Shooting Star

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Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease

Effects of tofacitinib monotherapy on patient-reported outcomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs

Baseline and changes from baseline by visit prior to month 3 for patient-reported outcome measures; *p < 0.01; **p < 0.001; ***p < 0.0001 vs placebo. an = 237; bn = 240; cn = 237; dn = 238; en = 231; fn = 241; gn = 243. BID twice daily, HAQ-DI Health Assessment Questionnaire-Disability Index, LSM least squares mean, Pain Patient Global Assessment of Pain, PtGA Patient Global Assessment of Disease Activity, SD standard deviation, SE standard error. (DOCX 13 kb

Gaming with eutrophication: Contribution to integrating water quantity and quality management at catchment level

The Metropolitan Region of Sao Paulo (MRSP) hosts 18 million inhabitants. A complex system of 23 interconnected reservoirs was built to ensure its water supply. Half of the potable water produced for MRSP's population (35 m3/s) is imported from a neighbour catchment, the other half is produced within the Alto Tietê catchment, where 99% of the population lives. Perimeters of land use restriction were defined to contain uncontrolled urbanization, as domestic effluents were causing increasing eutrophication of some of these reservoirs. In the 90's catchment committees and sub committees were created to promote discussion between stakeholders and develop catchment plans. The committees are very well structured "on paper". However, they are not very well organised and face a lack of experience. The objective of this work was to design tools that would strengthen their discussion capacities. The specific objective of the AguAloca process was to integrate the quality issue and its relation to catchment management as a whole in these discussions. The work was developed in the Alto Tietê Cabeceiras sub-catchment, one of the 5 sub catchments of the Alto-Tietê. It contains 5 interconnected dams, and presents competitive uses such as water supply, industry, effluent dilution and irrigated agriculture. A RPG was designed following a companion modelling approach (Etienne et al., 2003). It contains a friendly game-board, a set of individual and collective rules and a computerized biophysical model. The biophysical model is used to simulate water allocation and quality processes at catchment level. It articulates 3 modules. A simplified nutrient discharge model permits the estimation of land use nutrient exportation. An arc-node model simulates water flows and associated nutrient charges from one point of the hydrographical network to another. The Vollenweider model is used for simulating specific reservoir dynamics. The RPG allows players to make individual and collective decisions related to water allocation and the management of its quality. Impacts of these decisions are then simulated using the biophysical model. Specific indicators of the game are then updated and may influence player's behaviour (actions) in following rounds. To introduce discussions on the management of water quality at a catchment level, an issue that is rarely explicitly dealt with, four game sessions were implemented involving representatives of basin committees and water and sanitation engineers. During the game session, the participants took advantage of the water quality output of the biophysical model to test management alternatives such as rural sewage collection or effluent dilution. The biophysical model accelerated calculations of flows and eutrophication rates that were then returned to the game board with explicit indicators of quantity and quality. Players could easily test decisions impacting on qualitative water processes and visualize the simulation results directly on the game board that was representing a friendly, virtual and simplified catchment. The Agualoca game proved its ability to turn complex water processes understandable for a non totally initiated public. This experience contributed to a better understanding of multiple-use water management and also of joint management of water quality and quantity. (Résumé d'auteur

Effect of Palliative Care–Led Meetings for Families of Patients With Chronic Critical Illness: A Randomized Clinical Trial

Family caregivers of patients with chronic critical illness experience significant psychological distress

Cancer in general responders participating in world trade center health programs, 2003-2013

© The Author(s) 2020. Published by Oxford University Press. Background: Following the September 11, 2001, attacks on the World Trade Center (WTC), thousands of workers were exposed to an array of toxins known to cause adverse health effects, including cancer. This study evaluates cancer incidence in the WTC Health Program General Responder Cohort occurring within 12 years post exposure. Methods: The study population consisted of 28729 members of the General Responder Cohort enrolled from cohort inception, July 2002 to December 31, 2013. Standardized incidence ratios (SIRs) were calculated with cancer case inclusion and follow-up starting post September 11, 2001 (unrestricted) and, alternatively, to account for selection bias, with case inclusion and follow-up starting 6 months after enrollment in the WTC Health Program (restricted). Case ascertainment was based on linkage with six state cancer registries. Under the restricted criterion, hazard ratios were estimated using multivariable Cox proportional hazards models for all cancer sites combined and for prostate cancer. Results: Restricted analyses identified 1072 cancers in 999 responders, with elevations in cancer incidence for all cancer sites combined (SIR = 1.09, 95% confidence interval [CI] = 1.02 to 1.16), prostate cancer (SIR = 1.25, 95% CI = 1.11 to 1.40), thyroid cancer (SIR = 2.19, 95% CI = 1.71 to 2.75), and leukemia (SIR = 1.41, 95% CI = 1.01 to 1.92). Cancer incidence was not associated with any WTC exposure index (composite or individual) for all cancer sites combined or for prostate cancer. Conclusion: Our analyses show statistically significant elevations in cancer incidence for all cancer sites combined and for prostate and thyroid cancers and leukemia. Multivariable analyses show no association with magnitude or type of exposure

Unifying soil organic matter formation and persistence frameworks: the MEMS model

Soil organic matter (SOM) dynamics in ecosystem-scale biogeochemical models have traditionally been simulated as immeasurable fluxes between conceptually defined pools. This greatly limits how empirical data can be used to improve model performance and reduce the uncertainty associated with their predictions of carbon (C) cycling. Recent advances in our understanding of the biogeochemical processes that govern SOM formation and persistence demand a new mathematical model with a structure built around key mechanisms and biogeochemically relevant pools. Here, we present one approach that aims to address this need. Our new model (MEMS v1.0) is developed from the Microbial Efficiency-Matrix Stabilization framework, which emphasizes the importance of linking the chemistry of organic matter inputs with efficiency of microbial processing and ultimately with the soil mineral matrix, when studying SOM formation and stabilization. Building on this framework, MEMS v1.0 is also capable of simulating the concept of C saturation and represents decomposition processes and mechanisms of physico-chemical stabilization to define SOM formation into four primary fractions. After describing the model in detail, we optimize four key parameters identified through a variance-based sensitivity analysis. Optimization employed soil fractionation data from 154 sites with diverse environmental conditions, directly equating mineral-associated organic matter and particulate organic matter fractions with corresponding model pools. Finally, model performance was evaluated using total topsoil (0–20&thinsp;cm) C data from 8192 forest and grassland sites across Europe. Despite the relative simplicity of the model, it was able to accurately capture general trends in soil C stocks across extensive gradients of temperature, precipitation, annual C inputs and soil texture. The novel approach that MEMS v1.0 takes to simulate SOM dynamics has the potential to improve our forecasts of how soils respond to management and environmental perturbation. Ensuring these forecasts are accurate is key to effectively informing policy that can address the sustainability of ecosystem services and help mitigate climate change.</p

Influence of the 6^1S_0-6^3P_1 Resonance on Continuous Lyman-alpha Generation in Mercury

Continuous coherent radiation in the vacuum-ultraviolet at 122 nm (Lyman-alpha) can be generated using sum-frequency mixing of three fundamental laser beams in mercury vapour. One of the fundamental beams is at 254 nm wavelength, which is close to the 6^1S_0-6^3P_1 resonance in mercury. Experiments have been performed to investigate the effect of this one-photon resonance on phasematching, absorption and the nonlinear yield. The efficiency of continuous Lyman-alpha generation has been improved by a factor of 4.5.Comment: 8 pages, 7 figure