Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

Background The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. Methods In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. Results A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. Conclusions In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .)

Can we set a global threshold age to define mature forests?

Globally, mature forests appear to be increasing in biomass density (BD). There is disagreement whether these increases are the result of increases in atmospheric CO2 concentrations or a legacy effect of previous land-use. Recently, it was suggested that a threshold of 450 years should be used to define mature forests and that many forests increasing in BD may be younger than this. However, the study making these suggestions failed to account for the interactions between forest age and climate. Here we revisit the issue to identify: (1) how climate and forest age control global forest BD and (2) whether we can set a threshold age for mature forests. Using data from previously published studies we modelled the impacts of forest age and climate on BD using linear mixed effects models. We examined the potential biases in the dataset by comparing how representative it was of global mature forests in terms of its distribution, the climate space it occupied, and the ages of the forests used. BD increased with forest age, mean annual temperature and annual precipitation. Importantly, the effect of forest age increased with increasing temperature, but the effect of precipitation decreased with increasing temperatures. The dataset was biased towards northern hemisphere forests in relatively dry, cold climates. The dataset was also clearly biased towards forests <250 years of age. Our analysis suggests that there is not a single threshold age for forest maturity. Since climate interacts with forest age to determine BD, a threshold age at which they reach equilibrium can only be determined locally. We caution against using BD as the only determinant of forest maturity since this ignores forest biodiversity and tree size structure which may take longer to recover. Future research should address the utility and cost-effectiveness of different methods for determining whether forests should be classified as mature

The Spheres & Shield Maze Task: A virtual reality serious game for the assessment of risk taking in decision making

[EN] Risk taking (RT) is an essential component in decision-making process that depicts the propensity to make risky decisions. RT assessment has traditionally focused on self-report questionnaires. These classical tools have shown clear distance from real-life responses. Behavioral tasks assess human behavior with more fidelity, but still show some limitations related to transferability. A way to overcome these constraints is to take advantage from virtual reality (VR), to recreate real-simulated situations that might arise from performance-based assessments, supporting RT research. This article presents results of a pilot study in which 41 individuals explored a gamified VR environment: the Spheres & Shield Maze Task (SSMT). By eliciting implicit behavioral measures, we found relationships between scores obtained in the SSMT and self-reported risk-related constructs, as engagement in risky behaviors and marijuana consumption. We conclude that decontextualized Virtual Reality Serious Games are appropriate to assess RT, since they could be used as a cross-disciplinary tool to assess individuals' capabilities under the stealth assessment paradigm.This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness funded projects "Advanced Therapeutic Tools for Mental Health'' (DPI2016-77396-R), and "Assessment and Training on Decision Making in Risk Environments'' (RTC-2017-6523-6) (MINECO/AEI/FEDER,UE) and by the Generalitat Valenciana funded project "Rebrand'' (PROMETEU/2019/105).Juan-Ripoll, CD.; Soler-Domínguez, JL.; Chicchi-Giglioli, IA.; Contero, M.; Alcañiz Raya, ML. (2020). The Spheres & Shield Maze Task: A virtual reality serious game for the assessment of risk taking in decision making. Cyberpsychology Behavior and Social Networking. 23(11):773-781. https://doi.org/10.1089/cyber.2019.0761S7737812311Bechara, A., Damasio, H., Tranel, D., & Damasio, A. R. (2005). 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Study of lead levels in soils by weathering of metallic Pb bullets used in dove hunting in Córdoba, Argentina

A study of level of Pb in soils of the center-north of the Province of Córdoba, a worldwide recognized tourist region for dove hunting, was performed in this work. The native forest of the region has a great population of doves associated with the grainproductivefields of the surrounding. Contamination of soils due to hunting activities is regulated by national and local norms. The Córdoba Environmental Secretary by resolution no. 1115/2011 approved a new regulation that categorizes this activity as generator of Y31 (Pb) industrial waste. Lead from pellets alloy is deposited on the soil of the shootingfields. Samples were taken at depth of 50 mm from 315 pits referenced by GPS in accordance with local environmental authorities as well as the hunting outfitters companies. Sampling sites are distributed between parallels 31 °S (S31) up to 30 °S (S30) and between meridians W64 up to W63. Soils samples were analyzed by X-rayfluorescence spectroscopy while Pb bullets were analyzed by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The average concentration obtained for Pb in dry soil sieved (200 mesh) was 80 ppm. Powder XRD patterns of crust material removed from the corroded surface of weathered bullets were obtained. Three Pb mineral compounds were identified by XRD analysis and also studied by optical microscopy and SEM.submittedVersionFil: Bonzi, Edgardo Venusto. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Rubio, Marcelo. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Rubio, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Rubio, Marcelo. Ministerio de Ciencia y Tecnología de la Provincia de Córdoba. Centro de Excelencia en Procesos y Productos de Córdoba; Argentina.Física Atómica, Molecular y Química (física de átomos y moléculas incluyendo colisión, interacción con radiación, resonancia magnética, Moessbauer Efecto.

Natural coagulates for wastewater treatment; a review for application and mechanism

The increase of water demand and wastewater generation is among the global concerns in the world. The less effective management of water sources leads to serious consequences, the direct disposal of untreated wastewater is associated with the environmental pollution, elimination of aquatic life and the spread of deadly epidemics. The flocculation process is one of the most important stages in water and wastewater treatment plants, wherein this phase the plankton, colloidal particles, and pollutants are precipitated and removed. Two major types of coagulants are used in the flocculation process included the chemical and natural coagulants. Many studies have been performed to optimize the flocculation process while most of these studies have confirmed the hazardous effects of chemical coagulants utilization on the ecosystem. This chapter reviews a summary of the coagulation/flocculation processes using natural coagulants as well as reviews one of the most effective natural methods of water and wastewater treatment

Conducting retrospective impact analysis to inform a medical research charity’s funding strategies: The case of Asthma UK

© 2013 Hanney et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies. METHODS: We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the ‘Centre’) which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts. RESULTS: Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthma-related clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important. CONCLUSIONS: We systematically demonstrate that all types of Asthma UK’s research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study’s findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact.This study was funded by Asthma UK

Stroke genetics: prospects for personalized medicine.

Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice