La República en armas: política, «ciudadanía armada» y elecciones en el Perú, 1871-1872

The analysis of the electoral process 1871-72 is incomplete if we do not consider the military uprising led by the Gutierrez brothers and the resistance of the «armed citizens» that served as epilogue to the presidential election of 1872. Unlike other civic organizations in the past Sociedad Independencia Electoral did manage to control the armed revolt, moving, therefore, the axis of political power from the provinces – where the «constitutional» revolutions were traditionally defined – to Lima, the capital city of the republic. Changes in the nature of the country, within the army, in the economy and in the political strategies of civilians produced important transformations in the former electoral model, which has resisted for many decades the passage of time.El análisis del proceso electoral 1871-1872 resulta incompleto si no se considera el levantamiento militar encabezado por los hermanos Gutiérrez y la resistencia de los «ciudadanos armados» que le sirvió de epílogo. El triunfo político de la Sociedad Independencia Electoral, que, a diferencia de otros grupos civiles en el pasado, sí logró hegemoneizar la revuelta armada, trasladó el eje del poder desde las provincias —lugar donde tradicionalmente se gestaban y se definían las «revoluciones constitucionales»— a la ciudad de Lima. Los cambios en la naturaleza del país, en el interior del ejército, en la economía y en las estrategias políticas de los civiles provocaron una importante variación del modelo político-electoral previo, el que resistió durante varias décadas el paso del tiempo

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Chile en el Perú: guerra y construcción estatal en Sudamérica, 1881-1884

This article analyzes the role played by the Chilean state during the War of the Pacific, 1879- 1884. It highlights the performance of its bureaucracy in the construction of a political network in Peru and also discusses the impact of the latter in Chile´s state making process. Between 1881- 1884 the Chilean State unfolds to a foreign territory and by doing so improves its administrative skills. This reasoning will lead it to explore its authoritarian nature in Peru, where the absence of the State and of civil society allowed its political and ideological predominance.Este artículo analiza el papel jugado por el Estado chileno durante la Guerra del Pacífico, 1879-1884. Iluminará el desempeño de sus burocracias en la construcción de redes políticas en el Perú así como también el impacto de dicho proceso en la construccion estatal en Chile. El caso chileno es el de un Estado que entre 1881 y 1884 se desdobla a un territorio extranjero y al hacerlo logrará perfeccionar sus saberes administrativos. Este razonamiento lo llevará a explorar los límites de su autoritarismo en el Perú donde no podrá ser confrontado de manera directa ni por el Estado peruano, al cual sustituye, ni por la sociedada civil, a la que somete política, militar e ideológicamente

Somatic double-hit in MTOR and RPS6 in hemimegalencephaly with intractable epilepsy

International audienceSingle germline or somatic activating mutations of mammalian target of rapamycin (mTOR) pathway genes are emerging as a major cause of type II focal cortical dysplasia (FCD), hemimegalencephaly (HME) and tuberous sclerosis complex (TSC). A double-hit mechanism, based on a primary germline mutation in one allele and a secondary somatic hit affecting the other allele of the same gene in a small number of cells, has been documented in some patients with TSC or FCD. In a patient with HME, severe intellectual disability, intractable seizures and hypochromic skin patches, we identified the ribosomal protein S6 (RPS6) p.R232H variant, present as somatic mosaicism at ∼15.1% in dysplastic brain tissue and ∼11% in blood, and the MTOR p.S2215F variant, detected as ∼8.8% mosaicism in brain tissue, but not in blood. Overexpressing the two variants independently in animal models, we demonstrated that MTOR p.S2215F caused neuronal migration delay and cytomegaly, while RPS6 p.R232H prompted increased cell proliferation. Double mutants exhibited a more severe phenotype, with increased proliferation and migration defects at embryonic stage and, at postnatal stage, cytomegalic cells exhibiting eccentric nuclei and binucleation, which are typical features of balloon cells. These findings suggest a synergistic effect of the two variants. This study indicates that, in addition to single activating mutations and double-hit inactivating mutations in mTOR pathway genes, severe forms of cortical dysplasia can also result from activating mutations affecting different genes in this pathway. RPS6 is a potential novel disease-related gene

El indulto como acontecimiento y el asalto al lenguaje de la memoria en Perú

Abstract: Objetive/context: This article is about the pardon granted to Alberto Fujimori on December 24, 2017. The analysis assumes the pardon as an exemplary event. That is, a point of inflection in Peruvian politics, which reveals a significant framework and discourse that attempt to make and assault on the language of memory, especially in terms of the idea of reconciliation. Methodology: The study was based on critical and in-depth analysis of a specific case: the pardon granted to Alberto Fujimori on December 24, 2017. We consider this pardon as an exemplary event that marks a different and revealing moment in the struggle for memory of the Peruvian internal armed conflict. Conclusions: To approach Alberto Fujimori's pardon as an event enables an in-depth examination of the political process and how its significant framework is constituted, as well as the symbolic field of its representation and achievement: its own unfoldment. This allows us to demarcate it and from there, understand how the assoult on the language of memory has proceeded. Originality: The event of the pardon granted to Alberto Fujimori on December 24, 2017 reveals the struggle for impunity, on one hand, and the struggle for justice, on the other. Studies on memory usually focus on aspects of struggle based in victims' associations or in processes of transitional justice, but rarely on facts that evidently provoke the tensions of memory. This is more likely about underlining the way in which discourses of justifications reveal the effort to establish a definitive meaning as the event, and reflects difference tensions and struggles surrounding, mainly, the sustainability of neoliberalism. Thus, pardon also constituted as a Point of inflection of the political process of the consolidation of democracy, revealing its extreme fragility.Resumo: Objetivo/contexto: este artigo trata do indulto concedido, em 24 de dezembro de 2017, a Alberto Fujimori. A análise assume o fato como um evento exemplar, isto é, um ponto de inflexão na política peruana, que revela um quadro significativo e um discurso que tenta atacar a linguagem da memória, especialmente a ideia de reconciliação. Metodologia: a pesquisa foi guiada por uma análise crítica e profunda de um caso específico, como foi o indulto concedido a Alberto Fujimori, em 24 de dezembro de 2017. Assumimos o fato como um acontecimento, ou seja, um evento exemplar que sinaliza um momento diferente e revelador nas lutas pela memória do conflito armado interno peruano. Conclusões: abordar o indulto a Alberto Fujimori como um acontecimento nos permite aprofundar no processo político e como o seu quadro significativo é constituído, e também o campo simbólico de sua representação e realização, seu próprio desenvolvimento. Isso nos permite demarcá-lo e poder, a partir daí, entender como ocorreu o ataque à linguagem da memória. Originalidade: o indulto outorgado a Alberto Fujimori, em 24 de dezembro de 2017, como acontecimento, nos permite visibilizar a luta pela impunidade, por um lado, e a luta por justiça, por outro. Normalmente, os estudos de memória se centram nos aspectos de luta a partir das associações de vítimas ou nos próprios processos de justiça transicional, mas pouco em fatos que evidentemente provocam a polarização e as tensões características da memória. Aqui, tratamos de enfatizar a maneira em que os discursos justificativos revelaram os esforços para estabelecer o sentido definitivo do evento e também refletiram tensões e várias lutas, principalmente em torno da sustentabilidade do neoliberalismo. Assim, o indulto também foi um ponto de inflexão do processo político de consolidação da democracia, que revelou sua extrema fragilidade.Resumen: Objetivo/contexto: Este artículo trata sobre el indulto otorgado el 24 de diciembre de 2017 a Alberto Fujimori. El análisis asume el hecho como un evento ejemplar, esto es, un punto de inflexión en la política peruana, revelador de un marco significante y un discurso que intentan tomar por asalto el lenguaje de la memoria, especialmente la idea de reconciliación. Metodología: La investigación fue guiada por un análisis crítico y profundo de un caso específico, como ha sido el indulto otorgado a Alberto Fujimori el 24 de diciembre de 2017. Asumimos el hecho como un acontecimiento, es decir, un evento ejemplar que señala un momento diferente y revelador en las pugnas por la memoria del conflicto armado interno peruano. Conclusiones: Abordar el indulto a Alberto Fujimori como un acontecimiento nos permite profundizar en el proceso político y cómo se constituye su marco significante, y también el campo simbólico de su representación y gesta, su propio desenvolvimiento. Esto nos posibilita demarcarlo y poder, desde allí, comprender cómo se ha procedido con el asalto al lenguaje de la memoria. Originalidad: El acontecimiento del indulto otorgado a Alberto Fujimori el 24 de diciembre de 2017 permite visibilizar la pugna por la impunidad, por un lado, y la lucha por la justicia, por el otro. Usualmente los estudios de memoria se centran en los aspectos de lucha desde las asociaciones de víctimas o en los propios procesos de justicia transicional, pero poco en hechos que evidentemente provocan la polarización y las tensiones propias de la memoria. Aquí se trata más bien de subrayar la manera como los discursos justificativos revelaron los esfuerzos por fijar el sentido definitivo del evento y reflejaron además tensiones y forcejeos diversos, principalmente alrededor de la sostenibilidad del neoliberalismo. Así, el indulto se constituyó además en un punto de inflexión del proceso político de consolidación de la democracia, dejando ver su extrema fragilidad

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Background: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death