SEARCH · PubMed Health

Results for “Explainability”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,045 records · Page 58Linked to original sources

PubMed1995

How could changes in diet explain changes in coronary heart disease mortality in Spain? The Spanish paradox.

We review and compare trends in coronary heart disease (CHD) and stroke mortality in Spain from 1966 to 1990 and changes in food consumption at national and regional levels. Since 1976, a decrease in cardiovascular disease (CVD) mortality in males and females has been observed, and standardized CHD mortality rates have fallen. Stroke mortality decreased during the same period. Trends in food consumption show increases in intakes of meat, dairy products, fish, and fruit, but decreases in consumption of olive oil, sugar, and all foods rich in carbohydrates. Although fat and saturated fat intakes increased, these changes were not accompanied by an increase in CHD mortality rates. This paradoxical situation can be explained by expanded access to clinical care, increased consumption of fruit and fish, improved control of hypertension, and a reduction in cigarette smoking. Diet appears to have an important role in this paradox, but it may not be as critical as other factors. Nevertheless, we suggest dietary guidelines for prevention of CHD in Spain.

Cerebrovascular Disorders↗

PubMed2003

Structural differences between rye and wheat breads but not total fiber content may explain the lower postprandial insulin response to rye bread.

BACKGROUND: Rye bread has a beneficial effect on the postprandial insulin response in healthy subjects. The role of rye fiber in insulin and glucose metabolism is not known. OBJECTIVE: The aim of the study was to determine the effect of the content of rye fiber in rye breads on postprandial insulin and glucose responses. DESIGN: Nineteen healthy postmenopausal women aged 61 +/- 1 y, with a body mass index (in kg/m(2)) of 26.0 +/- 0.6, and with normal glucose tolerance participated in the study. The test products were refined wheat bread (control), endosperm rye bread, traditional rye bread, and high-fiber rye bread; each bread provided 50 g available carbohydrate and was served with breakfast. Plasma glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and serum C-peptide were measured in fasting and 8 postprandial blood samples. In vitro starch hydrolysis and the microscopic structure of the breads were also determined. RESULTS: Postprandial insulin, glucose-dependent insulinotropic polypeptide, and C-peptide responses to the rye breads were significantly lower than the response to the control; no significant differences in insulin and C-peptide responses to the rye breads were found. Glucose and glucagon-like peptide 1 responses to the rye breads were not significantly different from those to the control, except at 150 and 180 min. In vitro starch hydrolysis was slower in all rye breads than in the control, and the structure of continuous matrix and starch granules differed between the rye and control breads. CONCLUSION: Total fiber content does not explain the lower postprandial insulin response to rye bread than to wheat bread, but structural differences between rye and wheat breads might.

Blood Glucose↗

PubMed2004

Waist circumference and not body mass index explains obesity-related health risk.

BACKGROUND: The addition of waist circumference (WC) to body mass index (BMI; in kg/m(2)) predicts a greater variance in health risk than does BMI alone; however, whether the reverse is true is not known. OBJECTIVE: We evaluated whether BMI adds to the predictive power of WC in assessing obesity-related comorbidity. DESIGN: Subjects were 14 924 adult participants in the third National Health and Nutrition Examination Survey, grouped into categories of BMI and WC in accordance with the National Institutes of Health cutoffs. Odds ratios for hypertension, dyslipidemia, and the metabolic syndrome were compared for overweight and class I obese BMI categories and the normal-weight category before and after adjustment for WC. BMI and WC were also included in the same regression model as continuous variables for prediction of the metabolic disorders. RESULTS: With few exceptions, overweight and obese subjects were more likely to have hypertension, dyslipidemia, and the metabolic syndrome than were normal-weight subjects. After adjustment for WC category (normal or high), the odds of comorbidity, although attenuated, remained higher in overweight and obese subjects than in normal-weight subjects. However, after adjustment for WC as a continuous variable, the likelihood of hypertension, dyslipidemia, and the metabolic syndrome was similar in all groups. When WC and BMI were used as continuous variables in the same regression model, WC alone was a significant predictor of comorbidity. CONCLUSIONS: WC, and not BMI, explains obesity-related health risk. Thus, for a given WC value, overweight and obese persons and normal-weight persons have comparable health risks. However, when WC is dichotomized as normal or high, BMI remains a significant predictor of health risk.

Abdomen↗

PubMed1995

Does weight loss from middle age to old age explain the inverse weight mortality relation in old age?

The authors examined body mass index at middle age, body mass index in old age, and weight change between age 50 years and old age in relation to mortality in old age. The study population from the Established Populations for Epidemiologic Studies of the Elderly consisted of 6,387 whites age 70 years or older who experienced 2,650 deaths during the period 1982-1987. Mortality risk was highest for persons in the heaviest quintile of body mass index at age 50 (men, relative risk (RR) = 1.33, 95% confidence interval (CI) 1.13-1.57; women, RR = 1.31, 95% CI 1.12-1.53) compared with persons in the middle quintile. This pattern was reversed for body mass index in old age, with persons in the lowest quintile having the highest mortality risk (men, RR = 1.40, 95% CI 1.19-1.65; women, RR = 1.38, 95% CI 1.17-1.63) relative to persons in the middle quintile. This reversal was explained, in part, by weight change. Compared with persons with stable weight, those who lost 10 percent or more of body weight between age 50 and old age had the highest risk of mortality (men, RR = 1.69, 95% CI 1.45-1.97; women, RR = 1.62, 95% CI 1.38-1.90). Exclusion of participants who lost 10 percent or more of their weight and adjustment for health status eliminated the higher risk of death associated with low weight. The inverse association of weight and mortality in old age appears to reflect illness-related weight loss from heavier weight in middle-age. Weight history may be critical to understanding weight and mortality relations in old age.

Aged↗

PubMed1988

Atrial natriuretic factor in pregnancy-induced hypertension and preeclampsia: increased plasma concentrations possibly explaining these hypovolemic states with paradoxical hyporeninism.

Plasma immunoreactive atrial natriuretic factor 99-126 (ir ANF), plasma volume, plasma renin activity, and plasma aldosterone were measured during pregnancy in 14 normotensive nonpregnant women, 15 normotensive pregnant women, 35 patients with pregnancy-induced hypertension (PIH), and in ten patients with preeclampsia (PE). Repeated measurements were carried out 2 months after delivery in a subgroup of the same patients. The plasma levels of ANF were found to be higher in pregnant normotensive women than in nonpregnant normotensive women, but the decrease of plasma ANF 2 months after delivery was not significant on the basis of seven paired data, so that it cannot presently be stated with certainty that pregnancy per se stimulates ANF secretion. Still higher levels of ANF were found in PIH and, especially, in PE. A positive correlation was found in the pooled population of normotensive and hypertensive pregnant women between plasma ANF and mean arterial pressure. A greater decrease of plasma ANF was found after delivery in the hypertensive patients than in the normotensive controls. This excludes an absolute deficiency of ANF secretion in the pathogenesis of hypertension. These findings suggest a compensatory role of ANF in the prevention of blood pressure increase. Plasma renin activity (PRA) and plasma aldosterone concentrations were higher in normotensive pregnant women than in normotensive nonpregnant women. Compared to normal pregnancy, plasma volume was decreased in PIH (-17%) and in PE (-25%), whereas PRA was less increased in both groups and plasma aldosterone concentration was less increased only in the PE group. The simultaneous high levels of plasma ANF may explain this inappropriate hypostimulation of renin secretion by hypovolemia in these hypertensive states.

Adult↗

PubMed2002

Effect of day and night temperature on internode and stem length in chrysanthemum: is everything explained by DIF?

In many plant species, including chrysanthemum, a strong positive correlation between internode length and DIF [difference between day (DT) and night (NT) temperature] has been observed. However, Langton and Cockshull (1997. Scientia Horticulturae 69: 229-237) reported no such relationship and showed that absolute DT and NT explained internode length rather than DIF. To investigate these conflicting results and to clarify the validity of the DIF concept, cut chrysanthemums (Chrysanthemum 'Reagan Improved') were grown in growth chambers at all 16 combinations of four DT and four NT (16, 20, 24 and 28 degrees C) with a 12 h day length. Length of internode 10, number of internodes and stem length were measured on days 5, 10, 17, 22 and 27 after starting the temperature treatments. Internode length on day 10 showed a positive linear relationship with DIF (R2 = 0.64). However, when internodes had reached their final length in all treatments (day 27), a much stronger positive linear relation was observed (R2 = 0.81). A model to predict final internode length was developed based on the absolute DT and NT responses: both responses were optimum curves and no significant interaction between DT and NT occurred [final internode length (mm) = -32.23 + 3.56DT + 1.08NT - 0.0687DT2 - 0.0371NT2; R2 = 0.91, where TD is day temperature and TN is night temperature]. It is shown that DIF can predict final internode length only within a temperature range where effects of DT and NT are equal in magnitude and opposite in sign (18-24 degrees C). Internode appearance rate, as well as stem length formed during the experiment, showed an optimum response to DT.

Chrysanthemum↗

PubMed2025

Integrating explainable artificial intelligence with multiomics systems biology and electronic health record data mining for personalized drug repurposing in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by region- and patient-specific molecular heterogeneity, which hinders therapeutic design. In this study, we introduce PRISM-ML (PRecision-medicine using Interpretable Systems and Multiomics with Machine Learning), an open-source integrated analysis pipeline that combines interpretable machine learning with systems biology and electronic health records data mining to elucidate the molecular diversity of AD and predict promising drug repurposing opportunities. First, we integrated and harmonized transcriptomic (bulk RNA-seq) and genomic (genome-wide association study) data from 2105 brain samples, each with matched data from the same individual (1363 AD patients, 742 controls; 9 tissues), sourced from three independent studies. Random forest classifiers with SHapley Additive exPlanations identified patient-specific biomarkers; unsupervised clustering resolved 36 molecularly distinct subtissues (defined as clusters of samples within a brain tissue that share a specific expression pattern); and gene-gene coexpression networks prioritized 262 high-centrality bottleneck genes as putative regulators of dysregulated pathways. Next, knowledge graph-based drug repurposing predicted six Food and Drug Administration (FDA)-approved drugs that simultaneously target multiple bottleneck genes and multiple AD-relevant pathways. Notably, in a large US de-identified insurance-claims database (n = 364 733), exposure to promethazine, one of the candidate drugs, was associated with a 57%-62% lower incidence of AD versus an active antihistamine comparator (adjusted hazard ratio 0.38; inverse-probability weighted 0.43; both P < .001), providing real-world support for its repurposing potential. In summary, PRISM-ML, as an explainable multiomics analysis pipeline, is readily transferable to other complex diseases, advancing precision medicine.

Alzheimer Disease↗

PubMed2025

APNet, an explainable sparse deep learning model to discover differentially active drivers of severe COVID-19.

MOTIVATION: Computational analyses of bulk and single-cell omics provide translational insights into complex diseases, such as COVID-19, by revealing molecules, cellular phenotypes, and signalling patterns that contribute to unfavourable clinical outcomes. Current in silico approaches dovetail differential abundance, biostatistics, and machine learning, but often overlook nonlinear proteomic dynamics, like post-translational modifications, and provide limited biological interpretability beyond feature ranking. RESULTS: We introduce APNet, a novel computational pipeline that combines differential activity analysis based on SJARACNe co-expression networks with PASNet, a biologically informed sparse deep learning model, to perform explainable predictions for COVID-19 severity. The APNet driver-pathway network ingests SJARACNe co-regulation and classification weights to aid result interpretation and hypothesis generation. APNet outperforms alternative models in patient classification across three COVID-19 proteomic datasets, identifying predictive drivers and pathways, including some confirmed in single-cell omics and highlighting under-explored biomarker circuitries in COVID-19. AVAILABILITY AND IMPLEMENTATION: APNet's R, Python scripts, and Cytoscape methodologies are available at https://github.com/BiodataAnalysisGroup/APNet.

COVID-19↗

PubMed2025

XPRS: a tool for interpretable and explainable polygenic risk score.

SUMMARY: The polygenic risk score (PRS) is an important method for assessing genetic susceptibility to diseases; however, its clinical utility is limited by a lack of interpretability tools. To address this problem, we introduce eXplainable PRS (XPRS), an interpretation and visualization tool that decomposes PRSs into genes/regions and single nucleotide polymorphism (SNP) contribution scores via Shapley additive explanations (SHAPs), which provide insights into specific genes and SNPs that significantly contribute to the PRS of an individual. This software features a multilevel visualization approach, including Manhattan plots, LocusZoom-like plots, and tables at the population and individual levels, to highlight important genes and SNPs. By implementing with a user-friendly web interface, XPRS allows for straightforward data input and interpretation. By bridging the gap between complex genetic data and actionable clinical insights, XPRS can improve communication between clinicians and patients. AVAILABILITY AND IMPLEMENTATION: The XPRS software is publicly available on GitHub at https://github.com/nayeonkim93/XPRS and can see the demo through our cloud-based web service at https://xprs.leelabsg.org/.

Software↗

PubMed2025

scACCorDiON: a clustering approach for explainable patient level cell-cell communication graph analysis.

MOTIVATION: Combining single-cell sequencing with ligand-receptor (LR) analysis paves the way for the characterization of cell communication events in complex tissues. In particular, directed weighted graphs naturally represent cell-cell communication events. However, current computational methods cannot yet analyze sample-specific cell-cell communication events, as measured in single-cell data produced in large patient cohorts. Cohort-based cell-cell communication analysis presents many challenges, such as the nonlinear nature of cell-cell communication and the high variability given by the patient-specific single-cell RNAseq datasets. RESULTS: Here, we present scACCorDiON (single-cell Analysis of Cell-Cell Communication in Disease clusters using Optimal transport in Directed Networks), an optimal transport algorithm exploring node distances on the Markov Chain as the ground metric between directed weighted graphs. Benchmarking indicates that scACCorDiON performs a better clustering of samples according to their disease status than competing methods that use undirected graphs. We provide a case study of pancreas adenocarcinoma, where scACCorDion detects a sub-cluster of disease samples associated with changes in the tumor microenvironment. Our study case corroborates that clusters provide a robust and explainable representation of cell-cell communication events and that the expression of detected LR pairs is predictive of pancreatic cancer survival. AVAILABILITY AND IMPLEMENTATION: The code of scACCorDiON is available at https://scaccordion.readthedocs.io/en/latest/. and https://doi.org/10.5281/zenodo.15267648. The survival analysis package can be found at https://github.com/CostaLab/scACCorDiON.su.

Humans↗

PubMed1997

Enhanced choline acetyltransferase activity does not explain the action of inhaled convulsants.

Enhancement of choline acetyltransferase (ChAT) activity and increased intraneuronal acetylcholine (ACh) may explain the convulsant activity of some inhaled compounds. Enflurane, for example, enhances such activity. Accordingly, we measured choline acetyltransferase (ChAT) activity in rat cortical synaptosomes in the presence of two inhaled convulsants, flurothyl (CF3CH2OCH2CF3) and 1,2-dichlorohexafluorocyclobutane at partial pressures below and greatly exceeding those which produce convulsions in vivo. Neither agent changed the kinetic parameters, maximum velocity (vmax) or Michaelis constant (Km). The vmax for controls in the flurothyl series was 016 (0.06) nmol mg-1 min-1 and the Km was 0.23 (0.11) mmol litre-1. For the 1,2-dichlorohexafluorocyclobutane series of experiments the results for the controls were vmax 0.23 (0.10) nmol mg-1 min-1 and Km 0.20 (0.08) mmol litre-1. Modification of ChAT activity did not contribute to the excitatory effects of these agents.

Administration, Inhalation↗

PubMed2006

Large volume N2O uptake alone does not explain the second gas effect of N2O on sevoflurane during constant inspired ventilation.

BACKGROUND: The second gas effect (SGE) is considered to be significant only during periods of large volume N(2)O uptake (VN(2)O); however, the SGE of small VN(2)O has not been studied. We hypothesized that the SGE of N(2)O on sevoflurane would become less pronounced when sevoflurane administration is started 60 min after the start of N(2)O administration when VN(2)O has decreased to approximately 125 ml min(-1), and that the kinetics of sevoflurane under these circumstances would become indistinguishable from those when sevoflurane is administered in O(2). METHODS: Seventy-two physical status ASA I-II patients were randomly assigned to one of six groups (n=12 each). In the first four groups, sevoflurane (1.8% vaporizer setting) administration was started 0, 2, 5 and 60 min after starting 2 litre min(-1) O(2) and 4 litre min(-1) N(2)O, respectively. In the last two groups, sevoflurane (1.8 or 3.6% vaporizer setting) was administered in 6 litre min(-1) O(2). The ratios of the alveolar fraction of sevoflurane (Fa) over the inspired fraction (Fi), or Fa/Fi, were compared between the groups. RESULTS: Sevoflurane Fa/Fi was larger in the N(2)O groups than in the O(2) groups, and it was identical in all four N(2)O groups. CONCLUSIONS: We confirmed the existence of a SGE of N(2)O. Surprisingly, when using an Fa of 65% N(2)O, the magnitude of the SGE was the same with large or small VN(2)O. The classical model and the graphical representation of the SGE alone should not be used to explain the magnitude of the SGE. We speculate that changes in ventilation/perfusion inhomogeneity in the lungs during general anaesthesia result in a SGE at levels of VN(2)O previously considered by most to be too small to exert a SGE.

Adolescent↗

PubMed1995

Evolution of the neurohormonal hypothesis to explain the progression of chronic heart failure.

During the last 20 years, physicians have generally regarded heart failure as a haemodynamic disorder in an attempt to explain patients' symptoms and disability. This model led to the widespread evaluation of peripheral vasodilators and the development of novel positive inotropic agents, but long-term use of these drugs failed to improve symptoms and was frequently accompanied by an increase in the risk of death. These clinical observations raised concerns about the validity of the haemodynamic hypothesis and led to the development of alternative models of heart failure--most importantly, the neurohormonal hypothesis. According to the neurohormonal model, heart failure develops and progresses because endogenous neurohormonal systems that are activated by the initial injury to the heart exert a deleterious effect on the circulation. Recognition of the importance of neurohormonal activation has led to the intense interest in the use of neurohormonal antagonists--converting--enzyme inhibitors and beta-adrenergic blockers--in the treatment of chronic heart failure. The results of randomized clinical trials with a variety of neurohormonal antagonists have been encouraging, and widespread acceptance of these drugs is expected to lead to clinical benefits for many patients.

Adrenergic beta-Antagonists↗

PubMed2006

Factors explaining the under-use of reperfusion therapy among ideal patients with ST-segment elevation myocardial infarction.

AIMS: To determine the relative impact of time to hospital arrival, baseline cardiovascular risk (i.e.TIMI mortality risk index), intracerebral haemorrhage risk, and comorbid disease burden on the likelihood of not receiving reperfusion therapy among ST-segment elevation myocardial infarction (STEMI) patients without contraindications to treatment. METHODS AND RESULTS: Retrospective population-based cohort of 3994 patients admitted to 103 acute care hospitals with chest pain and STEMI within 12 h of symptom onset in Ontario, Canada, between 1999 and 2001. Patients with one or more documented absolute or relative contraindication (n = 909) were excluded from the analyses. Reperfusion therapy was defined as the receipt of either fibrinolysis or primary percutaneous coronary intervention. Multivariable analysis and likelihood chi2 was used to quantify the importance of each factor in predicting the non-utilization of therapy. In total, 23.1% of patients received no reperfusion therapy. Listed in order from greatest to least importance, predictors of non-utilization of reperfusion therapy included increasing time to hospital presentation (likelihood chi2 31.6, P < 0.001), higher intracerebral haemorrhage risk (likelihood chi2 27.1, P < 0.001), higher baseline cardiovascular risk (likelihood chi2 25.4, P < 0.001), and greater number of chronic comorbid conditions (likelihood chi2 15.4, P < 0.001). The importance of each factor on non-utilization was independent, additive, not explained by age effects alone, or driven by subgroups traditionally under-represented in clinical trials. CONCLUSION: Care gaps in the use of reperfusion therapy widen with both increasing baseline cardiovascular risk and increasing intracerebral haemorrhage risk. Future studies should examine whether the implementation of clinical decision tools which allow for more accurate risk-benefit tradeoff predictions improve the treatment gaps when using life-saving therapies in this patient population.

Angina Pectoris↗

PubMed2001

Do health behaviour and psychosocial risk factors explain the European east-west gap in health status?

BACKGROUND: Mortality rates are much more favourable in Western European countries than in those of Eastern Europe. Health behaviour and psychosocial factors have been suggested to be important contributors to East-West differences in mortality and health status. METHODS: To compare reported health status as well as health behaviours and psychosocial factors which may be related to unequal health status in different parts of Europe, standardised postal surveys of representative populations samples were conducted in six Eastern and Western European areas. RESULTS: Higher mortality in the eastern populations was associated with more reported morbidity and generally more negative health ratings. Health behaviours and psychosocial factors were also more negative in the East. Multivariate analyses suggested that the East-West difference in health status may be partly explained by differences in health behaviours and psychosocial factors. CONCLUSION: Efforts to promote health in Eastern Europe should concentrate both on the promotion of healthier lifestyles and on improvement of social and economic conditions.

Adult↗

PubMed1987

Explaining variation in general practitioner referrals to hospital.

Reported rates of referral by individual general practitioners to hospitals range from less than 1% of all consultations to more than 20%. Research on variations in rates of referral by general practitioners in the UK is reviewed here. Studies have largely failed to account for variation either in terms of differences in the characteristics of patients or differences in the doctors and their practices. It is argued that this failure arises because most studies do not distinguish between different types of referral or reasons for making a referral. In order to begin to explain variations it is necessary to identify the stages in the complex process of decision making. A theoretical model of the referral decision is advanced, which is intended to provide a framework for further research on the referral process.

Decision Making↗

PubMed2005

Explaining variation in antidepressant prescribing rates in east London: a cross sectional study.

BACKGROUND: Rates of depression and anxiety in south Asian populations are lower than expected. It remains uncertain whether this reflects a real difference in prevalence or differences in case recognition and management. OBJECTIVE: To examine whether concordance of culture or ethnicity between doctors and patients affects the prescribing rates for antidepressant and anxiolytic medications in general practice populations, taking into account demography, practice size and organization. METHOD: A cross-sectional general practice study, using practice and demographic data from primary care trusts, doctors' place of qualification from the General Medical Council, combined with practice level prescribing data from the prescription pricing authority (PACT) for the period 2000-2002. Set in 139 practices in the east London primary care trusts (PCTs) of Tower Hamlets, Hackney and Newham, multiethnic areas with large populations of south Asian residents and doctors. The main outcome measure was the annual prescribing rates for each group of drugs, calculated as the mean of two years average daily quantities (ADQs) for each medication, divided by the practice population. RESULTS: In east London the median prescribing rate (ADQs) for all antidepressants was 7.97 (inter-quartile range 4.91-10.76), for all anxiolytics and hypnotics 2.27 (interquartile range 1.11-3.96). There were significant differences in prescribing rates between practices with UK trained GPs and practices with south Asian trained GPs, with the highest rates of antidepressant prescribing in practices with UK trained GPs and low proportions of south Asian patients. No differences were found in anxiolytic and hypnotic prescribing rates between these practices. 57% of the variation in prescribing between practices could be explained by a model including the place of GP qualification, the proportion of registered women, older (>65) patients, and the list size per full time GP. CONCLUSIONS: Compared with previous studies prescribing rates for antidepressants have almost doubled over five years, the greatest increase being for selective serotonin re-uptake inhibitors (SSRIs). There is a modest fall in prescribing rates for anxiolytics and hypnotics. Concordance between south Asian practice populations and doctors from similar south Asian cultures is not associated with an increase in antidepressant prescribing. Lower rates of prescribing in practices with south Asian trained doctors occur regardless of the ethnic composition of the practice population. Reasons for these differences are uncertain, but may include differences in explanatory models for presenting symptoms, and management strategies which rely less on a biomedical paradigm.

Aged↗

PubMed2001

Have the oldest old adults ever been frail in the past? A hypothesis that explains modern trends in survival.

Three important results concerning the shape and the trends of the human mortality rate were discussed recently in demographic and epidemiological literature. These are the deceleration of the mortality rate at old ages, the tendency to rectangularization of the survival curve, and the decline of the old age mortality observed in the second part of the 20th century. In this paper we show that all these results can be explained by using a model with a new type of heterogeneity associated with individual differences in adaptive capacity. We first illustrate the idea of such a model by considering survival in a mixture of two subpopulations of individuals (called "labile" and "stable"). These subpopulations are characterized by different Gompertz mortality patterns, such that their mortality rates cross over. The survival chances of individuals in these subpopulations have different sensitivities to changes in environmental conditions. Then we develop a more comprehensive model in which the mortality rate is related to the adaptive capacity of an organism. We show that the trends in survival patterns experienced by a mixture of such individuals resemble those obtained in an analysis of empirical data on survival in developed countries. Lastly, we present evidence of the existence of subpopulations of phenotypes in both humans and experimental organisms, which were used as prototypes in our models. The existence of such phenotypes provides the possibility that at least part of today's centenarians originated from an initially frail part of the cohort.

Adolescent↗