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PubMed2001

A homeostatic model of oxidative damage explains paradoxes observed in earlier aging experiments: a fusion and extension of older theories of aging.

The Rate of Living and the Threshold Theories of Aging are two contradicting approaches used to explain experimental facts about aging in fruit flies. In this paper we suggest an approach that unifies these theories and removes the contradiction. The approach involves quantitative description of the oxidative stress theory of aging, which is presented in the form of a mathematical homeostatic model. The crucial variable in the model is called 'homeostatic capacity', which is analogous to the classical notion of vitality. We model the process of aging as the age-related accumulation of damage produced by oxidative stress, which reduces the homeostatic capacity of the organism. The model is tested with the experimental data obtained in the classical experiments by Maynard Smith in 1958-1963. Our homeostatic model explains the well-known results of these experiments more accurate than any one of the early theories of aging. We form an hypothesis about the mechanisms underlying the results observed in the experiments and analyze a possible interplay of these mechanisms. Our virtual replication of Maynard Smith's classical experiments demonstrates that mathematical modeling can be a powerful tool to reveal and investigate the inherent genetic and physiological processes underlying the data observed in complicated insect experiments.

Aging↗

PubMed1997

Explained and unexplained medical symptoms in generalized anxiety and panic disorder: relationship to the somatoform disorders.

We have examined the numbers and types of symptoms in a sample of 90 patients with generalized anxiety disorder (GAD) and 77 patients with panic disorder (PD) collected from six different sites during the conduct of a multicenter clinical trial. This information was obtained utilizing the Health Questionnaire, a 47-item self-report list of medical symptoms, patterned after the Somatization Disorder section of the Diagnostic Interview Schedule. Although the patients in this sample had a wide variety of medically explained and unexplained physical symptoms, none of them qualified for a diagnosis of somatization disorder by DSM-III-R criteria. GAD and PD patients reported remarkably similar numbers of explained and unexplained medical symptoms. The panoply of somatic symptoms presented by these patients presents a formidable diagnostic challenge for clinicians. These findings suggest that the pattern of overutilization of medical services that is well documented for PD patients may also be found for GAD patients.

Adult↗

PubMed1992

General slowing alone cannot explain age-related search effects: reply to Cerella (1991)

Cerella (1991) has argued that the performance of older adults in the Fisk and Rogers (1991) study is a linear function of the performance of younger adults that is independent of task-specific cognitive requirements. We demonstrate that this is not the case. First, we show that the scatter plot analyses used by Cerella can hide the very task-specific age-related slowing they were designed to reveal. Second, we demonstrate that the percentage of variance explained by such analyses can be misleading. Third, we show that there are reliable differences across tasks in the parameters relating younger and older adults' performance. Finally, we argue that the general, task-independent proportionate slowing that Cerella suggested explains so much of the variance in age-related performance is actually an average slowing that is a function of a relatively small task-independent and a relatively large task-dependent factor.

Adult↗

PubMed1996

Usefulness of the protection motivation theory in explaining hearing protection device use among male industrial workers.

The present study examined the usefulness of personal variables: noise annoyance, and components of the protection motivation theory (R. W. Rogers, 1983) along with social-organizational factors in explaining hearing protection device (HPD) use among Israeli manufacturing workers. Participants were 281 men exposed to harmful noise levels for which routine HPD use is required by regulation. In practice, 3 HPD user groups were identified: nonusers (n = 38), occasional users (n = 125), and regular users (n = 118). HPD use was objectively verified. HPD use was primarily related to the personal variables but not to management pressure, coworker pressure, or family support. The most powerful predictors of HPD use were perceived self-efficacy (for long-term HPD use), perceived susceptibility (to hearing loss), and noise annoyance, together explaining 48% of the outcome variance. These findings have implications for interventions aimed at motivating workers to use HPDs regularly.

Adolescent↗

PubMed2000

On measures of explained variance in nonrecursive structural equation models.

Whereas measures of explained variance in a regression and an equation of a recursive structural equation model can be simply summarized by a standard R2 measure, this is not possible in nonrecursive models in which there are reciprocal interdependencies among variables. This article provides a general approach to defining variance explained in latent dependent variables of nonrecursive linear structural equation models. A new method of its estimation, easily implemented in EQS or LISREL and available in EQS 6, is described and illustrated.

Analysis of Variance↗

PubMed2001

Explaining employees' health care costs: a prospective examination of stressful job demands, personal control, and physiological reactivity.

The authors tested the ability of stressful demands and personal control in the workplace to predict employees' subsequent health care costs in a sample of 105 full-time nurses. Both subjective and objective measures of workload demands interacted with personal control perceptions in predicting the cumulative health care costs over the ensuing 5-year period. Tonic elevations in salivary cortisol, moreover, mediated the effects of demands and control on health care costs. Neither the job demands variables nor physiological reactivity measures, however, explained subsequent mental health. The results support findings from the epidemiological literature that demonstrate an important role for employees' control in explaining occupational inequalities in coronary heart disease and mortality. The authors argue that the results also encourage control-enhancing job design interventions by suggesting that their outcomes can benefit both organizations and their members.

Adult↗

PubMed2001

Mineral disequilibrium in lavas explained by convective self-mixing in open magma chambers.

Characteristic features of many porphyritic andesite and dacite lavas are that they are rich in crystals and display a range of disequilibrium features, including reversely zoned crystals, resorption surfaces, wide ranges of mineral compositions and minerals which are not in equilibrium with the surrounding rock matrix. These features are often interpreted as evidence of the mixing of magmas of contrasting composition, temperature and origin. Here, however, we propose that such features can also be caused by convection within a magma body with a single composition, that is heated from below and cooled from above. We describe petrological observations of andesite lava erupted at the Soufrière Hills volcano, Montserrat, which indicate a heating event and the intermingling of crystals that have very different thermal histories. We present experimental data on a representative groundmass composition of this lava, which indicate that it is difficult to explain the calcic compositions of plagioclase overgrowth rims and microphenocrysts unless parts of the magma were at temperatures much higher than the inferred average temperature. The concept of convective self-mixing allows us to explain the occurrence of compositions of minerals that apparently cannot coexist under equilibrium conditions.

Journal Article↗

PubMed2001

Himalayan tectonics explained by extrusion of a low-viscosity crustal channel coupled to focused surface denudation.

Recent interpretations of Himalayan-Tibetan tectonics have proposed that channel flow in the middle to lower crust can explain outward growth of the Tibetan plateau, and that ductile extrusion of high-grade metamorphic rocks between coeval normal- and thrust-sense shear zones can explain exhumation of the Greater Himalayan sequence. Here we use coupled thermal-mechanical numerical models to show that these two processes-channel flow and ductile extrusion-may be dynamically linked through the effects of surface denudation focused at the edge of a plateau that is underlain by low-viscosity material. Our models provide an internally self-consistent explanation for many observed features of the Himalayan-Tibetan system.

Journal Article↗

PubMed1994

Embryonic growth and the evolution of the mammalian Y chromosome. II. Suppression of selfish Y-linked growth factors may explain escape from X-inactivation and rapid evolution of Sry.

The mammalian Y chromosome may be an attractor for selfish growth factors. A suppressor of the selfish growth effects would be expected to spread were it to have an appropriate parent-specific expression rule. A suppressor could act by boosting the resource demands of competing female embryos. This possibility may explain incidences of the escape from X-inactivation and provides a rationale for why these genes typically have Y-linked homologues. Alternatively, a suppressor could act to decrease the resource demands of males with the selfish Y. This possibility is supported by the finding that the size of male, but not female, human infants is negatively correlated to the number of X chromosomes. A protracted arms race between a selfish gene and its suppressor may ensue. Both the variation in copy number of Zfy and the unusually fast sequence evolution of Sry may be explained by such an arms race. As required by the model, human Sry is known to have an X-linked suppressor. Preliminary evidence suggests that, as predicted, rapid sequence evolution of Sry may be correlated with female promiscuity. The case for fast sequence evolution as the product of maternal/foetal conflict is strengthened by consideration of the rapid evolution of placental lactogens in both ruminants and rodents.

Animals↗

PubMed2002

Segregation at three loci explains familial and population risk in Hirschsprung disease.

Hirschsprung disease (HSCR), the most common hereditary cause of intestinal obstruction, shows considerable variation and complex inheritance. Coding sequence mutations in RET, GDNF, EDNRB, EDN3 and SOX10 lead to long-segment (L-HSCR) and syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). We conducted a genome scan in families with S-HSCR and identified susceptibility loci at 3p21, 10q11 and 19q12 that seem to be necessary and sufficient to explain recurrence risk and population incidence. The gene at 10q11 is probably RET, supporting its crucial role in all forms of HSCR; however, coding sequence mutations are present in only 40% of linked families, suggesting the importance of noncoding variation. Here we show oligogenic inheritance of S-HSCR, the 3p21 and 19q12 loci as RET-dependent modifiers, and a parent-of-origin effect at RET. This study demonstrates by a complete genetic dissection why the inheritance pattern of S-HSCR is nonmendelian.

Alleles↗

PubMed1998

Explaining the effect of ethnic group on weight concern: finding a role for family values.

OBJECTIVE: To examine the impact of ethnic group on aspects of weight concern and to assess the role of family values in explaining this association. SUBJECTS AND MEASURES: 20 Asian and 20 white daughters gave a questionnaire to their mother, father and sibling closest in age, concerning their profile characteristics (age, education) values and beliefs and completed a matched questionnaire containing additional measures of aspects of their weight concern. RESULTS: The results showed no differences between the white and Asian daughters in terms of either their restrained eating or body dissatisfaction. However, the results showed consistent differences between the members of the two family groups in terms of the value placed on achievement, child/parent relationships, competition, the role of women, and some differences in terms of materialism, the value of appearance and their idea of the perfect female body. The results were then analysed to assess the best predictors of the daughter's weight concern. Whereas restrained eating was related to the mother's rating of the value of physical appearance and the sibling's ratings of competitiveness and a non-traditional role for women (40% of the variance), the results showed that body dissatisfaction was related to the daughter's rating of materialism, having a father who preferred a thinner female body, the siblings ratings of a non-traditional role for women, degree of concordance within the family concerning the value of competitiveness and the educational level of the 'head of the family' (49% of variance). CONCLUSION: Whereas a dichotomous model of ethnicity may be insufficient to explain differences in aspects of weight concern, an expanded model of cultural beliefs may be a more powerful construct. Accordingly, the absence or presence of differences in weight concern according to ethnic group may simply reflect the extent to which the different groups chosen for analysis are differentiated by these predictive values.

Adolescent↗

PubMed2001

Utility of health belief model as a guide for explaining or predicting breast cancer screening behaviours.

AIM: The purpose of this study was to assess the utility of HBM as a theoretical guide for predicting breast cancer screening and therefore for guiding intervention studies. BACKGROUND: Breast cancer is the leading cause of death for middle age women (35-50) and the second leading cause of cancer deaths in all women in the United States (US). Early detection of breast cancer through screening is the only option available to women. However, less than half of all women in the US participate in screening. The health belief model (HBM), which specifies interactions of values and beliefs about health and their influence on choices, has been widely used to explain screening behaviour. METHODS: An integrative research review analysed 16 published descriptive studies employing HBM. Literature was located through a search of research based studies listed in Cumulative Index of Nursing and Allied Health (CINAHL), Medline, and cancer literature databases and studies cited in other references between 1990 and 1999. FINDINGS: Application of HBM was inconsistent. No study tested nonlinear relationships between variables as specified in the model. At best, the model explained 47% of the variance in screening behaviour when socioeconomic status was included. Otherwise predictive power was low, ranging from 15 to 27%. CONCLUSIONS: While the model provides some description of the values, beliefs and behaviours of middle-aged women primarily, HBM does not appear to have the power to consistently predict behaviours. Further research is needed to provide more thorough depiction of the social, nonhealth care meaning of breast cancer.

Adult↗

PubMed1998

Assimilation of achromatic color cannot explain the brightness effects in the achromatic neon effect.

If the mouths of the pacmen of a Kanizsa square are colored, for example red, then an illusory red transparent square is seen. In many visual theories such 'neon color spreading' is explained by assimilation of chromatic and achromatic color. In this paper the achromatic case was investigated. In a two-alternative forced-choice task thirty observers judged the brightness of achromatic neon figures. The results suggest that assimilation of achromatic color inside and/or outside of the illusory figures cannot explain the brightness effects seen in achromatic neon color spreading. Although these displays may produce assimilation, it appears that contrast (perhaps acting nonlocally) is a stronger influence on their perceived brightness.

Color Perception↗

PubMed2001

Perceptual continuation and depth in visual phantoms can be explained by perceptual transparency.

We try to explain perceptual continuation and depth in the visual-phantom illusion in terms of perceptual transparency. Perceptual continuation of inducing gratings across the occluder in stationary phantoms could be explained with unique transparency, a notion proposed by Anderson (1997 Perception 26 419-453). This view is consistent with a number of previous reports including that of McCourt (1994 Vision Research 34 1609-1617) who criticized the stationary phantom illusion from the viewpoint of his counterphase lightness induction or grating induction, which might involve invalid transparency. Here we confirm that the photopic phantom illusion (Kitaoka et al, 1999 Perception 28 825-834) really gives in-phase lightness induction and involves bistable transparency. It is thus suggested that perceptual continuation and depth in the visual-phantom illusion depend on perceptual transparency.

Analysis of Variance↗

PubMed2001

Explaining mortality rate plateaus.

We propose a stochastic model of aging to explain deviations from exponential growth in mortality rates commonly observed in empirical studies. Mortality rate plateaus are explained as a generic consequence of considering death in terms of first passage times for processes undergoing a random walk with drift. Simulations of populations with age-dependent distributions of viabilities agree with a wide array of experimental results. The influence of cohort size is well accounted for by the stochastic nature of the model.

Aging↗

PubMed1989

Ordered appearance of antigenic variants of African trypanosomes explained in a mathematical model based on a stochastic switch process and immune-selection against putative switch intermediates.

Antigenic variation of African trypanosomes results from the periodic activation of a single new variant cell surface glycoprotein (VSG) gene out of a repertoire of about a 1000 VSG genes. In spite of the apparently random genetic basis of the process of antigenic variation, the relapsing parasitemias are characterized by an as yet unexplained order of appearance of major VSG variants. Here we mathematically test hypotheses concerning the blood-based parasitemia. In our model the antigenic switches occur at random at the DNA level. A variable proportion of the switches has a short intermediate phase in which two different VSGs simultaneously occur on the cell surface. We show that, in a theoretical population of 230 single expressor variants in an immunocompetent or in an immunodeficient host, it is not possible to explain the ordered appearance of variants by affecting the growth coefficients of single expressors or double expressors or by affecting the antigen switch probabilities. Rather, a realistic parasitemia can be obtained if the majority of switches has a double expressor switch-intermediate phase and if the double expressors have a differential susceptibility to the immune control. This study is significant in providing a theoretical basis for the ordered appearance of variants and in explaining previously unresolved discrepancies between the rate of appearance of new variants in culture and in vivo. In addition, testable predictions as to the development of the infections, switch rate of variants, fraction of double expressors, and parasite mortality coefficients are generated.

Animals↗

PubMed1996

Gly-63-->Gln substitution adjacent to His-64 in rodent carbonic anhydrase IVs largely explains their reduced activity.

Carbonic anhydrase (CA) IV is a glycosyl-phosphatidylinositol-anchored isozyme expressed on plasma membranes of capillary endothelial cells and certain epithelial cells of the nephron, the colon, and the genitourinary tract. CA IVs purified from bovine and rabbit lungs are high-activity enzymes, like human CA IV, while CA IV from mouse and rat lungs had only 10-20% as much catalytic activity. To explain the molecular basis for these differences in activity, we isolated and characterized the full-length cDNAs for bovine and rabbit CA IVs and compared their sequences to those we previously reported for human, murine, and rat CA IVs. These comparisons led us to postulate that a Gly-63-->Gln substitution adjacent to His-64 in the rodent enzymes accounts for their lower activity. To test this hypothesis, we made the Gly-63-->Gln mutants of bovine and rabbit CA IVs and the Gln-63-->Gly mutant of murine CA IV by site-directed mutagenesis, and compared the activities of mutant and wild-type CA IVs expressed in COS-7 cells. In addition, we produced recombinant cDNAs expressing secretory forms of the Gly-63 and Gln-63 forms of each of the three enzymes and compared the activities of the enzymes purified from transfected COS-7 cell secretions with the activities of CA IVs purified from lungs. These studies demonstrated that Gly-63 is important for the high activity of bovine and rabbit CA IVs, and they showed that the low activity of murine CA IV could be improved by the Gln-63-->Gly substitution. We suggest that the lower activity of the rodent CA IVs can be largely explained by the Gln-63 substitution which reduces the efficiency of proton transfer by the adjacent His-64.

Amino Acid Sequence↗

PubMed1999

Stripe formation in juvenile Pomacanthus explained by a generalized turing mechanism with chemotaxis.

Current interest in pattern formation can be traced to a seminal paper by Turing, who demonstrated that a system of reacting and diffusing chemicals, called morphogens, can interact so as to produce stable nonuniform concentration patterns in space. Recently, a Turing model has been suggested to explain the development of pigmentation patterns on species of growing angelfish such as Pomacanthus semicirculatus, which exhibit readily observed changes in the number, size, and orientation of colored stripes during development of juvenile and adult stages, but the model fails to predict key features of the observations on stripe formation. Here we develop a generalized Turing model incorporating cell growth and movement, we analyze the effects of these processes on patterning, and we demonstrate that the model can explain important features of pattern formation in a growing system such as Pomacanthus. The applicability of classical Turing models to biological pattern formation is limited by virtue of the sensitivity of patterns to model parameters, but here we show that the incorporation of growth results in robustly generated patterns without strict parameter control. In the model, chemotaxis in response to gradients in a morphogen distribution leads to aggregation of one type of pigment cell into a striped spatial pattern.

Animals↗