762 research outputs found

    Critical reflections on evidence, ethics and effectiveness in the management of tuberculosis: public health and global perspectives

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    BACKGROUND: Tuberculosis is a major cause of morbidity and mortality globally. Recent scholarly attention to public health ethics provides an opportunity to analyze several ethical issues raised by the global tuberculosis pandemic. DISCUSSION: Recently articulated frameworks for public health ethics emphasize the importance of effectiveness in the justification of public health action. This paper critically reviews the relationship between these frameworks and the published evidence of effectiveness of tuberculosis interventions, with a specific focus on the controversies engendered by the endorsement of programs of service delivery that emphasize direct observation of therapy. The role of global economic inequities in perpetuating the tuberculosis pandemic is also discussed. SUMMARY: Tuberculosis is a complex but well understood disease that raises important ethical challenges for emerging frameworks in public health ethics. The exact role of effectiveness as a criterion for judging the ethics of interventions needs greater discussion and analysis. Emerging frameworks are silent about the economic conditions contributing to the global burden of illness associated with tuberculosis and this requires remediation

    Complementary Sources of Protein Functional Information: The Far Side of GO.

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    The GO captures many aspects of functional annotations, but there are other alternative complementary sources of protein function information. For example, enzyme functional annotations are described in a range of resources from the Enzyme Commission (E.C.) hierarchical classification to the Kyoto Encyclopedia of Genes and Genomes (KEGG) to the Catalytic Site Atlas amongst many others. This chapter describes some of the main resources available and how they can be used in conjunction with GO

    Preventing Nerve Function Impairment in Leprosy: Validation and Updating of a Prediction Rule

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    Leprosy is caused by a bacterium that attacks the peripheral nerves. This may cause nerve function impairment (NFI), resulting in handicaps and disabilities. Therefore, prediction and prevention of NFI is extremely important in the management of leprosy. In 2000, a prediction rule for NFI was published, but circumstances have changed since the study was performed in the 1990s: the leprosy detection delay has shortened and the definition of NFI has changed. The original rule used ‘leprosy classification’ and ‘NFI present at diagnosis’ to predict future NFI. In the current patient population we studied an adjusted rule based on ‘leprosy classification’ and ‘presence of antibodies’. This adjusted rule predicted NFI more often than the original rule. With the adjusted rule it is now also possible to assess NFI risk before the first nerve damage event takes place. This may help doctors and health workers to improve surveillance for people at high risk. Early detection and treatment can then prevent permanent disabilities

    The coordination of cell growth during fission yeast mating requires Ras1-GTP hydrolysis

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    The spatial and temporal control of polarity is fundamental to the survival of all organisms. Cells define their polarity using highly conserved mechanisms that frequently rely upon the action of small GTPases, such as Ras and Cdc42. Schizosaccharomyces pombe is an ideal system with which to study the control of cell polarity since it grows from defined tips using Cdc42-mediated actin remodeling. Here we have investigated the importance of Ras1-GTPase activity for the coordination of polarized cell growth during fission yeast mating. Following pheromone stimulation, Ras1 regulates both a MAPK cascade and the activity of Cdc42 to enable uni-directional cell growth towards a potential mating partner. Like all GTPases, when bound to GTP, Ras1 adopts an active conformation returning to an inactive state upon GTP-hydrolysis, a process accelerated through interaction with negative regulators such as GAPs. Here we show that, at low levels of pheromone stimulation, loss of negative regulation of Ras1 increases signal transduction via the MAPK cascade. However, at the higher concentrations observed during mating, hyperactive Ras1 mutations promote cell death. We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. These results provide a striking demonstration that the deactivation stage of Ras signaling is fundamentally important in modulating cell polarity

    Sacral nerve stimulation versus the magnetic sphincter augmentation device for adult faecal incontinence: the SaFaRI RCT

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    Background: Preliminary studies using the FENIX™ (Torax Medical, Minneapolis, MN, USA) magnetic sphincter augmentation device suggest that it is safe to use for the treatment of adult faecal incontinence, but efficacy data are limited. Objective: To compare FENIX with sacral nerve stimulation for the treatment of adult faecal incontinence in terms of safety, efficacy, quality of life and cost-effectiveness. Design, setting and participants: Multicentre, parallel-group, unblinded, randomised trial comparing FENIX with sacral nerve stimulation in participants suffering moderate to severe faecal incontinence. Interventions: Participants were randomised on an equal basis to either sacral nerve stimulation or FENIX. Follow-up occurred 2 weeks postoperatively and at 6, 12 and 18 months post randomisation. Main outcome and measure: The primary outcome was success, defined as device in use and ≥ 50% improvement in Cleveland Clinic Incontinence Score at 18 months post randomisation. Secondary outcomes included complication rates, quality of life and cost-effectiveness. Between 30 October 2014 and 23 March 2017, 99 participants were randomised across 18 NHS sites (50 participants to FENIX vs. 49 participants to sacral nerve stimulation). The median time from randomisation to FENIX implantation was 57.0 days (range 4.0–416.0 days), and the median time from randomisation to permanent sacral nerve stimulation was 371.0 days (range 86.0–918.0 days). A total of 45 out of 50 participants underwent FENIX implantation and 29 out of 49 participants continued to permanent sacral nerve stimulation. The following results are reported, excluding participants for whom the corresponding outcome was not evaluable. Overall, there was success for 10 out of 80 (12.5%) participants, with no statistically significant difference between the two groups [FENIX 6/41 (14.6%) participants vs. sacral nerve stimulation 4/39 (10.3%) participants]. At least one postoperative complication was experienced by 33 out of 45 (73.3%) participants in the FENIX group and 9 out of 40 (22.5%) participants in the sacral nerve stimulation group. A total of 15 out of 50 (30%) participants in the FENIX group ultimately had to have their device explanted. Slightly higher costs and quality-adjusted life-years (incremental = £305.50 and 0.005, respectively) were observed in the FENIX group than in the sacral nerve stimulation group. This was reversed over the lifetime horizon (incremental = –£1306 and –0.23 for costs and quality-adjusted life-years, respectively), when sacral nerve stimulation was the optimal option (net monetary benefit = –£3283), with only a 45% chance of FENIX being cost-effective. Limitations: The SaFaRI study was terminated in 2017, having recruited 99 participants of the target sample size of 350 participants. The study is, therefore, substantially underpowered to detect differences between the treatment groups, with significant uncertainty in the cost-effectiveness analysis. Conclusions: The SaFaRI study revealed inefficiencies in the treatment pathways for faecal incontinence, particularly for sacral nerve stimulation. The success of both FENIX and sacral nerve stimulation was much lower than previously reported, with high postoperative morbidity in the FENIX group. Future work: Further research is needed to clarify the treatment pathways for sacral nerve stimulation and to determine its true clinical and cost-effectiveness. Trial registration: Current Controlled Trials ISRCTN16077538. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 18. See the NIHR Journals Library website for further project information

    Dynamic social networks in guppies (Poecilia reticulata)

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    One of the main challenges in the study of social networks in vertebrates is to close the gap between group patterns and dynamics. Usually scan samples or transect data are recorded to provide information about social patterns of animals, but these techniques themselves do not shed much light on the underlying dynamics of such groups. Here we show an approach which captures the fission-fusion dynamics of a fish population in the wild and demonstrates how the gap between pattern and dynamics may be closed. Our analysis revealed that guppies have complex association patterns that are characterised by close strong connections between individuals of similar behavioural type. Intriguingly, the preference for particular social partners is not expressed in the length of associations but in their frequency. Finally, we show that the observed association preferences could have important consequences for transmission processes in animal social networks, thus moving the emphasis of network research from descriptive mechanistic studies to functional and predictive ones. © 2014 Springer-Verlag Berlin Heidelberg

    Strength of Social Tie Predicts Cooperative Investment in a Human Social Network

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    Social networks – diagrams which reflect the social structure of animal groups – are increasingly viewed as useful tools in behavioural ecology and evolutionary biology. Network structure may be especially relevant to the study of cooperation, because the action of mechanisms which affect the cost:benefit ratio of cooperating (e.g. reciprocity, punishment, image scoring) is likely to be mediated by the relative position of actor and recipient in the network. Social proximity could thus affect cooperation in a similar manner to biological relatedness. To test this hypothesis, we recruited members of a real-world social group and used a questionnaire to reveal their network. Participants were asked to endure physical discomfort in order to earn money for themselves and other group members, allowing us to explore relationships between willingness to suffer a cost on another's behalf and the relative social position of donor and recipient. Cost endured was positively correlated with the strength of the social tie between donor and recipient. Further, donors suffered greater costs when a relationship was reciprocated. Interestingly, participants regularly suffered greater discomfort for very close peers than for themselves. Our results provide new insight into the effect of social structure on the direct benefits of cooperation

    Individual biases, cultural evolution, and the statistical nature of language universals: the case of colour naming systems

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    Language universals have long been attributed to an innate Universal Grammar. An alternative explanation states that linguistic universals emerged independently in every language in response to shared cognitive or perceptual biases. A computational model has recently shown how this could be the case, focusing on the paradigmatic example of the universal properties of colour naming patterns, and producing results in quantitative agreement with the experimental data. Here we investigate the role of an individual perceptual bias in the framework of the model. We study how, and to what extent, the structure of the bias influences the corresponding linguistic universal patterns. We show that the cultural history of a group of speakers introduces population-specific constraints that act against the pressure for uniformity arising from the individual bias, and we clarify the interplay between these two forces
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