Water Mass Transports and Pathways in the North Brazil- Equatorial Undercurrent Retroflection

The equatorial retroflection of the North Brazil Current (NBC) into the Equatorial Undercurrent (EUC) and its posterior tropical recirculation is a major regulator for the returning limb of the Atlantic Meridional Overturning Circulation. Indeed, most surface and thermocline NBC waters retroflect at the equator all the way into the central and eastern Atlantic Ocean, before they recirculate back through the tropics to the western boundary. Here, we use cruise data in the western equatorial Atlantic during April 2010 and reanalysis time series for the equatorial and tropical waters in both hemispheres in order to explore the recirculation pathways and transport variability. During the 1998–2016 period, the annual-mean EUC transports 15.1 ± 1.3 Sv at 32°W, with 2.8 ± 0.4 Sv from the North Atlantic and 11.4 ± 1.3 Sv from the South Atlantic. At 32°W most of the total EUC transport comes from the western boundary retroflection south of 3°N (7.2 ± 0.9 Sv), a substantial fraction retroflects north of 3°N (5.6 ± 0.4 Sv), and the remaining flow (2.3 Sv) joins through the interior basin. The South Atlantic subtropical waters feed the EUC at all thermocline depths while the North Atlantic and South Atlantic tropical waters do so at the surface and upper-thermocline levels. The EUC transport at 32°W has a pronounced seasonality, with spring and fall maxima and a range of 8.8 Sv. The 18 yr of reanalysis data shows a weak yet significant correlation with an Atlantic Niño index, and also suggests an enhanced contribution from the South Atlantic tropical waters during 2008–2016 as compared with 1997–2007En prensa3,17

Propuesta de un sistema espacialmente explícito para evaluar el peligro de incendios

Los incendios forestales suponen un factor muy destacado en la transformación ambiental de buena parte de los ecosistemas terrestres. Tienen impactos globales, afectando a la superficie forestal y a las emisiones de gases de efecto invernadero, y efectos locales, relacionados con la degradación de suelos, erosión, modificación de la dinámica de la vegetación y pérdida de recursos y de vidas humanas. La prevención de incendios resulta cada vez más crítica, para paliar los efectos negativos de los mismos. Se presentan en este trabajo las variables de entrada y el esquema de integración para estimar el peligro de ocurrencia de incendios que se desarrolló en el marco del proyecto Firemap. Se generó información de diversas fuentes, que hacen referencia a variables socio-económicas, así como al estado de los combustibles y las características del territorio, utilizando sistemas de información geográfica (SIG) e imágenes de satélite. Todas las variables se cartografiaron a una resolución espacial de un 1 km2 y se integraron en un servidor web, que estuvo operativo para su evaluación durante el verano de 2007. Se presenta la comparación entre la variación temporal de los índices generados y la ocurrencia observada en la Comunidad de Madrid, una de las regiones del estudio.Forest fires are a major factor of environmental transformation in several ecosystems. Fires have global impacts, affecting forested areas and having an important impact in greenhouse gas emissions. Additionally, fires have local impacts, associated to soil degradation, soil erosion, vegetation dynamics, and lost of lives and properties. Fire prevention is critical to reduce the negative impacts of fire. This paper presents the input variables and the integration scheme developed within the Firemap project (funded under the Spanish Ministry of Science and Technology) to map wildland fire occurrence probability. The project first generated fire risk variables related to several factors of fire ignition or propagation. They were generated from a wide variety of sources using geographic information systems and remote sensing technologies. All variables were mapped at 1 sq km spatial resolution, and were integrated into single indices. The risk system included the development of a dedicated web-mapping server to facilitate the access to the end-users. This service was tested in the summer of 2007 for semi-operational use. The paper presents the first validation results of the danger index, by comparing temporal trends of the different danger components to the fire occurrence in the Madrid region, one of the test sites

Propuesta de un sistema espacialmente explícito para evaluar el peligro de incendios

Los incendios forestales suponen un factor muy destacado en la transformación ambiental de buena parte de los ecosistemas terrestres. Tienen impactos globales, afectando a la superficie forestal y a las emisiones de gases de efecto invernadero, y efectos locales, relacionados con la degradación de suelos, erosión, modificación de la dinámica de la vegetación y pérdida de recursos y de vidas humanas. La prevención de incendios resulta cada vez más crítica, para paliar los efectos negativos de los mismos. Se presentan en este trabajo las variables de entrada y el esquema de integración para estimar el peligro de ocurrencia de incendios que se desarrolló en el marco del proyecto Firemap. Se generó información de diversas fuentes, que hacen referencia a variables socio-económicas, así como al estado de los combustibles y las características del territorio, utilizando sistemas de información geográfica (SIG) e imágenes de satélite. Todas las variables se cartografiaron a una resolución espacial de un 1 km2 y se integraron en un servidor web, que estuvo operativo para su evaluación durante el verano de 2007. Se presenta la comparación entre la variación temporal de los índices generados y la ocurrencia observada en la Comunidad de Madrid, una de las regiones del estudio.Forest fires are a major factor of environmental transformation in several ecosystems. Fires have global impacts, affecting forested areas and having an important impact in greenhouse gas emissions. Additionally, fires have local impacts, associated to soil degradation, soil erosion, vegetation dynamics, and lost of lives and properties. Fire prevention is critical to reduce the negative impacts of fire. This paper presents the input variables and the integration scheme developed within the Firemap project (funded under the Spanish Ministry of Science and Technology) to map wildland fire occurrence probability. The project first generated fire risk variables related to several factors of fire ignition or propagation. They were generated from a wide variety of sources using geographic information systems and remote sensing technologies. All variables were mapped at 1 sq km spatial resolution, and were integrated into single indices. The risk system included the development of a dedicated web-mapping server to facilitate the access to the end-users. This service was tested in the summer of 2007 for semi-operational use. The paper presents the first validation results of the danger index, by comparing temporal trends of the different danger components to the fire occurrence in the Madrid region, one of the test sites

Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 μg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1–10 μg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field

Dissecting the role of TP53 alterations in del(11q) chronic lymphocytic leukemia

© 2021 The Authors.[Background]: Several genetic alterations have been identified as driver events in chronic lymphocytic leukemia (CLL) pathogenesis and oncogenic evolution. Concurrent driver alterations usually coexist within the same tumoral clone, but how the cooperation of multiple genomic abnormalities contributes to disease progression remains poorly understood. Specifically, the biological and clinical consequences of concurrent high-risk alterations such as del(11q)/ATM-mutations and del(17p)/TP53-mutations have not been established.[Methods]: We integrated next-generation sequencing (NGS) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques to characterize the in vitro and in vivo effects of concurrent monoallelic or biallelic ATM and/or TP53 alterations in CLL prognosis, clonal evolution, and therapy response.[Results]: Targeted sequencing analysis of the co-occurrence of high-risk alterations in 271 CLLs revealed that biallelic inactivation of both ATM and TP53 was mutually exclusive, whereas monoallelic del(11q) and TP53 alterations significantly co-occurred in a subset of CLL patients with a highly adverse clinical outcome. We determined the biological effects of combined del(11q), ATM and/or TP53 mutations in CRISPR/Cas9-edited CLL cell lines. Our results showed that the combination of monoallelic del(11q) and TP53 mutations in CLL cells led to a clonal advantage in vitro and in in vivo clonal competition experiments, whereas CLL cells harboring biallelic ATM and TP53 loss failed to compete in in vivo xenotransplants. Furthermore, we demonstrated that CLL cell lines harboring del(11q) and TP53 mutations show only partial responses to B cell receptor signaling inhibitors, but may potentially benefit from ATR inhibition.[Conclusions]: Our work highlights that combined monoallelic del(11q) and TP53 alterations coordinately contribute to clonal advantage and shorter overall survival in CLL.Spanish Fondo de Investigaciones Sanitarias, Grant/Award Numbers: PI15/01471, PI18/01500); Fundación Memoria Don Samuel Solórzano Barruso, Grant/Award Number: RD12/0036/006

Development of a framework for fire risk assessment using remote sensing and geographic information system technologies

Forest fires play a critical role in landscape transformation, vegetation succession, soil degradation and air quality. Improvements in fire risk estimation are vital to reduce the negative impacts of fire, either by lessen burn severity or intensity through fuel management, or by aiding the natural vegetation recovery using post-fire treatments. This paper presents the methods to generate the input variables and the risk integration developed within the Firemap project (funded under the Spanish Ministry of Science and Technology) to map wildland fire risk for several regions of Spain. After defining the conceptual scheme for fire risk assessment, the paper describes the methods used to generate the risk parameters, and presents proposals for their integration into synthetic risk indices. The generation of the input variables was based on an extensive use of geographic information system and remote sensing technologies, since the project was intended to provide a spatial and temporal assessment of risk conditions. All variables were mapped at 1 km2 spatial resolution, and were integrated into a web-mapping service system. This service was active in the summer of 2007 for semi-operational testing of end-users. The paper also presents the first validation results of the danger index, by comparing temporal trends of different danger components and fire occurrence in the different study regions.The Firemap project was funded by the Spanish Ministry of Science and Education (CGL2004-060490C04-01/CLI) through the Environment and Climate programPeer reviewe

ICO-ICS Praxis para el tratamiento médico del cáncer epitelial de ovario

Tractament mèdic; Càncer epitelial d'ovari; CirurgiaTratamiento médico; Cáncer epitelial de ovario; CirugíaMedical treatment; Ovarian epithelial cancer; SurgeryEl càncer epitelial d'ovari (CEO) és la segona neoplàsia ginecològica més freqüent als països desenvolupats i constitueix la principal causa de mort per càncer ginecològic i la quarta causa de mort per càncer en dones a Europa i als Estats Units. Els objectius d'aquesta guia són -Desenvolupar, difondre, implementar i avaluar resultats de la ICO-ICSPraxi de CEO epitelial. -Disminuir la variabilitat terapèutica entre les pacients tractades als diversos centres d’aquesta institució. -Implementar els resultats de la terapèutica en les pacients amb CEO epitelial tractades d’acord amb les recomanacions d’aquesta guia

Stratification and therapeutic potential of PML in metastatic breast cancer.

Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification.The work of A.C. is supported by the Ramón y Cajal award, the Basque Department of Industry, Tourism and Trade (Etortek), Health (2012111086) and Education (PI2012-03), Marie Curie (277043), Movember Foundation (GAP1), ISCIII (PI10/01484, PI13/00031), FERO (VIII Fellowship) and ERC (336343). N.M.-M. and P.A. are supported by the Spanish Association Against Cancer (AECC), AECC JP Vizcaya and Guipuzcoa, respectively. J.U. and F.S. are Juan de la Cierva Researchers (MINECO). L.A., A.A.-A. and L.V.-J. are supported by the Basque Government of education. M.L.-M.C. acknowledges SAF2014-54658-R and Asociación Española contra el Cancer. R.B. acknowledges Spanish MINECO (BFU2014-52282-P, Consolider BFU2014-57703-REDC), the Departments of Education and Industry of the Basque Government (PI2012/42) and the Bizkaia County. M.S., V.S. and J.B. acknowledge Banco Bilbao Vizcaya Argentaria (BBVA) Foundation (Tumour Biomarker Research Program). M.S. and J.B. are supported by NIH grant P30 CA008748. M.dM.V. is supported by the Institute of Health Carlos III (PI11/02251, PI14/01328) and Basque Government, Health Department (2014111145). A.M. is supported by ISCIII (CP10/00539, PI13/02277) and Marie Curie CIG 2012/712404. V.S. is supported by the SCIII (PI13/01714, CP14/00228), the FERO Foundation and the Catalan Agency AGAUR (2014 SGR 1331). R.R.G. research support is provided by the Spanish Ministry of Science and Innovation grant SAF2013-46196, BBVA Foundation, the Generalitat de Catalunya (2014 SGR 535), Institució Catalana de Recerca i Estudis Avançats, the Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds (SAF2013-46196).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1259

The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent.

BACKGROUND AND AIMS Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. APPROACH AND RESULTS C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD + /NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. CONCLUSIONS Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.This work was supported by grants from Ministerio de Ciencia e Innovación, Programa Retos-Colaboración RTC2019-007125-1 (for Jorge Simon and Maria Luz Martinez-Chantar); Ministerio de Economía, Industria y Competitividad, Retos a la Sociedad AGL2017- 86927R (for F.M.); Instituto de Salud Carlos III, Proyectos de Investigación en Salud DTS20/00138 and DTS21/00094 (for Jorge Simon and Maria Luz Martinez-Chantar, and Asis Palazon. respectively); Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias co-founded by European Regional Development Fund/European Social Fund, “Investing in your future” PI19/00819, “Una manera de hacer Europa” FIS PI20/00765, and PI21/01067 (for Jose J. G. Marin., Pau Sancho-Bru,. and Mario F. Fraga respectively); Departamento de Industria del Gobierno Vasco (for Maria Luz Martinez-Chantar); Asturias Government (PCTI) co-funding 2018-2023/ FEDER IDI/2021/000077 (for Mario F. Fraga.); Ministerio de Ciencia, Innovación y Universidades MICINN: PID2020-117116RB-I00, CEX2021-001136-S PID2020-117941RB-I00, PID2020-11827RB-I00 and PID2019-107956RA-100 integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER (for Maria Luz Martinez-Chantar, Francisco J Cubero., Yulia A Nevzorova and Asis Palazon); Ayudas Ramón y Cajal de la Agencia Estatal de Investigación RY2013-13666 and RYC2018- 024183-I (for Leticia Abecia and Asis Palazon); European Research Council Starting Grant 804236 NEXTGEN-IO (for Asis Palazon); The German Research Foundation SFB/TRR57/P04, SFB1382-403224013/ A02 and DFG NE 2128/2-1 (for Francisco J Cubero and Yulia A Nevzorova); National Institute of Health (NIH)/National Institute of Alcohol Abuse and Alcoholism (NIAAA) 1U01AA026972-01 (For Pau Sancho-Bru); Junta de Castilla y León SA074P20 (for Jose J. G. Marin); Junta de Andalucía, Grupo PAIDI BIO311 (for Franz Martin); CIBERER Acciones Cooperativas y Complementarias Intramurales ACCI20-35 (for Mario F. Fraga); Ministerio de Educación, Cultura y Deporte FPU17/04992 (for Silvia Ariño); Fundació Marato TV3 201916-31 (for Jose J. G. Marin.); Ainize Pena-Cearra is a fellow of the University of the Basque Country (UPV/ EHU); BIOEF (Basque Foundation for Innovation and Health Research); Asociación Española contra el Cáncer (Maria Luz Martinez-Chantar and Teresa C. Delgado.); Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (for Maria Luz Martinez-Chantar); La Caixa Foundation Program (for Maria Luz Martinez-Chantar); Proyecto Desarrollo Tecnologico CIBERehd (for Maria Luz Martinez-Chantar); Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III.S

Patient preferences and treatment safety for uncomplicated vulvovaginal candidiasis in primary health care

<p>Abstract</p> <p>Background</p> <p>Vaginitis is a common complaint in primary care. In uncomplicated candidal vaginitis, there are no differences in effectiveness between oral or vaginal treatment. Some studies describe that the preferred treatment is the oral one, but a Cochrane's review points out inconsistencies associated with the report of the preferred way that limit the use of such data. Risk factors associated with recurrent vulvovaginal candidiasis still remain controversial.</p> <p>Methods/Design</p> <p>This work describes a protocol of a multicentric prospective observational study with one year follow up, to describe the women's reasons and preferences to choose the way of administration (oral vs topical) in the treatment of not complicated candidal vaginitis. The number of women required is 765, they are chosen by consecutive sampling. All of whom are aged 16 and over with vaginal discharge and/or vaginal pruritus, diagnosed with not complicated vulvovaginitis in Primary Care in Madrid.</p> <p>The main outcome variable is the preferences of the patients in treatment choice; secondary outcome variables are time to symptoms relief and adverse reactions and the frequency of recurrent vulvovaginitis and the risk factors. In the statistical analysis, for the main objective will be descriptive for each of the variables, bivariant analysis and multivariate analysis (logistic regression).. The dependent variable being the type of treatment chosen (oral or topical) and the independent, the variables that after bivariant analysis, have been associated to the treatment preference.</p> <p>Discussion</p> <p>Clinical decisions, recommendations, and practice guidelines must not only attend to the best available evidence, but also to the values and preferences of the informed patient.</p