767 research outputs found

    The Memorial Addresses Delivered in University Hall, November 26, 1880, at the Funeral of Professor James Craig Watson, … Professor in the University from 1859 to 1879

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    This is Judge Cooley\u27s tribute to former University of Michigan astronomer Professor James Craig Watson, who died unexpectedly at age 42 and is buried in Forest Hill Cemetery in Ann Arbor. While not specifically related to the law, Cooley memorializes Watson with his ringing prose: ... it was among the stars this great man found his chief delight, and fitting it was that he should do so. He knew the stars as one knows the faces of his friends ... But it is the last few pages of the tribute that Cooley asserts the glory of the State of Michigan and specifically, the University of Michigan: ... here was and always must have been his scientific home. It was the University of Michigan that he had crowned with a garland of stars, and from whose Observatory the lightning had announced his successive discoveries... Cooley\u27s finale quotes the Ordinance of 1787 that the fathers of the Republic bound the people of the territory [of Michigan] by the unalterable law, that \u27Religion, Morality, and Knowledge, being necessary to Good Government and the happiness of mankind, Schools and the means of Education shall forever be encouraged

    Simultaneous detection of Legionella species and L. anisa, L. bozemanii, L. longbeachae and L. micdadei using conserved primers and multiple probes in a multiplex real-time PCR assay

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    AbstractLegionnaires' disease is a severe respiratory disease that is estimated to cause between 8,000 and 18,000 hospitalizations each year, though the exact burden is unknown due to under-utilization of diagnostic testing. Although Legionella pneumophila is the most common species detected in clinical cases (80-90%), other species have also been reported to cause disease. However, little is known about Legionnaires' disease caused by these non-pneumophila species. We designed a multiplex real-time PCR assay for detection of all Legionella spp. and simultaneous specific identification of four clinically-relevant Legionella species, L. anisa, L. bozemanii, L. longbeachae, and L. micdadei, using 5′-hydrolysis probe real-time PCR. The analytical sensitivity for detection of nucleic acid from each target species was ≤50fg per reaction. We demonstrated the utility of this assay in spiked human sputum specimens. This assay could serve as a tool for understanding the scope and impact of non-pneumophila Legionella species in human disease

    Evaluation of IL-1 Blockade as an Adjunct to Linezolid Therapy for Tuberculosis in Mice and Macaques

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    In 2017 over 550,000 estimated new cases of multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) occurred, emphasizing a need for new treatment strategies. Linezolid (LZD) is a potent antibiotic for drug-resistant Gram-positive infections and is an effective treatment for TB. However, extended LZD use can lead to LZD-associated host toxicities, most commonly bone marrow suppression. LZD toxicities may be mediated by IL-1, an inflammatory pathway important for early immunity during M. tuberculosis infection. However, IL-1 can contribute to pathology and disease severity late in TB progression. Since IL-1 may contribute to LZD toxicity and does influence TB pathology, we targeted this pathway with a potential host-directed therapy (HDT). We hypothesized LZD efficacy could be enhanced by modulation of IL-1 pathway to reduce bone marrow toxicity and TB associated-inflammation. We used two animal models of TB to test our hypothesis, a TB-susceptible mouse model and clinically relevant cynomolgus macaques. Antagonizing IL-1 in mice with established infection reduced lung neutrophil numbers and partially restored the erythroid progenitor populations that are depleted by LZD. In macaques, we found no conclusive evidence of bone marrow suppression associated with LZD, indicating our treatment time may have been short enough to avoid the toxicities observed in humans. Though treatment was only 4 weeks (the FDA approved regimen at the time of study), we observed sterilization of the majority of granulomas regardless of co-administration of the FDA-approved IL-1 receptor antagonist (IL-1Rn), also known as Anakinra. However, total lung inflammation was significantly reduced in macaques treated with IL-1Rn and LZD compared to LZD alone. Importantly, IL-1Rn administration did not impair the host response against Mtb or LZD efficacy in either animal model. Together, our data support that inhibition of IL-1 in combination with LZD has potential to be an effective HDT for TB and the need for further research in this area

    Prison-Based Dog Training Programs: Standard Protocol

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    Across the United States, the number of prison-based dog training programs (PDPs) has increased substantially over the past several years. Currently, there are approximately 255 PDPs across 47 states that operate in a variety of correctional settings; however, there is little information available on how to successfully develop and implement a PDP. As a result, the research team from the Institute for Human-Animal Connection (IHAC) has developed a standard protocol to help guide PDP development and implementation. This report identifies common practices of PDPs and incorporates both general and context-specific recommendations that were gathered from interviews with PDP staff, relevant literature, and content experts. In total, 21 interviews with 20 programs were conducted. PDPs were asked about several program features, including policies and procedures, key personnel, funding, materials, physical spaces, supervision and monitoring, safety considerations, animal welfare, handler selection and training, and program benefits. This report highlights the benefits of PDPs to dogs, humans, prisons, local communities, and society as a whole and identifies challenges related to funding, staffing, and operating in a correctional setting. Findings from the protocol point to the importance of planning, staffing, communication, internal support, and training curriculum in successful program implementation

    Chemical diffusion of fluorine in melts in the system Na2OAl2O3SiO2

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    The volatilization of fluorine from three melts in the system Na2OAl2O3SiO2 has been investigated at 1 atm pressure and 1200–1400°C. The melts chosen have base compositions corresponding to albite, jadeite and a peraluminous melt with 75 mole % SiO2. Melt spheres were suspended from platinum loops in a vertical tube furnace in a flow of oxygen gas, then quenched, sectioned and analysed by electron microprobe. The microprobe scans indicate that transport of fluorine to the melt-vapor interface is by binary, concentration-independent interdiffusion of fluorine and oxygen. FO interdiffusivity increases in the order albite < peraluminous < jadeite. There is no simple reciprocal relationship between FO interdiffusivity and melt viscosity. Comparison with data on high-pressure interdiffusivity of fluorine and oxygen in jadeite melt indicates that FO interdiffusivity increases with pressure from 0.001 to 10 kbar while the activation energy remains unchanged. Fluorine chemical diffusivity in albite melt is substantially lower than H2O chemical diffusivity in obsidian melts suggesting that different diffusive mechanisms are responsible for the transport of F and H2O in igneous melts. Fluorine diffuses in albite melt via an anionic exchange with oxygen whereas water probably diffuses in obsidian melt via an alkali exchange mechanism

    Evaluation of IL-1 blockade as a host-directed therapy for tuberculosis in mice and macaques [preprint]

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    In 2017, there were over 550,000 estimated new cases of multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB), emphasizing a need for new treatment strategies. Linezolid (LZD) is a potent antibiotic for antibiotic-resistant Gram-positive infections and is an effective treatment for TB. However, extended LZD use can lead to LZD-associated host toxicities, most commonly bone marrow suppression. LZD toxicities may be mediated by IL-1, a pathway important for early immunity during M. tuberculosis infection that later contributes to pathology. We hypothesized LZD efficacy could be enhanced by modulation of IL-1 pathway to reduce BM toxicity and TB associated-inflammation. We used two animal models of TB to test our hypothesis, mice and cynomolgus macaques. Antagonizing IL-1 in chronically-infected mice reduced lung neutrophil numbers and partially restored the erythroid progenitor populations that are depleted by LZD. In macaques, we found no conclusive evidence of BM suppression associated with LZD, indicating our treatment time may have been short enough to avoid the toxicities observed in humans. Though treatment was only 1 month, the majority of granulomas were sterilized with reduced inflammation (assessed by PET/CT) in animals treated with both LZD and IL-1 receptor antagonist (IL-1Rn). However, overall lung inflammation was significantly reduced in macaques treated with both IL-1Rn and LZD, compared to LZD alone. Importantly, IL-1Rn administration did not noticeably impair the host response against Mtb or LZD efficacy in either animal model. Together, our data support that inhibition of IL-1 in combination with LZD has potential to be an effective HDT for TB
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