New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The "GEnomics of Musculo Skeletal Traits TranslatiOnal NEtwork" : Origins, Rationale, Organization, and Prospects

Musculoskeletal research has been enriched in the past ten years with a great wealth of new discoveries arising from genome wide association studies (GWAS). In addition to the novel factors identified by GWAS, the advent of whole-genome and whole-exome sequencing efforts in family based studies has also identified new genes and pathways. However, the function and the mechanisms by which such genes influence clinical traits remain largely unknown. There is imperative need to bring multidisciplinary expertise together that will allow translating these genomic discoveries into useful clinical applications with the potential of improving patient care. Therefore "GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork" (GEMSTONE) aims to set the ground for the: 1) functional characterization of discovered genes and pathways; 2) understanding of the correspondence between molecular and clinical assessments; and 3) implementation of novel methodological approaches. This research network is funded by The European Cooperation in Science and Technology (COST). GEMSTONE includes six working groups (WG), each with specific objectives: WG1-Study populations and expertise groups: creating, maintaining and updating an inventory of experts and resources (studies and datasets) participating in the network, helping to assemble focus groups defined by phenotype, functional and methodological expertise. WG2-Phenotyping: describe ways to decompose the phenotypes of the different functional studies into meaningful components that will aid the interpretation of identified biological pathways. WG3 Monogenic conditions - human KO models: makes an inventory of genes underlying musculoskeletal monogenic conditions that aids the assignment of genes to GWAS signals and prioritizing GWAS genes as candidates responsible for monogenic presentations, through biological plausibility. WG4 Functional investigations: creating a roadmap of genes and pathways to be prioritized for functional assessment in cell and organism models of the musculoskeletal system. WG5 Bioinformatics seeks the integration of the knowledge derived from the distinct efforts, with particular emphasis on systems biology and artificial intelligence applications. Finally, WG6 Translational outreach: makes a synopsis of the knowledge derived from the distinct efforts, allowing to prioritize factors within biological pathways, use refined disease trait definitions and/or improve study design of future investigations in a potential therapeutic context (e.g. clinical trials) for musculoskeletal diseases.Peer reviewe

The process of spatial construction of the Cordoba southern highlands and emerging environmental issues

Los problemas ambientales y riesgos emergentes en las sierras del sur cordobés encuentran su explicación en el proceso de organización del espacio resultante de la construcción social desde las relaciones de poder en un proceso histórico natural-social, donde el uso de los recursos y el espacio y su expresión en forma de modificación del medio y calidad de vida, reflejan la racionalidad dominante: la capitalista.Se plantea en esta instancia desentrañar el proceso histórico de ocupación, caracterizar los macroambientes como contextos condicionantes del espacio y analizar el impacto de los asentamientos, actividades y usos actuales del suelo, a fin de determinar áreas según los problemas ambientales detectados.La metodología consiste en reconstruir el proceso histórico de construcción del espacio es de base histórica. Datos con referencia espacial (censos, estadísticas) y entrevistas aportan a la reconstrucción del proceso de organización del espacio y los problemas ambientales derivados.Environmental problems and emerging risks in the mountains of southern Cordoba find their explanation in the process of organizing the space resulting from the social construction from power relations in a natural-social historical process, where the use of resources and space and its expression in the form of modification of the environment and quality of life, reflect the dominant rationality: the capitalist. In this instance, it is proposed to unravel the historical process of occupation, characterize the macro-environments as conditioning contexts of space and analyze the impact of settlements, activities and current uses of the land, in order to determine areas according to the detected environmental problems. The methodology consists of reconstructing the historical process of construction of the space on a historical basis. Data with spatial reference (censuses, statistics) and interviews contribute to the reconstruction of the process of organizing space and the resulting environmental problems.Fil: Sosa, Elina del Carmen. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Humanas. Departamento de Geografia; ArgentinaFil: Maldonado, Gabriela Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Humanas. Departamento de Geografia; ArgentinaFil: Grandis, Gilda Cristina. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Humanas. Departamento de Geografia; ArgentinaFil: Lucero, Franco Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Humanas. Departamento de Geografia; ArgentinaFil: Brandi, César Gustavo. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Humanas. Departamento de Geografia; Argentin

ZoneModa Journal 5 - Fashion Convergence

Il quinto numero di ZoneModa Journal, curato da Antonella Mascio e Junji Tsuchiy, \ue8 dedicato all\u2019esplorazione dei percorsi definiti dalle dinamiche convergenti, con l\u2019obiettivo di approfondire gli aspetti relativi alle innovazioni comunicative e alle attribuzioni di valore sociologico e simbolico che queste pongono in essere. Da un lato, infatti, i brand e le griffe di moda sembrano essere sempre pi\uf9 immersi nel processo della comunicazione coordinata, immaginata per poter essere fruibile nelle diverse piattaforme a disposizione; dall\u2019altro lato, per la loro forma caleidoscopica, i prodotti culturali e mediali si predispongono sempre pi\uf9 a letture diverse, contemplando anche la strada del fashion. A sua volta il consumatore-tipo dei prodotti di moda, nell\u2019ottica del processo riflessivo contemporaneo, si configura come \u201csoggetto desiderante che desidera non solo oggetti e altri soggetti, ma anche forme alternative di soggettivit\ue0\u201d (Edwards 2011, trad. it. 2012, p. 235) e, mediante l\u2019osservazione, la ricerca e l\u2019imitazione dei capi di abbigliamento, trova talvolta la possibilit\ue0 di esprimersi. Media e moda sembrano entrambi allargare il loro spazio sociale, utilizzando soprattutto il linguaggio delle immagini, del gusto, degli stereotipi, indicando ai pubblici nuovi modelli di riferimento, come possiamo leggere nei saggi del volume che qui presentiamo

Sorafenib: 10 years after the first pivotal trial

Sorafenib is an oral multikinase inhibitor with anticancer activity against a wide spectrum of cancers. It is currently approved for the treatment of patients with hepatocellular carcinoma, advanced renal cell carcinoma or progressive, locally advanced or metastatic differentiated thyroid carcinoma. In this review, we present a number of studies that investigated the efficacy and safety of sorafenib in these settings. We also discuss the perspectives on the use of this molecule, including the role of sorafenib as comparator for the development of new drugs, the combination of sorafenib with additional therapies (such as transarterial chemoembolization for hepatocellular carcinoma) and the use of this treatment in several other advanced refractory solid tumors

Sorafenib: The gold standard therapy in advanced hepatocellular carcinoma and beyond

Commentary- No Abstract availabl