A Preliminary Review of the Operation and Effect of the NAFTA Rules of Origin

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Deciphering biomarkers for leptomeningeal metastasis in malignant hemopathies (Lymphoma/Leukemia) patients by comprehensive multipronged proteomics characterization of cerebrospinal fluid

In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the cerebrospinal fluid (CSF) and has a very grim prognosis; the average life expectancy of patients who suffer it does not exceed 3 months. The early diagnosis of leptomeningeal disease is a challenge because, in most of the cases, it is an asymptomatic pathology. When the symptoms are clear, the disease is already in the very advanced stages and life expectancy is low. Consequently, there is a pressing need to determine useful CSF proteins to help in the diagnosis and/or prognosis of this disease. For this purpose, a systematic and exhaustive proteomics characterization of CSF by multipronged proteomics approaches was performed to determine different protein profiles as potential biomarkers. Proteins such as PTPRC, SERPINC1, sCD44, sCD14, ANPEP, SPP1, FCGR1A, C9, sCD19, and sCD34, among others, and their functional analysis, reveals that most of them are linked to the pathology and are not detected on normal CSF. Finally, a panel of biomarkers was verified by a prediction model for leptomeningeal disease, showing new insights into the research for potential biomarkers that are easy to translate into the clinic for the diagnosis of this devastating disease.We gratefully acknowledge financial support from the Spanish Health Institute, Carlos III (ISCIII), for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID-19 grant COV20EDU/00187). The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D + I2017-2020, funded by ISCIII and FEDER—Norma Galicia is supported by the CONACYT Program. P. Juanes-Velasco is supported by JCYL PhD Program “Nos Impulsa-JCYL” and scholarship JCYLEDU/601/2020

Behavioral interactions and trophic overlap between invasive signal crayfish Pacifastacus leniusculus (Decapoda, Astacidae) and native fishes in iberian rivers

The signal crayfish Pacifastacus leniusculus Dana, 1852 is a successful invasive species in the Iberian Peninsula. This is of particular conservation concern, as fish fauna is highly endemic and also threatened within this ecoregion. The aim of this study was to analyze behavioral interactions and trophic overlap between signal crayfish and native fishes in Iberian rivers (northern Spain). Video cameras were used to record fish "dominance/evasion" after spatial encounters with crayfish. Diet composition and isotopic signatures (¿13C and ¿15N) were compared to evaluate the niche overlap. Fish were dominant in 25% of the encounters with juvenile crayfish, whereas this percentage was only 4% with adult crayfish. Observations showed a high fish "evasion" response for Pyrenean stone loach Barbatula quignardi (B¿cescu-Me¿ter, 1967) (>30%). Dietary results showed a high trophic overlap between signal crayfish with the pelagic Pyrenean minnow Phoxinus bigerri Kottelat, 2007 and the benthic loach. However, the isotopic niche overlap was low, with brown trout Salmo trutta L., 1758 showing the highest area (only 0.1 ¿2). Overall, our findings suggest that interferences may occur with native species for food (i.e., benthic invertebrates). Consequently, measures should be applied to control invasive crayfish in Iberian rivers

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Data sources for drug utilization research in Latin American countries—A cross-national study: DASDUR-LATAM study

Purpose: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. Methods: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. Results: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. Conclusions: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.Fil: Lopes, Luciane C.. University Of Sorocaba; BrasilFil: Salas, Daiana Maribel. University of Pennsylvania; Estados UnidosFil: Osorio de Castro, Claudia Garcia Serpa. Fundación Oswaldo Cruz; BrasilFil: Freitas Leal, Lisiane. McGill University; CanadáFil: Doubova, Svetlana V.. Mexican Institute of Social Security; MéxicoFil: Cañás, Martín. Universidad Nacional Arturo Jauretche; Argentina. Federación Médica de la Provincia de Buenos Aires; ArgentinaFil: Dreser, Anahi. Instituto Nacional de Salud Pública; MéxicoFil: Acosta, Angela. Universidad ICESI; ColombiaFil: Oliveira Baldoni, Andre. Federal University of São João Del-Rei; BrasilFil: de Cássia Bergamaschi, Cristiane. University of Sorocaba; BrasilFil: Marques Mota, Daniel. Brazilian Health Regulatory Agency; BrasilFil: Gómez Galicia, Diana L.. Universidad Autónoma del Estado de Morelos; MéxicoFil: Sepúlveda Viveros, Dino. Universidad de Chile; ChileFil: Narvaez Delgado, Edgard. No especifíca;Fil: da Costa Lima, Elisangela. Universidade Federal do Rio de Janeiro; BrasilFil: Chandia, Felipe Vera. Pontificia Universidad Católica de Chile; ChileFil: Ferre, Felipe. Universidade Federal de Minas Gerais; BrasilFil: Marin, Gustavo Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Olmos, Ismael. State Health Services Administration; UruguayFil: Zimmermann, Ivan R.. Universidade do Brasília; BrasilFil: Fulone, Izabela. University of Sorocaba; BrasilFil: Roldán Saelzer, Juan. Instituto de Salud Pública; ChileFil: Sánchez Salgado, Juan Carlos. No especifíca;Fil: Castro Pastrana, Lucila I.. Universidad de Las Américas de Puebla; MéxicoFil: de Souza, Luiz Jupiter Carneiro. Fundación Oswaldo Cruz; BrasilFil: Machado Beltrán, Manuel. Universidad Nacional de Colombia; ColombiaFil: Tolentino Silva, Marcus. University of Sorocaba; BrasilFil: Mena, María Belén. Universidad Central del Ecuador; EcuadorFil: de França Fonteles, Marta Maria. Universidade Federal do Ceara; BrasilFil: Urtasun, Martín Alejandro. Universidad Nacional Arturo Jauretche; Argentina. Federación Médica de la Provincia de Buenos Aires; Argentin

Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology

<p>Abstract</p> <p>Background</p> <p>Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City.</p> <p>Methods</p> <p>Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level).</p> <p>Results</p> <p>Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high risk. There was a positive correlation between the average number of persons per household and the incidence of the pre-B immunophenotype (Pearson's r, 0.789; P = 0.02).</p> <p>Conclusions</p> <p>The frequency of ALL in Mexico City is among the highest in the world, similar to those found for Hispanics in the United States and in Costa Rica.</p

Combined fit to the spectrum and composition data measured by the Pierre Auger Observatory including magnetic horizon effects

The measurements by the Pierre Auger Observatory of the energy spectrum and mass composition of cosmic rays can be interpreted assuming the presence of two extragalactic source populations, one dominating the flux at energies above a few EeV and the other below. To fit the data ignoring magnetic field effects, the high-energy population needs to accelerate a mixture of nuclei with very hard spectra, at odds with the approximate E$^{-2}$ shape expected from diffusive shock acceleration. The presence of turbulent extragalactic magnetic fields in the region between the closest sources and the Earth can significantly modify the observed CR spectrum with respect to that emitted by the sources, reducing the flux of low-rigidity particles that reach the Earth. We here take into account this magnetic horizon effect in the combined fit of the spectrum and shower depth distributions, exploring the possibility that a spectrum for the high-energy population sources with a shape closer to E$^{-2}$ be able to explain the observations