Summary. The maximum likelihood approach to jointly model the survival time and its longitudinal covariates has been successful to model both processes in longitudinal studies. Random effects in the longitudinal process are often used to model the survival times through a proportional hazards model, and this invokes an EM algorithm to search for the maximum likelihood estimates (MLEs). Several intriguing issues are examined here, including the robustness of the MLEs against departure from the normal random effects assumption, and difficulties with the profile likelihood approach to provide reliable estimates for the standard error of the MLEs. We provide insights into the robustness property and suggest to overcome the difficulty of reliable estimates for the standard errors by using bootstrap procedures. Numerical studies and data analysis illustrate our points.

SummaryAlthough it is widely known that dietary restriction (DR) not only extends the longevity of a wide range of species but also reduces their reproductive output, the interrelationship of DR, longevity extension and reproduction is not well understood in any organism. Here we address the question: 'Under what nutritional conditions do the longevity-enhancing effects resulting from food restriction either counteract, complement or reinforce the mortality costs of reproduction? To answer this question we designed a fine-grained DR study involving 4800 individuals of the tephritid fruit fly, Anastrepha ludens , in which we measured sex-specific survival and daily reproduction in females in each of 20 different treatments (sugar : yeast ratios) plus 4 starvation controls. The database generated from this 3-year study consisted of approximately 100 000 life-days for each sex and 750 000 eggs distributed over the reproductive lives of 2400 females. The fertility and longevity-extending responses were used to create contour maps (X-Y grid) that show the demographic responses (Z-axis) across dietary gradients that range from complete starvation to both ad libitum sugar-only and ad libitum standard diet (3 : 1 sugar : yeast). The topographic perspectives reveal demographic equivalencies along nutritional gradients, differences in the graded responses of males and females, egg production costs that are sensitive to the interaction of food amounts and constituents, and orthogonal contours (equivalencies in longevity or reproduction) representing demographic thresholds related to both caloric content and sugar : yeast ratios. In general, the finding that lifespan and reproductive maxima occur at much different nutritional coordinates poses a major challenge for the use of food restriction (or a mimetic) in humans to improve health and extend longevity in humans.

The results of our nationwide, population-based study suggest that patients who undergo anaesthesia and surgery may be at increased risk of dementia.

The pre-LASIK refraction can be used theoretically to determine an accurate IOL power.

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Patterns of behavior were recorded every 10 min during a 2-h period each day from eclosion to death for individual Drosophila melanogaster (both sexes) and Ceratitis capitata (males-only) including walking, preening, feeding, flying, and resting for the former species, and walking, calling (signaling), supine (upside-down), and resting in the latter. Results reveal that, with the exception of preening in D. melanogaster, behavioral patterns are age-specific and the frequency of several behaviors (e.g. supine in medfly; walking and resting in D. melanogaster) are correlated with timeto-death. This is the first set of studies to report the age patterns over a range of behavioral categories throughout the lives of individuals and thus the first that systematically documents the behavior of individuals at advanced ages. We suggest that the new and unique behaviors (e.g. supine) that emerge from the aging process be referred to as degenerative behaviors, not only to distinguish them from the conventional behavioral classifications (innate, learned), but also to reflect their emergent nature.

Age of sexual maturity, daily and lifetime reproductive rates, and life span were recorded in a laboratory cohort of Mexican fruit flies consisting of over 1100 females maintained individually. The results revealed that, relative to the medfly, the Mexfly is slower maturing (14 vs 17 days), more fecund (1400 vs 650-1100 eggs/female), and longer lived (50 vs 35 days). The results reinforced the generality of several earlier findings on the medfly including the deceleration of mortality at older ages and the weakness of the correlation between the rate of egg laying at early ages and both subsequent reproduction and remaining longevity. Discussion includes perspectives on the role of artificial selection in shaping the demographic traits of the mass-reared strain of Mexfly used in this study, as well as the overall significance of large scale biodemographic studies in understanding aging and longevity.

Experiments based on over 400,000 medf lies revealed that females maintained on a normal diet (sucrose plus protein) have a higher life expectancy than males maintained on a normal diet, with a difference of 1.30 ؎ 0.27 days in favor of females. However, this sex differential reverses under protein deprivation, with a difference of 2.24 ؎ 0.18 days in favor of males. The reversal of the male-female life expectancy differential is caused by a sustained surge in early female mortality under protein deprivation that is tied to egg-laying and physiological processes. In contrast, male mortality and life expectancy are only mildly affected by protein deprivation. The surge in early mortality for female medf ly cohorts is an instance of a vulnerable period. These vulnerable periods are linked with patterns in hazard rates.Life expectancy or average lifespan of individuals is an important quantitative characteristic for comparing the survival and thus frailty of cohorts subjected to various genetic and͞or environmental influences. Genetic factors play an important role in determining life expectancy, as exemplified by the well-known sex differential in life expectancy (1-4). Although life expectancy is an overall measure of longevity, the specific dynamics of mortality and the aging process are reflected by the hazard rate or force of mortality.We report the results of an experiment concerning the survival of cohorts of male and female Mediterranean fruit flies (Ceratitis capitata) under a full sugar-plus-protein diet and under protein deprivation (sugar only). The motive for this study was our interest in determining why hazard rates in female medflies began to level off at an earlier age and at a lower level than hazard rates in male medflies. These mortality patterns were observed in several recent studies involving a total of more than 1.2 million medflies (5), all of which were protein-deprived. We initiated the current investigation to see whether this phenomenon was due to protein deprivation and whether protein deprivation has a sex-dependent effect on life expectancy and hazard rates. MATERIALS AND METHODSWe investigated these issues by maintaining large cohorts of medflies at the Moscamed medfly mass-rearing facility located in Metapa, Chiapas, Mexico. Technical details on fruit fly mass rearing are as described in ref. 6. Adult flies were maintained under the following environmental conditions: 12-h͞12-h light͞dark cycle, 24.0ЊC (Ϯ2ЊC), and 65% relative humidity (Ϯ9%). Medflies were kept on one of two dietary regimes: (i) a sugar-plus-protein diet in which flies were provided with sucrose and a protein source; and (ii) a proteinfree diet in which flies were provided with a diet consisting only of sucrose (protein-deprived). A total of 416,289 medflies (about equally divided between males and females) were maintained in 66 aluminum cages, 15 ϫ 60 ϫ 90 cm, each containing about 6,000 medflies, males and females grouped together. Thirty-three cages were assigned to the sugar-plusprotein diet and the oth...