118 research outputs found

    Nonmyeloablative regimen preserves "niches" allowing for peripheral expansion of donor T-cells

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    AbstractT-cell recovery following myeloablative preparatory regimens and cord blood transplantation in adult patients gen erally occurs between 1 and 3 years following allogeneic bone marrow transplantation. T-cell reconstitution may involve thymic education of donor-derived precursors or peripheral expansion of mature T-cells transferred in the graft. We measured quantitative and qualitative immunologic reconstitution, T-cell receptor spectratyping, and T-cell receptor excision circle (TREC) levels in adult recipients of umbilical cord blood transplants following a novel nonmyeloablative regimen. These results were compared to previously published results of similar patients receiving a myeloablative regimen and cord blood stem cells. With small numbers of patients treated so far, T-cells (CD3+) reached normal levels in adults 6 to 12 months following nonmyeloablative transplantation compared with 24 months in adults receiving a myeloablative regimen. At 12 months after transplantation, the numbers of phenotypically naive (CD45RA) T-cells were higher in those receiving the nonmyeloablative regimen. The T-cell repertoire in cord blood recipients treated with a nonmyeloablative regimen was markedly more diverse and robust compared with the repertoire in those receiving the myeloablative regimen at similar time points. TRECs (which are generated within the thymus and identify new thymic emigrants and those that have not divided) were detected 12 months after transplantation in the nonmyeloablative recipients, whereas TRECs were not detected in adults until 18 to 24 months in those receiving myeloablative regimens. Thus, in adults receiving a nonmyeloablative preparatory regimen, the quantitative and qualitative recovery of T-cells occurs through rapid peripheral expansion. The ability of patients receiving a nonmyeloablative regimen to recover within a few months suggests that the peripheral niches in which T-cells can proliferate are preserved in these patients compared to those receiving ablative regimens. Moreover, the presence of TREC-positive cells within 1 year suggests that thymic recovery is likewise accelerated in non myeloablative compared to myeloablative regimens.Biol Blood Marrow Transplant 2002;8(5):249-56

    Voices Raised, Spring 2022

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    Director\u27s column; workforce diversification; women\u27s leadership immersion; staff spotlight on Leah Ward; focus on equity, education, and research (UD Men for Gender Equity; Gender Equity Research Colloquium); diversity and inclusion; Women of UD; student organization spotlight; Voice of Black Women; staff summaries.https://ecommons.udayton.edu/wc_newsletter/1057/thumbnail.jp

    Optimising mechanical separation of anaerobic digestate for total solids and nutrient removal

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    Publication history: Accepted - 16 June 2023; Published - 28 June 2023.Mechanical separation of anaerobic digestate has been identified as a method to reduce pollution risk to waterways by partitioning phosphorus in the solid fraction and reducing its application to land. Separators have adjustable parameters which affect separation efficiency, and hence the degree of phosphorous partitioning, but information on how these parameters affect separation performance is limited in the literature. Two well known technologies were investigated, decanter centrifuge and screw press, to determine the most efficient method of separation. Counterweight load and the use of an oscillator were adjusted for the screw press, while bowl speed, auger differential speed, feed rate and polymer addition were modified for the decanter centrifuge. Separation efficiency was determined for total solids, phosphorus, nitrogen, potassium, and carbon, and the total solids content of resulting fractions was measured. The decanter centrifuge had higher separation efficiency for phosphorus in all cases, ranging from 51% to 71.5%, while the screw press had a phosphorus separation efficiency ranging from 8.5% to 10.9% for digestate of ~5% solids (slurry/grass silage mix). Separation by decanter centrifuge partitioned up to 56% of nitrogen in the solid fraction leaving a reduced nitrogen content in the liquid fraction available for land spreading; this nitrogen would most likely need to be replaced by chemical fertiliser which would add to the cost of the system. The decanter centrifuge is better suited to cases where phosphorus recovery is the most important factor, while the screw press could be advantageous in cases where cost is a limiting factor.This project was supported by The Bryden Centre. The Bryden Centre project is supported by the European Union’s INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB). The views and opinions expressed in this paper do not necessarily reflect those of the European Commission or the Special EU Programmes Body (SEUPB). The work was also supported by Queen’s University Belfast and the Agri-Food and Biosciences Institute in Northern Ireland

    An economic analysis of anaerobic digestate fuel pellet production: can digestate fuel pellets add value to existing operations?

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    Publication history: Accepted - 9 April 2021; Published online - 16 April 2021.Anaerobic digestion provides renewable energy through waste valorisation, but the digestate by-product is underutilised and presents a risk to water quality. Mechanical separation partitions phosphorous into the solid fraction and further processing into a fuel pellet can provide an additional source of energy and revenue. Previous economic analyses looked only at aspects of the system (e.g. operational costs solely) and the system requires further investigation to determine viability. In this paper, an economic assessment of digestate fuel pellet production at farm-scale anaerobic digestion plants was carried out. The significance of this work is to provide a comprehensive assessment of the energy, phosphorous, and economic balances involved in digestate fuel pellet production at existing anaerobic digestion plants. The aim of this paper is to determine the financial viability of digestate fuel pellet production with objectives to compare two mechanical separation technologies: screw press, and decanting centrifuge. Economies of scale hold true for digestate pellet production and the available digestate in typical UK farm-based anaerobic digestion plants ( 500 kWe) is insufficient for profitability, with pellet production costing from £176/t (decanting centrifuge) to £215/t (screw press), compared to a typical wood pellet sale price of £185/t. Increasing digestate quantity by collaboration of plant operators can reduce the cost of pellet production to between £95/t and £121/t, improving financial viability and increasing the profit per head of cattle by 9–20% on a typical dairy farm utilising anaerobic digestion. The system has potential to aid rural development while also protecting the environment and contributing to the diversification of energy supply.This project was supported by The Bryden Centre. The Bryden Centre project is supported by the European Union’s INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB). The views and opinions expressed in this paper do not necessarily reflect those of the European Commission or the Special EU Programmes Body (SEUPB). The work was also supported by Queen’s University Belfast and the Agri-Food and Biosciences Institute in Northern Ireland

    Effect of anaerobic digestate fuel pellet production on Enterobacteriaceae and Salmonella persistence

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    Publication history: Accepted - 10 June 2022; Published online - 7 July 2022.Production of digestate pellets for fuel has been identified as a promising circular economy approach to provide renewable energy and additional income to farms, while at the same time presenting the potential to divert raw digestate from nutrient-saturated land and reduce the risk to water quality. Although previous research has investigated the feasibility of pellet production, there has been little focus on the bio-safety aspects of the system. Little is currently known about the persistence of bacteria present in the digestate and the potential impacts on human health for those handling this product. The aim of the present research was to determine the effect that each step in the pellet production process has on bacteria numbers: anaerobic digestion, mechanical separation, solid drying, and pelletisation. Enterobacteriaceae enumeration by colony count method was used to quantify bacteria, and the presence of Salmonella at each stage was determined. The Enterobacteriaceae count reduced with each stage, and the final pelletisation step reduced bacteria numbers to below detectable levels (<10 colony forming units/g). Salmonella was only detected in the starting slurry and absent from digestate onwards. Storage of the pellets under winter and simulated summer conditions showed no reactivation of Enterobacteriaceae over time. The pelletisation process produces a digestate product with Enterobacteriaceae counts below the maximum threshold (PAS110 specification) for transport off the source farm, but care must still be taken when handling digestate pellets as complete sterilisation has not been confirmed.This project was supported by The Bryden Centre. The Bryden Centre project is supported by the European Union's INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB). The work was also supported by Queen's University Belfast and the Agri-Food and Biosciences Institute in Northern Ireland

    Adapting and developing an academic and community practice collaborative care model for metastatic breast cancer care (Project ADAPT): Protocol for an implementation science-based study

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    BACKGROUND: Metastatic breast cancer (MBC) remains incurable despite significant treatment advances. Coordinating care for patients with MBC can be challenging given the various treatment options, available clinical trials, and frequent need for ancillary services. To optimize MBC care, we designed a project for adapting and developing an academic and community practice collaborative care model for MBC care (Project ADAPT), based on the Ending Metastatic Breast Cancer for Everyone (EMBRACE) program developed at Dana Farber Cancer Institute. OBJECTIVE: We aim to describe the implementation science-based study design and innovative components of Project ADAPT. METHODS: Project ADAPT uses the Dynamic Adaptation Process informed by the Exploration, Preparation, Implementation, Sustainment framework. Washington University School of Medicine (WUSM) partnered with 3 community hospitals in the St. Louis region covering rural and urban settings. The exploration and preparation phases provide patient and provider feedback on current referral practices to finalize the approach for the implementation phase. At the implementation phase, we will enroll patients with MBC at these 3 community sites to evaluate potential collaborative care at WUSM and assess the impact of this collaborative care model on referral satisfaction and acceptability for patients with MBC and their providers. Patients may then return to their community site for care or continue to receive part of their care at WUSM. We are incorporating virtual and digital health strategies to improve MBC care coordination in order to minimize patient burden. RESULTS: The exploration phase is ongoing. As of August 2021, we have recruited 21 patient and provider participants to complete surveys of the current collaborative care process at WUSM. Using a 2-tailed paired t test, 44 patients (including 10 patients from the exploration phase) and 32 oncologists are required to detect an effect size of 0.5 with 80% power at a level of significance of .05. Throughout this phase and in preparation for the implementation phase, we have iteratively updated and refined our surveys for the implementation phase based on testing of our data collection instruments. Our partner sites are in various stages of the single institutional review board (IRB) approval process. We have ongoing engagement with all partner sites, which has helped solidify our participant recruitment strategies and design patient-friendly recruitment materials. In addition, we have included a patient advocate on the research team. Members of the research team have launched a single IRB Support Network at WUSM to create a repository of the single IRB procedures in order to streamline the partner site onboarding process and facilitate enhanced collaboration across institutions. CONCLUSIONS: With this robust model, we expect that patients with MBC will receive optimal care regardless of geographical location and the model will improve patient and provider experiences when navigating the health system. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35736

    Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment

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    Background: Artemisinin combination treatments (ACT) are recommended as first line treatment for falciparum malaria throughout the malaria affected world. We reviewed the efficacy of a 3-day regimen of mefloquine and artesunate regimen (MAS ), over a 13 year period of continuous deployment as first-line treatment in camps for displaced persons and in clinics for migrant population along the Thai-Myanmar border. Methods and Findings: 3,264 patients were enrolled in prospective treatment trials between 1995 and 2007 and treated with MAS. The proportion of patients with parasitaemia persisting on day-2 increased significantly from 4.5% before 2001 to 21.9% since 2002 (p&lt;0.001). Delayed parasite clearance was associated with increased risk of developing gametocytaemia (AOR = 2.29; 95% CI, 2.00-2.69, p = 0.002). Gametocytaemia on admission and carriage also increased over the years (p = 0.001, test for trend, for both). MAS efficacy has declined slightly but significantly (Hazards ratio 1.13; 95% CI, 1.07-1.19, p&lt;0.001), although efficacy in 2007 remained well within acceptable limits: 96.5% (95% CI, 91.0-98.7). The in vitro susceptibility of P. falciparum to artesunate increased significantly until 2002, but thereafter declined to levels close to those of 13 years ago (geometric mean in 2007: 4.2 nM/l; 95% CI, 3.2-5.5). The proportion of infections caused by parasites with increased pfmdr1 copy number rose from 30% (12/ 40) in 1996 to 53% (24/45) in 2006 (p = 0.012, test for trend). Conclusion: Artesunate-mefloquine remains a highly efficacious antimalarial treatment in this area despite 13 years of widespread intense deployment, but there is evidence of a modest increase in resistance. Of particular concern is the slowing of parasitological response to artesunate and the associated increase in gametocyte carriage. © 2009 Carrara et al

    Risk of tuberculosis after initiation of antiretroviral therapy among persons with HIV in Europe.

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    OBJECTIVES Tuberculosis (TB) risk after initiation of antiretroviral treatment (ART) is not well described in a European setting, with an average TB incidence of 25/105 in the background population. METHODS We included all adult persons with HIV starting ART in the RESPOND cohort between 2012 and 2020. TB incidence rates (IR) were assessed for consecutive time intervals post-ART initiation. Risk factors for TB within 6 months from ART initiation were evaluated using Poisson regression models. RESULTS Among 8441 persons with HIV, who started ART, 66 developed TB during 34,239 person-years of follow-up [PYFU], corresponding to 1.87/1000 PYFU (95% confidence interval [CI]: 1.47-2.37). TB IR was highest in the first 3 months after ART initiation (14.41/1000 PY (95%CI 10.08-20.61]) and declined at 3-6, 6-12, and >12 months post-ART initiation (5.89 [95%CI 3.35-10.37], 2.54 [95%CI 1.36-4.73] and 0.51 [95%CI 0.30-0.86]), respectively. Independent risk factors for TB within the first 6 months after ART initiation included follow-up in Northern or Eastern Europe region, African origin, baseline CD4 count 100,000 copies/mL, injecting drug use and heterosexual transmission. CONCLUSIONS TB IR was highest in the first 3 months post-ART initiation and was associated with baseline risk factors, highlighting the importance of thorough TB risk assessment at ART initiation
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