816 research outputs found

    Management of gastrointestinal stromal tumours in the Imatinib era: a surgeon's perspective

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    <p>Abstract</p> <p>Background</p> <p>Surgical resection has remained the mainstay of treatment of GIST with a 5-year-survival of 28–35%. Tyrosine kinase inhibitor (Imatinib) has revolutionised the treatment of these tumours. The current research is directed towards expanding the role of this drug in the treatment of GIST. We present our experience of managing GIST in this institute.</p> <p>Methods</p> <p>This is a case note study of patients identified from a prospectively kept database from January 2000 to August 2007.</p> <p>Results</p> <p>16 patients were diagnosed with GIST. The median age was 66 years (range 46 to 82) and the male to female ratio was 9:7. Eleven patients underwent surgery, 9 of which had R0 resection (2 laparoscopic, 1 converted to open), one had an open biopsy and one had a debulking procedure. 3 patients were inoperable and 2 were found to be unfit for surgery. Five patients received Imatinib (2 postoperatively). The risk assessment based on morphological criteria showed that 4 patients had low, 4 had intermediate and 8 had high malignant potential. The median follow up was for 12 months (range 3–72); 2 patients died of unrelated causes at 6 and 9 months after diagnosis.</p> <p>Conclusion</p> <p>Most GISTs can be managed effectively using existing protocols. However currently there is no evidence based guidance available on the management of GIST in the following situations-role of debulking surgery, the follow up of benign tumours not requiring surgical resection and role of laparoscopic surgery. Further research is needed to answer these questions.</p

    Tuning the Exo-Space Weather Radio for Stellar Coronal Mass Ejections

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    Coronal mass ejections (CMEs) on stars other than the Sun have proven very difficult to detect. One promising pathway lies in the detection of type II radio bursts. Their appearance and distinctive properties are associated with the development of an outward propagating CME-driven shock. However, dedicated radio searches have not been able to identify these transient features in other stars. Large Alfv\'en speeds and the magnetic suppression of CMEs in active stars have been proposed to render stellar eruptions "radio-quiet". Employing 3D magnetohydrodynamic simulations, we study here the distribution of the coronal Alfv\'en speed, focusing on two cases representative of a young Sun-like star and a mid-activity M-dwarf (Proxima Centauri). These results are compared with a standard solar simulation and used to characterize the shock-prone regions in the stellar corona and wind. Furthermore, using a flux-rope eruption model, we drive realistic CME events within our M-dwarf simulation. We consider eruptions with different energies to probe the regimes of weak and partial CME magnetic confinement. While these CMEs are able to generate shocks in the corona, those are pushed much farther out compared to their solar counterparts. This drastically reduces the resulting type II radio burst frequencies down to the ionospheric cutoff, which impedes their detection with ground-based instrumentation.Comment: 13 Pages, 6 Figures, 2 Tables. Accepted for publication in The Astrophysical Journa

    Jejunal perforation caused by a feeding jejunostomy tube: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Percutaneous endoscopic gastrostomy and feeding jejunostomy are used for providing long-term nutritional support to patients with neurological disorders. Various mechanical complications of these procedures are described.</p> <p>Case presentation</p> <p>We report a case of a 17-year-old boy with cerebral injury who had a percutaneous endoscopic gastrostomy tube changed to a feeding jejunostomy tube. Twenty-four hours later he developed abdominal pain and became clinically septic. A contrast study through the feeding tube and a subsequent computed tomography scan did not reveal any intra-abdominal pathology. At laparotomy it was discovered that the tip of the feeding tube had perforated through the jejunal wall and was lying outside the lumen. This was successfully treated by re-inserting a feeding jejunostomy tube distally and closure of the perforation and previous FJ site</p> <p>Conclusion</p> <p>We suggest that the threshold for contrast studies and operative intervention should be low in neurologically impaired patients to avoid the delay in treatment of tube-related complications.</p

    Ethical issues in implementation research: a discussion of the problems in achieving informed consent

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    Background: Improved quality of care is a policy objective of health care systems around the world. Implementation research is the scientific study of methods to promote the systematic uptake of clinical research findings into routine clinical practice, and hence to reduce inappropriate care. It includes the study of influences on healthcare professionals' behaviour and methods to enable them to use research findings more effectively. Cluster randomized trials represent the optimal design for evaluating the effectiveness of implementation strategies. Various codes of medical ethics, such as the Nuremberg Code and the Declaration of Helsinki inform medical research, but their relevance to cluster randomised trials in implementation research is unclear. This paper discusses the applicability of various ethical codes to obtaining consent in cluster trials in implementation research. Discussion: The appropriate application of biomedical codes to implementation research is not obvious. Discussion of the nature and practice of informed consent in implementation research cluster trials must consider the levels at which consent can be sought, and for what purpose it can be sought. The level at which an intervention is delivered can render the idea of patient level consent meaningless. Careful consideration of the ownership of information, and rights of access to and exploitation of data is required. For health care professionals and organizations, there is a balance between clinical freedom and responsibility to participate in research. Summary: While ethical justification for clinical trials relies heavily on individual consent, for implementation research aspects of distributive justice, economics, and political philosophy underlie the debate. Societies may need to trade off decisions on the choice between individualized consent and valid implementation research. We suggest that social sciences codes could usefully inform the consideration of implementation research by members of Research Ethics Committees

    Evolution combined with genomic study elucidates genetic bases of isobutanol tolerance in Escherichia coli

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    <p>Abstract</p> <p>Background</p> <p>Isobutanol is a promising next-generation biofuel with demonstrated high yield microbial production, but the toxicity of this molecule reduces fermentation volumetric productivity and final titer. Organic solvent tolerance is a complex, multigenic phenotype that has been recalcitrant to rational engineering approaches. We apply experimental evolution followed by genome resequencing and a gene expression study to elucidate genetic bases of adaptation to exogenous isobutanol stress.</p> <p>Results</p> <p>The adaptations acquired in our evolved lineages exhibit antagonistic pleiotropy between minimal and rich medium, and appear to be specific to the effects of longer chain alcohols. By examining genotypic adaptation in multiple independent lineages, we find evidence of parallel evolution in <it>marC</it>, <it>hfq</it>, <it>mdh</it>, <it>acrAB, gatYZABCD</it>, and <it>rph </it>genes. Many isobutanol tolerant lineages show reduced RpoS activity, perhaps related to mutations in <it>hfq </it>or <it>acrAB</it>. Consistent with the complex, multigenic nature of solvent tolerance, we observe adaptations in a diversity of cellular processes. Many adaptations appear to involve epistasis between different mutations, implying a rugged fitness landscape for isobutanol tolerance. We observe a trend of evolution targeting post-transcriptional regulation and high centrality nodes of biochemical networks. Collectively, the genotypic adaptations we observe suggest mechanisms of adaptation to isobutanol stress based on remodeling the cell envelope and surprisingly, stress response attenuation.</p> <p>Conclusions</p> <p>We have discovered a set of genotypic adaptations that confer increased tolerance to exogenous isobutanol stress. Our results are immediately useful to further efforts to engineer more isobutanol tolerant host strains of <it>E. coli </it>for isobutanol production. We suggest that <it>rpoS </it>and post-transcriptional regulators, such as <it>hfq</it>, RNA helicases, and sRNAs may be interesting mutagenesis targets for future global phenotype engineering.</p

    Mutation in Mouse Hei10, an E3 Ubiquitin Ligase, Disrupts Meiotic Crossing Over

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    Crossing over during meiotic prophase I is required for sexual reproduction in mice and contributes to genome-wide genetic diversity. Here we report on the characterization of an N-ethyl-N-nitrosourea-induced, recessive allele called mei4, which causes sterility in both sexes owing to meiotic defects. In mutant spermatocytes, chromosomes fail to congress properly at the metaphase plate, leading to arrest and apoptosis before the first meiotic division. Mutant oocytes have a similar chromosomal phenotype but in vitro can undergo meiotic divisions and fertilization before arresting. During late meiotic prophase in mei4 mutant males, absence of cyclin dependent kinase 2 and mismatch repair protein association from chromosome cores is correlated with the premature separation of bivalents at diplonema owing to lack of chiasmata. We have identified the causative mutation, a transversion in the 5′ splice donor site of exon 1 in the mouse ortholog of Human Enhancer of Invasion 10 (Hei10; also known as Gm288 in mouse and CCNB1IP1 in human), a putative B-type cyclin E3 ubiquitin ligase. Importantly, orthologs of Hei10 are found exclusively in deuterostomes and not in more ancestral protostomes such as yeast, worms, or flies. The cloning and characterization of the mei4 allele of Hei10 demonstrates a novel link between cell cycle regulation and mismatch repair during prophase I

    Canadian and English students' beliefs about waterpipe smoking: a qualitative study

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    <p>Abstract</p> <p>Background</p> <p>Waterpipe smoking is becoming popular among western students. The aim was to understand the appeal to students of this form of smoking when other forms of smoking are becoming less common.</p> <p>Methods</p> <p>Waterpipe smokers were identified by snowball sampling and interviewed following a semi-structured schedule in waterpipe cafes and in their homes. Constant comparative analysis was used to derive themes for the analysis.</p> <p>Results</p> <p>Waterpipe smokers saw smoking as an alternative to more expensive nights out in bars. The appeal was related to the communal activity and the novelty of the experience. Respondents had not thought deeply about the health risks and reasoned that if no warnings about waterpipe smoking were apparent (unlike cigarette smoking) then it was probably safe. These observations were reinforced by observations about the mildness of the smoke, the fruit flavours, and beliefs about the filtering of the water. Waterpipe smokers felt no pressure to stop smoking and therefore had not tried to do so, but felt it might be something they did not continue after university. Waterpipe smoking was not linked in students' minds to other forms of smoking except in one individual who was using waterpipe smoking to help quit cigarettes.</p> <p>Conclusion</p> <p>In the absence of public health information, students have fallen back on superficial experiences to form views that waterpipe smoking is less harmful than other forms of smoking and it is currently much more acceptable in student society than other forms of smoking.</p
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