459 research outputs found

    Integrating modes of policy analysis and strategic management practice : requisite elements and dilemmas

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    There is a need to bring methods to bear on public problems that are inclusive, analytic, and quick. This paper describes the efforts of three pairs of academics working from three different though complementary theoretical foundations and intervention backgrounds (i.e., ways of working) who set out together to meet this challenge. Each of the three pairs had conducted dozens of interventions that had been regarded as successful or very successful by the client groups in dealing with complex policy and strategic problems. One approach focused on leadership issues and stakeholders, another on negotiating competitive strategic intent with attention to stakeholder responses, and the third on analysis of feedback ramifications in developing policies. This paper describes the 10 year longitudinal research project designed to address the above challenge. The important outcomes are reported: the requisite elements of a general integrated approach and the enduring puzzles and tensions that arose from seeking to design a wide-ranging multi-method approach

    A Database of Wing Diversity in the Hawaiian Drosophila

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    Background. Within genus Drosophila, the endemic Hawaiian species offer some of the most dramatic examples of morphological and behavioral evolution. The advent of the Drosophila grimshawi genome sequence permits genes of interest to be readily cloned from any of the hundreds of species of Hawaiian Drosophila, offering a powerful comparative approach to defining molecular mechanisms of species evolution. A key step in this process is to survey the Hawaiian flies for characters whose variation can be associated with specific candidate genes. The wings provide an attractive target for such studies: Wings are essentially two dimensional, and genes controlling wing shape, vein specification, pigment production, and pigment pattern evolution have all been identified in Drosophila. Methodology/Principal Findings. We present a photographic database of over 180 mounted, adult wings from 73 species of Hawaiian Drosophila. The image collection, available at FlyBase.org, includes 53 of the 112 known species of picture wing\u27\u27 Drosophila, and several species from each of the other major Hawaiian groups, including the modified mouthparts, modified tarsus, antopocerus, and haleakalae (fungus feeder) groups. Direct image comparisons show that major wing shape changes can occur even between closely related species, and that pigment pattern elements can vary independently of each other. Among the 30 species closest to grimshawi, diverse visual effects are achieved by altering a basic pattern of seven wing spots. Finally, we document major pattern variations within species, which appear to result from reduced diffusion of pigment precursors through the wing blade. Conclusions/Significance. The database highlights the striking variation in size, shape, venation, and pigmentation in Hawaiian Drosophila, despite their generally low levels of DNA sequence divergence. In several independent lineages, highly complex patterns are derived from simple ones. These lineages offer a promising model system to study the evolution of complexity

    Primula vulgaris (primrose) genome assembly, annotation and gene expression, with comparative genomics on the heterostyly supergene

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    Primula vulgaris (primrose) exhibits heterostyly: plants produce self-incompatible pin- or thrum-form flowers, with anthers and stigma at reciprocal heights. Darwin concluded that this arrangement promotes insect-mediated cross-pollination; later studies revealed control by a cluster of genes, or supergene, known as the S (Style length) locus. The P. vulgaris S locus is absent from pin plants and hemizygous in thrum plants (thrum-specific); mutation of S locus genes produces self-fertile homostyle flowers with anthers and stigma at equal heights. Here, we present a 411 Mb P. vulgaris genome assembly of a homozygous inbred long homostyle, representing ~87% of the genome. We annotate over 24,000 P. vulgaris genes, and reveal more genes up-regulated in thrum than pin flowers. We show reduced genomic read coverage across the S locus in other Primula species, including P. veris, where we define the conserved structure and expression of the S locus genes in thrum. Further analysis reveals the S locus has elevated repeat content (64%) compared to the wider genome (37%). Our studies suggest conservation of S locus genetic architecture in Primula, and provide a platform for identification and evolutionary analysis of the S locus and downstream targets that regulate heterostyly in diverse heterostylous species

    Scientific imperatives, clinical implications, and theoretical underpinnings for the investigation of the relationship between genetic variables and patient-reported quality-of-life outcomes

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    Objectives There is emerging evidence for a genetic basis of patient-reported quality-of-life (QOL) outcomes that can ultimately be incorporated into clinical research and practice. Objectives are (1) to provide arguments for the timeliness of investigating the genetic basis of QOL given the scientific advances in genetics and patient-reported QOL research; (2) to describe the clinical implications of such investigations; (3) to present a theoretical foundation for investigating the genetic underpinnings of QOL; and (4) to describe a series of papers resulting from the GENEQOL Consortium that was established to move this work forward. Methods Discussion of scientific advances based on relevant literature. Results In genetics, technological advances allow for increases in speed and efficiency and decreases in costs in exploring the genetic underpinnings of disease processes, drug metabolism, treatment response, and survival. In patient-based research, advances yield empirically based and stringent approaches to measurement that are scientifically robust. Insights into the genetic basis of QOL will ultimately allow early identification of patients susceptible to QOL deficits and to target care. The Wilson and Cleary model for patient-reported outcomes was refined by incorporating the genetic underpinnings of QOL. Conclusions This series of papers provides a path for QOL and genetics researchers to work together to move this field forward and to unravel the intricate interplay of the genetic underpinnings of patient-reported QOL outcomes. The ultimate result will be a greater understanding of the process relating disease, patient, and doctor that will have the potential to lead to improved survival, QOL, and health services deliver

    Genetic aspects of dental disorders

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    The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.This paper reviews past and present applications of quantitative and molecular genetics to dental disorders. Examples are given relating to craniofacial development (including malocclusion), oral supporting tissues (including periodontal diseases) and dental hard tissues (including defects of enamel and dentine as well as dental caries). Future developments and applications to clinical dentistry are discussed. Early investigations confirmed genetic bases to dental caries, periodontal diseases and malocclusion, but research findings have had little impact on clinical practice. The complex multifactorial aetiologies of these conditions, together with methodological problems, have limited progress until recently. Present studies are clarifying previously unrecognized genetic and phenotypic heterogeneities and attempting to unravel the complex interactions between genes and environment by applying new statistical modelling approaches to twin and family data. linkage studies using highly polymorphic DNA markers are providing a means of locating candidate genes, including quantitative trait loci (QTL). In future, as knowledge increases: it should be possible to implement preventive strategies for those genetically-predisposed individuals who are identified-predisposed individuals who are identified to be at risk.Grant C. Townsend, Michael J. Aldred and P. Mark Bartol

    Possible failure of novel direct-acting oral anticoagulants in management of pulmonary embolism: a case report

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    BACKGROUND: The relative effectiveness of vitamin K antagonists compared with novel oral anticoagulants in treating pulmonary embolism remains unclear. Recent trials comparing the efficacy of vitamin K antagonists with factor Xa inhibitors for the treatment of pulmonary emboli have been non-inferiority studies based primarily on risk reduction (such as bleeding events), rather than resolution of specific diseases such as pulmonary embolism. Consequently, there is a lack of evidence indicating which of these agents are more effective. Here, we present a case where pulmonary emboli were treated with novel oral anticoagulants followed by warfarin to discuss the potential limitations in the use of novel oral anticoagulants as prevention or treatment of thromboembolism and the continued role for warfarin in this setting. CASE PRESENTATION: A 34-year-old African American woman presented to our clinic with shortness of breath and pleuritic chest pain several months post-surgery. She was identified as having multiple bilateral pulmonary embolisms and was treated with several novel oral anticoagulants, which failed to resolve the clots. Complete resolution was achieved upon switching to warfarin. CONCLUSIONS: The patient described in this report failed to respond to novel oral anticoagulant therapy, but her emboli resolved when she was treated with warfarin. This study challenges the notion that factor Xa inhibitors are better alternatives to vitamin K anticoagulants in the treatment of pulmonary emboli based on their safety profile and ease of use alone. As a result, further post-marketing investigations into the efficacy of these agents in the management of pulmonary emboli may be warranted
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