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Effects of progressive resistance training on body composition in frail older adults: results of a randomized, controlled trial.

BACKGROUND: Progressive resistance exercise training (PRT) has been shown to increase muscle strength and fat-free mass (FFM) in elderly persons. Limited information is available regarding the effects of PRT on lean and fat mass in frail elderly persons. METHODS: Ninety-one community-dwelling sedentary men and women, 78 years and older with physical frailty (defined using standardized objective criteria) were enrolled in a 9-month trial of exercise training (ET). Physical frailty was defined as having 2 of the 3 following criteria: modified Physical Performance Test score between 18 and 32, peak aerobic power between 10 and 18 ml/kg/min, or self-report of difficulty or assistance with two instrumental activities of daily living or one basic activity of daily living. Participants were randomly assigned to either a control (CTL) group that performed a low intensity home exercise program or a supervised ET group that performed 3 months of low intensity exercise and 3 months of PRT. RESULTS: After completion of PRT, ET participants had greater improvements than did CTL participants in maximal voluntary force production for knee extension (mean Delta +5.3 +/- 13 ft/lb vs +1.1 +/- 11 ft/lb, p =.05), measured using isokinetic dynamometry. Total body FFM (measured using dual energy x-ray absorptiometry) increased in the ET group, but not in the CTL group (mean Delta +0.84 +/- 1.4 kg vs +0.01 +/- 1.5 kg, p =.005). Total, trunk, intra-abdominal, and subcutaneous fat mass (measured using dual energy x-ray absorptiometry and (1)H-magnetic resonance imaging) did not change in response to PRT. CONCLUSIONS: Three months of supervised PRT induced improvements in maximal voluntary thigh muscle strength and whole body FFM in frail, community-dwelling elderly women and men. This supervised exercise program may not be sufficient to reduce whole-body or intra-abdominal fat area in this population.

Aged↗

The endeavor of high maintenance homeostasis: resting metabolic rate and the legacy of longevity.

Metabolism, the continuous conversion between structural molecules and energy, is life in essence. Size, metabolic rate, and maximum life span appear to be inextricably interconnected in all biological organisms and almost follow a "universal" law. The notion of metabolic rate as the natural "rate of living" filled most of the academic discussion on aging in the early 20th century to be later replaced by the free-radical theory of aging. We argue that the rate of living theory was discarded too quickly and that studying factors affecting resting metabolic rate during the aging process may provide great insight into the core mechanisms explaining differential longevity between individuals, and possibly the process leading to frailty. We predict that measures of resting metabolic rate will be introduced in geriatric clinical practice to gather information on the degree of multisystem dysregulation, exhaustion of energy reserve, and risk of irreversible frailty.

Adaptation, Physiological↗

Neglect of dropout underestimates effects of death in longitudinal studies.

Investigations of terminal declines in mental abilities have assessed cognitive performance at a single time point and retrospectively compared survivors and decedents at a single later census date. Neglect of outcomes other than death, such as dropout, causes a loss of information on the relative frailty of survivors and deceased persons before the census date and on incidence of mortality and frailty among survivors after the census date. This discards information on differences in health status between younger and older survivors. The Heim AH4-1 intelligence test was given to 4,228 people between the ages of 42 and 92 years, and both deaths and dropouts were logged during three successive census periods during the subsequent 11 years. Within and across census periods, effects of impending death and dropout did not differ, decreasing with time from initial assessment. Thus the effects of terminal decline, or indeed of any other variable affecting cognitive performance, are miscalculated if dropout is ignored.

Adult↗

Determining the pattern of community care: is coresidence more important than caregiver relationship?

Researchers have previously emphasized the importance of kinship tie to explaining the pattern of care received by a disabled elder. For example, it has been argued that spouses are a distinct group of caregivers, i.e., they provide more care with less help from others and experience more stress. However, based on the theory of primary group structures and functions, this study hypothesized that coresidence rather than the kinship tie is more important in determining the pattern of caregiving. When spouses are compared to other coresiding caregivers, patterns of informal care and use of formal services are similar. Variance in amounts of informal care is explained by elder gender and frailty level rather than by caregiver relationship. Similarly, level of frailty was the only important predictor of use of formal services.

Activities of Daily Living↗

Osteoporosis considerations in the frail elderly.

Osteoporosis is a growing public health problem throughout the world, in part because of the increasing numbers of people living beyond the age of 65 years. Skeletal fractures are the clinical manifestation of the disease, with older patients the most severely affected. Conditions associated with frailty such as falls and reduced muscle strength likely contribute to fractures, causing substantial mortality, morbidity, and economic cost. Screening guidelines for osteoporosis have been issued recently and take into account multiple risk factors for this condition. Falls are the chief mechanism by which osteoporotic fractures occur. Nonpharmacologic interventions for osteoporosis mainly address fall and frailty prevention, whereas pharmacologic interventions target bone loss through decreasing bone resorption, increasing bone formation, or a combination of both processes. Although guidelines for intervention strategies are in flux, it is now suggested that absolute fracture risk rather than diagnostic thresholds be used to determine the timing for therapeutic intervention. Individual risks and benefits of therapies need to be considered before choosing a therapeutic regimen.

Aged↗

Unforeseen inpatient mortality among veterans with schizophrenia.

BACKGROUND: Patients with schizophrenia have co-occurring medical conditions, like other patients, but may lack the capacity to provide good self-care or to work with their providers to ensure appropriate medical treatment. We hypothesized that death among patients with schizophrenia occurs more frequently after minimal care of comorbid conditions. METHODS: All patients who died in veterans affairs (VA) hospitals during FY02 were categorized as to type of death: unforeseen (age <80 years, 1-2 inpatient days past year), cancer, organ failure (heart, lungs, kidneys), frailty (dementias, hip fractures, dehydration, etc.), or other deaths. Logistic regression explored factors in unforeseen death. RESULTS: During the year, 27,798 patients died in VA facilities; 3% had schizophrenia (n = 943). Roughly two-thirds of all deaths were from cancer or organ failure, 11% frailty, 9% other, and 8% met criteria for unforeseen death. Among patients with schizophrenia, however, 20% fell into the unforeseen death category. In an adjusted model, schizophrenia was associated with a 2-fold increased risk of unforeseen death compared with any other category (odds ratio = 2.4, 95% confidence interval 1.6-3.4). Unforeseen death was less likely among patients with substance abuse diagnoses in the year before death and more likely when patients had no outpatient medical care. CONCLUSIONS: VA patients with schizophrenia were more likely to die as inpatients with little previous-year care compared with other inpatient decedents without schizophrenia. Outreach efforts may be necessary to engage patients with schizophrenia in treatment of potentially life-threatening conditions.

Adult↗

Beyond Glycaemia: Fear of Hypoglycaemia, Cognition and Functional Mobility After Advanced Hybrid Closed-Loop Therapy in Older Adults With Type 1 Diabetes: A Prespecified Secondary Analysis of a Randomised, Single-Centre Study.

BACKGROUND: Evidence on psychological, cognitive and functional outcomes of advanced diabetes technologies in older adults with long-standing type 1 diabetes (T1D) remains limited. We evaluated whether initiation of advanced hybrid closed-loop (AHCL) therapy was associated with changes in fear of hypoglycaemia, diabetes distress, psychological well-being, cognition, frailty-related measures and mobility-related function in adults aged &#x2265;&#x2009;65&#x2009;years with T1D. METHODS: This prespecified, exploratory secondary analysis was conducted within a single-centre, open-label, randomised, controlled, parallel-group trial including adults aged &#x2265;&#x2009;65&#x2009;years with long-standing T1D. Participants were randomly assigned (1:1) to initiate AHCL therapy using the MiniMed 780G system or to continue standard diabetes treatment. The secondary outcomes included WHO-5, the 17-item Diabetes Distress Scale (DDS), Hypoglycemia Fear Survey-II (HFS-II), Montreal Cognitive Assessment, Digit Symbol Substitution Test, Fried frailty phenotype and performance-based functional measures. No formal sample-size calculation was performed for these secondary outcomes. RESULTS: Thirty-one participants were randomised and 29 completed 12&#x2009;months of follow-up and were included in the treatment-effect analyses. In the baseline-adjusted primary analysis, AHCL therapy was associated with a lower HFS-II score than standard treatment (adjusted mean difference -18.9; 95% CI: -32.4 to -5.4; nominal p&#x2009;=&#x2009;0.008), although this finding did not remain statistically significant after Holm correction (adjusted p&#x2009;=&#x2009;0.104) or in an exploratory model additionally adjusted for sex (difference -13.6; 95% CI: -32.2 to 5.0; p&#x2009;=&#x2009;0.145). Diabetes distress, psychological well-being, global cognition and processing speed did not differ between groups. In sex-adjusted sensitivity analyses, the between-group differences remained statistically significant for 6-min walk distance (92.6&#x2009;m; 95% CI: 36.8 to 148.3; p&#x2009;=&#x2009;0.002) and Timed Up and Go performance (-2.27&#x2009;s; 95% CI: -4.28 to -0.27; p&#x2009;=&#x2009;0.028), but not for gait speed (0.27&#x2009;m/s; 95% CI: -0.05 to 0.59; p&#x2009;=&#x2009;0.099). At 12&#x2009;months, 12 of 14 AHCL participants were robust and 2 were pre-frail; in the control group, 11 of 15 were robust and 4 were pre-frail. No participant was classified as frail at follow-up. CONCLUSIONS: In this small, selected cohort, AHCL therapy was associated with a nominally lower fear-of-hypoglycaemia score and better performance on selected mobility-related tests over 12&#x2009;months. The fear-of-hypoglycaemia finding did not remain statistically significant after correction for multiple comparisons or additional adjustment for sex. Six-minute walk distance and Timed Up and Go remained statistically significant in the exploratory sex-adjusted sensitivity analyses, whereas the gait-speed difference did not. No measurable between-group deterioration in global cognition or processing speed was observed. These exploratory findings require confirmation in larger studies with balanced representation by sex and direct measurement of physical activity. These findings also support a person-centred clinical message: older age alone should not be regarded as a barrier to AHCL when treatment is introduced with individualised education and appropriate ongoing support.

Humans↗

Estimating regression parameters and degree of dependence for multivariate failure time data.

Multivariate failure time data are frequently encountered in longitudinal studies when subjects may experience several events or when there is a grouping of individuals into a cluster. To take into account the dependence of the failure times within the unit (the individual or the cluster) as well as censoring, two multivariate generalizations of the Cox proportional hazards model are commonly used. The marginal hazard model is used when the purpose is to estimate mean regression parameters, while the frailty model is retained when the purpose is to assess the degree of dependence within the unit. We propose a new approach based on the combination of the two aforementioned models to estimate both these quantities. This two-step estimation procedure is quicker and more simple to implement than the EM algorithm used in frailty models estimation. Simulation results are provided to illustrate robustness, consistency, and large-sample properties of estimators. Finally, this method is exemplified on a diabetic retinopathy study in order to assess the effect of photocoagulation in delaying the onset of blindness as well as the dependence between the two eyes blindness times of a patient.

Biometry↗

Circadian rest-activity rhythms in demented and nondemented older community residents and their caregivers.

OBJECTIVE: Disruptive nocturnal behaviors (DNBs) of older people often threaten the caregiving arrangements on which their community tenure depends. Dementing disorders are especially prone to result in disrupted sleep and agitated behaviors ("sundowning"). The objective here was to develop an objective correlate of DNBs, by which their severity and effects on caregivers can be measured. DESIGN: Quantitative comparison of subjective sleep and motor activity patterns in older people and their caregivers. It was hypothesized that older people with reported DNBs would be more motorically active at night than their caregivers. SETTING: Subjects' homes. PARTICIPANTS: Twenty-five demented and 18 nondemented older day-care participants and their paired caregivers. MEASUREMENTS: Older subjects and caregivers simultaneously kept daily sleep logs and recorded wrist motor activity every .5 minute for 9 days. A novel method was devised to identify and exclude from analysis periods when the activity monitor was not being worn. Such periods were common. Activity data were analyzed by computing hourly means and by fitting cosine models by least squares. RESULTS: Demented older people were not significantly more active at night than their caregivers, though group differences varied by time of night. They were significantly less active in the daytime than were their caregivers. Nondemented older people were significantly more active at night than their caregivers and were as active by day as their caregivers. The caregivers of demented and nondemented older people had similar rest-activity patterns. The mean amplitudes of cosine models were smaller in the older adults. Acrophases (peaks) fell between 2 and 3 pm and did not differ significantly among the groups. CONCLUSIONS: As a result of increased nighttime motor activity and decreased daytime activity, rest-activity rhythms were flatter in older adults than in caregivers. This was not explained fully by age and does not necessarily imply that the output of a circadian pacemaker was low. Decreased daytime activity may have resulted from deficient physical stimulation or frailty. Frailty may also explain why nighttime activity was not more elevated in the demented older people. Increased nighttime activity is probably explained by depression, sleep-schedule disturbances, restless legs, or other sleep disorders. Judging by their shared variations of activity, caregivers interacted mainly with the demented older people at bedtime and at rising time in the morning.

Aged↗

Persistent pain in frail older adults after hip fracture repair.

OBJECTIVES: To identify factors associated with persistent hip pain in elderly hip fracture patients with physical frailty. DESIGN: Cohort study. SETTING: Community-based study conducted at academic medical center. PARTICIPANTS: Eighty-eight men and women (mean age+/-standard deviation 80+/-7 years) with a recent hip fracture (mean 14.5+/-4.8 weeks after hip fracture repair) and physical frailty, defined as a modified Physical Performance Test Score between 12 and 28, enrolled in an exercise intervention trial. MEASUREMENTS: Dependent variable was self-report of moderate to severe regional hip pain in the week preceding the baseline interview. Independent variables were self-reported demographic information, health characteristics, and activity of daily living (ADL) function; Yesavage Mood Score (YMS); 36-item Short Form percentile scores; and objective measurements of lower extremity strength, range of motion, balance, and gait. RESULTS: Forty-two percent of the sample reported moderate or severe hip pain at the baseline assessment. Moderate/severe pain was related to difficulty with ADL performance and multiple measures of quality of life. Variables independently associated with moderate/severe hip pain were frequency of pain medication use (adjusted odds ratio (AOR)=5.75, 95% confidence interval (CI)=2.23-14.82, P=.003), YMS score (AOR=2.69, 95% CI=1.18-6.12, P=.02), and knee extension at 60 degrees /s in the fractured limb (AOR=0.96, 95% CI=0.92-1.0, P=.05, model coefficient of determination=0.34). CONCLUSION: Persistent hip pain is a frequent symptom in frail elderly community-dwelling hip fracture patients. Pain medication use, symptoms of depression, and skeletal muscle weakness of the fractured leg are independent correlates of moderate to severe hip pain in this patient population. Clinicians should assess for, and address, persistent pain in this patient population.

Activities of Daily Living↗

The dynamic nature of mobility disability in older persons.

OBJECTIVES: To determine the rates of clinically meaningful transitions in mobility disability; evaluate how these transitions differ according to age, sex, and physical frailty; and depict the duration of the resulting episodes of mobility disability. DESIGN: Prospective cohort study. SETTING: General community in greater New Haven, Connecticut, from March 1998 to October 2004. PARTICIPANTS: Seven hundred fifty-four community-living older persons, aged 70 and older, who were nondisabled (i.e., required no personal assistance) in four activities of daily living. MEASUREMENTS: Mobility disability, defined as the inability to walk one quarter of a mile and to climb a flight of stairs, respectively without personal assistance, was assessed every month for up to 5 years. RESULTS: For both mobility tasks, rates per 1,000 person-months were higher for transitions from no disability to intermittent disability (34.7 for walking one quarter of a mile and 17.4 for climbing a flight of stairs), intermittent to continuous disability (52.0 and 42.5), continuous to intermittent disability (35.4 and 31.5), and intermittent to no disability (68.6 and 85.4) than for other transitions. Older age, female sex, and physical frailty were associated with greater likelihood of transition to states of greater disability and lower likelihood of regaining independent mobility. CONCLUSION: Mobility disability in older persons is a highly dynamic process, characterized by frequent transitions between states of independence and disability. Programs designed to enhance independent mobility should focus not only on the prevention of mobility disability but also on the restoration and maintenance of independent mobility in older persons who become disabled.

Activities of Daily Living↗

The epidemiology of bathing disability in older persons.

OBJECTIVES: To quantify the burden of bathing disability over time; to determine whether the burden of bathing disability differs according to age, sex, and physical frailty; and to evaluate the relationship between disability in bathing and disability in other essential activities of daily living (ADLs). DESIGN: Prospective cohort study. SETTING: General community in greater New Haven, Connecticut. PARTICIPANTS: Seven hundred fifty-four community-living older persons aged 70 and older who were nondisabled (required no personal assistance) in four essential ADLs: bathing, dressing, transferring from a chair, and walking inside the house. MEASUREMENTS: Bathing disability, defined as the inability to wash and dry one's whole body without personal assistance, was assessed every month for up to 6 years, along with disability in dressing, transferring, and walking. RESULTS: Over the course of 6 years, 440 participants (58.4%) had at least one episode of bathing disability, and 266 (34.0%) had multiple episodes, with the duration of each episode averaging about 6 months. Whether assessed as number of episodes, duration of episodes, incidence rates, or number of months per 100 months, the burden of bathing disability was greatest in participants who were physically frail and was consistently higher in women than men and in participants who were aged 80 and older than those who were aged 70 to 79. Most episodes of bathing disability (86.1%) were not preceded in the prior month by disability in dressing, transferring, or walking, and nearly half (48.3%) were not accompanied at onset by disability in one or more of these other ADLs. In a multivariable model that included age, sex, and physical frailty, the onset of bathing disability increased the likelihood of developing disability in the other essential ADLs the following month fivefold (hazard ratio=5.1, 95% confidence interval=4.1-6.4). CONCLUSION: Disability in bathing may serve as a sentinel event in the disabling process. Given the recurrent nature of bathing disability, programs designed to enhance independent bathing will need to focus not only on the prevention of bathing disability, but also on the restoration and maintenance of independent bathing in older persons who become disabled.

Activities of Daily Living↗

Semiparametric analysis of survival data with left truncation and dependent right censoring.

Studies of chronic life-threatening diseases often involve both mortality and morbidity. In observational studies, the data may also be subject to administrative left truncation and right censoring. Because mortality and morbidity may be correlated and mortality may censor morbidity, the Lynden-Bell estimator for left-truncated and right-censored data may be biased for estimating the marginal survival function of the non-terminal event. We propose a semiparametric estimator for this survival function based on a joint model for the two time-to-event variables, which utilizes the gamma frailty specification in the region of the observable data. First, we develop a novel estimator for the gamma frailty parameter under left truncation. Using this estimator, we then derive a closed-form estimator for the marginal distribution of the non-terminal event. The large sample properties of the estimators are established via asymptotic theory. The methodology performs well with moderate sample sizes, both in simulations and in an analysis of data from a diabetes registry.

Analysis of Variance↗

Estimating haplotype relative risks on human survival in population-based association studies.

Association-based linkage disequilibrium (LD) mapping is an increasingly important tool for localizing genes that show potential influence on human aging and longevity. As haplotypes contain more LD information than single markers, a haplotype-based LD approach can have increased power in detecting associations as well as increased robustness in statistical testing. In this paper, we develop a new statistical model to estimate haplotype relative risks (HRRs) on human survival using unphased multilocus genotype data from unrelated individuals in cross-sectional studies. Based on the proportional hazard assumption, the model can estimate haplotype risk and frequency parameters, incorporate observed covariates, assess interactions between haplotypes and the covariates, and investigate the modes of gene function. By introducing population survival information available from population statistics, we are able to develop a procedure that carries out the parameter estimation using a nonparametric baseline hazard function and estimates sex-specific HRRs to infer gene-sex interaction. We also evaluate the haplotype effects on human survival while taking into account individual heterogeneity in the unobserved genetic and nongenetic factors or frailty by introducing the gamma-distributed frailty into the survival function. After model validation by computer simulation, we apply our method to an empirical data set to measure haplotype effects on human survival and to estimate haplotype frequencies at birth and over the observed ages. Results from both simulation and model application indicate that our survival analysis model is an efficient method for inferring haplotype effects on human survival in population-based association studies.

Aged↗

An interpersonal approach to hysteria.

The author defines hysteria in terms of specific observable classes of interpersonal behaviors and examines the impact of these behaviors on the receiver. The hysteric communicates frailty and helplessness, thus structuring the interpersonal environment to ensure attention and inhibit aggression. The development of these roles is shown in histories of female hysterics, who were selectively reinforced for frailty, seductiveness, and passivity as children. The major classes of symptoms shown by adult hysterics--conversion symptoms and dissociative reactions--reflect these interpersonal roles. The author concludes that hysteria is a relatively specific interpersonal style that results from cultural, social, and interpersonal influences.

Attention↗

How important is functional status as a predictor of service use by older people?

In studies of older people, it is often assumed that biophysical, or functional, status is the primary determinant of formal service use. This article reports baseline data from a longitudinal study of a community-based, linked random sample of frail elders (n = 635) and their informal caregivers (n = 429) to investigate the relative contribution of social circumstances to the use of community-based formal services. Elder respondents were categorized into three groups defined by their primary source of care: (a) informal only, (b) mixed help with predominantly informal care, (c) mixed help with predominantly formal services. Of the respondents, 79% received most of their help from informal caregivers, whereas 21% relied on formal services for most of their assistance. A series of logistic regression models were developed to identify variables that discriminated between major sources of care. The social factor of living alone is the consistent predictor of reliance on formal services. Only for those elders living alone does the physical factor of level of frailty predict reliance on formal services. Elders who live with a caregiver, particularly a spouse, are likely not to use any formal services regardless of their level of frailty. Finally, elders reliant on formal services receive much less care overall.

Activities of Daily Living↗

Investigation of the Causal Association Between Biological Aging Indicators and Vascular Disease Through Two-Sample Mendelian Randomization Analysis.

ObjectiveThis study used two-sample Mendelian Randomization to investigate the causal link between multiple biological aging indicators and vascular disease.MethodsSummary genetic data was obtained from genome-wide association studies (GWAS) focusing on aging-related exposures and various vascular disease outcomes. The exposures included granulocyte proportions, PAI-1 (plasminogen activator inhibitor-1), telomere lengths, and the Frailty Index. The primary analysis employed the Inverse Variance Weighted (IVW) method to estimate causal relationships, supported by MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, including Cochran's Q test, MR-Egger regression, leave-one-out test, and the MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) test, were conducted to evaluate heterogeneity and pleiotropy.ResultsThe analysis revealed distinct pathways after sensitivity adjustments. A higher genetically predicted Frailty Index was associated with an increased risk of abdominal aortic aneurysm (OR=2.5935, 95% CI: 1.3936-4.8268, P=0.0026, false discovery rate (FDR)=0.0475), atherosclerosis excluding cerebral and coronary sclerosis (OR=2.0262, 95% CI:1.5179-2.705, P=1.66&#xd7;10-6, FDR=1&#xd7;10-4), and arterial thromboembolic events (OR = 4.0306, 95% CI: 1.7133-9.4818, P = 0.0014, FDR = 0.0337). Conversely, longer telomere length demonstrated a strong, specific protective effect against abdominal aortic aneurysm (OR=0.5008, 95% CI:0.4111-0.6100, P=6.42&#xd7;10-12, FDR=9.25&#xd7;10-10), indicating that shorter telomere length is associated with an increased risk of AAA. Furthermore, a lower granulocyte proportion was causally linked to an increased risk of thoracic aortic aneurysm (OR=0.0181, 95% CI: 0.0014-0.2376, P=0.0023, FDR=0.0465).ConclusionThis study identifies three genetic pathways linking biological aging to vascular disease, offering new molecular targets for its prevention and treatment.

Humans↗

Genetic improvement of laying hens viability using survival analysis.

The survival of about eight generations of a large strain of laying hens was analysed separating the rearing period (RP) from the production period (PP), after hens were housed. For RP (respectively PP), 97.8% (resp., 94.1% ) of the 109,160 (resp., 100,665) female records were censored after 106 days (resp., 313 days) on the average. A Cox proportional hazards model stratified by flock (= season) and including a hatch-within-flock (HWF) fixed effect seemed to reasonably fit the RP data. For PP, this model could be further simplified to a non-stratified Weibull model. The extension of these models to sire-dam frailty (mixed) models permitted the estimation of the sire genetic variances at 0.261 +/- 0.026 and 0.088 +/- 0.010 for RP and PP, respectively. Heritabilities on the log scale were equal to 0.48 and 0.19. Non-additive genetic effects could not be detected. Selection was simulated by evaluating all sires and dams, after excluding all records from the last generation. Then, actual parents of this last generation were distributed into four groups according to their own pedigree index. Raw survivor curves of the progeny of extreme parental groups substantially differed (e.g., by 1.7% at 300 days for PP), suggesting that selection based on solutions from the frailty models could be efficient, despite the very large proportion of censored records.

Journal Article↗