457 research outputs found

    2019 Menino Survey of Mayors

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    The 2019 Menino Survey of Mayors represents the sixth nationally representative survey of American mayors and is based on interviews with 119 sitting mayors from 38 states. The 2019 Survey explores mayoral views on issues ranging from infrastructure and transportation priorities — including mobility and public safety — to the changing nature of work. The 2019 Survey also provides the first in-depth examination of mayors’ reactions to and expectations for the Opportunity Zones program, a significant new federal initiative to stimulate urban development. The 2019 Survey continues with the support of Citi Community Development and The Rockefeller Foundation.Citi Community Development and The Rockefeller Foundatio

    Menino Survey of Mayors 2018 Results

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    Report on research findings.The 2018 Menino Survey of Mayors represents the fifth scientifically rigorous and nationally representative survey of American mayors released by the Boston University Initiatives on Cities and supported by Citi Community Development and The Rockefeller Foundation. The Survey, based on interviews with 110 sitting mayors conducted in 2018, reveals mayoral views on economic development—including corporate recruitment, financial incentives, the sharing economy, and social mobility—as well as public health, housing, and intergovernmental relations.Citi Community Development and The Rockefeller Foundatio

    2022 Menino Survey of Mayors: mayors and the climate crisis

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    The 2022 Menino Survey of Mayors represents the ninth nationally representative survey of American mayors and is based on interviews with 118 sitting mayors from 38 states. The 2022 Survey explores mayoral views on climate and energy, poverty and rising costs of living, and health and safety. The first set of findings, released in January 2023, delves into mayors’ current views on local climate action, focusing on their beliefs about the underlying issues and threats, their sense of the tools they have at their disposal, and their enthusiasm for using them. The 2022 Survey continues with the support of The Rockefeller Foundation.The Rockefeller Foundatio

    2020 Menino Survey of Mayors: COVID-19 recovery and the future of cities

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    The 2020 Menino Survey of Mayors details insights and perspectives shared by a representative sample of 130 mayors leading U.S. cities with populations of more than 75,000 residents. This year’s Survey explores mayoral views on COVID-19 recovery and implications, policing and protests, parks and greenspace, and the 2020 Census. This report focuses on the COVD-19 related findings and outlines mayors’ responses to the global pandemic, perceptions of its impact, and expectations for the future of their cities. The 2020 Survey continues with the support of Citi and The Rockefeller Foundation

    Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa.

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    OBJECTIVES: We report on outcomes after 7 years of a community-based antiretroviral therapy (ART) programme in Khayelitsha, South Africa, with death registry linkages to correct for mortality under-ascertainment. DESIGN: This is an observational cohort study. METHODS: Since inception, patient-level clinical data have been prospectively captured on-site into an electronic patient information system. Patients with available civil identification numbers who were lost to follow-up were matched with the national death registry to ascertain their vital status. Corrected mortality estimates weighted these patients to represent all patients lost to follow-up. CD4 cell count outcomes were reported conditioned on continuous virological suppression. RESULTS: Seven thousand, three hundred and twenty-three treatment-naive adults (68% women) started ART between 2001 and 2007, with annual enrolment increasing from 80 in 2001 to 2087 in 2006. Of 9.8% of patients lost to follow-up for at least 6 months, 32.8% had died. Corrected mortality was 20.9% at 5 years (95% confidence interval 17.9-24.3). Mortality fell over time as patients accessed care earlier (median CD4 cell count at enrolment increased from 43 cells/microl in 2001 to 131 cells/microl in 2006). Patients who remained virologically suppressed continued to gain CD4 cells at 5 years (median 22 cells/microl per 6 months). By 5 years, 14.0% of patients had failed virologically and 12.2% had been switched to second-line therapy. CONCLUSION: At a time of considerable debate about future global funding of ART programmes in resource-poor settings, this study has demonstrated substantial and durable clinical benefits for those able to access ART throughout this period, in spite of increasing loss to follow-up

    Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study.

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    OBJECTIVE: To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. METHODS: CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). RESULTS: DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. CONCLUSIONS: The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment

    Electron paramagnetic resonance for the detection of electrochemically generated hydroxyl radicals : issues associated with electrochemical oxidation of the spin trap

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    For the detection of electrochemically produced hydroxyl radicals (HO·) from the oxidation of water on a boron-doped diamond (BDD) electrode, electron paramagnetic resonance spectroscopy (EPR) in combination with spin trap labels is a popular technique. Here, we show that quantification of the concentration of HO· from water oxidation via spin trap electrochemical (EC)-EPR is problematic. This is primarily due to the spin trap oxidizing at potentials less positive than water, resulting in the same spin trap-OH· adduct as formed from the solution reaction of OH· with the spin trap. We illustrate this through consideration of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap for OH·. DMPO oxidation on a BDD electrode in an acidic aqueous solution occurs at a peak current potential of +1.90 V vs SCE; the current for water oxidation starts to rise rapidly at ca. +2.3 V vs SCE. EC-EPR spectra show signatures due to the spin trap adduct (DMPO-OH·) at potentials lower than that predicted thermodynamically (for water/HO·) and in the region for DMPO oxidation. Increasing the potential into the water oxidation region, surprisingly, shows a lower DMPO-OH· concentration than when the potential is in the DMPO oxidation region. This behavior is attributed to further oxidation of DMPO-OH·, production of fouling products on the electrode surface, and bubble formation. Radical scavengers (ethanol) and other spin traps, here N-tert-butyl-α-phenylnitrone, α-(4-pyridyl N-oxide)-N-tert-butylnitrone, and 2-methyl-2-nitrosopropane dimer, also show electrochemical oxidation signals less positive than that of water on a BDD electrode. Such behavior also complicates their use for the intended application

    Epidermal growth factor can signal via ÎČ-catenin to control proliferation of mesenchymal stem cells independently of canonical Wnt signalling

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    Bone marrow mesenchymal stem/stromal cells (MSCs) maintain bone homeostasis and repair through the ability to expand in response to mitotic stimuli and differentiate into skeletal lineages. Signalling mechanisms that enable precise control of MSC function remain unclear. Here we report that by initially examining differences in signalling pathway expression profiles of individual MSC clones, we identified a previously unrecognised signalling mechanism regulated by epidermal growth factor (EGF) in primary human MSCs. We demonstrate that EGF is able to activate -catenin, a key component of the canonical Wnt signalling pathway. EGF is able to induce nuclear translocation of - catenin in human MSCs but does not drive expression of Wnt target genes or T cell factor (TCF) activity in MSC reporter cell lines. Using an efficient Design of Experiments (DoE) statistical analysis, with different combinations and concentrations of EGF and Wnt ligands, we were able to confirm that EGF does not influence the Wnt/-catenin pathway in MSCs. We show that the effects of EGF on MSCs are temporally regulated to initiate early “classical” EGF signalling mechanisms (e.g via mitogen activated protein kinase) with delayed activation of -catenin. By RNA-sequencing, we identified gene sets that were exclusively regulated by the EGF/-catenin pathway, which were distinct from classical EGF-regulated genes. However, subsets of classical EGF gene targets were significantly influenced by EGF/-catenin activation. These signalling pathways cooperate to enable EGF-mediated proliferation of MSCs by alleviating the suppression of cell cycle pathways induced by classical EGF signallin

    Correcting for Mortality Among Patients Lost to Follow Up on Antiretroviral Therapy in South Africa: A Cohort Analysis

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    Loss to follow-up (LTF) challenges the reporting of antiretroviral treatment (ART) programmes, since it encompasses patients alive but lost to programme and deaths misclassified as LTF. We describe LTF before and after correction for mortality in a primary care ART programme with linkages to the national vital registration system

    Coral reef conservation solution-scape white paper

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    In the face of climate change, warming oceans, and repeated mass coral bleaching, coral reef conservation is at a timely crossroads. There is a new urgency to support and strengthen a rich history of conservation partnerships and actions, while also building toward new actions to meet unparalleled global threats. The goal of this white paper is to synthesize and summarize the diversity of tools, approaches and solutions for coral reef conservation implemented to date and to understand the enabling conditions that lead to successful coral reef conservation. Framed as a “solution-scape,” this white paper seeks to support ongoing decisions to strengthen existing assets and build new investments into portfolios of global coral reef conservation that are equitable and aligned with diverse cultures and worldviews
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