Analysis of the Cytoprotective Role of α-Crystallins in Cell Survival and Implication of the αA-Crystallin C-Terminal Extension Domain in Preventing Bax-Induced Apoptosis.

α-Crystallins, initially described as the major structural proteins of the lens, belong to the small heat shock protein family. Apart from their function as chaperones, α-crystallins are involved in the regulation of intracellular apoptotic signals. αA- and αB-crystallins have been shown to interfere with the mitochondrial apoptotic pathway triggering Bax pro-apoptotic activity and downstream activation of effector caspases. Differential regulation of α-crystallins has been observed in several eye diseases such as age-related macular degeneration and stress-induced and inherited retinal degenerations. Although the function of α-crystallins in healthy and diseased retina remains poorly understood, their altered expression in pathological conditions argue in favor of a role in cellular defensive response. In the Rpe65(-/-) mouse model of Leber's congenital amaurosis, we previously observed decreased expression of αA- and αB-crystallins during disease progression, which was correlated with Bax pro-death activity and photoreceptor apoptosis. In the present study, we demonstrated that α-crystallins interacted with pro-apoptotic Bax and displayed cytoprotective action against Bax-triggered apoptosis, as assessed by TUNEL and caspase assays. We further observed in staurosporine-treated photoreceptor-like 661W cells stably overexpressing αA- or αB-crystallin that Bax-dependent apoptosis and caspase activation were inhibited. Finally, we reported that the C-terminal extension domain of αA-crystallin was sufficient to provide protection against Bax-triggered apoptosis. Altogether, these data suggest that α-crystallins interfere with Bax-induced apoptosis in several cell types, including the cone-derived 661W cells. They further suggest that αA-crystallin-derived peptides might be sufficient to promote cytoprotective action in response to apoptotic cell death.

The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension.

CONTEXT: The Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years. OBJECTIVE: The objective of the study was to report results from the first 3 years of the extension, representing up to 6 years of denosumab exposure. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, international, open-label study of 4550 women. INTERVENTION: Women from the FREEDOM denosumab group received 3 more years of denosumab for a total of 6 years (long-term) and women from the FREEDOM placebo group received 3 years of denosumab (crossover). MAIN OUTCOME MEASURES: Bone turnover markers (BTMs), bone mineral density (BMD), fracture, and safety data are reported. RESULTS: Reductions in BTMs were maintained (long-term) or achieved rapidly (crossover) after denosumab administration. In the long-term group, BMD further increased for cumulative 6-year gains of 15.2% (lumbar spine) and 7.5% (total hip). During the first 3 years of denosumab treatment, the crossover group had significant gains in lumbar spine (9.4%) and total hip (4.8%) BMD, similar to the long-term group during the 3-year FREEDOM trial. In the long-term group, fracture incidences remained low and below the rates projected for a virtual placebo cohort. In the crossover group, 3-year incidences of new vertebral and nonvertebral fractures were similar to those of the FREEDOM denosumab group. Incidence rates of adverse events did not increase over time. Six participants had events of osteonecrosis of the jaw confirmed by adjudication. One participant had a fracture adjudicated as consistent with atypical femoral fracture. CONCLUSION: Denosumab treatment for 6 years remained well tolerated, maintained reduced bone turnover, and continued to increase BMD. Fracture incidence remained low.

Logistic services as competitive means : segmenting the retail market for softwood lumber

Abstract

Land use response to agricultural policy and market movements on Finnish dairy-farms

Selostus: Tuki- ja hintamuutosten vaikutus maitotilojen pellon käyttöön

Whole sales market for fresh potato in Finland

Selostus: Suomen ruokaperunamarkkinoiden toimivuus

Coworker networks in the labour market

This paper studies the role coworker-based networks play for individual labour marketoutcomes. I analyse how the provision of labour market relevant information by formercoworkers affects the employment probabilities and, if hired, the wages of male workerswho have previously become unemployed as the result of an establishment closure. Toidentify the causal effect of an individual worker's network on labour market outcomes, Iexploit exogenous variation in the strength of these networks that is due to the occurrenceof mass-layoffs in the establishments of former coworkers. The empirical analysis is basedon administrative data that comprise the universe of workers employed in Germany between1980 and 2001. The results suggest a strong positive effect of a higher employmentrate in a worker's network of former coworkers on his re-employment probability afterdisplacement: a 10 percentage point increase in the prevailing employment rate in thenetwork increases the re-employment probability by 7.5 percentage points. In contrast,there is no evidence of a statistically significant effect on wages.

Construcción de un índice de calidad ocupacional (ICO) para el análisis de la inserción profesional de los graduados universitarios = Building an employment quality index (EQI) to analyse graduates’ access to the labour market

En este trabajo se propone la construcción de un índice de calidad ocupacional (ICO) a partir de los datos de la Encuesta de Inserción Laboral de los Graduados de las Universidades Catalanas realizada por la Agencia para la Calidad del Sistema Universitario de Catalunya (AQU), que ha de permitir un mejor análisis de la información que proporciona la encuesta y facilitar su comparación con estudios similares. La encuesta se realiza tres años después de la graduación. En este artículo, se utiliza la segunda encuesta realizada el año 2005 entre 11.456 graduados (52,63%) de la promoción 2001 (AQU, 2005, Serra-Ramoneda, 2007). El índice se ha elaborado a partir de los indicadores objetivos ‘tipo y duración del contrato laboral’, ‘retribución económica’, ‘adecuación entre la formación universitaria y el empleo’ a los que se otorga una puntuación ponderada según las respuestas dadas por los graduados. La suma de las puntuaciones se matiza con un coeficiente derivado del indicador subjetivo ‘satisfacción con el trabajo en general’. A partir de la información proporcionada por el índice, se realiza un análisis comparativo del nivel de calidad ocupacional que han logrado los graduados de áreas de conocimiento, ámbitos de trabajo, ramas de actividad y ubicaciones territoriales del empleo diferentes. Los resultados obtenidos permiten observar que entre los graduados catalanes los siguientes hechos son buenos predictores de la calidad de la ocupación: haber estudiado una carrera que no sea de Humanidades, ser un hombre, haber desempeñado durante la carrera un trabajo relacionado con los estudios, estar ocupado en la construcción, en instituciones financieras o en servicios a empresas, haber tenido algún tipo de movilidad por motivos de trabajo, trabajar fuera de Cataluña y hacerlo en empresas grandes, especialmente con más de 500 trabajadores. Finalmente, se presentan algunas reflexiones y propuestas que pueden resultar de interés para la orientación de los estudiantes y la planificación universitaria

Heterogeneity, selection and labor market disparities

We study the incentives to acquire skill in a model where heterogeneous firmsand workers interact in a labor market characterized by matching frictions and costlyscreening. When effort in acquiring skill raises both the mean and the variance of theresulting ability distribution, multiple equilibria may arise. In the high-effort equilibrium, heterogeneity in ability is sufficiently large to induce firms to select the bestworkers, thereby confirming the belief that effort is important for finding good jobs.In the low-effort equilibrium, ability is not sufficiently dispersed to justify screening,thereby confirming the belief that effort is not so important. The model has implications for wage inequality, the distribution of firm characteristics, sorting patternsbetween firms and workers, and unemployment rates that can help explaining observedcross-country variation in socio-economic and labor market outcomes.

Time scarcity and the market for news

We develop a theory of news coverage in environments of information abundance. News consumersare time-constrained and browse through news items that are available across competingoutlets, choosing which ones to read or skip. Media firms are aware of consumers' preferences andconstraints, and decide on rankings of news items that maximize their profits. We find that, evenwhen readers and outlets are rational and unbiased and when markets are competitive, readersmay read more than they would like to, and the stories they read may be significantly differentfrom the ones they prefer. Next, we derive implications on diverse aspects of new and traditionalmedia. These include a rationale for tabloid news, a theory of optimal advertisement placementin newscasts, and a justification for readers' migration to online media platforms in order to circumventinefficient rankings found in traditional media. We then analyze methods for restoringreader-efficient standards and discuss the political economy implications of the theory.

The effects of monetary policy on stock market bubbles: Some evidence

We estimate the response of stock prices to exogenous monetary policy shocks usinga vector-autoregressive model with time-varying parameters. Our evidence points toprotracted episodes in which, after a a short-run decline, stock prices increase persistently in response to an exogenous tightening of monetary policy. That responseis clearly at odds with the "conventional" view on the effects of monetary policy onbubbles, as well as with the predictions of bubbleless models. We also argue that it isunlikely that such evidence be accounted for by an endogenous response of the equitypremium to the monetary policy shocks.

Can 3T multiparametric magnetic resonance imaging accurately detect prostate cancer extracapsular extension?

BACKGROUND: Accurate staging is essential to determine the correct management of patients diagnosed with prostate cancer. We assess the accuracy of 3T multiparametric magnetic resonance imaging (MRI) with endorectal coil (3TemMRI) in detecting prostate cancer local extension. METHODS: We retrospectively reviewed charts from January 2008 to July 2012 from all patients undergoing radical prostatectomy. Patients were only included if 3TemMRI and radical prostatectomy were performed at our institution. Based on the presence of extracapsular extension (ECE) at 3TemMRI, prostate cancer was dichotomized into locally advanced or organ-confined disease. The accuracy of 3TemMRI local staging was then evaluated using definitive pathology as a reference. RESULTS: Overall, 177 radical prostatectomies were performed within the timeframe. After applying exclusion criteria, 60 patients were included in the final analysis. The mean patient age was 67 ± 7 (standard deviation) years. Mean prostate-specific antigen value was 12.7 ± 12.7 ng/L. Based on preoperative characteristics, we considered 38 of the 60 patients (63%) patients high risk. 3TemMRI identified an organ-confined tumour in 46 patients and locally advanced disease in 14 patients. When correlated to final pathology, 3TemMRI specificity, sensitivity, negative and positive predictive values, and accuracy in detecting locally advanced prostate cancer were 90%, 35%, 57%, 79% and 62%, respectively. INTERPRETATION: This study shows that the use of preoperative 3TemMRI can be used to identify organ-confined prostate cancer when locally advanced disease is suspected.

Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension.

The 3-year FREEDOM trial assessed the efficacy and safety of 60 mg denosumab every 6 months for the treatment of postmenopausal women with osteoporosis. Participants who completed the FREEDOM trial were eligible to enter an extension to continue the evaluation of denosumab efficacy and safety for up to 10 years. For the extension results presented here, women from the FREEDOM denosumab group had 2 more years of denosumab treatment (long-term group) and those from the FREEDOM placebo group had 2 years of denosumab exposure (cross-over group). We report results for bone turnover markers (BTMs), bone mineral density (BMD), fracture rates, and safety. A total of 4550 women enrolled in the extension (2343 long-term; 2207 cross-over). Reductions in BTMs were maintained (long-term group) or occurred rapidly (cross-over group) following denosumab administration. In the long-term group, lumbar spine and total hip BMD increased further, resulting in 5-year gains of 13.7% and 7.0%, respectively. In the cross-over group, BMD increased at the lumbar spine (7.7%) and total hip (4.0%) during the 2-year denosumab treatment. Yearly fracture incidences for both groups were below rates observed in the FREEDOM placebo group and below rates projected for a "virtual untreated twin" cohort. Adverse events did not increase with long-term denosumab administration. Two adverse events in the cross-over group were adjudicated as consistent with osteonecrosis of the jaw. Five-year denosumab treatment of women with postmenopausal osteoporosis maintained BTM reduction and increased BMD, and was associated with low fracture rates and a favorable risk/benefit profile.

Iowa's People: a resource for extension educators, June 1989

Statistics about people and their families interest community planners, social scientists, Extension educators, and others because the family is the fundamental social institution in our society. The purpose of this publication is to bring together in one reference many statistics about people in Iowa counties that have been published separately elsewhere. Most of the data presented are limited to only one year. This cross-sectional view is similar to a photograph that shows only one point in time. At an earlier or later time it might appear differently. Although the statistics reported in the various tables and figures represent different years, the data presented were the most recent available at the time this publication was prepared.