404 research outputs found

    Rossby wave dynamics of the North Pacific extra-tropical response to El Niño: importance of the basic state in coupled GCMs

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    The extra-tropical response to El Nino in a "low" horizontal resolution coupled climate model, typical of the Intergovernmental Panel on Climate Change fourth assessment report simulations, is shown to have serious systematic errors. A high resolution configuration of the same model has a much improved response that is similar to observations. The errors in the low resolution model are traced to an incorrect representation of the atmospheric teleconnection mechanism that controls the extra-tropical sea surface temperatures (SSTs) during El Nino. This is due to an unrealistic atmospheric mean state, which changes the propagation characteristics of Rossby waves. These erroneous upper tropospheric circulation anomalies then induce erroneous surface circulation features over the North Pacific. The associated surface wind speed and direction errors create erroneous surface flux and upwelling anomalies which finally lead to the incorrect extra-tropical SST response to El Nino in the low resolution model. This highlights the sensitivity of the climate response to a single link in a chain of complex climatic processes. The correct representation of these processes in the high resolution model indicates the importance of horizontal resolution in resolving such processes

    Violence and creation: the recovery of the body in the work of Elaine Scarry

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    Elaine Scarry’s book The Body in Pain justly deserves it place as one the pivotal works that opened up the field of ‘body studies’. The text needs to be evaluated in the retrospective terms of the field it established, and also with respect to the changing status of both ‘torture’ and ‘war’ in contemporary state politics. Scarry’s analysis of the relationship between making and unmaking, tools and weapons, under-estimates the reversibility and the situated relational character of these processes and artefacts. The changing nature of modern conflict, and the rising concern with global terrorism rather than ‘conventional’ and ‘nuclear’ war, makes the ‘referential instability’ of the body difficult to recuperate in post-conflict discourse. At the same, the normalisation of the logic of torture in the contemporary governance of the bodies of the most vulnerable in society makes Scarry’s analysis all the more prescient

    Identification of bacterial glycosidases in rat cecal contents

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    Cecal contents of conventional and germfree rats were examined for glycosidases which may have a role in degrading glycoprotein oligosaccharides. Utilizing p-nitrophenylglycosides as substrates, we identified glycosidases in bacteria-free supernatants from cecal contents which act on β-linkages. These cecal glycosidases appear to be of bacterial origin since: (1) direct comparisons of the enzymes in similar contents from germfree rats showed negligible activities; (2) most of the glycosidase levels in bacterial extracts were at least as high as those of soluble supernatants; and (3) disk gel electrophoresis of contents and bacterial extracts revealed in both preparations a β- N -acetylglucosaminidase band with similar R f s. Also, the blood group B antigenicity of germfree cecal glycoproteins was greatly decreased by conventional cecal contents. These findings indicate that β-galactosidase and β- N -acetylgalactosaminidase in cecal contents are bacterial in origin, and they may have a role in the bacterial catabolism of intestinal glycoproteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44391/1/10620_2005_Article_BF01309607.pd

    Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences

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    PMCID: PMC3566971This 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

    Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone

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    We report on the comparative genomics and characterization of the virulence phenotypes of four &lt;i&gt;S. pneumoniae&lt;/i&gt; strains that belong to the multidrug resistant clone PMEN1 (Spain&lt;sup&gt;23F&lt;/sup&gt; ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant

    Simulating the midlatitude atmospheric circulation: what might we gain from high-resolution modeling of air-sea interactions?

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    Purpose of Review. To provide a snapshot of the current research on the oceanic forcing of the atmospheric circulation in midlatitudes and a concise update on previous review papers. Recent findings. Atmospheric models used for seasonal and longer timescales predictions are starting to resolve motions so far only studied in conjunction with weather forecasts. These phenomena have horizontal scales of ~ 10–100 km which coincide with energetic scales in the ocean circulation. Evidence has been presented that, as a result of this matching of scale, oceanic forcing of the atmosphere was enhanced in models with 10–100 km grid size, especially at upper tropospheric levels. The robustness of these results and their underlying mechanisms are however unclear. Summary. Despite indications that higher resolution atmospheric models respond more strongly to sea surface temperature anomalies, their responses are still generally weaker than those estimated empirically from observations. Coarse atmospheric models (grid size greater than 100 km) will miss important signals arising from future changes in ocean circulation unless new parameterizations are developed

    National policy development for cotrimoxazole prophylaxis in Malawi, Uganda and Zambia: the relationship between Context, Evidence and Links

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    BACKGROUND: Several frameworks have been constructed to analyse the factors which influence and shape the uptake of evidence into policy processes in resource poor settings, yet empirical analyses of health policy making in these settings are relatively rare. National policy making for cotrimoxazole (trimethoprim-sulfamethoxazole) preventive therapy in developing countries offers a pertinent case for the application of a policy analysis lens. The provision of cotrimoxazole as a prophylaxis is an inexpensive and highly efficacious preventative intervention in HIV infected individuals, reducing both morbidity and mortality among adults and children with HIV/AIDS, yet evidence suggests that it has not been quickly or evenly scaled-up in resource poor settings. METHODS: Comparative analysis was conducted in Malawi, Uganda and Zambia, using the case study approach. We applied the 'RAPID' framework developed by the Overseas Development Institute (ODI), and conducted a total of 47 in-depth interviews across the three countries to examine the influence of context (including the influence of donor agencies), evidence (both local and international), and the links between researcher, policy makers and those seeking to influence the policy process. RESULTS: Each area of analysis was found to have an influence on the creation of national policy on cotrimoxazole preventive therapy (CPT) in all three countries. In relation to context, the following were found to be influential: government structures and their focus, donor interest and involvement, healthcare infrastructure and other uses of cotrimoxazole and related drugs in the country. In terms of the nature of the evidence, we found that how policy makers perceived the strength of evidence behind international recommendations was crucial (if evidence was considered weak then the recommendations were rejected). Further, local operational research results seem to have been taken up more quickly, while randomised controlled trials (the gold standard of clinical research) was not necessarily translated into policy so swiftly. Finally the links between different research and policy actors were of critical importance, with overlaps between researcher and policy maker networks crucial to facilitate knowledge transfer. Within these networks, in each country the policy development process relied on a powerful policy entrepreneur who helped get cotrimoxazole preventive therapy onto the policy agenda. CONCLUSIONS: This analysis underscores the importance of considering national level variables in the explanation of the uptake of evidence into national policy settings, and recognising how local policy makers interpret international evidence. Local priorities, the ways in which evidence was interpreted, and the nature of the links between policy makers and researchers could either drive or stall the policy process. Developing the understanding of these processes enables the explanation of the use (or non-use) of evidence in policy making, and potentially may help to shape future strategies to bridge the research-policy gaps and ultimately improve the uptake of evidence in decision making

    Tailoring Adjuvant Endocrine Therapy for Postmenopausal Breast Cancer: A CYP2D6 Multiple-Genotype-Based Modeling Analysis and Validation

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    Purpose: Previous studies have suggested that postmenopausal women with breast cancer who present with wild-type CYP2D6 may actually have similar or superior recurrence-free survival outcomes when given tamoxifen in place of aromatase inhibitors (AIs). The present study established a CYP2D6 multiple-genotype-based model to determine the optimal endocrine therapy for patients harboring wild-type CYP2D6. Methods: We created a Markov model to determine whether tamoxifen or AIs maximized 5-year disease-free survival (DFS) for extensive metabolizer (EM) patients using annual hazard ratio (HR) data from the BIG 1-98 trial. We then replicated the model by evaluating 9-year event-free survival (EFS) using HR data from the ATAC trial. In addition, we employed two-way sensitivity analyses to explore the impact of HR of decreased-metabolizer (DM) and its frequency on survival by studying a range of estimates. Results: The 5-year DFS of tamoxifen-treated EM patients was 83.3%, which is similar to that of genotypically unselected patients who received an AI (83.7%). In the validation study, we further demonstrated that the 9-year EFS of tamoxifentreated EM patients was 81.4%, which is higher than that of genotypically unselected patients receiving tamoxifen (78.4%) and similar to that of patients receiving an AI (83.2%). Two-way sensitivity analyses demonstrated the robustness of the results
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