Impaired musculoskeletal response to age and exercise in PPARβ(-/-) diabetic mice.

Fragility fractures are recognized complication of diabetes, but yet the underlying mechanisms remain poorly understood. This is particularly pronounced in type 2 diabetes in which the propensity to fall is increased but bone mass is not necessarily low. Thus, whether factors implicated in the development of insulin resistance and diabetes directly impact on the musculoskeletal system remains to be investigated. PPARβ(-/-) mice have reduced metabolic activity and are glucose intolerant. We examined changes in bone and muscle in PPARβ(-/-) mice and investigated both the mechanism behind those changes with age as well as their response to exercise. Compared with their wild type, PPARβ(-/-) mice had an accelerated and parallel decline in both muscle and bone strength with age. These changes were accompanied by increased myostatin expression, low bone formation, and increased resorption. In addition, mesenchymal cells from PPARβ(-/-) had a reduced proliferation capacity and appeared to differentiate into more of an adipogenic phenotype. Concomitantly we observed an increased expression of PPARγ, characteristic of adipocytes. The anabolic responses of muscle and bone to exercise were also diminished in PPARβ(-/-) mice. The periosteal bone formation response to direct bone compression was, however, maintained, indicating that PPARβ controls periosteal bone formation through muscle contraction and/or metabolism. Taken together, these data indicate that PPARβ deficiency leads to glucose intolerance, decreased muscle function, and reduced bone strength. On a molecular level, PPARβ appears to regulate myostatin and PPARγ expression in muscle and bone, thereby providing potential new targets to reverse bone fragility in patients with metabolic disturbances.

Catholic Confession of Sins as Third-Party Moral Enforcement

Catholicism has built up a legalistic religion based on two pillars: salvation by works and 'auricular' confession of sins to a priest with judicial functions. Since the Reformation, many consider auricular confession inferior to less institutional and more individual conceptions of faith. This article analyzes how all these historical solutions trade off specialization advantages against exchange costs to produce moral enforcement. After showing the behavioral foundations of confession and the adaptiveness of its historical evolution, it tests hypotheses on its efficacy, exploitation and opportunity cost. Econometric evidence supports the efficacy but not the exploitative character of Catholic confession. It also explains its secular decline as a consequence of two factors. First, the rise in education, which makes moral self-enforcement less costly. Second, the productivity gap suffered by confession, given its necessarily interpersonal nature.

Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms.

BACKGROUND: High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients. METHODS AND FINDINGS: In the present study, we correlated the occurrence of variants at three such SNPs (rs12979860, rs12980275, and rs8099917) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO) involving 253 Caucasian patients. The favorable SNP variants (CC, AA, and TT, respectively) were associated with lower baseline IP-10 (P = 0.02, P = 0.01, P = 0.04) and were less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P = 0.01). Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants (P = 0.0013, P = 0.029, P = 0.0004 respectively). Among HCV genotype 1 infected carriers of the favorable C, A, or T alleles, IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 (first phase decline), which translated into increased rates of RVR (62%, 53%, and 39%) and SVR (85%, 76%, and 75% respectively) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients, baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR, which in turn independently predicted SVR. CONCLUSIONS: Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA, RVR, and final therapeutic outcome.

Iowa Budget Report, January 2005

The FY 2006 budget we present to you today was built from the ground up and is the result of a budget process that focuses on priorities and results. Faced with difficult choices, we are heartened by the progress we have achieved with your cooperation and collaboration. Fulfilling our responsibility to Iowa children, together we have focused resources on cing class sizes and reversed an eight-year decline in test scores. As a result, Iowa students have reachieved four straight years of improved test scores, ranking among America’s best.

Heart failure as a predictor of functional dependence in hospitalized elderly

AbstractOBJECTIVEIdentify whether Heart Failure (HF) is a predictor of functional dependence for Basic Activities of Daily Living (BADL) in hospitalized elderly.METHODSWe investigated medical records and assessed dependence to BADL (by the Katz Index) of 100 elderly admitted to a geriatric ward of a university hospital. In order to verify if HF is a predictor of functional dependence, linear regression analyzes were performed.RESULTSThe prevalence of HF was 21%; 95% of them were dependent for BADLs. Bathing was the most committed ADL. HF is a predictor of dependence in hospitalized elderlies, increasing the chance of functional decline by 5 times (95% CI, 0.94-94.48), the chance of functional deterioration by 3.5 times (95% CI, 1.28-11.66; p <0.02) and reducing 0.79 points in the Katz Index score (p <0.05).CONCLUSIONHF is a dependency predictor of ADL in hospitalized elderly, who tend to be more dependent, especially for bathing.

The Effect of Four-Lane to Three-Lane Conversion on the Number of Crashes and Crash Rates in Iowa Roads, June 2005

We analyze crash data collected by the Iowa Department of Transportation using Bayesian methods. The data set includes monthly crash numbers, estimated monthly traffic volumes, site length and other information collected at 30 paired sites in Iowa over more than 20 years during which an intervention experiment was set up. The intervention consisted in transforming 15 undivided road segments from four-lane to three lanes, while an additional 15 segments, thought to be comparable in terms of traffic safety-related characteristics were not converted. The main objective of this work is to find out whether the intervention reduces the number of crashes and the crash rates at the treated sites. We fitted a hierarchical Poisson regression model with a change-point to the number of monthly crashes per mile at each of the sites. Explanatory variables in the model included estimated monthly traffic volume, time, an indicator for intervention reflecting whether the site was a “treatment” or a “control” site, and various interactions. We accounted for seasonal effects in the number of crashes at a site by including smooth trigonometric functions with three different periods to reflect the four seasons of the year. A change-point at the month and year in which the intervention was completed for treated sites was also included. The number of crashes at a site can be thought to follow a Poisson distribution. To estimate the association between crashes and the explanatory variables, we used a log link function and added a random effect to account for overdispersion and for autocorrelation among observations obtained at the same site. We used proper but non-informative priors for all parameters in the model, and carried out all calculations using Markov chain Monte Carlo methods implemented in WinBUGS. We evaluated the effect of the four to three-lane conversion by comparing the expected number of crashes per year per mile during the years preceding the conversion and following the conversion for treatment and control sites. We estimated this difference using the observed traffic volumes at each site and also on a per 100,000,000 vehicles. We also conducted a prospective analysis to forecast the expected number of crashes per mile at each site in the study one year, three years and five years following the four to three-lane conversion. Posterior predictive distributions of the number of crashes, the crash rate and the percent reduction in crashes per mile were obtained for each site for the months of January and June one, three and five years after completion of the intervention. The model appears to fit the data well. We found that in most sites, the intervention was effective and reduced the number of crashes. Overall, and for the observed traffic volumes, the reduction in the expected number of crashes per year and mile at converted sites was 32.3% (31.4% to 33.5% with 95% probability) while at the control sites, the reduction was estimated to be 7.1% (5.7% to 8.2% with 95% probability). When the reduction in the expected number of crashes per year, mile and 100,000,000 AADT was computed, the estimates were 44.3% (43.9% to 44.6%) and 25.5% (24.6% to 26.0%) for converted and control sites, respectively. In both cases, the difference in the percent reduction in the expected number of crashes during the years following the conversion was significantly larger at converted sites than at control sites, even though the number of crashes appears to decline over time at all sites. Results indicate that the reduction in the expected number of sites per mile has a steeper negative slope at converted than at control sites. Consistent with this, the forecasted reduction in the number of crashes per year and mile during the years after completion of the conversion at converted sites is more pronounced than at control sites. Seasonal effects on the number of crashes have been well-documented. In this dataset, we found that, as expected, the expected number of monthly crashes per mile tends to be higher during winter months than during the rest of the year. Perhaps more interestingly, we found that there is an interaction between the four to three-lane conversion and season; the reduction in the number of crashes appears to be more pronounced during months, when the weather is nice than during other times of the year, even though a reduction was estimated for the entire year. Thus, it appears that the four to three-lane conversion, while effective year-round, is particularly effective in reducing the expected number of crashes in nice weather.

Validity of the Katz Index to assess activities of daily living by informants in neuropathological studies

Abstract OBJECTIVE To analyze the evidences of construct validity of the Katz Index for the retrospective assessment of activities of daily living (ADL) by informants, to assist neuropathological studies in the elderly. METHOD A cross-sectional study analyzed the functional ability of ADL measure by the Katz Index, of 650 cases randomly selected from the Brazilian Brain Bank of the Ageing Brain Study Group (BBBABSG) database. Sample was divided in two subsamples for the analysis (N=325, each) and then stratified according to cognitive decline assessed by the Clinical Dementia Rating Scale (CDR). Factor analyses with calculations of internal consistency and invariance were performed. RESULTS Factor analysis evidenced a unidimensional instrument with optimal internal consistency, in all subgroups. Goodness of fit indices were obtained after two treatments of covariance, indicating adequacy of the scale for assessing ADL by informants. The scale is invariant to cognitive decline meaning that it can be used for subjects with or without cognitive impairment. CONCLUSION Katz Index is valid for the retrospective assessment of basic ADL by informants, with optimal reliability.

Micobiota associada a folhas de bananeira em Cabo Verde

A bananeira tem um elevado valor social e económico para Cabo Verde, desempenhando um papel fundamental na dieta alimentar das populações. Nos últimos anos a produtividade da cultura tem vindo a decair e de entre as causas responsáveis pelo declínio dos bananais incluem-se micoses. Com a finalidade de determinar o possível envolvimento de fungos nas doenças foliares fez-se o levantamento da micobiota associada a necroses foliares. Material foliar com lesões de diversos tipos foi recolhido em bananais de 10 localidades da Ilha de Santiago e observado ou colocado em câmara húmida sobre meio gelosado. As estruturas de fungos detectadas sobre as folhas foram montadas em lactofenol e utilizadas para identificação até ao nível da espécie, dos fungos registados, utilizando para o efeito critérios clássicos em sistemática micológica. Foram identificados 48 táxones, sendo 44 fungos mitospóricos e 4 fungos ascomicetas. Muitos dos fungos identificados não são considerados fitopatogénicos na bananeira, estando referidos como endófitos ou saprófitas na cultura. Os principais fungos patogénicos identificados foram Cladosporium musae, Colletotrichum gloeosporiodes, C. musae, Cordana musae, Deightoniella torulosa, Lasiodiplodia theobromae e Ramichloridium musae. A maioria das espécies apresentou larga distribuição nas zonas de produção amostradas.

Incidence of invasive cervical cancer in the Swiss canton of Vaud, and a note on screening.

Age adjusted incidence rates (World standard) from invasive cervical cancer in the Swiss canton of Vaud decreased from 17.7/100,000 in 1968-70 to 9.9/100,000 in 1983-85. The decline was substantial in younger middle age, but no appreciable trend was observed in women over 70. This is consistent with available interview based information on the pattern of cervical screening in the Swiss population. Although there was no organised screening programme in Switzerland, over 80% of women aged 20-44 and 65% of those aged 45-64 reported one or more screening smears over the previous 3 years, compared to only 22% of women aged 65 or over. In the last calendar period, there was an apparent increase in the incidence of invasive cervical cancer (from 2.5 to 6.1/100,000) in women aged 25-29. Although based on small absolute numbers, this is in agreement with incidence and mortality data from other countries, and may therefore confirm a change in risk factor exposure in younger women.

Life expectancy with and without disability

Average life expectancy reached 78.8 years in Europe in 2002 (WHO 2003); most Europeans can, therefore, now anticipate living well past 75 years of age. Projections in industrialized nations suggest a continuing mortality decline in the next decades 1 while birth rates will probably continue to decline, resulting in further ageing of these nations. As those aged 80 years and over are the fastest expanding segment of the older population, concerns are growing about a potential dramatic increase in the number of disabled persons. The ageing of the population and the related increase in chronic disease burden have already had major impacts on most Western health-care systems, and will probably further affect these systems in the future as the baby-boom generation becomes older. For instance, in Switzerland, it is estimated that costs due to long-term care could more than double by 2030, from 6.5 to 15.3 billion SFr.2 Similar trends are expected in most European countries. As a consequence, postponement of the onset of disability, with a compression of functional dependency into a shorter period towards the end of life, is becoming a major goal. To successfully achieve this goal and improve the control of growing health and social care expenditures, various strategies of health promotion and disease prevention are developed and tested. Although several of these experiences had some effects on functional decline and institutional placement, they have not been shown to be cost-effective. Additional strategies are, therefore, needed to prevent or delay the onset of disability in older persons, reduce functional impairment, and face the challenge of an increasing disabled elderly population.

Healthy, wealthy, wise, and happy? An exploratory analysis of the interplay between aging and subjective well-being in low and middle income countries

In this paper, we address the relationship between age and several dimension of subjective well-being. Whilst literature generally finds a U-shaped age-profile in subjective well-being, this age-pattern might only hold after controlling for objective life circumstances. The observed U-shaped age-profile might further not generalize to other dimensions of well-being and might vary across countries and cultures. Our study examines the relationship between age and several dimensions of well-being as well as the effect of objective life circumstances using the WHO Study on Global AGEing and Adult Health (SAGE). Our results suggest a decreasing age profile in the raw data associated with evaluative well-being, while experienced well-being shows a rather flat or slightly increasing pattern. However, age per se is not a cause of a decline in evaluative well-being. The negative age-profile in evaluative well-being is mainly explained by changes in life circumstances associated with aging. Controlling for socio-demographic factors, we find higher levels of well-being for older persons relative to their middle-aged counterparts. In contrast, we find that changes in life circumstances have a much smaller effect on experienced well-being.

Iowa Budget Report for Fiscal year 2008, January 2007

The FY 2008 budget we present to you today was built from the ground up and is the result of a budget process that focuses on priorities and results. Faced with difficult choices, we are heartened by the progress we have achieved with your cooperation and collaboration. Fulfilling our responsibility to Iowa children, together we have focused resources on cing class sizes and reversed an eight-year decline in test scores. As a result, Iowa students have reachieved four straight years of improved test scores, ranking among America’s best.

Conditional Involvement of CONSTITUTIVE PHOTOMORPHOGENIC1 in the Degradation of Phytochrome A.

All higher plants possess multiple phytochrome photoreceptors, with phytochrome A (phyA) being light labile and other members of the family being relatively light stable (phyB-phyE in Arabidopsis [Arabidopsis thaliana]). phyA also differs from other members of the family because it enables plants to deetiolate in far-red light-rich environments typical of dense vegetational cover. Later in development, phyA counteracts the shade avoidance syndrome. Light-induced degradation of phyA favors the establishment of a robust shade avoidance syndrome and was proposed to be important for phyA-mediated deetiolation in far-red light. phyA is ubiquitylated and targeted for proteasome-mediated degradation in response to light. Cullin1 and the ubiquitin E3 ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) have been implicated in this process. Here, we systematically analyze the requirement of cullins in this process and show that only CULLIN1 plays an important role in light-induced phyA degradation. In addition, the role of COP1 in this process is conditional and depends on the presence of metabolizable sugar in the growth medium. COP1 acts with SUPPRESSOR OF PHYTOCHROME A (SPA) proteins. Unexpectedly, the light-induced decline of phyA levels is reduced in spa mutants irrespective of the growth medium, suggesting a COP1-independent role for SPA proteins.

Intellectual property rights and efficient firm organization

I show that intellectual property rights yield static efficiency gains, irrespective oftheir dynamic role in fostering innovation. I develop a property-rights model of firmorganization with two dimensions of non-contractible investment. In equilibrium, thefirst best is attained if and only if ownership of tangible and intangible assets is equallyprotected. If IP rights are weaker, firm structure is distorted and efficiency declines:the entrepreneur must either integrate her suppliers, which prompts a decline in theirinvestment; or else risk their defection, which entails a waste of her human capital. Mymodel predicts greater prevalence of vertical integration where IP rights are weaker,and a switch from integration to outsourcing over the product cycle. Both empiricalpredictions are consistent with evidence on multinational companies. As a normativeimplication, I find that IP rights should be strong but narrowly defined, to protect abusiness without holding up its potential spin-offs.

Heterogeneous information and trade policy

Protectionism enjoys surprising popular support, in spite of deadweight losses. At thesame time, trade barriers appear to decline with public information about protection.This paper develops an electoral model with heterogeneously informed voters whichexplains both facts and predicts the pattern of trade policy across industries. In themodel, each agent endogenously acquires more information about his sector of employment. As a result, voters support protectionism, because they learn more about thetrade barriers that help them as producers than those that hurt them as consumers.In equilibrium, asymmetric information induces a universal protectionist bias. Thestructure of protection is Pareto inefficient, in contrast to existing models. The modelpredicts a Dracula effect: trade policy for a sector is less protectionist when there ismore public information about it. Using a measure of newspaper coverage across industries, I find that cross-sector evidence from the United States bears out my theoreticalpredictions.