1,195 research outputs found

    Hydrographic Surveys in the Arctic

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    Indenture, Marshall County, MS 12 November 1855

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    https://egrove.olemiss.edu/aldrichcorr_c/1106/thumbnail.jp

    Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

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    Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc

    Nonimmune fetal hydrops and lysosomal storage disease: the finding of vacuolated lymphocytes in ascitic fluid in two cases

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102650/1/pd4274.pd

    Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double-blind, pilot study.

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    The primary treatment outcomes of a phase 2, randomized, double-blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200 m in the 6-min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3-min stair climb test [3MSCT]), exercise capacity (cardio-pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty-five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0-4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain

    Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce Disease Severity and Immune Responses in Inflammatory Arthritis

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    Abstract Background Novel biological therapies have revolutionised the management of Rheumatoid Arthritis (RA) but no cure currently exists. Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling via growth factors, cytokines, chemokines and extracellular vesicles (EVs) in the cell secretome; however, MSCs are still not available in the clinic. We evaluated the therapeutic potential of MSCs-derived EVs in an antigen-induced model of arthritis (AIA). Methods EVs isolated from MSCs in normal (21% O 2 , 5% CO 2 ) or hypoxic (2% O 2 , 5% CO 2 ) culture or from MSCs pre-conditioned with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed 3 days post arthritis induction through histopathological analysis of knee joints. Spleens and lymph nodes were collected and assessed for T cell polarisation within the immune response to AIA. Activated naïve CD4+ T cells from spleens of healthy mice were cultured with EVs or MSCs to assess deactivation capabilities. Results All EV treatments significantly reduced knee-joint swelling and histopathological signs of AIA with enhanced responses to normoxic and pro-inflammatory primed EVs. Polarisation of T cells towards CD4+ helper cells expressing IL17a (Th17) was reduced when EV treatments from MSCs cultured in hypoxia or pro-inflammatory priming conditions were applied. Conclusions Hypoxically cultured EVs present a priming methodology that is as effective in reducing swelling, IL-17a expression, Th17 polarisation and T cell proliferation as pro-inflammatory priming. EVs present an effective novel technology for cell-free therapeutic translation in treating inflammatory arthritis and autoimmune disorders such as RA

    eOrganic: The organic agriculture community of practice for eXtension

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    eOrganic is the organic agriculture community of practice (CoP) and resource area for eXtension. eOrganic\u27s primary community of interest (CoI) is organic farmers and the agricultural professionals who support them. The 250 members of the eOrganic CoP include farmers, researchers, certifiers, and extension/other agricultural professionals. eOrganic\u27s mission is to build a diverse national CoP and use web technologies to synthesize existing information, emerging science, and practical knowledge into information resources and training materials for its CoI. eOrganic strategies to achieve that mission include collaborative publication, stakeholder engagement, community development, projectmanagement, evaluation, and fundraising. eOrganic\u27s public site currently offers 240 articles, 250 videos, 80 webinars and broadcasts, and 100 frequently asked questions (FAQs). eOrganic CoP members have answered more than 1000 \u27Ask an Expert\u27 questions. eOrganic authors collaboratively develop articles in eOrganic\u27s collaborative workspace, which undergo review by two anonymous reviewers andNational Organic Program (NOP) compliance review. eOrganic will offer online courses in 2012. eOrganic stakeholders evaluated eOrganic articles and videos in 2010 and overall they stated that they were relevant, science-based, and useful. Three quarters of webinar and broadcast participants said the webinar improved their understanding of the topic, and 83% said they would recommend the webinar to others. Sixty-nine percent of webinar survey respondents stated that they changed practices or provided others with information as the result of the webinar. eOrganic surveyed active CoP members in 2011. Members view eOrganic as important because it is the only national organic agriculture resource with direct ties to university research and they considered all of eOrganic\u27s core activities important. eOrganic is supported by small grants from eXtension and subawards in more than 20 U.S. Department of Agriculture (USDA), National Institute of Food and Agriculture (NIFA) research/extension projects. To enhance its financial sustainability, eOrganic will work to solidify its partnership with NIFA programs and diversify its funding sources to include course fees and underwriters
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