Independent Candidaturas in Mexico: A Paradoxical Experience

El objetivo de este artículo es evaluar el desempeño electoral de las candidaturas independientes en México a partir de su adopción en el año 2014. En específico, este trabajo analiza sus fundamentos jurídicos, sus requisitos legales y económicos (en comparación con las candidaturas tradicionales de los candidatos de los partidos políticos). En la segunda parte del trabajo se analiza el desempeño electoral de los candidatos independientes en los procesos electorales llevados a cabo en los años 2015 y 2016. Finalmente, se proponen algunas conclusiones que giran en torno a una cuestión central: a pesar de que las candidaturas independientes se introdujeron con la finalidad de estimular la participación ciudadana, han recibido poco apoyo electoral y, en general, han sido utilizadas de forma creciente por políticos vinculados a los partidos tradicionales que desean emprender una carrera política personal.The aim this paper is to evaluate the performance of the independent candidates in Mexico, since its legal adoption in 2014. Specifically, this paper analyses its legal foundations, the legal and the economic requirements –compared to the traditional candidacies of the political parties. The second part of the paper analyses the performance of the independent candidates in the electoral processes carried out in the years 2015, 2016 and 2017. Finally, some conclusions are proposed that revolve around a central question: although the Independents candidacies were introduced with the aim of stimulating the citizen participation, they have received generally a minor electoral support, and they have been increasingly used by politicians linked to traditional parties who wish to begin a personal political career

Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer's disease and type 2 diabetes

Background Both Alzheimer's disease (AD) and type 2 diabetes (T2D) share common pathological features including inflammation, insulin signaling alterations, or vascular damage. AD has no successful treatment, and the close relationship between both diseases supports the study of antidiabetic drugs to limit or slow down brain pathology in AD. Empagliflozin (EMP) is a sodium-glucose co-transporter 2 inhibitor, the newest class of antidiabetic agents. EMP controls hyperglycemia and reduces cardiovascular comorbidities and deaths associated to T2D. Therefore, we have analyzed the role of EMP at the central level in a complex mouse model of AD-T2D. Methods We have treated AD-T2D mice (APP/PS1xdb/db mice) with EMP 10 mg/kg for 22 weeks. Glucose, insulin, and body weight were monthly assessed. We analyzed learning and memory in the Morris water maze and the new object discrimination test. Postmortem brain assessment was conducted to measure brain atrophy, senile plaques, and amyloid-beta levels. Tau phosphorylation, hemorrhage burden, and microglia were also measured in the brain after EMP treatment. Results EMP treatment helped to maintain insulin levels in diabetic mice. At the central level, EMP limited cortical thinning and reduced neuronal loss in treated mice. Hemorrhage and microglia burdens were also reduced in EMP-treated mice. Senile plaque burden was lower, and these effects were accompanied by an amelioration of cognitive deficits in APP/PS1xdb/db mice. Conclusions Altogether, our data support a feasible role for EMP to reduce brain complications associated to AD and T2D, including classical pathological features and vascular disease, and supporting further assessment of EMP at the central level

A simplified genomic profiling approach predicts outcome in metastatic colorectal cancer

The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on TP53 and/or RAS genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of TP53/RAS, the expected response is much worse compared to patients with exclusive TP53/RAS mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy

Elementos de Matemáticas y aplicaciones

Material elaborado por profesores de la UCM para la asignatura de este nombre del grado en Ingeniería Matemáticas, el grado en Matemáticas y el grado en Matemáticas y Estadística. Contenidos: - Números enteros. Dígitos de control y criptografía. - Grupos de simetrías. Mosaicos. - Trigonometría plana y esférica. Aplicaciones (Navegación, Astronomía de posición, GPS). - Dinámica discreta. Aplicaciones (Finanzas, introducción al caos). - Teoría de grafos. Algoritmo de ordenación de Google

CLASH: Mass Distribution in and around MACS J1206.2-0847 from a Full Cluster Lensing Analysis

We derive an accurate mass distribution of the galaxy cluster MACS J1206.2-0847 (z=0.439) from a combined weak-lensing distortion, magnification, and strong-lensing analysis of wide-field Subaru BVRIz' imaging and our recent 16-band Hubble Space Telescope observations taken as part of the Cluster Lensing And Supernova survey with Hubble (CLASH) program. We find good agreement in the regions of overlap between several weak and strong lensing mass reconstructions using a wide variety of modeling methods, ensuring consistency. The Subaru data reveal the presence of a surrounding large scale structure with the major axis running approximately north-west south-east (NW-SE), aligned with the cluster and its brightest galaxy shapes, showing elongation with a \sim 2:1 axis ratio in the plane of the sky. Our full-lensing mass profile exhibits a shallow profile slope dln\Sigma/dlnR\sim -1 at cluster outskirts (R>1Mpc/h), whereas the mass distribution excluding the NW-SE excess regions steepens further out, well described by the Navarro-Frenk-White form. Assuming a spherical halo, we obtain a virial mass M_{vir}=(1.1\pm 0.2\pm 0.1)\times 10^{15} M_{sun}/h and a halo concentration c_{vir} = 6.9\pm 1.0\pm 1.2 (\sim 5.7 when the central 50kpc/h is excluded), which falls in the range 4 <7 of average c(M,z) predictions for relaxed clusters from recent Lambda cold dark matter simulations. Our full lensing results are found to be in agreement with X-ray mass measurements where the data overlap, and when combined with Chandra gas mass measurements, yield a cumulative gas mass fraction of 13.7^{+4.5}_{-3.0}% at 0.7Mpc/h (\approx 1.7r_{2500}), a typical value observed for high mass clusters.Comment: Accepted by ApJ (30 pages, 17 figures), one new figure (Figure 10) added, minor text changes; a version with high resolution figures available at http://www.asiaa.sinica.edu.tw/~keiichi/upfiles/MACS1206/ms_highreso.pd

The Insulin Journey in the Human Body

Insulin represents the paramount anabolic hormone and the master regulator of glucose, lipid, and protein metabolism. This chapter describes the sequential stages of the physiologic journey of insulin in the human body, from its synthesis/secretion to its action in peripheral tissues and, ultimately, to its clearance and degradation. These stages include i) insulin synthesis and release from pancreatic beta cells; ii) insulin first-pass metabolism and partial clearance in the liver; iii) insulin action on the vasculature and exit from the capillary beds; iv) insulin action in peripheral and central target tissues (skeletal muscle, adipose tissue, liver, and central nervous system); and v) final insulin degradation in the kidney. Each of these stages is regulated by complex intracellular mechanisms that take place in different tissues and allow for the anabolic actions of insulin. Understanding the abovementioned stages is pivotal to comprehending the clinical consequences of impaired insulin secretion and action, as defects in one or more of these stages can be associated with the development of insulin resistance, metabolic syndrome, and type 2 diabetes mellitus. Additionally, a thorough knowledge of the insulin bodily journey can assist clinicians in therapeutic decision-making for diabetic patients on exogenous insulin therapy in different clinical settings

Cytokine storm modulation in COVID-19: a proposed role for vitamin D and DPP-4 inhibitor combination therapy (VIDPP-4i)

A dysregulated immune response characterized by the hyperproduction of several pro-inflammatory cytokines (a.k.a. 'cytokine storm') plays a central role in the pathophysiology of severe coronavirus disease 2019 (COVID-19)&nbsp;caused by the&nbsp;severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this&nbsp;Perspective article&nbsp;we discuss the evidence for synergistic anti-inflammatory and immunomodulatory properties exerted by vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors, the latter being a class of antihyperglycemic agents used for the treatment of Type 2 diabetes, which have also been reported as immunomodulators. Then, we provide the rationale for investigation of vitamin D and DPP-4 inhibitor combination therapy (VIDPP-4i) as an immunomodulation strategy to ratchet down the virulence of SARS-CoV-2, prevent disease progression and modulate the cytokine storm in COVID-19

Long-term metformin therapy and vitamin B12 deficiency: an association to bear in mind

To date, metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile. Indeed, metformin is the most widely used oral insulin-sensitizing agent, being prescribed to more than 100 million people worldwide, including patients with prediabetes, insulin resistance, and polycystic ovary syndrome. However, over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency. Of note, evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status. Vitamin B12 (also referred to as cobalamin) is a water-soluble vitamin that is mainly obtained from animal-sourced foods. At the cellular level, vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection. Thus, vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities (e.g., megaloblastic anemia and formation of hypersegmented neutrophils), progressive axonal demyelination and peripheral neuropathy. Nevertheless, no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy, and vitamin B12 deficiency remains frequently unrecognized in such individuals. Therefore, in this "field of vision" article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients, which could serve as a practical guide for identifying individuals at high risk for this condition. Moreover, we discuss additional relevant topics related to this field, including: (1) The lack of consensus about the exact definition of vitamin B12 deficiency; (2) The definition of reliable biomarkers of vitamin B12 status; (3) Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis; and (4) Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency. Finally, we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency, particularly when this condition is induced by metformin

The Contribution of Halos with Different Mass Ratios to the Overall Growth of Cluster-Sized Halos

We provide a new observational test for a key prediction of the \Lambda CDM cosmological model: the contributions of mergers with different halo-to-main-cluster mass ratios to cluster-sized halo growth. We perform this test by dynamically analyzing seven galaxy clusters, spanning the redshift range $0.13 < z_c < 0.45$ and caustic mass range $0.4-1.5$ $10^{15} h_{0.73}^{-1}$ M$_{\odot}$, with an average of 293 spectroscopically-confirmed bound galaxies to each cluster. The large radial coverage (a few virial radii), which covers the whole infall region, with a high number of spectroscopically identified galaxies enables this new study. For each cluster, we identify bound galaxies. Out of these galaxies, we identify infalling and accreted halos and estimate their masses and their dynamical states. Using the estimated masses, we derive the contribution of different mass ratios to cluster-sized halo growth. For mass ratios between ~0.2 and ~0.7, we find a ~1 $\sigma$ agreement with \Lambda CDM expectations based on the Millennium simulations I and II. At low mass ratios, $\lesssim 0.2$, our derived contribution is underestimated since the detection efficiency decreases at low masses, $\sim 2 \times 10^{14}$ $h_{0.73}^{-1}$ M$_{\odot}$. At large mass ratios, $\gtrsim 0.7$, we do not detect halos probably because our sample, which was chosen to be quite X-ray relaxed, is biased against large mass ratios. Therefore, at large mass ratios, the derived contribution is also underestimated.Comment: 25 pages, 16 figures, 6 tables, 2 machine readable tables, accepted for publication in ApJ, updated acknowledgements and data table format modifications mad