Some observations of the vibrations of slender rotating shafts

March 1982Includes bibliographical references (page 29)The linear theory of a slender, initially bowed, rotating shaft is reviewed for both free and forced vibrations, and found to compare well with a simple experiment on such a shaft. The shaft behavior passing through the critical speed is described in detail, and the maximum bowed-out static deflection of the shaft was found dependent on the external damping and the initial bowing. The amplitude of the oscillatory deflections of the shaft due to gravity loads increased somewhat near the critical speed, but these increases were small compared to the large static deflection of the shaft. During rapid passage through the critical speed, low frequency whirling modes were excited transiently. At higher rotation speeds, the second critical speed was observed, and also the first mode was excited subharmonically and appeared as a backward whirl mode relative to the rotating shaft

Do high-risk medicines alerts influence practice?

Background: Medicine-related adverse events are prevalent, costly and mostly preventable. The High Risk Medicines Working Party (Victoria) developed and distributed three highrisk medicines alerts &ndash; wrong route of administration of oral medicines, subcutaneous insulin and unfractionated heparin &ndash; and accompanying audit tools in 2008 and 2009.Aims: To determine the impact of the three high-risk medicines alerts on Victorian health services; to assess the clinical relevance and utility of the audit tools; to identify barriers to implementing recommendations; and to obtain feedback and suggestions for future alert topics.Method: A cross-sectional survey was undertaken from 6 to 31 July 2009 using an online questionnaire. The questionnaire was distributed to 90 metropolitan, regional and rural public health services in Victoria and approximately 200 members of the Quality Use of Medicines Network (Victoria).Results: Most of the 90 respondents were pharmacists (53%) and nurses (31%). 53 (59%) respondents reported making changes as a result of receiving the high-risk medicines alerts &ndash; 21 (40%) concerned the wrong route of administration, 12 (23%) subcutaneous insulin and 7 (13%) unfractionated heparin. Barriers to implementation included time constraints, inadequate staff and resources, excessive paperwork and competing priorities. A minority of respondents indicated some alerts were not relevant to small rural services. Suggestions forimproving the audit tools included making them less labour intensive, enabling electronic responses and ensuring their distribution is coordinated with other medicine-related tools.Conclusion: High-risk medicines alerts and the accompanying audit tools facilitated change but there were some barriers to their implementation, such as time and resource constraints. Not all alerts and audit tools were relevant to all health services.<br /

Glycolytic and Non-glycolytic Functions of Mycobacterium tuberculosis Fructose-1,6-bisphosphate Aldolase, an Essential Enzyme Produced by Replicating and Non-replicating Bacilli

The search for antituberculosis drugs active against persistent bacilli has led to our interest in metallodependent class II fructose- 1,6-bisphosphate aldolase (FBA-tb), a key enzyme of gluconeogenesis absent from mammalian cells. Knock-out experiments at the fba-tb locus indicated that this gene is required for the growth of Mycobacterium tuberculosis on gluconeogenetic substrates and in glucose-containing medium. Surface labeling and enzymatic activity measurements revealed that this enzyme was exported to the cell surface of M. tuberculosis and produced under various axenic growth conditions including oxygen depletion and hence by non-replicating bacilli. Importantly, FBA-tb was also produced in vivo in the lungs of infected guinea pigs and mice. FBA-tb bound human plasmin(ogen) and protected FBA-tb-bound plasmin from regulation by α 2-antiplasmin, suggestive of an involvement of this enzyme in host/pathogen interactions. The crystal structures of FBA-tb in the native form and in complex with a hydroxamate substrate analog were determined to 2.35- and 1.9-Å resolution, respectively. Whereas inhibitor attachment had no effect on the plasminogen binding activity of FBA-tb, it competed with the natural substrate of the enzyme, fructose 1,6-bisphosphate, and substantiated a previously unknown reaction mechanism associated with metallodependent aldolases involving recruitment of the catalytic zinc ion by the substrate upon active site binding. Altogether, our results highlight the potential of FBA-tb as a novel therapeutic target against both replicating and non-replicating bacilli.Fil: Santangelo, María de la Paz. State University of Colorado - Fort Collins; Estados Unidos. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gest, Petra M.. State University of Colorado - Fort Collins; Estados UnidosFil: Guerin, Marcelo E.. Universidad del País Vasco; EspañaFil: Coinçon, Mathieu. University of Montreal; CanadáFil: Pham, Ha. State University of Colorado - Fort Collins; Estados UnidosFil: Ryan, Gavin. State University of Colorado - Fort Collins; Estados UnidosFil: Puckett, Susan E.. Cornell University; Estados UnidosFil: Spencer, John S.. State University of Colorado - Fort Collins; Estados UnidosFil: Gonzalez Juarrero, Mercedes. State University of Colorado - Fort Collins; Estados UnidosFil: Daher, Racha. Universite de Paris XI. Institut de Chimie Moléculaire et des Matériaux d'Orsay; FranciaFil: Lenaerts, Anne J.. State University of Colorado - Fort Collins; Estados UnidosFil: Schnappinger, Dirk. Cornell University; Estados UnidosFil: Therisod, Michel. Universite de Paris XI. Institut de Chimie Moléculaire et des Matériaux d'Orsay; FranciaFil: Ehrt, Sabine. Cornell University; Estados UnidosFil: Sygusch, Jurgen. University of Montreal; CanadáFil: Jackson, Mary. State University of Colorado - Fort Collins; Estados Unido

Primary Lung Dendritic Cell Cultures to Assess Efficacy of Spectinamide-1599 Against Intracellular Mycobacterium tuberculosis

There is an urgent need to treat tuberculosis (TB) quickly, effectively and without side effects. Mycobacterium tuberculosis (Mtb), the causative organism of TB, can survive for long periods of time within macrophages and dendritic cells and these intracellular bacilli are difficult to eliminate with current drug regimens. It is well established that Mtb responds differentially to drug treatment depending on its extracellular and intracellular location and replicative state. In this study, we isolated and cultured lung derived dendritic cells to be used as a screening system for drug efficacy against intracellular mycobacteria. Using mono- or combination drug treatments, we studied the action of spectinamide-1599 and pyrazinamide (antibiotics targeting slow-growing bacilli) in killing bacilli located within lung derived dendritic cells. Furthermore, because IFN-γ is an essential cytokine produced in response to Mtb infection and present during TB chemotherapy, we also assessed the efficacy of these drugs in the presence and absence of IFN-γ. Our results demonstrated that monotherapy with either spectinamide-1599 or pyrazinamide can reduce the intracellular bacterial burden by more than 99.9%. Even more impressive is that when TB infected lung derived dendritic cells are treated with spectinamide-1599 and pyrazinamide in combination with IFN-γ a strong synergistic effect was observed, which reduced the intracellular burden below the limit of detection. We concluded that IFN-γ activation of lung derived dendritic cells is essential for synergy between spectinamide-1599 and pyrazinamide

'Ain't it a Ripping Night': Alcoholism and the Legacies of Empire in Salman Rushdie's Midnight's Children.

In the era of decolonisation that followed the Second World War, various authors sought to engage with India and the Empire’s past anew throughout their novels, identifying medicine and illness as key parts of Imperial authority and colonial experience. Salman Rushdie’s approach to the Raj in Midnight’s Children (1981) focused on the broad sweep of colonial life, juxtaposing the political and the personal. This article argues that Rushdie explores the history of colonial India by employing alcohol and alcoholism as lenses through which to explore the cultural, political and medical legacies of Empire. Through analysis of Midnight’s Children as well as a range of medical sources related to alcohol and inebriation, it will illustrate how drinking is central to Rushdie’s approach to secular and religious identities in newly independent India, as well as a means of satirising and undermining the supposed benefit that Empire presented to India and Indians