43 research outputs found

    Properties of dust in the detached shells around U Ant, DR Ser, and V644 Sco

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    Understanding the properties of dust produced during the asymptotic giant branch phase of stellar evolution is important for understanding the evolution of stars and galaxies. Recent observations of the carbon AGB star R Scl have shown that observations at far-infrared and submillimetre wavelengths can effectively constrain the grain sizes in the shell, while the total mass depends on the structure of the grains (solid vs. hollow or fluffy). We aim to constrain the properties of the dust observed in the submillimetre in the detached shells around the three carbon AGB stars U Ant, DR Ser, and V644 Sco, and to investigate the constraints on the dust masses and grain sizes provided by far-infrared and submm observations. We observed the carbon AGB stars U Ant, DR Ser, and V644 Sco at 870 micron using LABOCA on APEX. Combined with observations from the optical to far-infrared, we produced dust radiative transfer models of the spectral energy distributions (SEDs) with contributions from the stars, present-day mass-loss and detached shells. We tested the effect of different total dust masses and grain sizes on the SED, and attempted to consistently reproduce the SEDs from the optical to the submm. We derive dust masses in the shells of a few 10e-5 Msun, assuming spherical, solid grains. The best-fit grain radii are comparatively large, and indicate the presence of grains between 0.1 micron-2 micron. The LABOCA observations suffer from contamination from 12CO(3-2), and hence gives fluxes that are higher than the predicted dust emission at submm wavelengths. We investigate the effect on the best-fitting models by assuming different degrees of contamination and show that far-infrared and submillimetre observations are important to constrain the dust mass and grain sizes in the shells.Comment: Accepted by A&

    Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis

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    Leishmania parasites infect macrophages, causing a wide spectrum of human diseases, from cutaneous to visceral forms. In search of novel therapeutic targets, we performed comprehensive in vitro and ex vivo mapping of the signaling pathways upstream and downstream of antioxidant transcription factor [nuclear factor erythroid 2-related factor 2 (Nrf2)] in cutaneous leishmaniasis (CL), by combining functional assays in human and murine macrophages with a systems biology analysis of in situ (skin biopsies) CL patient samples. First, we show the PKR pathway controls the expression and activation of Nrf2 in Leishmania amazonensis infection in vitro. Nrf2 activation also required PI3K/Akt signaling and autophagy mechanisms. Nrf2- or PKR/Akt-deficient macrophages exhibited increased levels of ROS/RNS and reduced expression of Sod1 Nrf2-dependent gene and reduced parasite load. L. amazonensis counteracted the Nrf2 inhibitor Keap1 through the upregulation of p62 via PKR. This Nrf2/Keap1 observation was confirmed in situ in skin biopsies from Leishmania-infected patients. Next, we explored the ex vivo transcriptome in CL patients, as compared to healthy controls. We found the antioxidant response element/Nrf2 signaling pathway was significantly upregulated in CL, including downstream target p62. In silico enrichment analysis confirmed upstream signaling by interferon and PI3K/Akt, and validated our in vitro findings. Our integrated in vitro, ex vivo, and in silico approach establish Nrf2 as a central player in human cutaneous leishmaniasis and reveal Nrf2/PKR crosstalk and PI3K/Akt pathways as potential therapeutic targets

    Current trends in cannulation and neuroprotection during surgery of the aortic arch in Europe†‡

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    OBJECTIVES To conduct a survey across European cardiac centres to evaluate the methods used for cerebral protection during aortic surgery involving the aortic arch. METHODS All European centres were contacted and surgeons were requested to fill out a short, comprehensive questionnaire on an internet-based platform. One-third of more than 400 contacted centres completed the survey correctly. RESULTS The most preferred site for arterial cannulation is the subclavian-axillary, both in acute and chronic presentation. The femoral artery is still frequently used in the acute condition, while the ascending aorta is a frequent second choice in the case of chronic presentation. Bilateral antegrade brain perfusion is chosen by the majority of centres (2/3 of cases), while retrograde perfusion or circulatory arrest is very seldom used and almost exclusively in acute clinical presentation. The same pumping system of the cardio pulmonary bypass is most of the time used for selective cerebral perfusion, and the perfusate temperature is usually maintained between 22 and 26°C. One-third of the centres use lower temperatures. Perfusate flow and pressure are fairly consistent among centres in the range of 10-15 ml/kg and 60 mmHg, respectively. In 60% of cases, barbiturates are added for cerebral protection, while visceral perfusion still receives little attention. Regarding cerebral monitoring, there is a general tendency to use near-infrared spectroscopy associated with bilateral radial pressure measurement. CONCLUSIONS These data represent a snapshot of the strategies used for cerebral protection during major aortic surgery in current practice, and may serve as a reference for standardization and refinement of different approache

    Transcriptional Analysis of Murine Macrophages Infected with Different Toxoplasma Strains Identifies Novel Regulation of Host Signaling Pathways

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    Most isolates of Toxoplasma from Europe and North America fall into one of three genetically distinct clonal lineages, the type I, II and III lineages. However, in South America these strains are rarely isolated and instead a great variety of other strains are found. T. gondii strains differ widely in a number of phenotypes in mice, such as virulence, persistence, oral infectivity, migratory capacity, induction of cytokine expression and modulation of host gene expression. The outcome of toxoplasmosis in patients is also variable and we hypothesize that, besides host and environmental factors, the genotype of the parasite strain plays a major role. The molecular basis for these differences in pathogenesis, especially in strains other than the clonal lineages, remains largely unexplored. Macrophages play an essential role in the early immune response against T. gondii and are also the cell type preferentially infected in vivo. To determine if non-canonical Toxoplasma strains have unique interactions with the host cell, we infected murine macrophages with 29 different Toxoplasma strains, representing global diversity, and used RNA-sequencing to determine host and parasite transcriptomes. We identified large differences between strains in the expression level of known parasite effectors and large chromosomal structural variation in some strains. We also identified novel strain-specifically regulated host pathways, including the regulation of the type I interferon response by some atypical strains. IFNÎČ production by infected cells was associated with parasite killing, independent of interferon gamma activation, and dependent on endosomal Toll-like receptors in macrophages and the cytoplasmic receptor retinoic acid-inducible gene 1 (RIG-I) in fibroblasts.National Institutes of Health (U.S.) (R01-AI080621)New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (Developmental Grant AIO57159)Pew Charitable Trusts (Biomedical Scholars Program)Robert A. Swanson Career Development awardThe Knights Templar Eye Foundation, Inc.Pre-Doctoral Grant in the Biological Sciences (5-T32-GM007287-33)Cleo and Paul Schimmel Foundatio

    Glucose sensing in the pancreatic beta cell: a computational systems analysis

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    Artistas sobre outras obras

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    Este nĂșmero da Revista EstĂșdio assinala a crescente maturação de um espaço de comunicação algo alternativo, onde artistas falam de artistas, dĂŁo a conhecer obras menos conhecidas, e ocupam uma ĂĄrea de curadoria expontĂąnea e paralela aos centros do arte world. DĂĄ-se a palavra aos prĂłprios criadores, e hĂĄ seis anos que o seu olhar vem enriquecendo um patrimĂłnio crescente, com especiais ligaçÔes aos paĂ­ses onde se fala as lĂ­nguas ibĂ©ricas. A presença de obras de Portugal, Espanha, Brasil, Angola, Argentina, PerĂș, Venezuela, BolĂ­via e muitos outros paĂ­ses tornou-se habitual, fazendo da EstĂșdio uma instĂąncia da semiosfera (Lotman). Mais do que a presença, Ă© a dimensĂŁo do conhecimento transmitido, a que se segue, naturalmente, o estabelecimento de novas teias de referĂȘncia entre os artistas destes paĂ­ses: hĂĄ novos grupos, novas cumplicidades, novas realizaçÔes dentro deste EstĂșdio, que completa seis anos de publicação persistente. A Revista EstĂșdio Ă© tambĂ©m mais uma via disponĂ­vel para o exercĂ­cio da interpretação, atravĂ©s de descodificaçÔes mais informadas, mais negociadas, dos textos artĂ­sticos, pois sĂŁo efectuadas por outros artistas. Reuniram-se nesta edição 24 artigos originais, mantendo a sua linha editorial inicial. O projecto mantĂ©m a sua componente de resistĂȘncia, de plataforma de conhecimento para os pares, nĂŁo abdicando tambĂ©m da validação externa, ou seja, do uso de protocolos de produção e transmissĂŁo de conhecimento. Falamos pois das normas de redação, de referenciação, de estruturação de textos e de articulação de argumentos, visuais ou verbais. Estabelece-se neste volume uma articulação entre cinema, vĂ­deo, redes, escultura, instalação, fotografia, performance, banda desenhada, pintura, cerĂąmica, poesia concreta, livros de artista, sendo este conjunto nĂŁo exaustivo testemunha do grau de hibridação que hoje o discurso artĂ­stico convoca. Apanhando-lhe o pulso, a EstĂșdio acompanha a arte desde os seus produtores, dos seus procedimentos, dos seus recursos, dos seus resultados. A EstĂșdio permite visitar muitos estĂșdios.info:eu-repo/semantics/publishedVersio

    Track D Social Science, Human Rights and Political Science

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

    Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

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    BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

    Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

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    Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

    Mortality of emergency abdominal surgery in high-, middle- and low-income countries

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    Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1⋅6 per cent at 24 h (high 1⋅1 per cent, middle 1⋅9 per cent, low 3⋅4 per cent; P < 0⋅001), increasing to 5⋅4 per cent by 30 days (high 4⋅5 per cent, middle 6⋅0 per cent, low 8⋅6 per cent; P < 0⋅001). Of the 578 patients who died, 404 (69⋅9 per cent) did so between 24 h and 30 days following surgery (high 74⋅2 per cent, middle 68⋅8 per cent, low 60⋅5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2⋅78, 95 per cent c.i. 1⋅84 to 4⋅20) and low-income (OR 2⋅97, 1⋅84 to 4⋅81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)
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