Ordenamiento territorial en el municipio. Una guía metodológica

El objetivo de este documento es aportar a los gobiernos locales una síntesis clara y sencilla sobre los principales conceptos y los pasos metodológicos más importantes a considerar para la elaboración de un Plan de Ordenamiento Territorial (POT).EEA BarilocheFil: Mendez Casariego, Hugo. Instituto Nacional de Tecnologia Agropecuaria (INTA). Estacion Experimental Agropecuaria Bariloche. Area de Desarrollo Rural; ArgentinaFil: Pascale Medina, Carla. Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO). Alianza Sudamericana de Suelos de la Alianza Mundial por el Suelo; Argentin

Distintas fracciones de fósforo en suelos del norte de Entre Ríos

p.59-62El objetivo del presente trabajo fue evaluar y relacionar las distintas fracciones de fósforo en dos series de suelos con características vérticas. Durante las cuatro estaciones del año, se efectuaron las siguientes determinaciones analíticas: P total, P inorgánico total, P orgánico total, P-Bray 1, P-Olsen, Carbono orgánico total y pH en agua, en las series de suelos G arat (A rgiacuol vértico) y Esmeralda (Peluderte argiacuólico) bajo pastizal natura. El contenido de P total fue bajo y el porcentaje de P orgánico fue de un 63 por ciento, presentando su mayor valor durante el invierno. Esta variación estacional no fue significativa en los contenidos de P-Bray y P-Olsen. Esta homogeneidad puede estar relacionada con las características intrínsecas de los suelos vérticos, hecho que les confiere una especial capacidad buffer de fosfatos. Los niveles de P extractable fueron siempre deficientes, extrayendo Olsen un 62 por ciento del total extraído por Bra

Guía de prospectiva para el ordenamiento territorial rural de la Argentina a nivel municipal

Esta guía ha sido elaborada para motivar y sensibilizar a los tomadores de decisiones de los municipios a incorporar la dimensión de futuro en los procesos de Ordenamiento Territorial Rural (OTR). Con tal fin, los autores presentan algunas estrategias conceptuales y metodológicas para abordar estudios de prospectiva en el marco de los procesos de OTR, tomando como base las experiencias y aprendizajes de la Provincia de Mendoza. La Guía está elaborada para ser aprovechada por un público amplio: planificadores, tomadores de decisiones, gestores del territorio y actores sociales, entre otros. Es evidente el reconocimiento que hacen sus autores acerca de la necesidad de participación de muy diversos agentes económicos, sociales y políticos en un proceso de ordenamiento territorial rural. Este es otro mérito importante, pues la Guía es cuidadosa en evitar intentar ser una especie de manual a seguir puntualmente a rajatabla, ni tampoco ser tan general como para ajustarse casi a cualquier proceso de planeación del territorio. Se ubica en un punto intermedio, a partir del cual puede ser aprovechable por los diferentes públicos.CR Mendoza-San JuanFil. Vitale Gutierrez, Javier Alejandro. Instituto Nacional de Tecnología Agropecuaria (INTA). Centro Regional Mendoza San Juan; ArgentinaFil. Vitale Gutierrez, Javier Alejandro. Universidad Nacional de Cuyo. Centro de Estudios Prospectivos; ArgentinaFil: Pascale Medina, Carla. Food and Agriculture Organization (FAO). Alianza Sudamericana de Suelos; ArgentinaFil: Barrientos, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Ciencias Humanas, Sociales y Ambientales, Mendoza; ArgentinaFil: Papagno, Silvina Graciela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Prospectiva y Políticas Públicas; Argentin

Argentina: Soil Organic Carbon Sequestration Potential National Map. National Report. Version 1.0. Year: 2021

Soil organic carbon (SOC) is a key factor affecting soil physical fertility, as it improves several soil properties such as infiltration, structural stability, porosity, aeration and structure. It also improves soil chemical fertility since C is part of the soil organic matter, which constitutes the main reservoir of nutrients for crops (nitrogen, sulfur, zinc, among others). SOC is positively correlated with soil microbial biomass that acts on nutrient cycling and metabolization processes of toxic molecules. The total SOC stock in topsoil (0-30cm) is about 19.7 Pg C (FAO-ITPS GSOC map, 2018). Thus, due to the size of the soil carbon pool, even small increments in the net soil C storage may represent a substantial C sink potential. Although agricultural greenhouse gas emissions (GHGs) contribute to an important share of Argentina GHG emissions (135.53 MtCO2eq, 37% of total country GHG emissions; SAyDS, 2019), increasing ASOC stocks through judicious land use and sustainable soil management (SSM) practices may represent an important strategy to reduce and mitigate GHG emissions. In Argentina, the total productive area is about 157 million hectares (INDEC, 2021). Agricultural área (croplands) is about 40 (forty) million hectares, predominantly under no tillage system (91% agricultural area; AAPRESID, 2020). Soybean is the main product (45 million tons in 17 million hectares), followed by corn (44 million tons in 6.3 million hectares), wheat (17 million tons in 6.5 million hectares), barley (4.1 million tons in 0.1 million hectares) and sunflower (2.7 million tons in 1.3 million hectares).The rest of the area (over 124 Million hectares) is occupied with grasslands and shrublands dedicated to livestock production, and other agricultural uses. In the last decade’s agricultural land increased and SOC content decayed. This process of land use change was explained by increasing soybean monoculture and displacing livestock area, reducing SOC content (Lavado & Taboada, 2009). There has been an intense expansion of agriculture at the expense of grasslands, native forests and other natural resources in semiarid, sub-humid and subtropical regions of the country (Volante et al., 2012). Currently, soils of the Chaco-Pampean region exhibit SOC levels between 40-70% of the contents of virgin soils (Alvarez & Steinbach, 2009; Sainz Rozas et al., 2011; Milesi Delaye et al., 2013). Several farming practices may be used to restore or diminish the SOC loss, reduce soil erosion, sequester atmospheric carbon dioxide (CO2 ) and improve the soil quality (Poffenbarger et al., 2020). Among these practices, the inclusion of cover crops (CC) during winter has been postulated as one of the most promising activities (Ruis & Blanco-Canqui, 2017). The inclusion of CC showed average SOC sequestration rates of 0.45 tC/ha/yr (± 0.03), in Argentina (Alvarez et al., 2017; Beltran et al., 2018; Romaniuk et al., 2018). Increasing nutrient availability, crop growth and residue returns by increasing fertilizer use showed an increment of SOC around 0.18 tC/ha/yr (± 0.03) (Duval et al., 2020; Restovich et al., 2019). The inclusion of cycles with perennial pastures in crop rotations showed average SOC sequestration rates of 0.76 tC/ha/yr (± 0.03), exhibiting the greatest potential to increase SOC stocks (Costantini et al., 2016; Gil et al., 2016). Sustainable soil management (SSM) practices (FAO, 2020) such as the above mentioned practices have demonstrated potential to increase SOC stocks in different agricultural systems in Argentina, and thus sequester atmospheric CO2 as SOC to mitigate GHG emissions. However, SOC sequestration from these practices show highly variable sequestration rates, depending on edapho-climatic conditions, land use and management, among other factors. It is therefore relevant to identify which regions, soils, climates and systems have a greater potential to increase SOC stocks, in order to establish priorities for research and implementation of private and public policies. In this Soil organic carbon (SOC) is a key factor affecting soil physical fertility, as it improves several soil properties such as infiltration, structural stability, porosity, aeration and structure. It also improves soil chemical fertility since C is part of the soil organic matter, which constitutes the main reservoir of nutrients for crops (nitrogen, sulfur, zinc, among others). SOC is positively correlated with soil microbial biomass that acts on nutrient cycling and metabolization processes of toxic molecules. The total SOC stock in topsoil (0-30cm) is about 19.7 Pg C (FAO-ITPS GSOC map, 2018). Thus, due to the size of the soil carbon pool, even small increments in the net soil C storage may represent a substantial C sink potential. Although agricultural greenhouse gas emissions (GHGs) contribute to an important share of Argentina GHG emissions (135.53 MtCO2eq, 37% of total country GHG emissions; SAyDS, 2019), increasing ASOC stocks through judicious land use and sustainable soil management (SSM) practices may represent an important strategy to reduce and mitigate GHG emissions. In Argentina, the total productive area is about 157 million hectares (INDEC, 2021). Agricultural área (croplands) is about 40 (forty) million hectares, predominantly under no tillage system (91% agricultural area; AAPRESID, 2020). Soybean is the main product (45 million tons in 17 million hectares), followed by corn (44 million tons in 6.3 million hectares), wheat (17 million tons in 6.5 million hectares), barley (4.1 million tons in 0.1 million hectares) and sunflower (2.7 million tons in 1.3 million hectares).The rest of the area (over 124 Million hectares) is occupied with grasslands and shrublands dedicated to livestock production, and other agricultural uses. In the last decade’s agricultural land increased and SOC content decayed. This process of land use change was explained by increasing soybean monoculture and displacing livestock area, reducing SOC content (Lavado & Taboada, 2009). There has been an intense expansion of agriculture at the expense of grasslands, native forests and other natural resources in semiarid, sub-humid and subtropical regions of the country (Volante et al., 2012). Currently, soils of the Chaco-Pampean region exhibit SOC levels between 40-70% of the contents of virgin soils (Alvarez & Steinbach, 2009; Sainz Rozas et al., 2011; Milesi Delaye et al., 2013). Several farming practices may be used to restore or diminish the SOC loss, reduce soil erosion, sequester atmospheric carbon dioxide (CO2) and improve the soil quality (Poffenbarger et al., 2020). Among these practices, the inclusion of cover crops (CC) during winter has been postulated as one of the most promising activities (Ruis & Blanco-Canqui, 2017). The inclusion of CC showed average SOC sequestration rates of 0.45 tC/ha/yr (± 0.03), in Argentina (Alvarez et al., 2017; Beltran et al., 2018; Romaniuk et al., 2018). Increasing nutrient availability, crop growth and residue returns by increasing fertilizer use showed an increment of SOC around 0.18 tC/ha/yr (± 0.03) (Duval et al., 2020; Restovich et al., 2019). The inclusion of cycles with perennial pastures in crop rotations showed average SOC sequestration rates of 0.76 tC/ha/yr (± 0.03), exhibiting the greatest potential to increase SOC stocks (Costantini et al., 2016; Gil et al., 2016). Sustainable soil management (SSM) practices (FAO, 2020) such as the above mentioned practices have demonstrated potential to increase SOC stocks in different agricultural systems in Argentina, and thus sequester atmospheric CO2 as SOC to mitigate GHG emissions. However, SOC sequestration from these practices show highly variable sequestration rates, depending on edapho-climatic conditions, land use and management, among other factors. It is therefore relevant to identify which regions, soils, climates and systems have a greater potential to increase SOC stocks, in order to establish priorities for research and implementation of private and public policies.Fil: Frolla, Franco Daniel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bordenave; ArgentinaFil: Angelini, Marcos Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentina. Wageningen University. Soil Geography and Landscape group; Holanda. International Soil Reference and Information Centre. World Soil Information; HolandaFil: Beltran, Marcelo Javier. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Peralta, Guillermo Ezequiel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Di Paolo, Luciano E. Global Soil Partnership Secretariat - FAO; ItaliaFil: Rodriguez, Dario Martin. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Schulz, Guillermo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Pascale Medina, Carla. Food and Agriculture Organization (FAO). Alianza Sudamericana de Suelos; Argentin

Fósforo extractable y fósforo orgánico lábil como indicadores de calidad de suelos de Entre Ríos

p.41-46En un Argiudol vértico de la provincia de Entre Ríos, se estudió la variación de los niveles de P extractable según los métodos de Bray y Olsen , y el P orgánico lábil. El fósforo orgánico lábil encontró su máximo en la situación prístina del monte y fue disminuyendo con la degradación. El coeficiente de correlación entre P orgánico lábil y C oxidable fue r igual a 0,95 (p menor a 0,05) y con C liviano fue rigual a 0,96 (p menor a 0,05). En cuanto a los niveles de P extractable por Bray y Olsen , sus tendencias pueden estar influidas por la fertilización fosfatada, aporte necesario en este tipo de suelos para un normal desarrollo de los cultivos, por lo que no podrían tomarse como indicadores válidos. El P orgánico lábil se comportó como un indicador sensible a la degradación o disminución de calidad del suelo , y su variación estuvo correlacionada con la declinación de los contenidos de carbono

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival