Rio de la Plata estuary response to wind variability in synoptic to intraseasonal scales: 2. Currents' vertical structure and its implications for the salt wedge structure

The first acoustic Doppler current profiler current data collected at two locations of the Río de la Plata salt wedge during a period of around 6 months and salinity profiles gathered at and around those locations are used to study the vertical structure of currents' response to wind variability in synoptic to intraseasonal timescales and its implications for stratification. Results indicate that the estuary rapidly responds to prevailing southwesterlies/northeasterlies with currents that decay toward the bottom with only little rotation in depth. For the less frequent southeasterlies/northwesterlies the estuary develops a strong vertical structure with a defined inversion in current direction between surface and bottom layers. These patterns derive from the estuary's geometry and bathymetry. Results have important implications for the salinity vertical structure that are verified on the analyzed profiles. First, the combination of the bathymetry and coastline with the prevailing wind variability is highly favorable to the maintenance of a salt wedge structure in this estuary. Second, weakening and eventually breakdown of stratification can only occur for intense and/or persistent southeasterly winds, which even can be very strong, are not frequent. This can explain why the Río de la Plata displays the unusual feature of being an area of spawning and a nursery for a number of coastal species that use the wedge as an essential element for their reproduction. Results show that stratification is highly affected by short-term wind variability, which is its major characteristic in the area, changing the classical concept of summer-winter seasonality as the main feature of estuarine variability.Fil: Simionato, Claudia Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; ArgentinaFil: Meccia, Virna Loana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Guerrero, Raul. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Dragani, Walter Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; ArgentinaFil: Nuñez, Mario Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentin

About the vertical structure of currents in the intermediate Rio de la Plata: observational study

The Río de la Plata is one of the most important estuarine systems of the world and the most developed basin of eastern South America. Water levels and currents have been measured at many locations of the river and a number of depth-integrated (2-D) models have been applied to determine its circulation. Nevertheless, the three-dimensional characteristics of the currents have been never analyzed neither by means of direct observations nor by means of 3-D models. In this work current data measured using an Acoustic Doppler Current Profiler are presented to show the vertical structure of currents in the intermediate Rio de la Plata. In February 2-3 2000, a transect of approximately 16 Km long was repeated eleven times during 25 hours obtaining 1972 current profiles. After applying a specific processing, sinusoids with M2 (12.42 hours) period was fitted to the data series using least squares fitting method. The M2 amplitudes and phases of the EW and NS components of the current and both components corresponding to the mean flow (residuals) were obtained along the transversal section of the transect. Results showed that currents present strong vertical gradients not only in the phases of the semidiurnal constituent but also in the mean flux in the intermediate zone of the Rio de la Plata. Although the intermediate Rio de la Plata is a very shallow basin results reveal that the current from upper to bottom layers can rotate more than 90°. These results indicate that currents respond strongly to the local winds but their effects are mainly manifested at the upper layer. Finally, results indicate that 3-D baroclinic models (including temperature and salinity fields and a realistic atmospheric forcing) should be used in order to obtain a reliable and complete representation of currents especially at the intermediate and outer zone of the Rio de la Plata.El Rio de la Plata es uno de los sistemas fluviales más importantes del mundo y la cuenca más desarrollada del sudeste sudamericano. Los niveles del agua y las corrientes han sido medidos en un gran número de sitios del río y, por otro lado, diversos modelos integrados en la vertical (2-D) han sido aplicados para determinar su circulación. Sin embargo, hasta el momento, las características tridimensionales de las corrientes no han sido descriptas ni mediante observaciones directas ni por medio de modelos 3-D. En este trabajo los datos de corrientes medidos con un Perfilador de Corrientes Acústico Doppler (del inglés ADCP) son presentados para mostrar la compleja estructura vertical de las corrientes en el Río de la Plata intermedio. Entre el 2 y 3 de febrero de 2000 se repitió once veces durante 25 horas una transecta de aproximadamente 16 Km de longitud obteniéndose un total de 1972 perfiles de corriente. Después de aplicar un procesamiento específico las series fueron ajustadas a sinusoides con periodo correspondiente a la componente de marea M2 (12.42 horas) utilizando el método de mínimos cuadrados. Se obtuvo así las amplitudes y fases de las componentes EW y NS de la corriente correspondientes a la M2 y las dos componentes para el flujo medio (residuos) a lo largo de la transecta estudiada. Los resultados muestran que las corrientes en la zona intermedia del Río de la Plata presentan intensos gradientes verticales no solo en las fases de las componentes semidiurnas sino también en las del flujo medio. Aunque el Río de la Plata intermedio es una cuenca muy somera los resultados revelan que las corrientes pueden variar su dirección en más de 90° entre las capas superior e inferior de la columna de agua. Estos resultados indican que las corrientes responden fuertemente a los vientos locales, pero sus efectos son principalmente manifestados en la capa superior. Finalmente, los resultados indican que para obtener una representación confiable y completa de las corrientes especialmente en las zonas intermedia y exterior del Río de la Plata deberían implementarse modelos baroclínicos 3- D que incluyan tanto los campos térmicos y salinos como así también forzantes atmosféricos realistas.Asociación Argentina de Geofísicos y Geodesta

Efficacy and safety of nilotinib as frontline treatment in elderly (> 65 years) chronic myeloid leukemia patients outside clinical trials

Here, we report real-world evidence on the safety and efficacy of nilotinib as a first-line treatment in elderly patients with chronic phase CML, treated in 18 Italian centers. Sixty patients aged > 65 years (median age 72 years (65-84)) were reported: 13 patients were older than 75 years. Comorbidities were recorded at baseline in 56/60 patients. At 3 months of treatment, all patients obtained complete hematological response (CHR), 43 (71.6%) an early molecular response (EMR), while 47 (78%) reached a complete cytogenetic response (CCyR). At last follow-up, 63.4% of patients still had a deep molecular response (MR4 or better), 21.6% reached MR3 as best response and 11.6% persisted without MR. Most patients (85%) started the treatment at the standard dose (300 mg BID), maintained at 3 months in 80% of patients and at 6 months in 89% of them. At the last median follow-up of 46.3 months, 15 patients discontinued definitively the treatment (8 due to side effects, 4 died for unrelated CML causes, 1 for failure, 2 were lost to follow-up). One patient entered in treatment-free remission. As to safety, 6 patients (10%) experienced cardiovascular events after a median time of 20.9 months from the start. Our data showed that nilotinib could be, as first-line treatment, effective and relatively safe even in elderly CML patients. In this setting, more data in the long term are needed about possible dose reduction to improve the tolerability, while maintaining the optimal molecular response

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

About the vertical structure of currents in the intermediate Rio de la Plata: Observational study

The Río de la Plata is one of the most important estuarine systems of the world and the most developed basin of eastern South America. Water levels and currents have been measured at many locations of the river and a number of depth-integrated (2-D) models have been applied to determine its circulation. Nevertheless, the three-dimensional characteristics of the currents have been never analyzed by means of 3-D models. The lack of direct measurements of current profiles is a possible reason that explains the absence of 3-D models implemented in the estuary. In this work current data measured using an Acoustic Doppler Current Profiler are presented to show the complex vertical structure of currents in the intermediate Río de la Plata. In February 2-3 2000, a transect of approximately 16 Km long was repeated eleven times during 25 hours obtaining one current profile (0.5-m vertical resolution) every 45 seconds. After applying a specific processing the EW and NS components of the velocity were obtained for each of the 85 by 12 time series placed regularly in a rectangular matrix throughout the transect. These time series were fitted to two sinusoids with M2 (12.42 hours) and O1 (25.82 hours) periods using least squares fitting techniques. This procedure yields the M2 and O1 amplitudes and phases of the EW and NS components of the current at each grid point in addition to the both components corresponding to the mean flow (residuals). In this paper amplitude and phase of the components associated to the M2 constituent and mean flow are described. Results showed that currents present strong vertical gradients not only in the semidiurnal constituent but also in the mean flux in the intermediate zone of the Río de la Plata. Although the intermediate Río de la Plata is a very shallow basin results revel that inversion of current from upper to bottom layers occurs. These results indicate that currents respond strongly to the local winds but their effects are mainly manifested at the upper layer. Finally, our results indicate that 3-D models should be used in order to obtain a reliable and complete representation of currents in the Río de la Plata.El Río de la Plata es uno de los sistemas estuarinos más importantes del mundo y la cuenca más desarrollada del este de América del Sur. Se han medido los niveles de agua y las corrientes en muchas ubicaciones del río y se han aplicado varios modelos integrados en profundidad (2-D) para determinar su circulación. Sin embargo, las características tridimensionales de las corrientes nunca han sido analizadas mediante modelos 3-D. La falta de mediciones directas de los perfiles de corriente es una posible razón que explica la ausencia de modelos 3D implementados en la ría. En este trabajo se presentan datos de corrientes medidos usando un Perfilador de Corrientes Doppler Acústico para mostrar la compleja estructura vertical de las corrientes en el Río de la Plata intermedio. Del 2 al 3 de febrero de 2000, se repitió un transecto de aproximadamente 16 km de largo once veces durante 25 horas obteniendo un perfil de corriente (resolución vertical de 0,5 m) cada 45 segundos. Después de aplicar un procesamiento específico, se obtuvieron los componentes EW y NS de la velocidad para cada una de las series de tiempo de 85 por 12 colocadas regularmente en una matriz rectangular a lo largo del transecto. Estas series de tiempo se ajustaron a dos sinusoides con períodos M2 (12,42 horas) y O1 (25,82 horas) utilizando técnicas de ajuste por mínimos cuadrados. Este procedimiento produce las amplitudes y fases M2 y O1 de los componentes EW y NS de la corriente en cada punto de la red, además de ambos componentes correspondientes al caudal medio (residuales). En este trabajo se describe la amplitud y fase de los componentes asociados al constituyente M2 y al flujo medio. Los resultados mostraron que las corrientes presentan fuertes gradientes verticales no solo en la constituyente semidiurna sino también en el flujo medio en la zona intermedia del Río de la Plata. Aunque el Río de la Plata intermedio es una cuenca muy poco profunda, los resultados revelan que se produce una inversión de la corriente desde las capas superiores a las inferiores. Estos resultados indican que las corrientes responden fuertemente a los vientos locales pero sus efectos se manifiestan principalmente en la capa superior. Finalmente, nuestros resultados indican que se deben utilizar modelos 3-D para obtener una representación confiable y completa de las corrientes en el Río de la Plata.Fil: Dragani, Walter Cesar. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Simionato, Claudia Gloria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Nuñez, Mario Nestor. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentin

Tidal and residual currents observations at the San Matías and San José Gulfs, Northern Patagonia, Argentina

Four current time series, collected at costal locations of the San Matías and San Jose' gulfs, Argentina, are analyzed for tidal and residual currents. Tides dominate San Matías Gulf dynamics, accounting for more than 72% of the variance, whereas winds dominate at San José Gulf, explaining approximately 70% of the variance. Tides display a dominating semidiurnal regime, in compliance with what is know from the few tidal stations available and numerical simulations. At San Matías, coastal tidal currents speed increases northward, exceeding 0.6 m 8-1 at San Antonio Este. Higher order harmonics because of nonlinear interactions are large; in every sampled site, M4 and M6 currents are stronger than the diurnal constituents and have amplitudes around 5% of those from M2. At Las Grutas (San Matías Gulf), simultaneous wind observations were collected. Currents respond almost instantaneously to wind variability in the form of two modes. The first one results from winds blowing along the northwest-southeast axis and is very weak; the second one results from winds blowing from any other direction and is characterized by strong meridional currents. Even though bimodal patterns are typical of semienclosed basins, the characteristic wind directions in this gulf are not related with the orientation of its mouth but could result of the circulation in the form of two gyres suggested by numerical simulations. Energy peaks are observed at the 4 to 8 days' band and at around 12 and 20 days. Therefore, currents rapidly respond to wind variability in every timescale, from synoptic to intraseasonal.Fil: Moreira, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; ArgentinaFil: Simionato, Claudia Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; ArgentinaFil: Dragani, Walter Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; ArgentinaFil: Nuñez, Mario Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentin

Wave simulation in the outer Río de la Plata estuary: evaluation of SWAN model

This work discusses the implementation and validation of the SWAN model forced by NCEP/NCAR reanalyzed 10 m winds in the outer Río de la Plata (RDP) and adjacent continental shelf that will be used to study the wave climate in the region. Thirteen-month-long in situ data series of wave parameters are used to validate the results from numerical simulations. A set of numerical experiments is carried out in order to find a suitable computational domain to generate realistic simulations in the mouth of the RDP estuary. Numerical experiments including current and sea level fields are run, demonstrating that simulated wave parameters at the outer RDP are not significantly improved. A correction coefficient, dependent on wind speed, is applied to the wind drag factor in order to minimize the differences between simulated and observed wave parameters. The relatively low resolution wave model that satisfactorily simulates in situ wave heights and directions but slightly underestimates periods is a reliable tool for future applications and investigations.Fil: Dragani, Walter Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Garavento, E.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Simionato, Claudia Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Nuñez, Mario Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Martin, P.. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; ArgentinaFil: Campos, M. I.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentin

Multiple genetic loci modulate lung adenocarcinoma clinical staging

Purpose: The main prognostic factor of lung cancer patient outcome is clinical stage, a parameter of tumor aggressiveness. Our study was conducted to test whether germ line variations modulate individual differences in clinical stage. Experimental Design: We conducted a case-only genome-wide association study (GWAS) using a 620,901 single-nucleotide polymorphism (SNP) array in a first series of 600 lung adenocarcinoma (ADCA) patients and in a replication series of 317 lung ADCA patients. Results: GWAS identified 54 putatively associated SNPs, 3 of which were confirmed in the replication series. Joint analysis of the two series pointed to 22 statistically associated (P < 0.01) genetic variants that together explained about 20% of the phenotypic variation in clinical staging (P<2 × 10-16) andshoweda statistically significant difference in overall survival (P = 8.0 × 10-8). The strongest statistical association was observed at rs10278557 (P = 1.1 × 10-5), located in the mesenchyme homeobox 2 (MEOX2) gene. Conclusion: These data point to the role of germ line variations involving multiple loci in modulating clinical stage and, therefore, prognosis in lung ADCA patients. © 2011 AACR

Association of lung adenocarcinoma clinical stage with gene expression pattern in noninvolved lung tissue

Associations between clinical outcome of cancer patients and the gene expression signature in primary tumors at time of diagnosis have been reported. To test whether gene expression patterns in noninvolved lung tissue might correlate with clinical stage in lung adenocarcinoma (ADCA) patients, we compared the transcriptome of noninvolved lung samples from 60 ADCA smoker patients of clinical stage I versus 60 patients with stage >I. Quantitative PCR of 10 genes with the most significant differential expression confirmed the statistical association with clinical stage in eight genes, six of which were downregulated in high-stage patients. Five of these six genes were also downregulated in lung ADCA tissue as compared to noninvolved tissue. Studies in vitro indicated that four of the genes (SLC14A1, SMAD6, TMEM100 and TXNIP) inhibited colony formation of lung cancer cell lines transfected to overexpress the genes, suggesting their potential tumor-suppressor activity. Our findings suggest that individual variations in the transcriptional profile of noninvolved lung tissue may reflect the lung ADCA patient's predisposition to tumor aggressiveness. © 2012 UICC