL. The test-retest reliability was found to be adequate for most scales, and there is some preliminary evidence that the S-PRT is responsive to patient-reported changes in determinants of their HRQL. Clinical uses and directions for future research are discussed.
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The two-year experience with pathoanatomic service experimentally organized on the basis of large pathoanatomic units of hospitals in Riga, Vilnius, Khmelnitsky, Chelyabinsk and Tambov, has shown that such practice improved the quality of research and the work of pathoanatomic service as a whole. The main results of the experiment are the following: intensification of medical activities; shortening (up to 24-48 h) of time needed for histologic study of biopsy samples due to the introduction of the advanced methods of medical care; specialization of the physicians in different fields of pathology; collective decision on the biopsies and section material; optimal conditions for mastering professional skills and training of pathologic anatomists; pathoanatomic studies, organizational, consultative and methodologic work in rural regions; improvements of material resources and technical equipment of the service.
PURPOSE: The value of genetic information for improving the performance of clinical risk prediction models has yielded variable conclusions. Many methodological decisions have the potential to contribute to differential results. We performed multiple modeling experiments integrating clinical and demographic data from electronic health records with genetic data to understand which decisions may affect performance. METHODS: Clinical data in the form of structured diagnostic codes, medications, procedural codes, and demographics were extracted from 2 large independent health systems, and polygenic risk scores (PRS) were generated across all patients of European ancestry with genetic data in the corresponding biobanks. Crohn's disease was studied based on its substantial genetic component, established electronic health records-based definition, and sufficient prevalence for training and testing. We investigated the impact of choices regarding the PRS integration method, training sample, model complexity, and performance metrics. RESULTS: Overall, our results showed that including PRS resulted in higher performance, but this gain was only robust in situations with limited clinical information. We found consistent performance increases from more compute-intensive models, such as random forest, but the impact of other decisions varied by site. CONCLUSION: This work highlights the importance of considering methodological decision points in interpreting the impact of PRS on prediction performance in clinical models.
Older widows' experience of living alone is described in this research. Based on Husserl's (1913/1962) philosophy, a phenomenological method was used. Prior to data-gathering, knowledge pertaining to older widows' experience was bracketed. During semi-structured, tape-recorded conversations, seven older widows described how they lived at home alone. From data pertaining to their actions, intentions and perceptions, four phenomena of the lived experience were developed: (a) making aloneness acceptable; (b) going my own way; (c) reducing my risks; and (d) sustaining myself.
Although Alzheimer's disease and related disorders may have a heavy impact on informal caregivers, estimates of informal care costs have been neglected and when included in cost of illness studies, valuations have been highly variable. Although these variations are in part due to differences in samples and the difficulty in measuring caregiving time, this illustrates the need to standardise the methodology not only for valuing formal, but also informal care costs. Methods used for valuing informal care are identified, together with theoretical and practical challenges in measurement. In particular the measurement of time and it's associated satisfaction or utility is complex and valuations of time need to consider aspects of the caregiving experience which influence the marginal valuation of the time spent caring. More empirical work is required to elicit information on both the positive and negative satisfaction associated with caregiving and to incorporate this into valuations of the costs related to informal care.