Complexity Theory and Its Evolution in Public Administration and Policy Studies

This paper traces the evolution of the application of the complexity sciences in the literature of public administration and public policy. A four stage evolutionary model is used to track the development of this literature. The evolution of the literature has now reached a third evolutionary stage. This third stage is a proliferant stage in the development of the literature in which applications and knowledge production has increased dramatically

Dynamic Parameters of Balance Which Correlate to Elderly Persons with a History of Falls

Poor balance in older persons contributes to a rise in fall risk and serious injury, yet no consensus has developed on which measures of postural sway can identify those at greatest risk of falling. Postural sway was measured in 161 elderly individuals (81.8y±7.4), 24 of which had at least one self-reported fall in the prior six months, and compared to sway measured in 37 young adults (34.9y±7.1). Center of pressure (COP) was measured during 4 minutes of quiet stance with eyes opened. In the elderly with fall history, all measures but one were worse than those taken from young adults (e.g., maximal COP velocity was 2.7× greater in fallers than young adults; p<0.05), while three measures of balance were significantly worse in fallers as compared to older persons with no recent fall history (COP Displacement, Short Term Diffusion Coefficient, and Critical Displacement). Variance of elderly subjects' COP measures from the young adult cohort were weighted to establish a balance score (“B-score”) algorithm designed to distinguish subjects with a fall history from those more sure on their feet. Relative to a young adult B-score of zero, elderly “non-fallers” had a B-score of 0.334, compared to 0.645 for those with a fall history (p<0.001). A weighted amalgam of postural sway elements may identify individuals at greatest risk of falling, allowing interventions to target those with greatest need of attention

Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study

BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS:We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate [greater than or equal to]80%, minor allele frequency [greater than or equal to]10%, Hardy-Weinberg test p [greater than or equal to] 0.001).RESULTS:In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value < 10-5). The two sets of SNPs were in high linkage disequilibrium (minimum r2 = 0.58). The top 30 SNPs for generalized estimating equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. CONCLUSION: Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging

Successful Resource Seeking Strategies: An Agent Based Model of Budgetary Competition

The strategies that bureaucratic actors employ to secure resources are the result of a complex interplay between motivational states and environmental conditions. The strategies employed by bureaucrats to secure resources are now best understood as heuristics. Heuristics that may be adaptive in securing resources under some conditions may be maladaptive under different environmental circumstances (Gigerenzer 2000; 2008). This study reviews the various strategies employed by bureaucrats to secure financial resources through the lens of Downs’ typology of bureaucrats to determine the fundamental heuristics the successful strategies employ. We sought inspiration from both the extant literature and models of bureaucratic behavior within organizations beginning with Downs (1967) and continuing with the work of Bowling, Cho, and Wright (2004), and the methodological innovations afforded by agent-based modeling. By making certain basic assumptions regarding decision-making heuristics, we show a remarkable consistency between Downs, Bowling and her colleagues, and our own findings

Self-reported Adherence with the Use of a Device in a Clinical Trial as Validated by Electronic Monitors: the VIBES Study

Background: Adherences to treatments that require a behavioral action often rely on self-reported recall, yet it is vital to determine whether real time self reporting of adherence using a simple logbook accurately captures adherence. The purpose of this study was to determine whether real time self-reported adherence is an accurate measurement of device usage during a clinical trial by comparing it to electronic recording. Methods: Using data collected from older adult men and women (N=135, mean age 82.3 yrs; range 66 to 98 yrs) participating in a clinical trial evaluating a vibrating platform for the treatment of osteoporosis, daily adherence to platform treatment was monitored using both self-reported written logs and electronically recorded radio-frequency identification card usage, enabling a direct comparison of the two methods over one year. Agreement between methods was also evaluated after stratification by age, gender, time in study, and cognition status. Results: The two methods were in high agreement (overall intraclass correlation coefficient = 0.96). The agreement between the two methods did not differ between age groups, sex, time in study and cognitive function. Conclusions: Using a log book to report adherence to a daily intervention requiring a behavioral action in older adults is an accurate and simple approach to use in clinical trials, as evidenced by the high degree of concordance with an electronic monitor

Genetics of Bone and Muscle Interactions in Humans

Purpose of Review To summarize the evidence from recent studies on the shared genetics between bone and muscle in humans. Recent Findings Genome-wide association studies (GWAS) have successfully identified a multitude of loci influencing the variability of different bone or muscle parameters, with multiple loci overlapping between the traits. In addition, joint analyses of multiple correlated musculoskeletal traits (i.e., multivariate GWAS) have underscored several genes with possible pleiotropic effects on both bone and muscle including MEF2C and SREBF1. Notably, several of the proposed pleiotropic genes have been validated using human cells or animal models. Summary It is clear that the study of pleiotropy may provide novel insights into disease pathophysiology potentially leading to the identification of new treatment strategies that simultaneously prevent or treat both osteoporosis and sarcopenia. However, the role of muscle factors (myokines) that stimulate bone metabolism, as well as osteokines that affect muscles, is in its earliest stage of understandin

Body Composition and Genetic Lipodystrophy Risk Score Associate With Nonalcoholic Fatty Liver Disease and Liver Fibrosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150618/1/hep41391.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150618/2/hep41391_am.pd

In silico discovery of blood cell macromolecular associations

Background Physical molecular interactions are the basis of intracellular signalling and gene regulatory networks, and comprehensive, accessible databases are needed for their discovery. Highly correlated transcripts may reflect important functional associations, but identification of such associations from primary data are cumbersome. We have constructed and adapted a user-friendly web application to discover and identify putative macromolecular associations in human peripheral blood based on significant correlations at the transcriptional level. Methods The blood transcriptome was characterized by quantification of 17,328 RNA species, including 341 mature microRNAs in 105 clinically well-characterized postmenopausal women. Intercorrelation of detected transcripts signal levels generated a matrix with > 150 million correlations recognizing the human blood RNA interactome. The correlations with calculated adjusted p-values were made easily accessible by a novel web application. Results We found that significant transcript correlations within the giant matrix reflect experimentally documented interactions involving select ubiquitous blood relevant transcription factors (CREB1, GATA1, and the glucocorticoid receptor (GR, NR3C1)). Their responsive genes recapitulated up to 91% of these as significant correlations, and were replicated in an independent cohort of 1204 individual blood samples from the Framingham Heart Study. Furthermore, experimentally documented mRNAs/miRNA associations were also reproduced in the matrix, and their predicted functional co-expression described. The blood transcript web application is available at http://app.uio.no/med/klinmed/correlation-browser/blood/index.php and works on all commonly used internet browsers. Conclusions Using in silico analyses and a novel web application, we found that correlated blood transcripts across 105 postmenopausal women reflected experimentally proven molecular associations. Furthermore, the associations were reproduced in a much larger and more heterogeneous cohort and should therefore be generally representative. The web application lends itself to be a useful hypothesis generating tool for identification of regulatory mechanisms in complex biological data sets.publishedVersio

Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study

Objectives: To relate cancer since entry into the Framingham Heart Study with the risk of incident Alzheimer’s disease and to estimate the risk of incident cancer among participants with and without Alzheimer’s disease. Design: Community based prospective cohort study; nested age and sex matched case-control study. Setting: Framingham Heart Study, USA. Participants: 1278 participants with and without a history of cancer who were aged 65 or more and free of dementia at baseline (1986-90). Main outcome measures Hazard ratios and 95% confidence intervals for the risks of Alzheimer’s disease and cancer. Results: Over a mean follow-up of 10 years, 221 cases of probable Alzheimer’s disease were diagnosed. Cancer survivors had a lower risk of probable Alzheimer’s disease (hazard ratio 0.67, 95% confidence interval 0.47 to 0.97), adjusted for age, sex, and smoking. The risk was lower among survivors of smoking related cancers (0.26, 0.08 to 0.82) than among survivors of non-smoking related cancers (0.82, 0.57 to 1.19). In contrast with their decreased risk of Alzheimer’s disease, survivors of smoking related cancer had a substantially increased risk of stroke (2.18, 1.29 to 3.68). In the nested case-control analysis, participants with probable Alzheimer’s disease had a lower risk of subsequent cancer (0.39, 0.26 to 0.58) than reference participants, as did participants with any Alzheimer’s disease (0.38) and any dementia (0.44). Conclusions: Cancer survivors had a lower risk of Alzheimer’s disease than those without cancer, and patients with Alzheimer’s disease had a lower risk of incident cancer. The risk of Alzheimer’s disease was lowest in survivors of smoking related cancers, and was not primarily explained by survival bias. This pattern for cancer is similar to that seen in Parkinson’s disease and suggests an inverse association between cancer and neurodegeneration

Factors associated with hallux valgus in a population-based study of older women and men: the MOBILIZE Boston Study

OBJECTIVE: To examine potential risk factors for hallux valgus in community-dwelling elders. METHOD: Data from 600 MOBILIZE Boston Study participants (386 women and 214 men) were analyzed. Hallux valgus was defined as \u3e15 degrees angular deviation of the hallux with respect to the first metatarsal bone toward the lesser toes. Associations of hallux valgus with age, body mass index (BMI), race, education, pes planus, foot pain, and in women, history of high heel shoe use, were assessed using sex-specific Poisson regression with robust variance estimation for risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Hallux valgus was present in 58% of women and 25% of men. Higher BMI was inversely associated with presence of hallux valgus in women (P trend=0.001), with the strongest inverse association observed in those with BMI of 30.0 or more compared to those with normal BMI (RR=0.7, 95% CI: 0.5, 0.9). Women, who usually wore high-heeled shoes during ages 20-64 years compared to those who did not, had increased likelihood of hallux valgus (RR=1.2, 95% CI: 1.0, 1.5). Among men, those with BMI between 25.0 and 29.9 had increased likelihood of hallux valgus compared to those with normal BMI (RR=1.9, 95% CI: 1.0, 3.5). Men with pes planus were more likely to have hallux valgus (RR=2.1, 95% CI: 1.3, 3.3) compared to men without pes planus. CONCLUSION: In women, hallux valgus was associated with lower BMI and high heel use during ages 20-64, while in men, associations were observed with higher BMI and pes planus. Our results suggest that the etiologic mechanisms for hallux valgus may differ between men and women. Elsevier Ltd. All rights reserved