A Comparison of Procedures to Test for Moderators in Mixed-Effects Meta-Regression Models

Several alternative methods are available when testing for moderators in mixed-effects meta-regression models. A simulation study was carried out to compare different methods in terms of their Type I error and statistical power rates. We included the standard (Wald-type) test, the method proposed by Knapp and Hartung (2003) in 2 different versions, the Huber-White method, the likelihood ratio test, and the permutation test in the simulation study. These methods were combined with 7 estimators for the amount of residual heterogeneity in the effect sizes. Our results show that the standard method, applied in most meta-analyses up to date, does not control the Type I error rate adequately, sometimes leading to overly conservative, but usually to inflated, Type I error rates. Of the different methods evaluated, only the Knapp and Hartung method and the permutation test provide adequate control of the Type I error rate across all conditions. Due to its computational simplicity, the Knapp and Hartung method is recommended as a suitable option for most meta-analyses

Cholestasis associated to inborn errors in bile acid synthesis

Several metabolic pathways are involved in the biotransformation of C27 neutral cholesterol to C24 primary bile acids (BAs), mainly cholic acid (CA) and chenodeoxycholic acid (CDCA), which are then conjugated with glycine or taurine. This process can start with the modification of the steroid ring or the shortening of the side chain and involves enzymes present in different subcellular compartments. Inborn errors affecting the biogenesis of organelles, such as peroxisomes, or the expression or function of specific enzymes of these convergent routes result in: i) the lack of mature C24-BAs, with the subsequent impairment in digestion and absorption of dietary fat and liposoluble vitamins, such as vitamin K, which may account for a deficient hepatic synthesis of several coagulation factors; ii) the accumulation of intermediate metabolites, which may affect hepatocyte physiology, causing cholestasis as a commonly shared alteration besides other deleterious hepatic events; and iii) extrahepatic clinical manifestations due to accumulation of toxic metabolites in other territories, such as the nervous system, causing neurological disorders. In general, diseases whose primary alteration is a genetic defect in BA synthesis are diagnosed in children or young individuals with a very low incidence. The symptomatology can markedly vary among individuals, ranging from mild to severe conditions. Oral therapy, based on the enrichment of the BA pool with natural C24-BAs, such as CA, CDCA, glyco-CA, or ursodeoxycholic acid (UDCA), depending on the exact deficiency causing the disease, may be beneficial in preventing life-threatening situations. In contrast, in other cases, a liver transplant is the only option for these patients. This review describes the updated information on the genetic and molecular bases of these diseases and the current approaches to achieve a selective diagnosis and specific treatment

Micrometric control of the optics of the human eye: environment or genes?

Purpose: The human eye has typically more optical aberrations than conventional artificial optical systems. While the lower order modes (defocus and astigmatism) are well studied, our purpose is to explore the influence of genes versus the environment on the higher order aberrations of the optical components of the eye. Methods: We have performed a classical twin study in a sample from the Region of Murcia (Spain). Optical aberrations using a Hartmann-Shack sensor (AOnEye Voptica SL, Murcia, Spain) and corneal aberrations (using corneal topography data) were measured in 138 eyes corresponding to 69 twins; 36 monozygotic (MZ) and 33 dizygotic (DZ) pairs (age 55 years, SD 7 years). Intraclass correlation coefficients (ICCs) were used to estimate how strongly aberrations of twins resemble each other, and genetic models were fitted to quantify heritability in the selected phenotypes. Results: Genes had a significant influence in the variance of most of the higher order aberration terms (heritability from 40% to 70%). This genetic influence was observed similarly in both cornea and complete eye aberrations. Additionally, the compensation factor of spherical aberration in the eye (i.e., how much corneal spherical aberration was compensated by internal spherical aberration) was found under genetic influence (heritability of 68%). Conclusions: There is a significant genetic contribution to the variance of aberrations of the eye, not only at macroscopic levels, as in myopia or astigmatism, but also at microscopic levels, where a few micrometers changes in surface topography can produce a large difference in the value of the optical aberrations

Formando Redes

Alfabetización Informática es un proyecto que forma parte del Programa Solidaridad Estudiantil, dependiente de la Secretaría de Extensión Universitaria y de la Secretaría de Asuntos Estudiantiles, de la Universidad Nacional de Córdoba. Somos parte de los estudiantes universitarios que basados en la metodología de la Educación Popular orientamos y acompañamos a los  Adultos y, especialmente a Adultos Mayores en el proceso de Aprender las herramientas informáticas básicas, claves para acceder a la comunicación e información actual. Pero no estamos solos, distintas organizaciones nos ceden desinteresadamente sus espacios para realizar nuestros talleres  y nosotros asumimos la coordinación de los encuentros. Lejos de  impartir un mero curso de dirección vertical lo que intentamos trasmitir es lo que sabemos, compartiendo conceptos, experiencias y principalmente, disipando dudas de la manera más amena. Antes de comenzar los talleres tenemos una  preparación previa que consiste en encuentros para coordinar las intervenciones y compartir nuestras experiencias de acción. También nos organizamos en “Comisiones” para adaptar los contenidos,  materiales y metodología según las necesidades de cada organización ya que son contextos muy heterogéneos. Tenemos la férrea convicción de que la  educación resume las palabras Aprender y Transmitir, Formarse y Compartir. En esencia, el deseo de democratización más básico, el de saber. Democratizando el acceso al conocimiento... ¿Por qué los adultos Mayores? Los adultos mayores se encuentran en una etapa de la vida que se caracteriza por ser continua y gradual, la vejez es un proceso de declinación y en muchos sentidos envejecer no es otra cosa que la pérdida de nuestra capacidad de adaptación, es por eso que desde el proyecto Alfabetización Informática simplemente deseamos comprender la necesidad de los ancianos de permanecer integrados en la sociedad de manera tal que se sientan  seguros de sí mismos y productivos. También queremos estimular su participación mediante una actitud comprensiva, cálida, realista ya que creemos que esto favorece la instalación de una transferencia positiva a través del calor humano y de actitudes de óptima empatía que reaseguran al anciano y fortalecen la configuración de su personalidad. Amén de su integración a las Tics que la sociedad actual demanda.

Monitoring the hepatobiliary function using image techniques and labeled cholephilic compounds

Evaluation of the hepatobiliary function is critical for the clinicians, not only for the diagnosis of a large variety of liver diseases but also in the follow-up and management of some patients, for instance, those with different degrees of cholestasis suffering from a drug-induced liver injury (DILI) or scheduled for liver resection. Currently, the determination of global liver function mainly relies on laboratory tests, clinical scores, and data from images obtained with ultrasonography, computed tomography (CT), or magnetic resonance. Nuclear medicine scanning, displaying either planar or three-dimensional spatial distribution of liver function, is enhanced when using hepatotropic tracers based on classical radioisotopes such as technetium-99m (99mTc) and with higher resolution using metabolized probes such as those based on monosaccharide derivatives labeled with 18F. Other cholephilic compounds, and hence selectively secreted into bile, have been proposed to visualize the correct function of the liver parenchyma and the associated secretory machinery. This review aims to summarize the state-of-the-art regarding the techniques and chemical probes available to monitor liver and gallbladder function, in some cases based on imaging techniques reflecting the dynamic of labeled cholephilic compounds

Immunolocalization and temporal distribution of cytokine expression during the development of vein graft intimal hyperplasia in an experimental model

AbstractPurpose: Vein graft stenosis caused by intimal hyperplasia (IH) accounts for 30% to 50% of late bypass graft failures; however, the biochemical mediators of vein graft IH have been poorly defined. We attempted to evaluate the spatial and temporal distribution of five principal cytokines (interleukin-1 beta [IL-1β], platelet-derived growth factor AA [PDGF-AA], basic fibroblast growth factor [bFGF], interferon gamma [INFγ], and tumor necrosis factor alpha [TNF-α]) during the development of IH in a rat vein graft model.Methods: Rat epigastric vein interposition grafts in the femoral artery were harvested at 6 hours, 2 days, 1 week, 2 weeks, and 4 weeks after the grafting procedure and studied with immunohistochemical and standard histologic techniques. The cytokine expression in the endothelium and media/neointima was quantified as the percentage of immunopositive cells per high-power field.Results: Maximal hyperplasia occurred 2 weeks after the grafting procedure. Peak expression of IL-1β and bFGF occurred by 2 days. PDGF-AA expression paralleled the development of IH, peaking at 2 weeks and then declining. TNF-α expression increased at 1 week and remained elevated. INFγ was seen only in control grafts.Conclusions: The coordinated early release of IL-1β and bFGF and the down-regulation of INFγ seem to trigger an inflammatory response, thereby initiating IH. The process then is propagated by the release of PDGF-AA and TNF-α, with concomitant smooth muscle cell proliferation and production of extracellular matrix. It is likely that this complex milieu of local paracrine signaling is required to generate the hyperplastic response seen in failing vein grafts. (J Vasc Surg 1996;24:463-71.

MATRIX16: A 16-Channel Low-Power TDC ASIC with 8 ps Time Resolution

This paper presents a highly configurable 16-channel TDC ASIC designed in a commercial 180 nm technology with the following features: time-of-flight and time-over-threshold measurements, 8.6 ps LSB, 7.7 ps jitter, 5.6 ps linearity error, up to 5 MHz of sustained input rate per channel, 9.1 mW of power consumption per channel, and an area of 4.57 mm2 . The main contributions of this work are the novel design of the clock interpolation circuitry based on a resistive interpolation mesh circuit and the capability to operate at different supply voltages and operating frequencies, thus providing a compromise between TDC resolution and power consumption. Keywords: TDC; time-to-digital converter; fast timing; PET; VLSI; ASIC; ToF; ToT; low power; frontend electronic

RECOVERING THE VISIGOTH PALACE IN PLA DE NADAL (RIBA-ROJA DE TÚRIA, VALENCIA)

[EN] The palace was a monumental building with two towers on the front, a central courtyard, a ground floor with utilitarian function and a luxury upper floor with an aristocratic and representative character and an extraordinary architectural decoration. The building was used a short time, less than a century, because a great fire caused its collapse and destruction of the building. After a lot of historical, archaeological and architectural dimension studies, there is a new interpretation of the palatine building. For the 3-D modelling of the palace, we use a data collection with a laser-scanner, and the plans from the excavation and the architectural modulation previously elaborated. The conclusions of the multidisciplinary work from the reconstruction have been used extensively in archaeological publications and, especially in the didactic information for the new Visigoth Museum and other touristic activities. There's also a 3-D printed model of the reconstruction.[ES] Fue un edificio monumental con dos torres en fachada, patio central, planta baja con función utilitaria, planta superior lujosa con carácter señorial y extraordinaria decoración arquitectónica. Duró poco tiempo, menos de un siglo. Se derrumbó y destruyó por un gran incendio. Tras una serie de estudios históricos, arqueológicos y de modulación arquitectónica, se ha propuesto una nueva interpretación del conjunto. Para el alzamiento infográfico se empezó por un nuevo levantamiento en escáner –laser, sobre el que se levantó la reconstrucción previamente preparada tras el estudio de la planimetría de la excavación y de la modulación arquitectónica. El resultado del trabajo multidisciplinar de la reconstrucción se ha usado profusamente en publicaciones científicas arqueológicas y, especialmente, en la información didáctica del nuevo museo visigodo y en otras actividades de difusión turística. También ha servido para realizar una maqueta con una impresora 3D.Ribera, A.; Escriva, I.; Macias, J.; Marin, JJ.; Morin, J.; Puche, J.; Rossello, M.... (2016). RECUPERANDO EL PALACIO VISIGODO DE PLA DE NADAL (RIBAROJA DE TÚRIA, VALENCIA). En 8th International congress on archaeology, computer graphics, cultural heritage and innovation. Editorial Universitat Politècnica de València. 416-418. https://doi.org/10.4995/arqueologica8.2016.4042OCS41641

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

Cholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with dismal prognosis. The etiologies of most CCAs are unknown, but primary sclerosing cholangitis (PSC) is a risk factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are lacking. We aimed to characterize the transcriptomic profile of serum and urine extracellular vesicles (EVs) from patients with CCA, PSC, ulcerative colitis (UC), and healthy individuals. Serum and urine EVs were isolated by serial ultracentrifugations and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting. EVs transcriptome was determined by Illumina gene expression array [messenger RNAs (mRNA) and non-coding RNAs (ncRNAs)]. Differential RNA profiles were found in serum and urine EVs from patients with CCA compared to control groups (disease and healthy), showing high diagnostic capacity. The comparison of the mRNA profiles of serum or urine EVs from patients with CCA with the transcriptome of tumor tissues from two cohorts of patients, CCA cells in vitro, and CCA cellsderived EVs, identified 105 and 39 commonly-altered transcripts, respectively. Gene ontology analysis indicated that most commonly-altered mRNAs participate in carcinogenic steps. Overall, patients with CCA present specific RNA profiles in EVs mirroring the tumor, and constituting novel promising liquid biopsy biomarkers

B-Chronic Lymphocytic Leukemia Autophagyc Cell Death by the Use of Manganese Doped Zinc Oxide Nanoparticles and PhotoDynamic Therapy

B-Chronic Lymphocytic Leukemia (B-CLL) usually follows an adverse, relentless clinical course by slowly developing drug resistance to fludarabine and other chemotherapeutic agents, as well as by acquiring new different genetic abnormalities. As B-CLL cells spontaneously produce high amounts of Reactive Oxygen Species (ROS) having an altered redox state in relation to that of normal B lymphocytes, we decided to probe different metal Zinc nanoparticles (ZnNPs) and quantify the levels of Singlet Oxigen (SO) to see if variations of its intracellular concentrations could execute and accelerate deadly programs in leukemic cells rather than in normal B lymphocytes, when applied with Photodynamic Therapy (PDT). In this way, we developed and tested a variety of metal ZnNPs of which one made of 0.5% Manganese Doped Zinc Oxide (ZnO:Mn) was finally selected for further testing as it had the best fludarabine resistant B-CLL cells in vitro killing activity, specially when combined with PDT. An interesting and rapidly dying process of B-CLL cells, known as autophagy, was always seen under Transmission Electronic Microscopy (TEM) when incubated with these 0.5% Mn doped ZnO NPs. This phenomenon correlated well with those intracellular increases of SO when PDT was administered, and measured by a novel method first described by us. As this therapy seems to be very specific to fludarabine resistant B-CLL cells, producing almost no damage to normal lymphocytes, it could surely contribute in the near future as a new innovative targeted strategy to be delivered in the clinical setting for the definitive benefit of these bad prognostic patients.Fil: Peña Luengas, Sandra. Universidad de Puerto Rico; Puerto RicoFil: Marin, Gustavo Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; ArgentinaFil: Rodríguez Nieto, Felipe Jorge. Universidad Nacional Arturo Jauretche; ArgentinaFil: Dreon, Marcos Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Roque, Gustavo. Secretaria de Gobierno de Salud. Instituto Nacional Central Único Coordinador de Ablación e Implante; ArgentinaFil: Nuñez, Luis. Universidad de Puerto Rico; Puerto RicoFil: Sanchez, Francisco Homero. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Tarditti, Adrian. Secretaria de Gobierno de Salud. Instituto Nacional Central Único Coordinador de Ablación e Implante; ArgentinaFil: Schinella, Guillermo Raúl. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Farmacología; ArgentinaFil: Pistaccio, Luis. Secretaria de Gobierno de Salud. Instituto Nacional Central Único Coordinador de Ablación e Implante; ArgentinaFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Tau, Jose María. Secretaria de Gobierno de Salud. Instituto Nacional Central Único Coordinador de Ablación e Implante; ArgentinaFil: Ichim, Thomas. Medistem; Estados UnidosFil: Riordan, Neil. Medistem; Estados UnidosFil: Rivera Montalvo, Luis. Universidad de Puerto Rico; Puerto RicoFil: Mansilla, Eduardo. Secretaria de Gobierno de Salud. Instituto Nacional Central Único Coordinador de Ablación e Implante; Argentin