Biological Activity and Implications of the Metalloproteinases in Diabetic Foot Ulcers

Inadequate metabolic control predisposes diabetic patient to a series of complications on account of diabetes mellitus (DM). Among the most common complications of DM is neuropathy, which causes microvascular damage by hyperglycemia in the lower extremities which arrives characterized by a delayed closing. The global prevalence of diabetic neuropathy (DN) was 66% of people with diabetes in 2015, representing the principal cause of total or partial lower extremities amputation, with 22.6% of the patients with DN. Matrix metalloproteinases (MMPs) are involved in healing. The function that these mainly play is the degradation during inflammation that has as consequence the elimination of the extracellular matrix (ECM), the disintegration of the capillary membrane to give way to angiogenesis and cellular migration for the remodeling of damaged tissue. The imbalance in MMPs may increase the chronicity of a wound, what leads to chronic foot ulcers and amputation. This chapter focuses on the role of MMPs in diabetic wound healing

Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia

BACKGROUND: The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. RESULTS: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. CONCLUSIONS: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201

The Pierre Auger Observatory III: Other Astrophysical Observations

Astrophysical observations of ultra-high-energy cosmic rays with the Pierre Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference, Beijing, China, August 201

Evolution after Anti-TNF Discontinuation in Patients with Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study

OBJECTIVES:The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.METHODS:This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.RESULTS:A total of 1, 055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn''s disease and ulcerative colitis patients, respectively. In both Crohn''s disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn''s disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.CONCLUSIONS:The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe

Sexto reporte de eventos adversos con tratamientos biológicos en Argentina. Informe del registro BIOBADASAR

Objetivo: actualizar los resultados del registro BIOBADASAR sobre seguridad, duración y causas de interrupción del tratamiento luego de 8 años de seguimiento. Métodos: BIOBADASAR es un registro de seguridad de terapias biológicas establecido por la Sociedad Argentina de Reumatología. Se presenta la descripción de BIOBADASAR 3.0, una cohorte compuesta por 53 centros de Argentina seguidos prospectivamente desde agosto de 2010 hasta enero de 2018

Antennas for the detection of radio emission pulses from cosmic-ray induced air showers at the Pierre Auger Observatory

The Pierre Auger Observatory is exploring the potential of the radio detection technique to study extensive air showers induced by ultra-high energy cosmic rays. The Auger Engineering Radio Array (AERA) addresses both technological and scientific aspects of the radio technique. A first phase of AERA has been operating since September 2010 with detector stations observing radio signals at frequencies between 30 and 80 MHz. In this paper we present comparative studies to identify and optimize the antenna design for the final configuration of AERA consisting of 160 individual radio detector stations. The transient nature of the air shower signal requires a detailed description of the antenna sensor. As the ultra-wideband reception of pulses is not widely discussed in antenna literature, we review the relevant antenna characteristics and enhance theoretical considerations towards the impulse response of antennas including polarization effects and multiple signal reflections. On the basis of the vector effective length we study the transient response characteristics of three candidate antennas in the time domain. Observing the variation of the continuous galactic background intensity we rank the antennas with respect to the noise level added to the galactic signal

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

The rapid atmospheric monitoring system of the Pierre Auger Observatory

The Pierre Auger Observatory is a facility built to detect air showers produced by cosmic rays above 10(17) eV. During clear nights with a low illuminated moon fraction, the UV fluorescence light produced by air showers is recorded by optical telescopes at the Observatory. To correct the observations for variations in atmospheric conditions, atmospheric monitoring is performed at regular intervals ranging from several minutes (for cloud identification) to several hours (for aerosol conditions) to several days (for vertical profiles of temperature, pressure, and humidity). In 2009, the monitoring program was upgraded to allow for additional targeted measurements of atmospheric conditions shortly after the detection of air showers of special interest, e. g., showers produced by very high-energy cosmic rays or showers with atypical longitudinal profiles. The former events are of particular importance for the determination of the energy scale of the Observatory, and the latter are characteristic of unusual air shower physics or exotic primary particle types. The purpose of targeted (or 'rapid') monitoring is to improve the resolution of the atmospheric measurements for such events. In this paper, we report on the implementation of the rapid monitoring program and its current status. The rapid monitoring data have been analyzed and applied to the reconstruction of air showers of high interest, and indicate that the air fluorescence measurements affected by clouds and aerosols are effectively corrected using measurements from the regular atmospheric monitoring program. We find that the rapid monitoring program has potential for supporting dedicated physics analyses beyond the standard event reconstruction

Identifying clouds over the Pierre Auger Observatory using infrared satellite data

We describe a new method of identifying night-time clouds over the Pierre Auger Observatory using infrared data from the Imager instruments on the GOES-12 and GOES-13 satellites. We compare cloud. identifications resulting from our method to those obtained by the Central Laser Facility of the Auger Observatory. Using our new method we can now develop cloud probability maps for the 3000 km(2) of the Pierre Auger Observatory twice per hour with a spatial resolution of similar to 2.4 km by similar to 5.5 km. Our method could also be applied to monitor cloud cover for other ground-based observatories and for space-based observatories. (C) 2013 Elsevier B.V. All rights reserved.The successful installation, commissioning, and operation of the Pierre Auger Observatory would not have been possible without the strong commitment and effort from the technical and adminis- trative staff in Malargüe. We are very grateful to the following agencies and organiza- tions for financial support: Comisión Nacional de Energía Atómica, Fundación Antorchas, Gobierno De La Provincia de Mendoza, Municipalidad de Malargüe, NDM Holdings and Valle Las Leñas, in gratitude for their continuing cooperation over land access, Argentina; the Australian Research Council; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Projetos (FINEP), Fundação de Amparo à Pesquisa do Estado de Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Ministério de Ciência e Tecnolo- gia (MCT), Brazil; AVCR AV0Z10100502 and AV0Z10100522, GAAV KJB100100904, MSMT-CR LA08016, LG11044, MEB111003, MSM0021620859, LA08015, TACR TA01010517 and GA UK 119810, Czech Republic; Centre de Calcul IN2P3/CNRS, Centre Na- tional de la Recherche Scientifique (CNRS), Conseil Régional Ile-de- France, Département Physique Nucléaire et Corpusculaire (PNC- IN2P3/CNRS), Département Sciences de l’Univers (SDU-INSU/ CNRS), France; Bundesministerium für Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), Finanzministeri- um Baden-Württemberg, Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF), Ministerium für Wissenschaft und Forschung, Nordrhein-Westfalen, Ministerium für Wissenschaft, Forschung und Kunst, Baden-Württemberg, Germany; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), Italy; Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico; Ministerie van Ond- erwijs, Cultuur en Wetenschap, Nederlandse Organisatie voor Wet- enschappelijk Onderzoek (NWO), Stichting voor Fundamenteel Onderzoek der Materie (FOM), Netherlands; Ministry of Science and Higher Education, Grant Nos. N N202 200239 and N N202 207238, Poland; Portuguese national funds and FEDER funds with- in COMPETE - Programa Operacional Factores de Competitividade through Fundação para a Ciência e a Tecnologia, Portugal; Roma- nian Authority for Scientific Research ANCS, CNDI-UEFISCDI part- nership projects nr.20/2012 and nr.194/2012, project nr.1/ ASPERA2/2012 ERA-NET and PN-II-RU-PD-2011-3-0145-17, Roma- nia; Ministry for Higher Education, Science, and Technology, Slove- nian Research Agency, Slovenia; Comunidad de Madrid, FEDER funds, Ministerio de Ciencia e Innovación and Consolider-Ingenio 2010 (CPAN), Xunta de Galicia, Spain; The Leverhulme Foundation, Science and Technology Facilities Council, United Kingdom; Department of Energy, Contract Nos. DE-AC02-07CH11359, DE- FR02-04ER41300, DE-FG02-99ER41107, National Science Founda- tion, Grant No. 0450696, The Grainger Foundation USA; NAFO- STED, Vietnam; Marie Curie-IRSES/EPLANET, European Particle Physics Latin American Network, European Union 7th Framework Program, Grant No. PIRSES-2009-GA-246806; and UNESCO. We would like to thank the former Michigan Tech students: Nathan Kelley-Hoskins, Kyle Luck and Arin Nelson for their impor- tant contribution to the development of this paper. We would like to thank NOAA for the GOES satellite data that we freely down- loaded from their website. Also, we would like to mention in these acknowledgments Dr. Steve Ackerman and Dr. Tony Schreiner for very valuable conversationsPeer reviewe