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PubMed1992

A note on last case influence using the partial likelihood approach under heavy censoring.

The Cox proportional hazards model always treats the last observation in a time ordered data set as an inexact survival time. In certain situations this can lead to this observation always having a low case influence and consequently never being highlighted by a case influence analysis. Thus an influential value can become non-influential by a miscalculation of survival time and this, in turn, can affect conclusions of an analysis based on statistical significance (P-values).

Bias↗

PubMed1976

Maternal mortality rates in eclampsia.

This study evaluates the dominant factors that influence the course of eclampsia toward a lethal outcome by means of statistical analysis of various clinical, laboratory, and morphologic data of 365 cases of toxemia with convulsions, that included 49 deaths and 33 autopsies, registered during a 9 year period. This communication suggests that the death of eclamptic patients resulted from a combination of several factors that showed a very wide individual variation. Since advancing age of the mother was associated with a high incidence of coincidental renal and vascular diseases, this was the most clearly influential factor. The presence of twins, delay in hospitalization, under haste in deciding upon cesarean delivery, and underestimation of the initial clinical condition were all influential factors, although without statistical significance. Cesarean section, performed in 141 instances of ante- and intrapartum eclasmpsia (40.4 per cent), was not associated with a higher maternal mortality rate.

Adolescent↗

PubMed1975

Rate of participation and expertise as factors influencing leader choice.

Seventy-two female subjects were placed in four-person problem-solving groups. A confederate in each group was identified as either expert or inexpert, made expert or inexpert contributions, and either talked a lot or relatively little. The problem was made high or low in ambiguity. It was hypothesized that, as previous studies have shown, a high rate of participation would influence choice of the confederate as leader in the inexpert condition but that talkativeness would not be influential in the expert condition. The results supported the hypothesis. The characteristics of the confederate were somewhat less influential when the problem was low in ambiguity. The results were discussed in terms of what talkativeness may signify to other group members. When talkativeness is not resisted by the group it is tentative evidence that the talker is perceived as an appropriate, qualified, and legitimate leader.

Aptitude↗

PubMed1992

Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites.

To investigate the capacity of lupus autoAb to produce glomerular immune deposits (ID) and nephritis, 24 murine monoclonal (m) anti-DNA antibodies (Ab), derived from either MRL-lpr/lpr, SNF1 or NZB lupus-prone mice and selected based on properties shared with nephritogenic Ig, were administered i.p. (as hybridomas) and i.v. (as purified Ig) to normal mice; at least four mice/mAb were evaluated. Three general patterns of immune deposit formation (IDF) were observed: extracellular ID within glomeruli (+/- blood vessels, N = 8); intranuclear ID (N = 5); or minimal or no ID (N = 11). The four MRL m anti-DNA Ab that produced significant extracellular ID demonstrated different disease profiles including: (a) mesangial and subendothelial ID with anti-basement membrane staining, associated with proliferative glomerulonephritis, PMN infiltration, and proteinuria; (b) diffuse fine granular mesangial and extraglomerular vascular ID, associated with proliferative glomerulonephritis and proteinuria; (c) dense intramembranous ID and intraluminal ID, associated with capillary wall thickening, mesangial interposition and expansion, aneurysmal dilatation and intraluminal occlusion of glomerular capillary loops, and heavy proteinuria; and (d) mesangial and extraglomerular vascular ID, associated with mild segmental mesangial expansion, without proteinuria. These MRL mAb were derived from four different mice, and they had variable pIs and isotypes. They all cross reacted with multiple autoantigens (autoAg), however, their autoAg binding profiles were distinguishable. Among the SNF1 derived mAb, four produced histologically and clinically indistinguishable disease characterized by diffuse mesangial and capillary wall ID, associated with cellular proliferation/infiltration and proteinuria. Three of the four mAb were derived from the same mouse and were clonally related; they were: IgG2b with SWR allotype, relatively cationic, highly cross reactive with similar Ag binding patterns, idiotypically related and encoded by identical VH and nearly identical VL sequences. We conclude that both the capacity of lupus autoAb to form ID and the location of IDF are dependent on properties unique to individual Ig. The results also indicate that the Ag binding region of the autoAb is influential in this process, and they suggest that multiple Ab-Ag interactions contribute to IDF in individuals with lupus nephritis. Furthermore, these observations raise the possibility that the pathologic and clinical abnormalities resulting from these interactions are influenced by the location of IDF, and that the dominant interaction, in a given individual, may be highly influential in the phenotypic expression of nephritis.

Animals↗

PubMed1991

Structure-function relationships in the cysteine proteinases actinidin, papain and papaya proteinase omega. Three-dimensional structure of papaya proteinase omega deduced by knowledge-based modelling and active-centre characteristics determined by two-hydronic-state reactivity probe kinetics and kinetics of catalysis.

1. A model of the three-dimensional structure of papaya proteinase omega, the most basic cysteine proteinase component of the latex of papaya (Carica papaya), was built from its amino acid sequence and the two currently known high-resolution crystal structures of the homologous enzymes papain (EC 3.4.22.2) and actinidin (EC 3.4.22.14). The method used a knowledge-based approach incorporated in the COMPOSER suite of programs and refinement by using the interactive graphics program FRODO on an Evans and Sutherland PS 390 and by energy minimization using the GROMOS program library. 2. Functional similarities and differences between the three cysteine proteinases revealed by analysis of pH-dependent kinetics of the acylation process of the catalytic act and of the reactions of the enzyme catalytic sites with substrate-derived 2-pyridyl disulphides as two-hydronic-state reactivity probes are reported and discussed in terms of the knowledge-based model. 3. To facilitate analysis of complex pH-dependent kinetic data, a multitasking application program (SKETCHER) for parameter estimation by interactive manipulation of calculated curves and a simple method of writing down pH-dependent kinetic equations for reactions involving any number of reactive hydronic states by using information matrices were developed. 4. Papaya proteinase omega differs from the other two enzymes in the ionization characteristics of the common (Cys)-SH/(His)-Im+H catalytic-site system and of the other acid/base groups that modulate thiol reactivity towards substrate-derived inhibitors and the acylation process of the catalytic act. The most marked difference in the Cys/His system is that the pKa for the loss of the ion-pair state to form -S-/-Im is 8.1-8.3 for papaya proteinase omega, whereas it is 9.5 for both actinidin and papain. Papaya proteinase omega is similar to actinidin in that it lacks the second catalytically influential group with pKa approx. 4 present in papain and possesses a catalytically influential group with pKa 5.5-6.0. 5. Papaya proteinase omega occupies an intermediate position between actinidin and papain in the sensitivity with which hydrophobic interaction in the S2 subsite is transmitted to produce changes in transition-state geometry in the catalytic site, a fact that may be linked with differences in specificity in P2-S2 interaction exhibited by the three enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed2024

Organ-delimited gene regulatory networks provide high accuracy in candidate transcription factor selection across diverse processes.

Organ-specific gene expression datasets that include hundreds to thousands of experiments allow the reconstruction of organ-level gene regulatory networks (GRNs). However, creating such datasets is greatly hampered by the requirements of extensive and tedious manual curation. Here, we trained a supervised classification model that can accurately classify the organ-of-origin for a plant transcriptome. This K-Nearest Neighbor-based multiclass classifier was used to create organ-specific gene expression datasets for the leaf, root, shoot, flower, and seed in Arabidopsis thaliana. A GRN inference approach was used to determine the: i. influential transcription factors (TFs) in each organ and, ii. most influential TFs for specific biological processes in that organ. These genome-wide, organ-delimited GRNs (OD-GRNs), recalled many known regulators of organ development and processes operating in those organs. Importantly, many previously unknown TF regulators were uncovered as potential regulators of these processes. As a proof-of-concept, we focused on experimentally validating the predicted TF regulators of lipid biosynthesis in seeds, an important food and biofuel trait. Of the top 20 predicted TFs, eight are known regulators of seed oil content, e.g., WRI1, LEC1, FUS3. Importantly, we validated our prediction of MybS2, TGA4, SPL12, AGL18, and DiV2 as regulators of seed lipid biosynthesis. We elucidated the molecular mechanism of MybS2 and show that it induces purple acid phosphatase family genes and lipid synthesis genes to enhance seed lipid content. This general approach has the potential to be extended to any species with sufficiently large gene expression datasets to find unique regulators of any trait-of-interest.

Arabidopsis↗

PubMed1991

Possibilities of consensus: toward democratic moral discourse.

The concept of consensus is often appealed to in discussions of biomedical ethics and applied ethics, and it plays an important role in many influential ethical theories. Consensus is an especially influential notion among theorists who reject ethical realism and who frame ethics as a practice of discourse rather than a body of objective knowledge. It is also a practically important notion when moral decision making is subject to bureaucratic organization and oversight, as is increasingly becoming the case in medicine. Two models of consensus are examined and criticized: pluralistic consensus and overlapping consensus. As an alternative to these models, the paper argues that consensus refers to the dialogic aspects of a broader normative conception of democratic moral agency. When the preconditions for that dialogic democratic practice are met, consensus has a justificatory role in ethics; when they are not, consensus, as distinct from mere agreement, does not emerge and can have no moral authority.

Bioethical Issues↗

PubMed1991

Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung.

To determine if chemotherapy dose intensity (DI) influences treatment outcome, 60 published studies in limited- and extensive-stage small-cell carcinoma of the lung (SCCL) were retrospectively analyzed for relationship between intended DI and response (complete response [CR] or partial response [PR]) or median survival (MS). Agents used in the regimens included cyclophosphamide (C), doxorubicin (A), vincristine (V), etoposide (E), and cisplatin (P). Relative DI (RDI) of each study regimen was calculated against a reference regimen, and weighted regression analysis was used. Additionally, analysis of individual drug RDI within combinations was performed. For CAV, increasing RDI of the regimen showed no correlation with outcome. For the individual drugs, C RDI correlated positively, while A RDI correlated negatively with attainment of CR in limited disease, but both only after unduly influential observations were eliminated. In extensive-stage disease, A RDI correlated positively with CR+, PR but only in randomized trials, and this correlation lost statistical significance after unduly influential observations were eliminated. For CAE and CAVE, the RDI of the regimens correlated positively with MS in extensive-stage disease as did the C RDI. In limited disease, the C RDI correlated negatively with MS. For EP, no significant correlations were seen. We conclude that DI-outcome correlations are not consistent for these chemotherapy regimens in SCCL. Meta-analysis of retrospective data can generate hypotheses for testing in prospective clinical trials, but study sample and method of analysis can appreciably affect conclusions.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Political contributions from the health and insurance industries.

During a major election year, interest surges in discovering the sources of campaign funds for influential members of Congress and presidential candidates. This study traces the contributors from the health and insurance industries during the 1990 campaign and presents preliminary figures for the 1992 campaign. Health interests contributed $16.3 million to congressional candidates in 1990, many of whom sit on influential committees and subcommittees. The insurance industry gave $10.9 million that same year. In either case, more than half of the funds came from political action committees (PACs); the rest, from individuals. As of 30 June 1992 health industry PACs had given more than $8.3 million to candidates for federal office in the 1992 campaign; insurance PACs had contributed $6.4 million.

Data Collection↗

PubMed1977

Visual set and anxiety in the Stroop phenomenon.

The effects of a visual set, the Stroop phenomenon, and anxiety--as measured by the Spielberger State-Trait Anxiety Inventory--upon response latency were examined. Three variations of the set were presented, a color congruent with the response color, a color conflicting with the response color, or no color. Two response conditions were required, reading the color word or reporting the color in which the word was printed. "Reporting the color" had a significantly longer response latency than "reading the word" for all 60 subjects, female volunteers from freshman psychology classes. There was also a significant interaction between anxiety and the Stroop. The medium-anxiety group showed the least discrepancy between the response conditions of the Stroop, indicating the interference effect present in the Stroop phenomenon was least influential for this group. A consistent though not significant difference between the congruent set and conflicting set conditions for the color response as opposed to the word response indicated that, when the set is similar to the response, it is more influential than when it is unrelated.

Adolescent↗

PubMed1992

Factors influencing the selection of dental hygiene as a profession.

Since the mid-1970s, the dental hygiene profession has experienced a decline in the number of applicants. Reasons cited for this decline are fewer traditional college-age students, an increase in the career opportunities available to women, and a decrease in student financial aid. Four-year dental hygiene programs have experienced applicant decline faster than two-year programs. The purpose of this study was to determine factors that influenced university freshmen to designate dental hygiene as a career choice. Factors examined included reasons for choosing or not choosing a career in dental hygiene, and retention in the college major chosen. A questionnaire was mailed to three groups of students who entered the University of North Carolina-Chapel Hill as freshmen from 1985 through 1987: (1) all students who designated dental hygiene as a major on their entrance application; (2) a random sample who did not; and (3) all the freshman during that time period who subsequently matriculated into the dental hygiene program. The overall response rate was 78% (n = 80). Subjects began to explore career opportunities at a mean age of 16. Having a family member/friend in the selected field was found to be the most influential factor in career selection. Among dental hygiene students, contact with a dental hygienist was perceived to be influential in their career choice. Entering college freshmen exhibited a lack of knowledge about the dental hygiene profession, and most had not received any information about dental hygiene in high school. These findings can be used to develop recruitment strategies.

Adult↗

PubMed1977

Prolactin and murine mammary tumorigenesis: a review.

It is unequivocal that prolactin is an influential hormone in murine mammary tumorigenesis. The Berenblum hypothesis (7), a well-known theoretical model of tumorigenesis that depicts this oncogenic process as a two-step mechanism, i.e., initiation and promotion, is a conceptual scheme in which the action of prolactin in mammary tumorigenesis may be understood. According to this conceptual model, prolactin would participate in both the initiation and promotion steps of mammary tumorigenesis, In the initiation phase, variations in prolactin secretion appear to influence the metabolism of the mammary epithelium, so that the epithelium would be either more receptive to or refractory to an initiating agent (e.g., chemical carcinogen, physical carcinogens, oncogenic viruses, ets.) i.e., a permissive action. In the promotion phase, prolactin may act as either a promoter or an antipromoter of the "transformed" mammary epithelium. In promotion, the hormone may either directly or indirectly (via the ovary) stimulate mitotic activity of the "transformed" epithelium. In antipromotion the hormone, in the presence of requisite hormones (e.g., glucocorticoids), may synergistically induce differentiation (e.g., lactation) in the "transformed" epithelium. A tumor would result in the former (promotion) but not in the latter (antipromotion) case. Whether or not prolactin is significantly influential in human breast tumorigenesis remains to be determined. This is an extremely important area of research which is justifiably receiving increased attention. For if prolactin can be shown to influence human breast epithelium in a manner similar to its effect on rodent mammary tissue, then prophylactic and/of chemotherapeutic control of human breast tumorigenesis may be feasible by appropriate drug-mediated prolactin suppression.

Adrenal Glands↗

PubMedDate not supplied

[Factors influencing the survival of amalgam restoration in Bangkok metropolitan school children].

The purpose of this study was to find out the factors influenced on the survival of amalgam dental restoration. The study population was the amalgam restoration of 726 molar teeth, 3 restoration types, cavity class I, class I other surface and class I compound, of Bangkok Metropolitan school children aged 6-12 years. The data showed how the survival of restoration placed in teeth varied with the restoration aged ranging 6-30 months. The result indicated that there were 48.10% of broken filling and 19.42% of secondary caries. The rate of broken filling was significantly related to the child age at the time of treatment, the restoration age, the surface texture of the restoration and the restoration type (p less than 0.01). As for the rate of secondary caries, there were significant correlation with the surface texture of the filling, the restoration type and the factor "broken filling" (p less than 0.01). By means of the linear multiple regression, it told us explicitly about the magnitude of the relation that the surface texture of the filling was the major influential factor which could predict the variance of broken filling about 18.29% while the broken filling was also the major influential factor which could predict the variance of secondary caries about 7.93%.

Age Factors↗

PubMedDate not supplied

Impact of an educational program on physician cancer control knowledge and activities.

Continuing medical education (CME) programs are a common way for physicians to keep up with new developments in medical care. CME has been criticized as poorly evaluated at best and ineffective at worst. Proposed modifications in the traditional CME format include a role for influential peers, physician discussion groups, and self-formulated contracts. As part of a project that is testing methods to improve primary care physician cancer control performance, we provided an eight-hour educational program that included these proposed modifications and that addressed early detection of breast, cervical, and colon cancer and counseling on nutrition and smoking cessation. Physician knowledge improved after the program in four of the five content areas. In addition, physicians reported significant increases in their cancer control activities after six months. We conclude that cancer control CME programs that use interactive discussion groups, influential peers, and self-formulated contracts are feasible, well received by physicians, and result in improvements in knowledge and self-reported cancer control behavior.

Education, Medical, Continuing↗

PubMed1977

The offspring of schizophrenics. II. Perinatal factors and IQ.

Within a sample of 60 children of schizophrenic parents, IQ and the correlates of IQ were examined. The Wechsler Intelligence Scale for Children was administered at age 7. The offspring of parents with schizophrenia were found to have a slightly lower IQ than their matched controls. This deficit could be attributed entirely to the male offspring. Using a second comparison group numbering several thousand, we computed correlations for various perinatal and socioeconomic factors with seven-year IQ. These correlations were also computed for the children of schizophrenics, and the difference in correlations was examined. IQs for the offspring of "continuous schizophrenics" (chronic, borderline, and chronic schizo-affective schizophrenics) were found to have lower correlations with socioeconomic indices and higher correlations, in a negative direction, with certain perinatal events. The findings were found to a lesser, nonsignificant degree among the small sample of offspring of acute schizophrenics. If these perinatal events are more negatively correlated with IQ because the children of continuous schizophrenics are specifically susceptible to them, it is possible that these factors are also influential in the later development of schizophrenia.

Acute Disease↗

PubMed1991

Why surgeons prefer not to care for trauma patients.

A survey of the Washington State Chapter of the American College of Surgeons was undertaken to document the opinions of surgeons on trauma care issues. Thirty-nine percent of the total sample of surgeons who responded would prefer not to treat any trauma patients. These surgeons were more likely to be older, to practice in an urban setting, to feel that trauma call has a negative impact on elective practice, and to believe more strongly that reimbursement from trauma patients is not equal to that of nontrauma patients. They also agreed more strongly with the statements that these patients require a greater time commitment and pose an increased medicolegal risk. The most significant influence on preference not to treat trauma patients was exerted by the perception of a negative impact on practice, older age, and perception of increased medicolegal risk. Reimbursement issues and location of practice were less influential factors. This information can be used to target concerns and barriers to active, willing participation in a trauma care system and to tailor strategies to deal with them effectively.

Adult↗

PubMed1990

A standard dose of radiation for "microscopic disease" is not appropriate.

Elective irradiation of sites of potential occult tumor spread is often part of a patient's radiation therapy program. The required radiation dose (D) depends on the probability that occult disease exists (P(occ)), the number of sites at risk (A), the number of tumor clonogens present (Ni), their radiation sensitivity, and the desired control rate. An exponential model of cell survival is used to quantify the importance of these factors. Control Probability = [1 - Pocc x (1 - e-Ni x (SF2)D/2)]A; SF2 = surviving fraction after 2 Gy. Implications for clinical radiation therapy include: 1. Since the number of clonogens in an occult site may vary from 10 degrees to 10(8), Ni is the major determinant of the required dose. The intrinsic radiation sensitivity of the clonogens (SF2) is also extremely important in determining the dose. Other factors are less influential since they vary less. 2. The variability of Ni (8 logs) is larger than the variation in cell number seen with gross disease (1 cm3 versus 1000 cm3, 3 logs). When Ni approximately 10(8), the required dose approaches that needed for small volume gross disease (10(9) cells, 1 cm3). 3. The dose prescribed to elective sites should reflect the risk of occult disease based on the primary tumor site, stage, and grade. 4. Regions where clinicoradiologic evaluation is difficult (e.g., pelvis and obese neck) require higher doses because macroscopic tumor deposits may exist. 5. Relatively low doses (10 to 30 Gy) are often thought to be inadequate for microscopic tumor. However, similar doses have been reported to sterilize microscopic tumor in ovarian, rectal, bladder, breast, and head and neck carcinomas. Relatively low doses should not be discounted since they may be useful in select cases when normal tissue tolerances and/or previous irradiation treatment limit the radiation dose.

Cell Survival↗

PubMed1979

Training, role models, and research activity among clinical psychologists.

Compared clinical psychologists (N = 270) with high and low publication rates through questionnaire responses. Highs report dissertation experiences more positively influenced their research motivation. Although the most influential professor in both groups was typically clinical, more highs found the professor emphasized another orientation, particularly empirical research, over clinical expertise. Highs report more time available, collaboration opportunities, and organizational acceptance for their research. Both groups favor empirical methods, although highs and lows agree that a small proportion of psychological research makes a significant contribution. Individual preferences probably interact with situational characteristics, both in training and work settings, to determine research activity.

Academic Dissertations as Topic↗