The GRADE System for Rating Clinical Guidelines

Brian Kavanagh critiques the GRADE system of grading guidelines, arguing that even though it has evolved through the Evidence-Based Medicine movement, there is no evidence that GRADE itself is reliable

Effects of Ploidy and Recombination on Evolution of Robustness in a Model of the Segment Polarity Network

Many genetic networks are astonishingly robust to quantitative variation, allowing these networks to continue functioning in the face of mutation and environmental perturbation. However, the evolution of such robustness remains poorly understood for real genetic networks. Here we explore whether and how ploidy and recombination affect the evolution of robustness in a detailed computational model of the segment polarity network. We introduce a novel computational method that predicts the quantitative values of biochemical parameters from bit sequences representing genotype, allowing our model to bridge genotype to phenotype. Using this, we simulate 2,000 generations of evolution in a population of individuals under stabilizing and truncation selection, selecting for individuals that could sharpen the initial pattern of engrailed and wingless expression. Robustness was measured by simulating a mutation in the network and measuring the effect on the engrailed and wingless patterns; higher robustness corresponded to insensitivity of this pattern to perturbation. We compared robustness in diploid and haploid populations, with either asexual or sexual reproduction. In all cases, robustness increased, and the greatest increase was in diploid sexual populations; diploidy and sex synergized to evolve greater robustness than either acting alone. Diploidy conferred increased robustness by allowing most deleterious mutations to be rescued by a working allele. Sex (recombination) conferred a robustness advantage through “survival of the compatible”: those alleles that can work with a wide variety of genetically diverse partners persist, and this selects for robust alleles

Imersão em água fria para o manejo da hipertermia severa Cold water immersion to the control of exertional heat illness

A incapacidade de dissipar o calor gerado pela atividade muscular prejudica o desempenho e aumenta a predisposição a lesões do organismo. A hipertermia severa induzida pelo esforço físico (HTE) prejudica a saúde e está associada à morbidade e mortalidade de indivíduos em diferentes atividades ocupacionais e atléticas. Estudos sobre a eficiência de métodos de resfriamento corporal têm recomendado a imersão em água fria para o tratamento da HTE. Sua utilização nos minutos iniciais pós-hipertemia parece a melhor recomendação por reduzir o tempo no qual a temperatura central permanece elevada. A manutenção de infraestrutura necessária para a realização desse procedimento deve ser considerada em atividades físicas e condições ambientais nas quais os indivíduos estão mais suscetíveis ao acometimento da HTE. As taxas de resfriamento observadas através da imersão em água a diferentes temperaturas podem servir de referência para o controle da duração do procedimento. Esta revisão analisa a recomendação da imersão em água fria como procedimento de resfriamento corporal para o manejo da HTE.<br>The incapacity of dissipating heat generated by muscular activity hampers performance and increases predisposition to physical injuries. Exertional heat illness (HTE) harms health and is associated with morbidity and mortality of individuals in different occupational and athletic activities. Studies on the efficiency of body cooling methods have recommended cold-water immersion for the treatment of HTE. Its use in the initial minutes of post-hyperthermia seems to be the best recommendation to reduce the time central temperature remains high. Maintenance of the infrastructure needed to perform this procedure should be considered in physical activities and environmental conditions in which the individuals are more prone to HTE. The cooling rates observed through water immersion in different water temperatures may serve as reference to the control of HTE procedure duration. This review analyses the recommendation of cold-water immersion as a body cooling procedure for management of HTE

Treatment of exertional heat stress developed during low or moderate physical work

We examined whether treatment for exertional heat stress via ice water immersion (IWI) or natural recovery is affected by the intensity of physical work performed and, thus, the time taken to reach hyperthermia. Nine adults (18-45 years; 17.9 +/- A 2.8 percent body fat; 57.0 +/- A 2.0 mL kg(-1) min(-1) peak oxygen uptake) completed four conditions incorporating either walking or jogging at 40 A degrees C (20 % relative humidity) while wearing a non-permeable rain poncho. Upon reaching 39.5 A degrees C rectal temperature (T (re)), participants recovered either via IWI in 2 A degrees C water or via natural recovery (seated in a similar to 29 A degrees C environment) until T (re) returned to 38 A degrees C. Cooling rates were greater in the IWI [T (re): 0.24 A degrees C min(-1); esophageal temperature (T (es)): 0.24 A degrees C min(-1)] than the natural recovery (T (re) and T (es): 0.03 A degrees C min(-1)) conditions (p 0.05). Cooling rates for T (re) and T (es) were greater in the 39.0-38.5 A degrees C (T (re): 0.19 A degrees C min(-1); T (es): 0.31 A degrees C min(-1)) compared with the 39.5-39.0 A degrees C (T (re): 0.11 A degrees C min(-1); T (es): 0.13 A degrees C min(-1)) period across conditions (p 0.05), albeit occurred faster during IWI. Percent change in plasma volume at the end of natural recovery and IWI was 5.96 and 9.58 %, respectively (p < 0.001). The intensity of physical work performed and, thus, the time taken to reach hyperthermia does not affect the effectiveness of either IWI treatment or natural recovery. Therefore, while the path to hyperthermia may be different for each patient, the path to recovery must always be immediate IWI treatment