Good Evenin\u27 / music by Will Marion Cook; words by Paul Laurence Dunbar

Cover: description reads A Real Native Southern Negro Melody and Music Supplement of the N. Y. American and Journal. Sunday, March 22, 1903; Publisher: Harry von Tilzer Music Publishing Co. (New York)https://egrove.olemiss.edu/sharris_b/1032/thumbnail.jp

Evah Dahkey is a King / music by John H. Cook; words by E. P. Moran and Paul Laurence Dunbar

Cover: caricature photo; Music Supplement of the New York American and Journal. Sunday, October 26, 1902); Publisher: Harry Von Tilzer Music Pub. Co. (Chicago)https://egrove.olemiss.edu/sharris_b/1030/thumbnail.jp

The cost-effectiveness of point of care testing in a general practice setting: results from a randomised controlled trial

Extent: 11p.Background: While point of care testing (PoCT) for general practitioners is becoming increasingly popular, few studies have investigated whether it represents value for money. This study aims to assess the relative cost-effectiveness of PoCT in general practice (GP) compared to usual testing practice through a pathology laboratory. Methods: A cost-effectiveness analysis based on a randomized controlled trial with 4,968 patients followed up for 18 months and fifty-three general practices in urban, rural and remote locations across three states in Australia. The incremental costs and health outcomes associated with a clinical strategy of PoCT for INR, HbA1c, lipids, and ACR were compared to those from pathology laboratory testing. Costs were expressed in year 2006 Australian dollars. Nonparametric bootstrapping was used to generate 95% confidence intervals. Results: The point estimate of the total direct costs per patient to the health care sector for PoCT was less for ACR than for pathology laboratory testing, but greater for INR, HbA1c and Lipids, although none of these differences was statistically significant. PoCT led to significant cost savings to patients and their families. When uncertainty around the point estimates was taken into account, the incremental cost-effectiveness ratio (ICER) for PoCT was found to be unfavourable for INR, but somewhat favourable for ACR, while substantial uncertainty still surrounds PoCT for HbA1c and Lipids. Conclusions: The decision whether to fund PoCT will depend on the price society is willing to pay for achievement of the non-standard intermediate outcome indicator. Trial registration: Australian New Zealand Clinical Trial Registry ACTRN12605000272695Caroline O Laurence, John R Moss, Nancy E Briggs, Justin J Beilby for PoCT Trial Management Grou

Modelling direct and indirect water requirements of construction

Water consumed directly by the construction industry is known to be of little importance. However, water consumed in the manufacture of goods and services required by construction may be significant in the context of a building\u27s life cycle water requirements and the national water budget. This paper evaluates the significance of water embodied in the construction of individual buildings. To do this, an input-output-based hybrid embodied water analysis was undertaken on 17 Australian non-residential case studies. It was found that there is a considerable amount of water embodied in construction. The highest value was 20.1 kilolitres (kL)/m2 gross floor area (GFA), representing many times the enclosed volume of the building, and many years worth of operational water. The water required by the main construction process is minimal. However, the water embodied in building materials is considerable. These findings suggest that the selection of elements and materials has a great impact on a building\u27s embodied water. This research allows the construction industry to evaluate design and construction in broad environmental terms to select options that might be cost neutral or possibly cost positive while retaining their environmental integrity. The research suggests policies focused on operational water consumption alone are inadequate. <br /

Depression and loneliness in Jamaicans with sickle cell disease

<p>Abstract</p> <p>Background</p> <p>Sickle cell disease (SCD) is the commonest genetic disorder in Jamaica, and has life-long implications for those afflicted with it. It is well known that depression and loneliness may exist in those with chronic diseases, but the coexistence of depression and loneliness in people with sickle cell disease is not clear. The aim of this study is to determine the prevalence of and factors associated with depression and loneliness in the Jamaica Sickle Cell Cohort Study and its age and sex matched controls.</p> <p>Methods</p> <p>277 patients with SCD and 65 controls were administered a questionnaire that studied demographics, disease severity, depression, and loneliness. Regression analyses were done to examine relationships between outcomes and associated variables.</p> <p>Results</p> <p>Depression was found in 21.6% of patients and 9.4% in controls. Loneliness scores were also significantly higher in patients (16.9 ± 5.1) than in controls (14.95 ± 4.69). Depression was significantly associated with unemployment [OR = 2.9, p-value: < 0.001], whereas unemployment (p-value: 0.002), and lower educational attainment were significantly associated with loneliness.</p> <p>In patients with SCD, depression was significantly associated with being unemployed (OR 2.4, 95% CI 1.2,4.6, p-value:0.01), presence of a leg ulcer (OR = 3.8, 95% CI: 1.7, 8.4, p-value: 0.001), frequent visits (OR = 3.3, 95% CI: 1.2, 8.9, p-value: 0.019), and frequent painful crises (OR = 2.5, 95% CI: 1.1, 5.8, p-value: 0.035). Not being employed (Coef.: 2.0; p-value: 0.004) and higher educational attainment (tertiary vs. primary education, Coef.: -5.5; p-value: < 0.001) were significant associations with loneliness after adjusting for genotype.</p> <p>Conclusions</p> <p>Health workers need to actively look for and manage these problems to optimize their patients' total biopsychosocial care.</p

Natural Selection Fails to Optimize Mutation Rates for Long-Term Adaptation on Rugged Fitness Landscapes

The rate of mutation is central to evolution. Mutations are required for adaptation, yet most mutations with phenotypic effects are deleterious. As a consequence, the mutation rate that maximizes adaptation will be some intermediate value. Here, we used digital organisms to investigate the ability of natural selection to adjust and optimize mutation rates. We assessed the optimal mutation rate by empirically determining what mutation rate produced the highest rate of adaptation. Then, we allowed mutation rates to evolve, and we evaluated the proximity to the optimum. Although we chose conditions favorable for mutation rate optimization, the evolved rates were invariably far below the optimum across a wide range of experimental parameter settings. We hypothesized that the reason that mutation rates evolved to be suboptimal was the ruggedness of fitness landscapes. To test this hypothesis, we created a simplified landscape without any fitness valleys and found that, in such conditions, populations evolved near-optimal mutation rates. In contrast, when fitness valleys were added to this simple landscape, the ability of evolving populations to find the optimal mutation rate was lost. We conclude that rugged fitness landscapes can prevent the evolution of mutation rates that are optimal for long-term adaptation. This finding has important implications for applied evolutionary research in both biological and computational realms

Dysregulated Cytokine Expression by CD4+ T cells from Post-Septic Mice Modulates both Th1 and Th2-Mediated Granulomatous Lung Inflammation

Previous epidemiological studies in humans and experimental studies in animals indicate that survivors of severe sepsis exhibit deficiencies in the activation and effector function of immune cells. In particular, CD4+ T lymphocytes can exhibit reduced proliferative capacity and improper cytokine responses following sepsis. To further investigate the cell-intrinsic defects of CD4+ T cells following sepsis, splenic CD4+ T cells from sham surgery and post-septic mice were transferred into lymphopenic mice. These recipient mice were then subjected to both TH1-(purified protein derivative) and TH2-(Schistosoma mansoni egg antigen) driven models of granulomatous lung inflammation. Post-septic CD4+ T cells mediated smaller TH1 and larger TH2 lung granulomas as compared to mice receiving CD4+ T cells from sham surgery donors. However, cytokine production by lymph node cells in antigen restimulation assays indicated increased pan-specific cytokine expression by post-septic CD4+ T cell recipient mice in both TH1 and TH2 granuloma models. These include increased production of TH2 cytokines in TH1 inflammation, and increased production of TH1 cytokines in TH2 inflammation. These results suggest that cell-intrinsic defects in CD4+ T cell effector function can have deleterious effects on inflammatory processes post-sepsis, due to a defect in the proper regulation of TH-specific cytokine expression

Clamp loader ATPases and the evolution of DNA replication machinery

Clamp loaders are pentameric ATPases of the AAA+ family that operate to ensure processive DNA replication. They do so by loading onto DNA the ring-shaped sliding clamps that tether the polymerase to the DNA. Structural and biochemical analysis of clamp loaders has shown how, despite differences in composition across different branches of life, all clamp loaders undergo the same concerted conformational transformations, which generate a binding surface for the open clamp and an internal spiral chamber into which the DNA at the replication fork can slide, triggering ATP hydrolysis, release of the clamp loader, and closure of the clamp round the DNA. We review here the current understanding of the clamp loader mechanism and discuss the implications of the differences between clamp loaders from the different branches of life

A framework for evolutionary systems biology

<p>Abstract</p> <p>Background</p> <p>Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.</p> <p>Results</p> <p>Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions <it>in silico</it>. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism.</p> <p>Conclusion</p> <p>EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications.</p