THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

Background 
The quality and quantity of individuals' social relationships has been linked not only to mental health but also to both morbidity and mortality.
Objectives 
This meta-analytic review was conducted to determine the extent to which social relationships influence risk for mortality, which aspects of social relationships are most highly predictive, and which factors may moderate the risk.
Data Extraction 
Data were extracted on several participant characteristics, including cause of mortality, initial health status, and pre-existing health conditions, as well as on study characteristics, including length of follow-up and type of assessment of social relationships.
Results 
Across 148 studies (308,849 participants), the random effects weighted average effect size was OR = 1.50 (95% CI 1.42 to 1.59), indicating a 50% increased likelihood of survival for participants with stronger social relationships. This finding remained consistent across age, sex, initial health status, cause of death, and follow-up period. Significant differences were found across the type of social measurement evaluated (p<0.001); the association was strongest for complex measures of social integration (OR = 1.91; 95% CI 1.63 to 2.23) and lowest for binary indicators of residential status (living alone versus with others) (OR = 1.19; 95% CI 0.99 to 1.44).
Conclusions 
The influence of social relationships on risk for mortality is comparable with well-established risk factors for mortality.

Please see later in the article for the Editors' Summary

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Social Relationships and Mortality Risk: A Meta-analytic Review

Many lines of evidence, including epidemiologic data and extensive clinical and experimental studies, indicate that early life events play a powerful role in influencing later susceptibility to certain chronic diseases. This review synthesizes evidence from several disciplines to support the contention that environmental factors acting during development should be accorded greater weight in models of disease causation.

/pdf/effect-of-in-utero-and-early-life-conditions-on-adult-health-5bbsqn8x56.pdf

Effect of In Utero and Early-Life Conditions on Adult Health and Disease

Epidemiological evidence increasingly suggests that environmental exposures early in development have a role in susceptibility to disease in later life. In addition, some of these environmental effects seem to be passed on through subsequent generations. Epigenetic modifications provide a plausible link between the environment and alterations in gene expression that might lead to disease phenotypes. An increasing body of evidence from animal studies supports the role of environmental epigenetics in disease susceptibility. Furthermore, recent studies have demonstrated for the first time that heritable environmentally induced epigenetic modifications underlie reversible transgenerational alterations in phenotype. Methods are now becoming available to investigate the relevance of these phenomena to human disease.

Environmental epigenomics and disease susceptibility.

Comprehensive geriatric assessment: a meta-analysis of controlled trials

Transgenerational effects of maternal nutrition or other environmental ‘exposures’ are well recognised, but the possibility of exposure in the male influencing development and health in the next generation(s) is rarely considered. However, historical associations of longevity with paternal ancestors’ food supply in the slow growth period (SGP) in mid childhood have been reported. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we identified 166 fathers who reported starting smoking before age 11 years and compared the growth of their offspring with those with a later paternal onset of smoking, after correcting for confounders. We analysed food supply effects on offspring and grandchild mortality risk ratios (RR) using 303 probands and

http://depts.washington.edu/lairdlab/pdfs/PembreyEtAl2006.pdf

Sex-specific, male-line transgenerational responses in humans.

Overfeeding and overeating in families are traditions that are often transferred from generation to generation. Irrespective of these family traditions, food availability might lead to overfeeding, in its turn leading to metabolic adaptations. Apart from selection, could these adaptations to the social environment have transgenerational effects? This study will attempt to answer the following question: Can overeating during a child's slow growth period (SGP), before their prepubertal peak in growth velocity influence descendants' risk of death from cardiovascular disease and diabetes? Data were collected by following three cohorts born in 1890, 1905 and 1920 in Overkalix parish in northern Sweden up until death or 1995. The parents' or grandparents' access to food during their SGP was determined by referring to historical data on harvests and food prices, records of local community meetings and general historical facts. If food was not readily available during the father's slow growth period, then cardiovascular disease mortality of the proband was low. Diabetes mortality increased if the paternal grandfather was exposed to a surfeit of food during his slow growth period. (Odds Ratio 4.1, 95% confidence interval 1.33-12.93, P=0.01). Selection bias seemed to be unlikely. A nutrition-linked mechanism through the male line seems to have influenced the risk for cardiovascular and diabetes mellitus mortality.

/pdf/cardiovascular-and-diabetes-mortality-determined-by-2g3wbuffdl.pdf

Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period.

Nutrition might induce, at some loci, epigenetic or other changes that could be transmitted to the next generation impacting on health. The slow growth period (SGP) before the prepubertal peak in growth velocity has emerged as a sensitive period where different food availability is followed by different transgenerational response (TGR). The aim of this study is to investigate to what extent the probands own childhood circumstances are in fact the determinants of the findings. In the analysis, data from three random samples, comprising 271 probands and their 1626 parents and grandparents, left after exclusions because of missing data, were utilized. The availability of food during any given year was classified based on regional statistics. The ancestors' SGP was set at the ages of 8-12 years and the availability of food during these years classified as good, intermediate or poor. The probands' childhood circumstances were defined by the father's ownership of land, the number of siblings and order in the sibship, the death of parents and the parents' level of literacy. An earlier finding of a sex-specific influence from the ancestors' nutrition during the SGP, going from the paternal grandmother to the female proband and from the paternal grandfather to the male proband, was confirmed. In addition, a response from father to son emerged when childhood social circumstances of the son were accounted for. Early social circumstances influenced longevity for the male proband. TGRs to ancestors' nutrition prevailed as the main influence on longevity.

/pdf/transgenerational-response-to-nutrition-early-life-3ciuas404y.pdf

Transgenerational response to nutrition, early life circumstances and longevity

Objectives: To investigate the possible influence of attendance at cultural events, reading books or periodicals, making music or singing in a choir as determinants for survival. Design: A simple random sample was drawn of 15 198 individuals aged 16–74 years. Of these, 85% (12 982) were interviewed by trained non-medical interviewers between 1982 and 1983 about cultural activities. They were followed up with respect to survival until 31 December 1991. Setting: Swedish interview survey of living conditions comprising a random sample of the adult Swedish population. Subjects: 12 675 people interviewed between 1982 and 1983. Main outcome measures: Survival of subjects after controlling for eight confounding variables: age, sex, education level, income, long term disease, social network, smoking, and physical exercise. Results: 6301 men and 6374 women were followed up; 533 men and 314 women died during this period. The control variables influenced survival in the expected directions except for social network for men; a significant negative effective was found when the analysis was made separately for men and women. We found an influence on mortality when the eight control variables were controlled for in people who rarely attended events compared with those attending most often, the relative risk being 1.57 (95% confidence interval 1.18 to 2.09). Conclusion: Attendance at cultural events may have a positive influence on survival. Long term follow up of large samples with confounders that are well controlled for and with the cultural stimulation more highly specified should be used to try to falsify the hypothesis before experiments start. Key messages When other determinants of survival were controlled for, this study found that people attending cultural events often had a better chance of survival than those attending rarely Education unexpectedly had no significant influence on survival when other variables were controlled for Long term follow up of large samples with con- founders that are well controlled for may provide empirical evidence to support experiments on the effects of cultural stimulation on people not attending events

/pdf/attendance-at-cultural-events-reading-books-or-periodicals-26ni9yis6x.pdf

Attendance at cultural events, reading books or periodicals, and making music or singing in a choir as determinants for survival: Swedish interview survey of living conditions

Social circumstances often impinge on later generations in a socio-economic manner, giving children an uneven start in life. Overfeeding and overeating might not be an exception. The pathways might ...

Lars Olov Bygren

Papers

Sex-specific, male-line transgenerational responses in humans.

Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period.

Transgenerational response to nutrition, early life circumstances and longevity

Attendance at cultural events, reading books or periodicals, and making music or singing in a choir as determinants for survival: Swedish interview survey of living conditions

Longevity determined by paternal ancestors' nutrition during their slow growth period.