Estimating scale economies and the optimal size of school districts: A flexible form approach

This paper investigates estimation methods to model the relationship between school district size, costs per student and the organisation of school districts. We show that the assumptions on the functional form strongly affect the estimated scale economies and offer two possible solutions to allow for more flexibility in the estimation method. First, we introduce a model by adding higher-degree district size polynomials, allowing for multiple optima. Second, we develop a Fourier cost function, innovative in the literature on scale economies in education. We then compare both models to classical approaches in the literature. We illustrate how a minor change in the estimation method can alter policy conclusions significantly using Flemish school district data. In doing so, we find sizeable potential cost savings from the consolidation of school districts, especially at the lower tail of the district-size distribution. The organisational transition from small to large school districts is characterised by an interval between two optima. Beyond an apparent slowdown in cost savings in medium-sized school districts, cost savings from school district consolidation increase again, up to the optimal size of around 6,500 students. Beyond this optimum, school districts incur diseconomies of scale. The commonly used quadratic form (U'-shaped cost function) overestimates scale economies, and fails to identify the interval between both optima

Relationship between hippocampal structure and memory function in elderly humans

With progressing age, the ability to recollect personal events declines, whereas familiarity-based memory remains relatively intact. It has been hypothesized that age-related hippocampal atrophy may contribute to this pattern because of its critical role for recollection in younger humans and after acute injury. Here, we show that hippocampal volume loss in healthy older persons correlates with gray matter loss (estimated with voxel-based morphometry) of the entire limbic system and shows no correlation with an electrophysiological (event-related potential [ERP]) index of recollection. Instead, it covaries with more substantial and less specific electrophysiological changes of stimulus processing. Age-related changes in another complementary structural measure, hippocampal diffusion, on the other hand, seemed to be more regionally selective and showed the expected correlation with the ERP index of recollection. Thus, hippocampal atrophy in older persons accompanies limbic atrophy, and its functional impact on memory is more fundamental than merely affecting recollection

Increasing Burden of Complex Multimorbidity Across Gradients of Cognitive Impairment

Introduction: This study evaluates the burden of multimorbidity (MM) across gradients of cognitive impairment (CI). Methods: Using data from the 2010 Health and Retirement Study, we identified individuals with no CI, mild CI, and moderate/ severe CI. In addition, we adopted an expansive definition of complex MM by accounting for the occurrence and co-occurrence of chronic conditions, functional limitations, and geriatric syndromes. Results: In a sample of 18 913 participants (weighted n = 87.5 million), 1.93% and 1.84% presented with mild and moderate/severe CI, respectively. The prevalence of most conditions constituting complex MM increased markedly across the spectrum of CI. Further, the percentage of individuals presenting with 10 or more conditions was 19.9%, 39.3%, and 71.3% among those with no CI, mild CI, and moderate/severe CI, respectively. Discussion: Greater CI is strongly associated with increased burden of complex MM. Detailed characterization of MM across CI gradients will help identify opportunities for health care improvement

Multimorbidity: constellations of conditions across subgroups of midlife and older individuals, and related Medicare expenditures

Introduction: The Department of Health and Human Services’ 2010 Strategic Framework on Multiple Chronic Conditions called for the identification of common constellations of conditions in older adults. Objectives: To analyze patterns of conditions constituting multimorbidity (CCMM) and expenditures in a US representative sample of midlife and older adults (50–64 and ≥65 years of age, respectively). Design: A cross-sectional study of the 2010 Health and Retirement Study (HRS; n=17,912). The following measures were used: (1) count and combinations of CCMM, including (i) chronic conditions (hypertension, arthritis, heart disease, lung disease, stroke, diabetes, cancer, and psychiatric conditions), (ii) functional limitations (upper body limitations, lower body limitations, strength limitations, limitations in activities of daily living, and limitations in instrumental activities of daily living), and (iii) geriatric syndromes (cognitive impairment, depressive symptoms, incontinence, visual impairment, hearing impairment, severe pain, and dizziness); and (2) annualized 2011 Medicare expenditures for HRS participants who were Medicare fee-for-service beneficiaries (n=5,677). Medicaid beneficiaries were also identified based on their self-reported insurance status. Results: No large representations of participants within specific CCMM categories were observed; however, functional limitations and geriatric syndromes were prominently present with higher CCMM counts. Among fee-for-service Medicare beneficiaries aged 50–64 years, 26.7% of the participants presented with ≥10 CCMM, but incurred 48% of the expenditure. In those aged ≥65 years, these percentages were 16.9% and 34.4%, respectively. Conclusion: Functional limitations and geriatric syndromes considerably add to the MM burden in midlife and older adults. This burden is much higher than previously reported

The Influence of Multimorbidity on Leading Causes of Death in Older Adults With Cognitive Impairment

Objective: The aim of this study is to evaluate the relationship of leading causes of death with gradients of cognitive impairment and multimorbidity. Method: This is a population-based study using data from the linked 1992- 2010 Health and Retirement Study and National Death Index (n = 9,691). Multimorbidity is defined as a combination of chronic conditions, functional limitations, and geriatric syndromes. Regression trees and Random Forest identified which combinations of multimorbidity associated with causes of death. Results: Multimorbidity is common in the study population. Heart disease is the leading cause in all groups, but with a larger percentage of deaths in the mild and moderate/severe cognitively impaired groups than among the noncognitively impaired. The different “paths” down the regression trees show that the distribution of causes of death changes with different combinations of multimorbidity. Discussion: Understanding the considerable heterogeneity in chronic conditions, functional limitations, geriatric syndromes, and causes of death among people with cognitive impairment can target care management and resource allocation

Complex multimorbidity and health outcomes in older adult cancer survivors

Objective: To characterize complex multimorbidity among cancer survivors and evaluate the association between cancer survivorship, time since cancer diagnosis, and self-reported fair/poor health, self-rated worse health in 2 years, and 2-year mortality. Methods: We used the 2010–2012 Health and Retirement Study. Cancer survivors were individuals who reported a (nonskin) cancer diagnosis 2 years or more before the interview. We defined complex multimorbidity as the co-occurrence of chronic conditions, functional limitations, and/or geriatric syndromes. In addition to descriptive analyses, we used logistic regression to evaluate the independent association between cancer survivor status and health outcomes. We also examined whether cancer survivorship differed by the number of years since diagnosis. Results: Among 15,808 older adults (age ≥50 years), 11.8% were cancer survivors. Compared with cancer-free individuals, a greater percentage of cancer survivors had complex multimorbidity: co-occurring chronic conditions, functional limitations, and geriatric syndromes. Cancer survivorship was significantly associated with self-reported fair/poor health, self-rated worse health in 2 years, and 2-year mortality. These effects declined with the number of years since diagnosis for fair/ poor health and mortality but not for self-rated worse health. Conclusion: Cancer survivor status is independently associated with more complex multimorbidity, and with worse health outcomes. These effects attenuate with time, except for patient perception of being in worse health

Tissue inhibitor of metalloproteinase-1 (TIMP-1) regulates mesenchymal stem cells through let-7f microRNA and Wnt/β-catenin signaling

Tissue inhibitor of metalloproteinases 1 (TIMP-1) is a matrix metalloproteinase (MMP)-independent regulator of growth and apoptosis in various cell types. The receptors and signaling pathways that are involved in the growth factor activities of TIMP-1, however, remain controversial. RNA interference of TIMP-1 has revealed that endogenous TIMP-1 suppresses the proliferation, metabolic activity, and osteogenic differentiation capacity of human mesenchymal stem cells (hMSCs). The knockdown of TIMP-1 in hMSCs activated the Wnt/β-catenin signaling pathway as indicated by the increased stability and nuclear localization of β-catenin in TIMP-1–deficient hMSCs. Moreover, TIMP-1 knockdown cells exhibited enhanced β-catenin transcriptional activity, determined by Wnt/β-catenin target gene expression analysis and a luciferase-based β-catenin– activated reporter assay. An analysis of a mutant form of TIMP-1 that cannot inhibit MMP indicated that the effect of TIMP-1 on β-catenin signaling is MMP independent. Furthermore, the binding of CD63 to TIMP-1 on the surface of hMSCs is essential for the TIMP-1–mediated effects on Wnt/β-catenin signaling. An array analysis of microRNAs (miRNAs) and transfection studies with specific miRNA inhibitors and mimics showed that let-7f miRNA is crucial for the regulation of β-catenin activity and osteogenic differentiation by TIMP-1. Let-7f was up-regulated in TIMP-1–depleted hMSCs and demonstrably reduced axin 2, an antagonist of β-catenin stability. Our results demonstrate that TIMP-1 is a direct regulator of hMSC functions and reveal a regulatory network in which let-7f modulates Wnt/β-catenin activity

Functional Status in Older Women Diagnosed with Pelvic Organ Prolapse

Background—Functional status plays an important role in the comprehensive characterization of older adults. Functional limitations are associated with an increased risk of adverse treatment outcomes, but there is limited data on the prevalence of functional limitations in older women with pelvic floor disorders. Objective—The aim of the study was to describe the prevalence of functional limitations based on health status in older women with pelvic organ prolapse. Study Design—This pooled, cross-sectional study utilized data from the linked Health and Retirement Study and Medicare files between 1992 and 2008. The analysis included 890 women ≥65 years with pelvic organ prolapse. We assessed self-reported functional status, categorized in strength, upper and lower body mobility, activities of daily living, and instrumental activities of daily living domains. Functional limitations were evaluated and stratified by respondents self-reported general health status. Descriptive statistics were used to compare categorical and continuous variables, and logistic regression was used to measure differences in the odds of functional limitation by increasing age. Results—The prevalence of functional limitations was 76.2% in strength, 44.9% in upper and 65.8% in lower body mobility, 4.5% in activities of daily living and 13.6% in instrumental activities of daily living. Limitations were more prevalent in women with poor or fair health status than in women with good health status, including 91.5% vs 69.9% in strength, 72.9% vs 33.5% in upper and 88.0% vs 56.8% in lower body mobility, 11.6% vs 0.9% in activities of daily living, and 30.6% vs 6.7% in instrumental activities of daily living, all p Conclusion—Functional limitations, especially in strength and body mobility domains, are highly prevalent in older women with pelvic organ prolapse, particularly in those with poor or fair self-reported health status. Future research is necessary to evaluate if functional status affects clinical outcomes in pelvic reconstructive and gynecologic surgery and whether it should be routinely assessed in clinical decision-making when treating older women with pelvic organ prolapse

Functional Status in Older Women Diagnosed with Pelvic Organ Prolapse

Background—Functional status plays an important role in the comprehensive characterization of older adults. Functional limitations are associated with an increased risk of adverse treatment outcomes, but there is limited data on the prevalence of functional limitations in older women with pelvic floor disorders. Objective—The aim of the study was to describe the prevalence of functional limitations based on health status in older women with pelvic organ prolapse. Study Design—This pooled, cross-sectional study utilized data from the linked Health and Retirement Study and Medicare files between 1992 and 2008. The analysis included 890 women ≥65 years with pelvic organ prolapse. We assessed self-reported functional status, categorized in strength, upper and lower body mobility, activities of daily living, and instrumental activities of daily living domains. Functional limitations were evaluated and stratified by respondents self-reported general health status. Descriptive statistics were used to compare categorical and continuous variables, and logistic regression was used to measure differences in the odds of functional limitation by increasing age. Results—The prevalence of functional limitations was 76.2% in strength, 44.9% in upper and 65.8% in lower body mobility, 4.5% in activities of daily living and 13.6% in instrumental activities of daily living. Limitations were more prevalent in women with poor or fair health status than in women with good health status, including 91.5% vs 69.9% in strength, 72.9% vs 33.5% in upper and 88.0% vs 56.8% in lower body mobility, 11.6% vs 0.9% in activities of daily living, and 30.6% vs 6.7% in instrumental activities of daily living, all p Conclusion—Functional limitations, especially in strength and body mobility domains, are highly prevalent in older women with pelvic organ prolapse, particularly in those with poor or fair self-reported health status. Future research is necessary to evaluate if functional status affects clinical outcomes in pelvic reconstructive and gynecologic surgery and whether it should be routinely assessed in clinical decision-making when treating older women with pelvic organ prolapse

Highly efficient synthesis of the tricyclic core of Taxol by cascade metathesis

An efficient enantioselective synthesis of the ABC tricyclic core of the anticancer drug Taxol is reported. The key step of this synthesis is a cascade metathesis reaction, which leads in one operation to the required tricycle if appropriate fine-tuning of the dienyne precursor is performed