2,311 research outputs found

    La influencia de la riqueza socioemocional sobre la velocidad del proceso exportador en empresas familiares y no familiares

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    This paper proposes that family firms do not necessarily internationalize less than non-family businesses, but rather, they do it more slowly. Lower speed of internationalization process of family business (measured by the speed of the export development process) is a consequence of the role of the socio-emotional wealth (SEW) in these firms. SEW operates through three different mechanisms: (1) long-term orientation, (2) risk avoidance, and (3) lack of resources to be independent. The empirical research, based on a panel of more than a thousand Spanish manufacturing firms along nine years (2006-2014), supports the hypothesis proposed, independently of firm’s previous size, age, and export commitment level.Este trabajo propone que las empresas familiares no necesariamente se internacionalizan menos que las empresas no familiares, sino que lo hacen más lentamente. La baja velocidad del proceso de internacionalización de la empresa familiar (medida por la velocidad del proceso de desarrollo exportador) es consecuencia del papel de la riqueza socioemocional (SEW) en estas empresas. La SEW opera a través de tres mecanismos diferentes: (1) orientación a largo plazo, (2) evitación de riesgos y (3) falta de recursos para ser independiente. La investigación empírica, basada en un panel de más de mil empresas manufactureras españolas a lo largo de nueve años (2006-2014), apoya la hipótesis propuesta, independientemente del tamaño, antigüedad y nivel de compromiso exportador anterior de la empresa

    Prevalence and sociodemographic determinants of public stigma towards people with HIV and its impact on HIV testing uptake: A cross-sectional study in 64 low- and middle-income countries

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    Background: HIV stigma and discrimination are drivers of adverse HIV outcomes because they deter individuals from engaging in the HIV care continuum. We estimate the prevalence of public stigma towards people with HIV, investigate individuals' sociodemographic determinants for reporting stigmatizing attitudes, and test the impact of HIV stigma on HIV testing uptake. Methods: This was an observational study based on an analysis of cross-sectional surveys from 64 low- and middle-income countries. We used nationally representative survey data for the population aged 15–49 years from 2015 to 2021, which was the latest available data. HIV public stigma was measured using an index of two questions about attitudes towards people with HIV. First, prevalence estimates of HIV stigma were calculated by country, across countries, and by sociodemographic characteristics. Second, country fixed-effects multivariable logistic regression models were fit to assess sociodemographic determinants of holding stigmatizing attitudes towards people with HIV. Additional logistic regression models assessed country-level income and HIV prevalence as determinants of stigma and assessed the role of HIV public stigma as a driver of testing uptake. Results: A total of 1 172 841 participants were included in the study. HIV stigma was prevalent in all countries, ranging from 12.87% in Rwanda to 90.58% in Samoa. There was an inverse dose–response association between HIV stigma and educational level, wealth quintile, and age group, whereby higher levels of each were associated with lower odds of holding stigmatized attitudes towards people with HIV. The odds of stigmatized attitudes were lower among men and individuals with adequate knowledge of HIV. HIV stigma was lower in countries with greater gross domestic product per capita and HIV prevalence. Holding stigmatized attitudes towards people with HIV was associated with lower testing uptake, including having ever tested or having tested in the last year. Conclusion: HIV stigma is present to a highly varying degree in all countries studied, so different approaches to reducing stigma towards people with HIV are required across settings. Action to eliminate HIV stigma is crucial if we are to progress towards ending HIV because holding stigmatized attitudes towards people with HIV was associated with reduced testin

    Fractalkine-CX3CR1 signaling is critical for progesterone-mediated neuroprotection in the retina

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    Retinitis pigmentosa (RP) encompasses a group of retinal diseases resulting in photoreceptor loss and blindness. We have previously shown in the rd10 mouse model of RP, that rd10 microglia drive degeneration of viable neurons. Norgestrel, a progesterone analogue, primes viable neurons against potential microglial damage. In the current study we wished to investigate this neuroprotective effect further. We were particularly interested in the role of fractalkine-CX3CR1 signaling, previously shown to mediate photoreceptor-microglia crosstalk and promote survival in the rd10 retina. Norgestrel upregulates fractalkine-CX3CR1 signaling in the rd10 retina, coinciding with photoreceptor survival. We show that Norgestrel-treated photoreceptor-like cells, 661Ws, and C57 explants modulate rd10 microglial activity in co-culture, resulting in increased photoreceptor survival. Assessment of Norgestrel’s neuroprotective effects when fractalkine was knocked-down in 661 W cells and release of fractalkine was reduced in rd10 explants confirms a crucial role for fractalkine-CX3CR1 signaling in Norgestrel-mediated neuroprotection. To further understand the role of fractalkine in neuroprotection, we assessed the release of 40 cytokines in fractalkine-treated rd10 microglia and explants. In both cases, treatment with fractalkine reduced a variety of pro-inflammatory cytokines. These findings further our understanding of Norgestrel’s neuroprotective properties, capable of modulating harmful microglial activity indirectly through photoreceptors, leading to increased neuroprotection

    Progesterone analogue protects stressed photoreceptors via bFGF-mediated calcium influx.

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    Retinitis pigmentosa (RP) is a degenerative retinal disease leading to photoreceptor cell loss. In 2011, our group identified the synthetic progesterone ‘Norgestrel’ as a potential treatment for RP. Subsequent research showed Norgestrel to work through progesterone receptor membrane component 1 (PGRMC1) activation and upregulation of neuroprotective basic fibroblast growth factor (bFGF). Using trophic factor deprivation of 661W photoreceptor-like cells, we aimed to further elucidate the mechanism leading to Norgestrel-induced neuroprotection. In the present manuscript, we show by flow cytometry and live-cell immunofluorescence that Norgestrel induces an increase in cytosolic calcium in both healthy and stressed 661Ws over 24h. Specific PGRMC1 inhibition by AG205 (1 μM) showed this rise to be PGRMC1-dependent, primarily utilising calcium from extracellular sources, for blockade of L-type calcium channels by verapamil (50 μM) prevented a Norgestrel-induced calcium influx in stressed cells. Calcium influx was also shown to be bFGF-dependent, for siRNA knock down of bFGF prevented Norgestrel-PGRMC1 induced changes in cytosolic calcium. Notably, we demonstrate PGRMC1-activation is necessary for Norgestrel-induced bFGF upregulation. We propose that Norgestrel protects through the following pathway: binding to and activating PGRMC1 expressed on the surface of photoreceptor cells, PGRMC1 activation drives bFGF upregulation and subsequent calcium influx. Importantly, raised intracellular calcium is critical to Norgestrel's protective efficacy, for extracellular calcium chelation by EGTA abrogates the protective effects of Norgestrel on stressed 661W cells in vitro

    Diagnosis of cardiac surgery-associated acute kidney injury: State of the art and perspectives

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    Producción CientíficaDiagnosis of cardiac surgery-associated acute kidney injury (CSA-AKI), a syndrome of sudden renal dysfunction occurring in the immediate post-operative period, is still sub-optimal. Standard CSA-AKI diagnosis is performed according to the international criteria for AKI diagnosis, afflicted with insufficient sensitivity, specificity, and prognostic capacity. In this article, we describe the limitations of current diagnostic procedures and of the so-called injury biomarkers and analyze new strategies under development for a conceptually enhanced diagnosis of CSA-AKI. Specifically, early pathophysiological diagnosis and patient stratification based on the underlying mechanisms of disease are presented as ongoing developments. This new approach should be underpinned by process-specific biomarkers including, but not limited to, glomerular filtration rate (GFR) to other functions of renal excretion causing GFR-independent hydro-electrolytic and acid-based disorders. In addition, biomarker-based strategies for the assessment of AKI evolution and prognosis are also discussed. Finally, special focus is devoted to the novel concept of pre-emptive diagnosis of acquired risk of AKI, a premorbid condition of renal frailty providing interesting prophylactic opportunities to prevent disease through diagnosis-guided personalized patient handling. Indeed, a new strategy of risk assessment complementing the traditional scores based on the computing of risk factors is advanced. The new strategy pinpoints the assessment of the status of the primary mechanisms of renal function regulation on which the impact of risk factors converges, namely renal hemodynamics and tubular competence, to generate a composite and personalized estimation of individual risk.Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - (grant PI18/00996, PI21/01226), Unión Europea, Red de Investigación Renal (Enfermedad Renal) - (grant RICORS2040)Unión Europea–NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR) - (grant RD21/0005/0004)Junta de Castilla y León (Consejería de Educación) y Fondo Europeo de Desarrollo Regional (FEDER) - (grant IES160P20

    Au@p4VP core@shell pH-sensitive nanocomposites suitable for drug entrapment

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    11 p.-2 schem.-1 graph. abst.We synthesize and characterize pH-responsive hybrid nanocomposites with SERS and drug loading applications. This colloidal system is structured by spherical 50 nm Au cores individually coated by a pH-sensitive shell of poly4-vinylpyridine (Au@p4VP). The synthesis of these hybrid nanocomposites is performed in two steps, a first one involves the fabrication of vinyl-functionalized Au nanoparticles, and a second one includes the controlled overgrowth of a p4VP shell by free radical polymerization. As a result, Au@p4VP hybrid systems with a mean diameter ranging from 150 to 57 nm are obtained upon varying the monomer concentration at synthesis. Au@p4VP nanocomposite exhibits pH-response capabilities, confirmed by cryo-TEM analysis, Small Angle X-ray Scattering (SAXS) and Zeta Potential (ZP) measurements at different pH conditions. The Au@p4VP particles also display a controllable swelling response, which depends on the cross-linker density within the polymer. This swelling capability is analyzed by Dynamic Light Scattering (DLS), and UV–vis spectroscopy at different pHs. The pH-responsive capability is here exploited for the chemical entrapment of doxorubicin hydrochloride (Dox) into the polymer network. The presence of this molecule is resolved by Surface Enhanced Raman Spectroscopy (SERS) measurements. The entrapment efficiency of Dox by the Au@p4VP system is determined via NMR spectroscopy of the supernatants.JCR acknowledges funding from UOC, internal grant N116139473, aimed at enhancing submission to H2020 calls. RCC, JLR and JRR acknowledge financial support from the Spanish MINECO projects CTQ2013-48418P, CTQ2016-76311-R, BFU2016-75319-R and MAT2014-55065R. IF, RCC and ABRM thank the financial support given by Junta de Andalucía (Spain) under the project number P12-FQM-2668. J.F.D acknowledges the networking contributions by the COST actions CM1407 and CM1470.Peer reviewe

    Educational Evaluation, Assessment, & Effectiveness Glossary: A Claremont Graduate University EDUC 445 Fall 2021 Course Publication

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    This glossary is intended to support professionals who are seeking to understand evaluation, assessment, and effectiveness in the context of K-12 and higher education. The definitions in this e-book represent the shared meanings that were co-created by education professionals in EDUC 445 at the Claremont Graduate University during Fall 2021 under the guidance of Dr. Gwen Garrison, PhD

    A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis

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    Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival –DFS-) 25.26 months, 95% CI 8. 74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32–18.88)
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