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We hypothesized that Barthel Scores, a measure of functional ability, in Centenarian subjects would be lower in Centenarians reporting early onset of a subset of age-associated illness than those reporting delayed or no onset of such illnesses. 409 participants or their proxies completed health history questionnaires and Barthel tests (males=97, mean age=102 +/- 3.0; females=312, mean age=10g +/- 2.6). We investigated the effect of sex, number of co-morbidities, and initial age of onset of initial age-associated disease on the Barthel score of participants at the time of study. After adjusting for age of onset of initial disease and number of comorbidities, sex is a significant predictor of Barthel score (p=0.001). In addition, when segregated by gender, the average Barthel score for male centenarians is 74.4 (95% CI 69.0, 79.7) and the average for females is 63.2 (95% CI, 59.96, 66.5) which is significantly different (p=0.0009). While there are far fewer of them, male Centenarians have a higher functional index than their female counterparts. Trends in functional decline seem to be unique for the two sexes.

PARTICIPANTS: A panel of centenarians along with some of their septuagenarian and octogenarian children will be presented. Interspersed between the interviews, we will present findings about centenarians and their children. These remarkable individuals are in many ways sentinels of this year's theme, Relationships in a Changing World: From Aging Cells to Aging Societies. In part because centenarians are becoming more common, age 85 doesn't seem so old to the rest of us anymore, an age that most of us should be able to achieve, hopefully in good health. Not too long ago, 65 was 'old'. In other words, centenarians 'raise the bar'. Questions to be explored with the panel include their secrets to aging well, perspectives of various historical events, their habits, feelings about marriage and other social relationships, family histories of longevity etc. Time will be made available for questions and observations from the audience.

Centenarians represent an extreme of life expectancy. They achieve their exceptional longevity in part by lacking genetic variations linked to premature death. Pedigree studies have shown a substantial familial component in the ability to survive to extreme old age, and a recent study demonstrated a locus on chromosome 4 linked to exceptional longevity, indicating the likely existence of at least one longevity-enabling gene in humans. The children of centenarians have markedly reduced relative risks for age-related diseases, particularly heart disease, hypertension, and diabetes, and are a promising model for genetic and phenotypic studies of 1) aging slowly relative to the general population and 2) the delay of and perhaps escape from important age-related diseases. These studies and those of other mammals and lower organisms show great promise for the delineation of important environmental and genetic determinants of aging well. [ABSTRACT FROM AUTHOR]

Design considerations are given for a sinusoidal pressure generator (SPG capable of providing sinusoidal pressures up to 26 atmos peak to peak, proportional to input voltage to within 5% over the frequency range from 0 to 10 000 cps. The pressure is generated in a fluid contained in a relatively rigid metal enclosure, by means of a stack of 24 disks of a piezoelectric ceramic, connected electrically in parallel, and arranged so that their displacements add. Several applications of the SPG are discussed including several types of evaluation tests for pressure gauges, evaluation of electromechanical drivers, tests of piezoelectric materials near zero frequency, and study of frequency-dependent effects in liquids. Preliminary relaxation data are shown for two associated liquids, diphenyl metachloride (Aroclor No. 1260) and glycerol. [ABSTRACT FROM AUTHOR]

The problem of operating condenser microphones in a vibration environment is considered, and it is pointed out that there is a precise relation between the vibration and pressure response for any given transducer. This relation is shown to be dependent on the mass per unit area of the microphone diaphragm, and graphs are given from which the suitability of a given microphone to perform its function in a vibration environment can be assessed. The results of measurements on a well-known type of condenser microphone are presented to support the theory, and the usefulness and disadvantages of vibration-isolating mounts and of systems using two transducers are discussed. A proposed design of a condenser microphone to be insensitive to vibration is described. [ABSTRACT FROM AUTHOR]

Abstract Background Population stratification can cause spurious associations in a genome-wide association study (GWAS), and occurs when differences in allele frequencies of single nucleotide polymorphisms (SNPs) are due to ancestral differences between cases and controls rather than the trait of interest. Principal components analysis (PCA) is the established approach to detect population substructure using genome-wide data and to adjust the genetic association for stratification by including the top principal components in the analysis. An alternative solution is genetic matching of cases and controls that requires, however, well defined population strata for appropriate selection of cases and controls. Results We developed a novel algorithm to cluster individuals into groups with similar ancestral backgrounds based on the principal components computed by PCA. We demonstrate the effectiveness of our algorithm in real and simulated data, and show that matching cases and controls using the clusters assigned by the algorithm substantially reduces population stratification bias. Through simulation we show that the power of our method is higher than adjustment for PCs in certain situations. Conclusions In addition to reducing population stratification bias and improving power, matching creates a clean dataset free of population stratification which can then be used to build prediction models without including variables to adjust for ancestry. The cluster assignments also allow for the estimation of genetic heterogeneity by examining cluster specific effects.

Abstract Background Imputation of missing genotypes is becoming a very popular solution for synchronizing genotype data collected with different microarray platforms but the effect of ethnic background, subject ascertainment, and amount of missing data on the accuracy of imputation are not well understood. Results We evaluated the accuracy of the program IMPUTE to generate the genotype data of partially or fully untyped single nucleotide polymorphisms (SNPs). The program uses a model-based approach to imputation that reconstructs the genotype distribution given a set of referent haplotypes and the observed data, and uses this distribution to compute the marginal probability of each missing genotype for each individual subject that is used to impute the missing data. We assembled genome-wide data from five different studies and three different ethnic groups comprising Caucasians, African Americans and Asians. We randomly removed genotype data and then compared the observed genotypes with those generated by IMPUTE. Our analysis shows 97% median accuracy in Caucasian subjects when less than 10% of the SNPs are untyped and missing genotypes are accepted regardless of their posterior probability. The median accuracy increases to 99% when we require 0.95 minimum posterior probability for an imputed genotype to be acceptable. The accuracy decreases to 86% or 94% when subjects are African Americans or Asians. We propose a strategy to improve the accuracy by leveraging the level of admixture in African Americans. Conclusion Our analysis suggests that IMPUTE is very accurate in samples of Caucasians origin, it is slightly less accurate in samples of Asians background, but substantially less accurate in samples of admixed background such as African Americans. Sample size and ascertainment do not seem to affect the accuracy of imputation.

Abstract Background One of the challenges of the analysis of pooling-based genome wide association studies is to identify authentic associations among potentially thousands of false positive associations. Results We present a hierarchical and modular approach to the analysis of genome wide genotype data that incorporates quality control, linkage disequilibrium, physical distance and gene ontology to identify authentic associations among those found by statistical association tests. The method is developed for the allelic association analysis of pooled DNA samples, but it can be easily generalized to the analysis of individually genotyped samples. We evaluate the approach using data sets from diverse genome wide association studies including fetal hemoglobin levels in sickle cell anemia and a sample of centenarians and show that the approach is highly reproducible and allows for discovery at different levels of synthesis. Conclusion Results from the integration of Bayesian tests and other machine learning techniques with linkage disequilibrium data suggest that we do not need to use too stringent thresholds to reduce the number of false positive associations. This method yields increased power even with relatively small samples. In fact, our evaluation shows that the method can reach almost 70% sensitivity with samples of only 100 subjects.

The sinusoidal pressure generator (SPG) produces pressure changes suitable for fundamental studies of liquids and also for calibration of pressure gauges. The present model yields pressure up to ten atmospheres at any frequency from zero to well over 10 000 cps. The pressures are proportional to the excitation voltage within ±5% from zero to 10 000 cps. The SPG consists of a piezoelectric driver (24 disks of a BaTiO3 ceramic), a fluid cavity and provisions for mounting test devices. All components are contained in a heavy-walled brass cylinder 4.0 in. in diameter and 3.2 in. high. The peak displacement obtainable without undue heating of the BaTiO3 is approximately 10-5 cm. The fluid cavity is approximately 1.25 in. in diameter and 0.040 in. deep and is sealed by a thin Mylar membrane. The monitor crystal is a BaTiO3 cylinder, 116 in. o.d. and 116 in. high (output sensitivity approximately 40 mv per atmosphere). The cavity forms one end of an interchangeable plug which accommodates pressure gauges having diameters up to about one inch. This plug can also be provided with a thick diaphragm, directly behind the fluid cavity, for deflection measurements by means of a very sensitive capacitance-type device, the Resonant Bridge Carrier System. Typical calibrations of commercial pressure gauges will be shown. [ABSTRACT FROM AUTHOR]