1,901 research outputs found
Educational Reform and Labor Market Outcomes: the Case of Argentina's Ley Federal de Educacion
In the nineties Argentina implemented a large education reform (Ley Federal de Educación – LFE) that mainly implied the extension of compulsory education in two additional years. The timing in the implementation substantially varied across provinces, providing a source of identification for unraveling the causal effect of the reform. The estimations from difference-in-difference models suggest that the LFE had an overall positive although mild impact on education and labor outcomes. The impact on the income-deprived youths was small for education outcomes and null for labor outcomes.Education, reform, labor market, wages, employment, Argentina
Sustainable tourism indicators as policy making tools: lessons from ETIS implementation at destination level
This paper aims to analyse the roles sustainable tourism indicators (STIs) play in policy making processes at destination level through a three-dimensional framework: 1) instrumental (direct use of information for decision-making), 2) conceptual (awareness raising) and 3) symbolic (legitimate decisions). The European Tourism Indicator System (ETIS) is taken as a reference system as the only common framework developed by the European Commission to measure and monitor tourism sustainability. Our empirical research follows a three-step approach. Firstly, we analysed ETIS to investigate its potential to be linked to tourism policy. Secondly, we took Zuid Limburg, the Netherlands as a case study, to assess the role of ETIS pilot implementation at the destination. Finally, we performed a comparative analysis of 11 destinations that have tested ETIS, to better frame the weight of the indicator roles in local policy making processes. We conclude that so far the STIs developed within ETIS have had limited instrumental and symbolic use, while their conceptual role, related to the social learning process resulting from their implementation, can be considered a pre-condition for other roles to emerge. Moreover, the indicators' role within policy making is closely linked to the specific governance context, influencing and being influenced by it
Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome)
Myotonic dystrophy, or Steinert’s disease, is themost common formofmuscular dystrophy that occurs in adults.Thismultisystemic
form involves the skeletalmuscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system.
Theweakness of the facialmuscles causes a characteristic facial appearance frequently associated with malocclusions. Young people
withmyotonic dystrophy, who also have severemalocclusions, have bad oral functions such as chewing, breathing, and phonation.
We present a case report of a 15-year-old boy with anterior open bite, upper and lower dental crowding, bilateral crossbite, and
constriction of the upper jaw with a high and narrow palate. The patient’s need was to improve his quality of life. Because of the
severity of skeletal malocclusion, it was necessary to schedule a combined orthodontic and surgical therapy in order to achieve the
highest aesthetic and functional result. Although therapy caused an improvement in patient’s quality of life, the clinical management
of the case was hard. The article shows a balance between costs and benefits of a therapy that challenges the nature of the main
problem of the patient, and it is useful to identify the most appropriate course of treatment for similar cases
Assessing forest availability for wood supply in Europe
The quantification of forests available for wood supply (FAWS) is essential for decision-making with regard to
the maintenance and enhancement of forest resources and their contribution to the global carbon cycle. The
provision of harmonized forest statistics is necessary for the development of forest associated policies and to
support decision-making. Based on the National Forest Inventory (NFI) data from 13 European countries, we
quantify and compare the areas and aboveground dry biomass (AGB) of FAWS and forest not available for wood
supply (FNAWS) according to national and reference definitions by determining the restrictions and associated
thresholds considered at country level to classify forests as FAWS or FNAWS.
FAWS represent between 75 and 95 % of forest area and AGB for most of the countries in this study. Economic
restrictions are the main factor limiting the availability of forests for wood supply, accounting for 67 % of the
total FNAWS area and 56 % of the total FNAWS AGB, followed by environmental restrictions. Profitability, slope
and accessibility as economic restrictions, and protected areas as environmental restrictions are the factors most
frequently considered to distinguish between FAWS and FNAWS. With respect to the area of FNAWS associated
with each type of restriction, an overlap among the restrictions of 13.7 % was identified. For most countries, the differences in the FNAWS areas and AGB estimates between national and reference definitions ranged from 0 to
5 %. These results highlight the applicability and reliability of a FAWS reference definition for most of the
European countries studied, thereby facilitating a consistent approach to assess forests available for supply for
the purpose of international reportinginfo:eu-repo/semantics/publishedVersio
Tau-Driven Neuronal and Neurotrophic Dysfunction in a Mouse Model of Early Tauopathy.
Tauopathies are neurodegenerative diseases characterized by intraneuronal inclusions of hyperphosphorylated tau protein and abnormal expression of brain-derived neurotrophic factor (BDNF), a key modulator of neuronal survival and function. The severity of both these pathological hallmarks correlate with the degree of cognitive impairment in patients. However, how tau pathology specifically modifies BDNF signaling and affects neuronal function during early prodromal stages of tauopathy remains unclear. Here, we report that the mild tauopathy developing in retinal ganglion cells (RGCs) of the P301S tau transgenic (P301S) mouse induces functional retinal changes by disrupting BDNF signaling via the TrkB receptor. In adult P301S mice, the physiological visual response of RGCs to pattern light stimuli and retinal acuity decline significantly. As a consequence, the activity-dependent secretion of BDNF in the vitreous is impaired in P301S mice. Further, in P301S retinas, TrkB receptors are selectively upregulated, but uncoupled from downstream extracellular signal-regulated kinase (ERK) 1/2 signaling. We also show that the impairment of TrkB signaling is triggered by tau pathology and mediates the tau-induced dysfunction of visual response. Overall our results identify a neurotrophin-mediated mechanism by which tau induces neuronal dysfunction during prodromal stages of tauopathy and define tau-driven pathophysiological changes of potential value to support early diagnosis and informed therapeutic decisions.
SIGNIFICANCE STATEMENT: This work highlights the potential molecular mechanisms by which initial tauopathy induces neuronal dysfunction. Combining clinically used electrophysiological techniques (i.e., electroretinography) and molecular analyses, this work shows that in a relevant model of early tauopathy, the retina of the P301S mutant human tau transgenic mouse, mild tau pathology results in functional changes of neuronal activity, likely due to selective impairment of brain-derived neurotrophic factor signaling via its receptor, TrkB. These findings may have important translational implications for early diagnosis in a subset of Alzheimer's disease patients with early visual symptoms and emphasize the need to clarify the pathophysiological changes associated with distinct tauopathy stages to support informed therapeutic decisions and guide drug discovery.journal articleresearch support, non-u.s. gov't2016 Feb 17importe
A New Genetic Risk Score to Predict the Outcome of Locally Advanced or Metastatic Breast Cancer Patients Treated With First-Line Exemestane: Results From a Prospective Study
Currently there are no reliable biomarkers to predict outcome of exemestane treatment. We designed a prospective study to investigate whether constitutive genetic background might affect response to therapy. In a population of 302 advanced breast cancer patients treated with exemestane we showed that a 5-polymorphism-based genetic score could be used to identify patients with different risks of progression and death.Introduction: Approximately 50% of locally advanced or metastatic breast cancer (MBC) patients treated with first-line exemestane do not show objective response and currently there are no reliable biomarkers to predict the outcome of patients using this therapy. The constitutive genetic background might be responsible for differences in the outcome of exemestane-treated patients. We designed a prospective study to investigate the role of germ line polymorphisms as biomarkers of survival. Patients and Methods: Three hundred two locally advanced or MBC patients treated with first-line exemestane were genotyped for 74 germ line polymorphisms in 39 candidate genes involved in drug activity, hormone balance, DNA replication and repair, and cell signaling pathways. Associations with progression-free survival (PFS) and overall survival (OS) were tested with multivariate Cox regression. Bootstrap resampling was used as an internal assessment of results reproducibility. Results: Cytochrome P450 19A1-rs10046TC/CC, solute carrier organic anion transporter 1B1-rs4149056TT, adenosine triphosphate binding cassette subfamily G member 2-rs2046134GG, fibroblast growth factor receptor-4-rs351855TT, and X-ray repair cross complementing 3-rs861539TT were significantly associated with PFS and then combined into a risk score (0-1, 2, 3, or 4-6 risk points). Patients with the highest risk score (4-6 risk points) compared with ones with the lowest score (0-1 risk points) had a median PFS of 10 months versus 26.3 months (adjusted hazard ratio [AdjHR], 3.12 [95% confidence interval (CI), 2.18-4.48]; P < .001) and a median OS of 38.9 months versus 63.0 months (AdjHR, 2.41 [95% CI, 1.22-4.79], P = .012), respectively. Conclusion: In this study we defined a score including 5 polymorphisms to stratify patients for PFS and OS. This score, if validated, might be translated to personalize locally advanced or MBC patient treatment and management
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Dominant β-catenin mutations cause intellectual disability with recognizable syndromic features
The recent identification of multiple dominant mutations in the gene encoding β-catenin in both humans and mice has enabled exploration of the molecular and cellular basis of β-catenin function in cognitive impairment. In humans, β-catenin mutations that cause a spectrum of neurodevelopmental disorders have been identified. We identified de novo β-catenin mutations in patients with intellectual disability, carefully characterized their phenotypes, and were able to define a recognizable intellectual disability syndrome. In parallel, characterization of a chemically mutagenized mouse line that displays features similar to those of human patients with β-catenin mutations enabled us to investigate the consequences of β-catenin dysfunction through development and into adulthood. The mouse mutant, designated batface (Bfc), carries a Thr653Lys substitution in the C-terminal armadillo repeat of β-catenin and displayed a reduced affinity for membrane-associated cadherins. In association with this decreased cadherin interaction, we found that the mutation results in decreased intrahemispheric connections, with deficits in dendritic branching, long-term potentiation, and cognitive function. Our study provides in vivo evidence that dominant mutations in β-catenin underlie losses in its adhesion-related functions, which leads to severe consequences, including intellectual disability, childhood hypotonia, progressive spasticity of lower limbs, and abnormal craniofacial features in adult
BAAV Mediated GJB2 Gene Transfer Restores Gap Junction Coupling in Cochlear Organotypic Cultures from Deaf Cx26Sox10Cre Mice
The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26Sox10Cre mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10–Cre line. Cx26Sox10Cre mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26Sox10Cre mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans
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