195 research outputs found

    Group Theory and Particles

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    We begin by a brief overview of the notion of groups and Lie groups. We then explain what group representations are and give their main properties. Finally, we show how group representation form a natural framework to understand the Standard Model of physics

    Analysis on Sharp and Smooth Interface

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    In biology, minimizing a free energy functional gives an equilibrium shape that is the most stable in nature. The formulation of these functionals can vary in many ways, in particular they can have either a smooth or sharp interface. Minimizing a functional can be done through variational calculus or can be proved to exist using various analysis techniques. The functionals investigated here have a smooth and sharp interface and are analyzed using analysis and variational calculus respectively. From the former we find the condition for extremum and its second variation. The second variation is commonly used to analyze stability of a surface that is a solution to the functional so having a surface is necessary. Comparatively, from the latter we find that there exists a minimizing surface for the functional; from this numerical and variational approaches to the problem can be justified

    Accelerating and enabling convergence of nonlinear solvers for Navier-Stokes equations by continuous data assimilation

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    This paper considers improving the Picard and Newton iterative solvers for the Navier-Stokes equations in the setting where data measurements or solution observations are available. We construct adapted iterations that use continuous data assimilation (CDA) style nudging to incorporate the known solution data into the solvers. For CDA-Picard, we prove the method has an improved convergence rate compared to usual Picard, and the rate improves as more measurement data is incorporated. We also prove that CDA-Picard is contractive for larger Reynolds numbers than usual Picard, and the more measurement data that is incorporated the larger the Reynolds number can be with CDA-Picard still being contractive. For CDA-Newton, we prove that the domain of convergence, with respect to both the initial guess and the Reynolds number, increases as as the amount of measurement data is increased. Additionally, for both methods we show that CDA can be implemented as direct enforcement of measurement data into the solution. Numerical results for common benchmark Navier-Stokes tests illustrate the theory

    Survival in Nuclear Waste, Extreme Resistance, and Potential Applications Gleaned from the Genome Sequence of Kineococcus radiotolerans SRS30216

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    Kineococcus radiotolerans SRS30216 was isolated from a high-level radioactive environment at the Savannah River Site (SRS) and exhibits γ-radiation resistance approaching that of Deinococcus radiodurans. The genome was sequenced by the U.S. Department of Energy's Joint Genome Institute which suggested the existence of three replicons, a 4.76 Mb linear chromosome, a 0.18 Mb linear plasmid, and a 12.92 Kb circular plasmid. Southern hybridization confirmed that the chromosome is linear. The K. radiotolerans genome sequence was examined to learn about the physiology of the organism with regard to ionizing radiation resistance, the potential for bioremediation of nuclear waste, and the dimorphic life cycle. K. radiotolerans may have a unique genetic toolbox for radiation protection as it lacks many of the genes known to confer radiation resistance in D. radiodurans. Additionally, genes involved in the detoxification of reactive oxygen species and the excision repair pathway are overrepresented. K. radiotolerans appears to lack degradation pathways for pervasive soil and groundwater pollutants. However, it can respire on two organic acids found in SRS high-level nuclear waste, formate and oxalate, which promote the survival of cells during prolonged periods of starvation. The dimorphic life cycle involves the production of motile zoospores. The flagellar biosynthesis genes are located on a motility island, though its regulation could not be fully discerned. These results highlight the remarkable ability of K radiotolerans to withstand environmental extremes and suggest that in situ bioremediation of organic complexants from high level radioactive waste may be feasible

    Etravirine pharmacokinetics in HIV-infected pregnant women

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    __Background__ The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women. __Methods__ IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL). __Results__ Fifteen women took etravirine 200 mg twice-daily. Etravirine AUC0-12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19-4.25) and no perinatal transmission occurred. __Conclusion__ Etravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available. __Clinical Trial registration:__ The IMPAACT protocol P1026s and PANNA study are registered at ClinicalTrials.gov under NCT00042289 and NCT00825929

    'Relief of oppression': An organizing principle for researchers' obligations to participants in observational studies in the developing world

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    <p>Abstract</p> <p>Background</p> <p>A central question in the debate about exploitation in international research is whether investigators and sponsors from high-income countries (HIC) have obligations to address background conditions of injustice in the communities in which they conduct their research, beyond the healthcare and other research-related needs of participants, to aspects of their basic life circumstances.</p> <p>Discussion</p> <p>In this paper, we describe <b>t</b>he Majengo sexually transmitted disease (STD) Cohort study, a long-term prospective, observational cohort of sex workers in Nairobi, Kenya. Despite important scientific contributions and a wide range of benefits to the women of the cohort, most of the women have remained in the sex trade during their long-standing participation in the cohort, prompting allegations of exploitation. The Majengo STD cohort case extends the debate about justice in international research ethics beyond clinical trials into long-term observational research. We sketch the basic features of a new approach to understanding and operationalizing obligations of observational researchers, which we call 'relief of oppression'. 'Relief of oppression' is an organizing principle, analogous to the principle of harm reduction that is now widely applied in public health practice. Relief of oppression aims to help observational researchers working in conditions of injustice and deprivation to clarify their ethical obligations to participants. It aims to bridge the gap between a narrow, transaction-oriented account of avoiding exploitation and a broad account emphasizing obligations of reparation for historic injustices. We propose that relief of oppression might focus researchers' consideration of benefits on those that have some relevance to background conditions of injustice, and so elevate the priority of these benefits, in relation to others that might be considered and negotiated with participants, according to the degree to which the participating communities are constrained in their realization of fundamental freedoms.</p> <p>Summary</p> <p>The over-arching aim of relief of oppression is that, within the range of benefits negotiated over time with the local communities and organizations, an increasing proportion reflects a shared interest in improving participants' fundamental freedoms. We describe how harm reduction serves as a useful analogy for how we envision relief of oppression functioning in international research.</p

    Decreased aortic growth and middle aortic syndrome in patients with neuroblastoma after radiation therapy

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    Background: Long-term CT follow-up studies are required in pediatric patients who have received intraoperative radiation therapy (IORT) and external beam radiation therapy (EBRT) to assess vascular toxicities and to determine the exact complication rate. Objective: To analyze with CT the effects of radiation therapy (RT) on the growth of the aorta in neuroblastoma patients.Materials and methods Abdominal CT scans of 31 patients with intraabdominal neuroblastoma (stage II–IV), treated with RT (20 IORT±EBRT, 11 EBRT alone), were analyzed retrospectively. The diameter of the abdominal aorta was measured before and after RT. These data were compared to normal and predicted normal aortic diameters of children, according to the model of Fitzgerald, Donaldson and Poznanski (aortic diameter in centimeters = 0.844 + 0.0599 × age in years), and to the diameters of a control group of children who had not undergone RT. Statistical analyses for the primary aims were performed using the chi-squared test, t-test, Mann-Whitney test, nonparametric Wilcoxon matched-pairs test and analysis of variance for repeated measures. Clinical files and imaging studies were evaluated for signs of late vascular complications of neuroblastoma patients who had received RT. Results: The mean diameter before and after RT and the growth of the aorta were significantly lower than expected in patients with neuroblastoma (P<0.05 for each) and when compared to the growth in a control group with normal and nonirradiated aortas. Among the patients who had received RT, there was no difference due to the type of RT. Seven patients from the IORT±EBRT group developed vascular complications, which included hypertension (five), middle aortic syndrome (two), death due to mesenteric ischemia (one) and critical aortic stenosis, which required aortic bypass surgery (two).Conclusion Patients with neuroblastoma who had received RT showed impaired growth of the abdominal aorta. Significant long-term vascular complications occurred in seven patients who received IORT±EBRT. Thus, CT evaluation of patients with neuroblastoma who receive RT should include not only reports of changes in tumor extension, but also documentation of perfusion, and the size and growth of the aorta and its branches over time

    A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol.

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    BACKGROUND: Standard therapy for borderline-resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins are unsatisfactory and overall survival remains poor. Meta-analysis of single-arm studies shows the potential of neo-adjuvant chemo-radiotherapy but the relative radio-resistance of pancreatic cancer means the efficacy of conventional dose schedules is limited. Stereotactic radiotherapy achieves sufficient accuracy and precision to enable pre-operative margin-intensive dose escalation with the goal of increasing rates of clear resection margins and local disease control. METHODS/DESIGN: SPARC is a "rolling-six" design single-arm study to establish the maximum tolerated dose for margin-intensive stereotactic radiotherapy before resection of pancreatic cancer at high risk of positive resection margins. Eligible patients will have histologically or cytologically proven pancreatic cancer defined as borderline-resectable per National Comprehensive Cancer Network criteria or operable tumour in contact with vessels increasing the risk of positive margin. Up to 24 patients will be recruited from up to 5 treating centres and a 'rolling-six' design is utilised to minimise delays and facilitate ongoing recruitment during dose-escalation. Radiotherapy will be delivered in 5 daily fractions and surgery, if appropriate, will take place 5-6 weeks after radiotherapy. The margin-intense radiotherapy concept includes a systematic method to define the target volume for a simultaneous integrated boost in the region of tumour-vessel infiltration, and up to 4 radiotherapy dose levels will be investigated. Maximum tolerated dose is defined as the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a dose limiting toxicity. Secondary endpoints include resection rate, resection margin status, response rate, overall survival and progression free survival at 12 and 24 months. Translational work will involve exploratory analyses of the cytological and humoral immunological responses to stereotactic radiotherapy in pancreatic cancer. Radiotherapy quality assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015. DISCUSSION: This prospective multi-centre study aims to establish the maximum tolerated dose of pre-operative margin-intensified stereotactic radiotherapy in pancreatic cancer at high risk of positive resection margins with a view to subsequent definitive comparison with other neoadjuvant treatment options
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