The Australasian Resuscitation In Sepsis Evaluation : fluids or vasopressors in emergency department sepsis (ARISE FLUIDS), a multi-centre observational study describing current practice in Australia and New Zealand

Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30-day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6- and 24-h post-enrolment, time to antimicrobial administration, intensive care admission, organ support and in-hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre-enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in-hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy

A dinâmica da presença brasileira no Índico e no Oriente. Séculos XVI-XIX

O propósito deste ensaio - que busca revisar e complementar a historiografia sobre o tema - é oferecer uma perspectiva brasileira do comércio para além do Cabo da Boa Esperança, examinar a presença brasileira no Estado da Índia e, ainda, resgatar as dinâmicas iniciativas dos comerciantes brasileiros, bem como destacar o importante papel dos portos brasileiros. Salienta a importância de Moçambique como ponto de convergência e de articulação entre o Oriente e o Ocidente, não apenas em termos comerciais mas também do ponto de vista cultural, referindo-se à contribuição brasileira aos costumes e à dieta dos habitantes da África Oriental, da Índia, da China e do Japão

The feminine sanctification in ivory images of Mary, mother of Jesus

Nos espaços coloniais do Império português, em seus contextos de encontros e confrontos, nos desafios da alteridade, a experiência intercultural pode ser identificada nas diversidades das iconografias religiosas. Neste artigo observa-se a sacralização do feminino, que, se para o Projeto da Conquista teve em Maria a imagem e o modelo de mulher segundo a fé católica, ambiguamente, em suas representações, vestígios técnicos, estéticos e míticos, aproximou a Mãe de Jesus de divindades femininas de devocional equivalência, de outras matrizes das sociedades colonizadas, conforme se pode comparar na Índia portuguesa. A imaginária mariana em marfim, produzida nesta que foi uma matéria-prima símbolo de prestígio e de grande valor comercial, denota as tensões do poder além da polarização e do subjugo do império.In a context permeated by conflicts, among the challenge of otherness, intercultural experiences can be identified in the colonial Portuguese Empire environment through the variety of religious iconography. In this paper, our aim is to analyze the feminine sanctification under two perspectives: if, in one hand, Mary was in the Conquer Project both the paradigm and model of woman according to the catholic doctrine, on the other, ambiguously, in its representation and technical, aesthetic and mythic traces, the Mother of Jesus was compared to female deities from religious matrices belonged to other colonized societies, as seen in the Portuguese India. Produced with ivory, symbol of prestige and great commercial value, the images of Mary represent the tensions for power beyond the polarization and the control of the Portuguese Empire

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.

BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. FINDINGS: A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity. INTERPRETATION: This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. FUNDING: UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR