1,002 research outputs found

    The United Nations and full employment.

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    Thesis (M.A.)--Boston UniversityThe Second World War prompted the nations of the world to join together in common effort to achieve a mutual goal. Experience had shown them peace could not be attained without ideal economic conditions, and such was noted in every international document up to, and including the United Nations Charter, and the independent organizations established since. [TRUNCATED

    Improving Pathways to Transit for Persons with Disabilities

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    Persons with disabilities can achieve a greater degree of freedom when they have full access to a variety of transit modes, but this can only be achieved when the pathways to transit – the infrastructure and conditions in the built environment – allow full access to transit stops, stations, and vehicles. Since passage of the Americans with Disabilities Act (ADA) in 1990, many transit agencies and governmental jurisdictions have made significant progress in this area. Policy initiatives, incremental enhancements, modifications, and other measures undertaken by transit agencies and their partners have significantly improved access to transit for persons with disabilities, others who rely on public transportation, and individuals who chose to utilize these services. This research study explores, through case study work, efforts that have been effective in improving pathways to transit. Interviews and site visits were conducted with five transit agencies, along with their partners, that are actively engaged in improving pathways to connect transit consumers – particularly people with disabilities – with transit stations and stops. These agencies are: Broward County Transit (Broward County, FL), Memphis Area Transit Authority (Memphis, TN), NJ TRANSIT (Newark and New Brunswick, NJ), Tri-County Metropolitan Transportation District of Oregon (Portland, OR), and Link Transit (Wenatchee, WA). Promising practices and/or lessons were identified through the case study analysis; these should be considered by any transit agency seeking to create improved access to its services for persons with disabilities

    In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

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    BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB

    A multistate modeling approach to investigate long-term effects of claw horn disruption lesions and early lesion development in dairy cows

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    Claw horn disruption lesions (CHDL) are a leading cause of lameness in dairy cattle, and the development, effect, and pathology of these lesions remains an open area of interest within dairy cattle health. Current literature typically attempts to measure the effect of risk factors on the development of CHDL over a relatively short time period. Further understanding of the interaction of CHDL and the long-term effect of early CHDL in a cow's life remains an important area of research which is so far mostly unexplored. In this study 57,974 cows from 1,332 herds were selected and their regular claw trimming records containing important claw health information were used to model the long-term effect of lesions in a cow's lifetime in a 6-state multistate model. A multistate model predicts the time before transition from any one state to another and the probability of transition to a future state. The 6 lesion states that were modeled were as follows: never had a lesion, first recorded lesion event, no recorded lesion after first lesion event, second or subsequent recorded lesion event, no recorded lesion after second or subsequent lesion event, and culled. The effect of various cow level covariates on the transition probabilities between various states was tested. For the first time, this study shows the importance and effect of the first lesion and other cow level factors on long-term claw health. Model results showed that the timing and severity of the first recorded lesion event significantly influenced the likelihood of a future lesion being present. Cows with CHDL present within the 180 d of first calving had a short-term increased risk and long-term decreased risk of a future lesion, compared with cows that present with CHDL later than 180 d of first lactation. Moreover, presence of a severe first lesion increased a cow's risk of a future lesion being present. The model was used to evaluate the relative difference between high-risk cows (age of first calving ≥793 d, breeding values in the lowest quartile) and low-risk cows (age of first calving ≤718 d, breeding values in the highest quartile). Our results indicated that these low-risk cows present with a lesion on an average 3 mo later than high-risk cows. Furthermore, results from the model evaluation of a simulated herd with cows with breeding values in the higher quartile indicated that cows present with a CHDL on an average 7.5 mo later compared with a herd where cows have breeding values distributed in a lower quartile

    Assessment of Tapentadol API Abuse Liability with the Researched Abuse, Diversion and Addiction-Related Surveillance System

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    Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted

    Optical Structure and Proper-Motion Age of the Oxygen-rich Supernova Remnant 1E 0102-7219 in the Small Magellanic Cloud

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    We present new optical emission-line images of the young SNR 1E 0102-7219 (E0102) in the SMC obtained with the HST Advanced Camera for Surveys (ACS). E0102 is a member of the oxygen-rich class of SNRs showing strong oxygen, neon , and other metal-line emissions in its optical and X-ray spectra, and an absence of H and He. The progenitor of E0102 may have been a Wolf-Rayet star that underwent considerable mass loss prior to exploding as a Type Ib/c or IIL/b SN. The ejecta in this SNR are fast-moving (V > 1000 km/s) and emit as they are compressed and heated in the reverse shock. In 2003, we obtained optical [O III], H-alpha, and continuum images with the ACS Wide Field Camera. The [O III] image captures the full velocity range of the ejecta, and shows considerable high-velocity emission projected in the middle of the SNR that was Doppler-shifted out of the narrow F502N bandpass of a previous Wide Field and Planetary Camera 2 image from 1995. Using these two epochs separated by ~8.5 years, we measure the transverse expansion of the ejecta around the outer rim in this SNR for the first time at visible wavelengths. From proper-motion measurements of 12 ejecta filaments, we estimate a mean expansion velocity for the bright ejecta of ~2000 km/s and an inferred kinematic age for the SNR of \~2050 +/- 600 years. The age we derive from HST data is about twice that inferred by Hughes et al.(2000) from X-ray data, though our 1-sigma error bars overlap. Our proper-motion age is consistent with an independent optical kinematic age derived by Eriksen et al.(2003) using spatially resolved [O III] radial-velocity data. We derive an expansion center that lies very close to X-ray and radio hotspots, which could indicate the presence of a compact remnant (neutron star or black hole).Comment: 28 pages, 8 figures. Accepted to the Astrophysical Journal, to appear in 20 April 2006 issue. Full resolution figures are posted at: http://stevenf.asu.edu/figure
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