9,585 research outputs found

    Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin\u27s lymphoma

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    Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

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    Wetlands Evaluation and Management in Virginia

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    Complex biotic communities which have lately been recognized as being of vital importance to aquatic and upland ecosystems have evolved at Virginia\u27s land-water interface. Most obvious are the beaches and vast intertidal stands of halophytic (salt-tolerant) plants on the periphery of the Atlantic Ocean, Chesapeake Bay and their subordinate estuaries. Less obvious, but no less important, are nonvegetated intertidal flats and coastal freshwater marshes. Inland swamps and freshwater marshes complete the inventory; though more limited in extent than their coastal analog. Complex biotic communities which have lately been recognized as being of vital importance to aquatic and upland ecosystems have evolved at Virginia\u27s land-water interface. Most obvious are the beaches and vast intertidal stands of halophytic (salt-tolerant) plants on the periphery of the Atlantic Ocean, Chesapeake Bay and their subordinate estuaries. Less obvious, but no less important, are nonvegetated intertidal flats and coastal freshwater marshes. Inland swamps and freshwater marshes complete the inventory; though more limited in extent than their coastal analog

    The Barrier Method: A Technique for Calculating Very Long Transition Times

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    In many dynamical systems there is a large separation of time scales between typical events and "rare" events which can be the cases of interest. Rare-event rates are quite difficult to compute numerically, but they are of considerable practical importance in many fields: for example transition times in chemical physics and extinction times in epidemiology can be very long, but are quite important. We present a very fast numerical technique that can be used to find long transition times (very small rates) in low-dimensional systems, even if they lack detailed balance. We illustrate the method for a bistable non-equilibrium system introduced by Maier and Stein and a two-dimensional (in parameter space) epidemiology model.Comment: 20 pages, 8 figure

    The ECHELON-2 trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma

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    BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy

    Fractionation effects in phase equilibria of polydisperse hard sphere colloids

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    The equilibrium phase behaviour of hard spheres with size polydispersity is studied theoretically. We solve numerically the exact phase equilibrium equations that result from accurate free energy expressions for the fluid and solid phases, while accounting fully for size fractionation between coexisting phases. Fluids up to the largest polydispersities that we can study (around 14%) can phase separate by splitting off a solid with a much narrower size distribution. This shows that experimentally observed terminal polydispersities above which phase separation no longer occurs must be due to non-equilibrium effects. We find no evidence of re-entrant melting; instead, sufficiently compressed solids phase separate into two or more solid phases. Under appropriate conditions, coexistence of multiple solids with a fluid phase is also predicted. The solids have smaller polydispersities than the parent phase as expected, while the reverse is true for the fluid phase, which contains predominantly smaller particles but also residual amounts of the larger ones. The properties of the coexisting phases are studied in detail; mean diameter, polydispersity and volume fraction of the phases all reveal marked fractionation. We also propose a method for constructing quantities that optimally distinguish between the coexisting phases, using Principal Component Analysis in the space of density distributions. We conclude by comparing our predictions to perturbative theories for near-monodisperse systems and to Monte Carlo simulations at imposed chemical potential distribution, and find excellent agreement.Comment: 21 pages, 23 figures, 2 table

    Treatment of multidrug-resistant tuberculosis in a remote, conflict-affected area of the Democratic Republic of Congo.

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    The Democratic Republic of Congo is a high-burden country for multidrug-resistant tuberculosis. Médecins Sans Frontières has supported the Ministry of Health in the conflict-affected region of Shabunda since 1997. In 2006, three patients were diagnosed with drug-resistant TB (DR-TB) and had no options for further treatment. An innovative model was developed to treat these patients despite the remote setting. Key innovations were the devolving of responsibility for treatment to non-TB clinicians remotely supported by a TB specialist, use of simplified monitoring protocols, and a strong focus on addressing stigma to support adherence. Treatment was successfully completed after a median of 24 months. This pilot programme demonstrates that successful treatment for DR-TB is possible on a small scale in remote settings
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