515 research outputs found

    The FENE dumbbell polymer model: existence and uniqueness of solutions for the momentum balance equation

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    We consider the FENE dumbbell polymer model which is the coupling of the incompressible Navier-Stokes equations with the corresponding Fokker-Planck-Smoluchowski di ffusion equation. We show global well-posedness in the case of a 2D bounded domain. We assume in the general case that the initial velocity is sufficiently small and the initial probability density is sufficiently close to the equilibrium solution; moreover an additional condition on the coeffcients is imposed. In the corotational case, we only assume that the initial probability density is sufficiently close to the equilibrium solution

    A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

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    BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874

    Modelling the impact of larviciding on the population dynamics and biting rates of Simulium damnosum (s.l.): implications for vector control as a complementary strategy for onchocerciasis elimination in Africa

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    Background: In 2012, the World Health Organization set goals for the elimination of onchocerciasis transmission by 2020 in selected African countries. Epidemiological data and mathematical modelling have indicated that elimination may not be achieved with annual ivermectin distribution in all endemic foci. Complementary and alternative treatment strategies (ATS), including vector control, will be necessary. Implementation of vector control will require that the ecology and population dynamics of Simulium damnosum sensu lato be carefully considered. Methods: We adapted our previous SIMuliid POPulation dynamics (SIMPOP) model to explore the impact of larvicidal insecticides on S. damnosum (s.l.) biting rates in different ecological contexts and to identify how frequently and for how long vector control should be continued to sustain substantive reductions in vector biting. SIMPOP was fitted to data from large-scale aerial larviciding trials in savannah sites (Ghana) and small-scale ground larviciding trials in forest areas (Cameroon). The model was validated against independent data from Burkina Faso/Côte d’Ivoire (savannah) and Bioko (forest). Scenario analysis explored the effects of ecological and programmatic factors such as pre-control daily biting rate (DBR) and larviciding scheme design on reductions and resurgences in biting rates. Results: The estimated efficacy of large-scale aerial larviciding in the savannah was greater than that of ground-based larviciding in the forest. Small changes in larvicidal efficacy can have large impacts on intervention success. At 93% larvicidal efficacy (a realistic value based on field trials), 10 consecutive weekly larvicidal treatments would reduce DBRs by 96% (e.g. from 400 to 16 bites/person/day). At 70% efficacy, and for 10 weekly applications, the DBR would decrease by 67% (e.g. from 400 to 132 bites/person/day). Larviciding is more likely to succeed in areas with lower water temperatures and where blackfly species have longer gonotrophic cycles. Conclusions: Focal vector control can reduce vector biting rates in settings where a high larvicidal efficacy can be achieved and an appropriate duration and frequency of larviciding can be ensured. Future work linking SIMPOP with onchocerciasis transmission models will permit evaluation of the impact of combined anti-vectorial and anti-parasitic interventions on accelerating elimination of the disease

    Demographic History of Indigenous Populations in Mesoamerica Based on mtDNA Sequence Data

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    The genetic characterization of Native American groups provides insights into their history and demographic events. We sequenced the mitochondrial D-loop region (control region) of 520 samples from eight Mexican indigenous groups. In addition to an analysis of the genetic diversity, structure and genetic relationship between 28 Native American populations, we applied Bayesian skyline methodology for a deeper insight into the history of Mesoamerica. AMOVA tests applying cultural, linguistic and geographic criteria were performed. MDS plots showed a central cluster of Oaxaca and Maya populations, whereas those from the North and West were located on the periphery. Demographic reconstruction indicates higher values of the effective number of breeding females (Nef) in Central Mesoamerica during the Preclassic period, whereas this pattern moves toward the Classic period for groups in the North and West. Conversely, Nef minimum values are distributed either in the Lithic period (i.e. founder effects) or in recent periods (i.e. population declines). The Mesomerican regions showed differences in population fluctuation as indicated by the maximum Inter-Generational Rate (IGRmax): i) Center-South from the lithic period until the Preclassic; ii) West from the beginning of the Preclassic period until early Classic; iii) North characterized by a wide range of temporal variation from the Lithic to the Preclassic. Our findings are consistent with the genetic variations observed between central, South and Southeast Mesoamerica and the North-West region that are related to differences in genetic drift, structure, and temporal survival strategies (agriculture versus hunter-gathering, respectively). Interestingly, although the European contact had a major negative demographic impact, we detect a previous decline in Mesoamerica that had begun a few hundred years before

    Congenital bipartite lunate presenting as a misdiagnosed lunate fracture: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>A rare case of congenital bipartite lunate in a child is reported. Carpal variants are very uncommon as independent entities, with only three previous reports of this condition in the English literature.</p> <p>Case presentation</p> <p>An 11-year-old Caucasian boy presented with pain in the left wrist after a fall. Radiographs in the emergency department demonstrated a lunate that was divided into palmar and dorsal parts, causing a misdiagnosis of fractured lunate. Magnetic resonance imaging was then used to differentiate between the two diagnoses.</p> <p>Conclusion</p> <p>Very few cases of bipartite lunate have been reported in the literature, and unless awareness is raised about congenital anomalies such as this variant, confusion may arise.</p

    Studies on the Epipolythiodioxopiperazine Alkaloid Verticillin D: Scaled Production, Streamlined Purification, and Absolute Configuration<strong> </strong>

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    Verticillins, epipolythiodioxopiperazine alkaloids that were first described over 50 years ago, have undergone extensive cytotoxic and pharmacological evaluations over the last decade. However, of the 27 verticillin analogues in the literature, the chemistry of verticillin D, which has two additional secondary hydroxy moieties, relative to verticillin A, has remained largely unexplored since its discovery in 1999. With the goal of advancing our understanding of verticillin D, there were three main objectives with this study: improving production, streamlining purification, and assigning absolute configuration via X-ray crystallography. To begin, the production of verticillin D was analyzed across seven fungal strains, and the top producer was further assessed under two fermentation conditions. Clonostachys rosea (strain MSX51257) biosynthesized the highest amount of verticillin D, with production peaking between 15-25 days on rice media. Interestingly, in contrast to similar studies that yield verticillin A, the biosynthesis of verticillin D was not accompanied by a suite of structurally related verticillin analogues. As such, the purification of verticillin D was more rapid and could be accomplished without the use of HPLC. These materials were used, in part, to determine the absolute configuration of verticillin D via X-ray crystallography, allowing for assignment of the asymmetric centers at both the 13 and 13′ positions as R, which has never been accomplished. This is only the third report of an X-ray structure of a verticillin analogue

    Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

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