The harmful impact, mechanism and potential treatment of exertional and non-exertional hyperthermia

This publication-based thesis aims to add to the existing knowledge surrounding three consecutive aspects of hyperthermia: (1) the threats to human health from hyperthermia, (2) the putative mechanisms underlying the systemic damage, and (3) potential treatments. The six primary research papers forming the basis of the thesis have been published in peer-reviewed journals, using a variety of methodologies, including field studies, lab-based studies and systematic reviews. Prolonged exertion, especially if causing hyperthermia, and passive heat illness, for example in heat waves or due to adverse effects of certain medications, are common causes of multi-organ failure and death. Similarities between the various hyperthermic states suggest that the raised temperature rather than the underlying cause in itself is predominant. Two of these effects, acute kidney injury (AKI) and electrolyte disturbancesin exertional heat illness(EHI), are examined further in papers one and two. The deleterious effects of hyperthermia may include the heat rendering the intestinal tract more permeable, allowing bacteria and toxins from the intestinal tract to enter the systemic circulation. Endurance exercise also appears to stimulate a systemic inflammatory response and increase intestinal permeability. Hyperthermia, especially when associated with exertion, is further characterised in papers three and four, which found that the intestinal permeability was higher after exercise-induced hyperthermia than passive hyperthermia or exercise, respectively, alone, suggesting synergistic effects. There may therefore be the possibility of reducing the systemic damage caused by the exertional and non-exertional hyperthermia by reducing the inflammatory response or the bacterial load in the circulation. Papers five and six are systematic reviews suggesting that in animals both drugs appear to be beneficial in reducing the harm and risk of death from hyperthermia. The work presented here allows the possibility for development of future work on reducing the inflammatory response and intestinal toxin absorption, for example with steroids or antibiotics, to reduce the risk of death and disability after heatstroke and hyperthermia

Book Reviews

Book reviews by Charles S. Desmond, James F. Thornburg, Edward J. Gray, Walter H. E. Jaeger, and Thomas L. Shaffer

Knowledge practices in design: The role of visual representations as 'epistemic objects'

We use a detailed study of the knowledge work around visual representations to draw attention to the multidimensional nature of `objects'. Objects are variously described in the literatures as relatively stable or in flux; as abstract or concrete; and as used within or across practices. We clarify these dimensions, drawing on and extending the literature on boundary objects, and connecting it with work on epistemic and technical objects. In particular, we highlight the epistemic role of objects, using our observations of knowledge work on an architectural design project to show how, in this setting, visual representations are characterized by a `lack' or incompleteness that precipitates unfolding. The conceptual design of a building involves a wide range of technical, social and aesthetic forms of knowledge that need to be developed and aligned. We explore how visual representations are used, and how these are meaningful to different stakeholders, eliciting their distinct contributions. As the project evolves and the drawings change, new issues and needs for knowledge work arise. These objects have an `unfolding ontology' and are constantly in flux, rather than fully formed. We discuss the implications for wider understandings of objects in organizations and for how knowledge work is achieved in practice

Duplex Ultrasonography to Predict Internal Carotid Artery Stenoses Exceeding 50% and 70% as Defined by NASCET: The Need for Multiple Criteria

Carotid duplex scanning is being used more frequently as the sole preoperative diagnostic imaging modality for patients considered candidates for carotid endarterectomy. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) has demonstrated the benefit of surgical treatment in patients with carotid stenoses exceeding 70%. The purpose of this study was to determine duplex criteria that accurately predict carotid stenoses exceeding 50% and 70% as defined by NASCET arteriographic criteria. One hundred forty-one patients (264 carotid arteries) considered surgical candidates were prospectively studied over a 2-year period by use of both duplex scanning and digital subtraction cerebral arteriography. Carotid artery stenosis was determined by a single radiologist using NASCET arteriographic criteria. Peak systolic velocity (PSV) and enddiastolic velocity (EDV) were measured in the internal carotid (ICA) and common carotid (CCA) arteries by use of duplex scanning. ICA/CCA velocity ratios were calculated for PSV and EDV. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated. PSVICA/CCA provided the highest sensitivity, and EDVICA the highest specificity in this study. Arteriographic stenoses exceeding 50% and 70% were reliably predicted with use of these duplex criteria. It is concluded that duplex criteria can predict carotid stenoses exceeding 50% and 70% as defined by NASCET arteriographic criteria. These criteria should be independently validated by other vascular laboratories.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68440/2/10.1177_153857449903300508.pd

Cytotoxicity models of Huntington's disease and relevance of hormetic mechanisms: A critical assessment of experimental approaches and strategies.

Abstract This paper assesses in vivo cytotoxicity models of Huntington's disease (HD). Nearly 150 agents were found to be moderately to highly effective in mitigating the pathological sequelae of cytotoxic induction of HD features in multiple rodent models. Typically, rodents are treated with a prospective HD-protective agent before, during, or after the application of a chemical or transgenic process for inducing histopathological and behavioral symptoms of HD. Although transgenic and knockout rodent models (1) display relatively high construct and face validity, and (2) are ever more routinely employed to mimic genetic-to-phenotypic expression of HD features, toxicant models are also often employed, and have served as valuable test beds for the elucidation of biochemical processes and discovery of therapeutic targets in HD. Literature searches of the toxicant HD rodent models yielded nearly 150 agents that were moderately to highly effective in mitigating pathological sequelae in multiple mouse and rat HD models. Experimental models, study designs, and exposure protocols (e.g., pre- and post-conditioning) used in testing these agents were assessed, including dosing strategies, endpoints, and dose-response features. Hormetic-like biphasic dose responses, chemoprotective mechanisms, and the translational relevance of the preclinical studies and their therapeutic implications are critically analyzed in the present report. Notably, not one of the 150 agents that successfully delayed onset and progression of HD in the experimental models has been successfully translated to the treatment of humans in a clinical setting. Potential reasons for these translational failures are (1) the inadequacy of dose-response analyses and subsequent lack of useful dosing data; (2) effective rodent doses that are too high for safe human application; (3) key differences between the experimental models and humans in pharmacokinetic/pharmacodynamic features, ages and routes of agent administration; (4) lack of robust pharmacokinetic, mechanistic or systematic approaches to probe novel treatment strategies; and (5) inadequacies of the chemically induced HD model in rats to mimic accurately the complex genetic and developmental origin and progression of HD in humans. These deficiencies need to be urgently addressed if pharmaceutical agents for the treatment of HD are going to be successfully developed in experimental models and translated with fidelity to the clinic

Job choice and post decision dissonance

The job choice and post decision attitudes and behavior of 431 accounting students were studied. Data on the attractiveness of working for different firms was shown to be a good predictor of both the job application and the job choice behavior of the individuals. Data collected after the job choice decision was made showed that the chosen firms increased in attractiveness after choice and the rejected firms decreased. After one year of employment, the subjects rated all firms lower in attractiveness than they had before they applied for jobs. It was concluded that attitudes toward firm attractiveness determine job choice behavior and that job choice behavior influences post employment attitudes about firm attractiveness.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22131/1/0000560.pd

Developing Mn-doped lead sulfide quantum dots for MRI labels

Magnetic interactions of Mn2+ions in lead sulfide (PbS) nanocrystals with protons in water are probed by NMR and MRI. A thin layer of capping molecules enables free solvent diffusion to the nanocrystal surface resulting in a decrease of proton relaxation times. Magnetic resonance imaging of neuronal cell pellets exposed to (PbMn)S at non-toxic concentrations demonstrates their prospects as MRI-labels

Aerosol meteorology of Maritime Continent for the 2012 7SEAS southwest monsoon intensive study - Part 2: Philippine receptor observations of fine-scale aerosol behavior

Abstract. The largest 7 Southeast Asian Studies (7SEAS) operations period within the Maritime Continent (MC) occurred in the August–September 2012 biomass burning season. Data included were observations aboard the M/Y Vasco, dispatched to the Palawan Archipelago and Sulu Sea of the Philippines for September 2012. At these locations, the Vasco observed MC smoke and pollution entering the southwest monsoon (SWM) monsoonal trough. Here we describe the research cruise findings and the finer-scale aerosol meteorology of this convectively active region. This 2012 cruise complemented a 2-week cruise in 2011 and was generally consistent with previous findings in terms of how smoke emission and transport related to monsoonal flows, tropical cyclones (TC), and the covariance between smoke transport events and the atmosphere's thermodynamic structure. Biomass burning plumes were usually mixed with significant amounts of anthropogenic pollution. Also key to aerosol behavior were squall lines and cold pools propagating across the South China Sea (SCS) and scavenging aerosol particles in their path. However, the 2012 cruise showed much higher modulation in aerosol frequency than its 2011 counterpart. Whereas in 2011 large synoptic-scale aerosol events transported high concentrations of smoke into the Philippines over days, in 2012 measured aerosol events exhibited a much shorter-term variation, sometimes only 3–12 h. Strong monsoonal flow reversals were also experienced in 2012. Nucleation events in cleaner and polluted conditions, as well as in urban plumes, were observed. Perhaps most interestingly, several cases of squall lines preceding major aerosol events were observed, as opposed to 2011 observations where these lines largely scavenged aerosol particles from the marine boundary layer. Combined, these observations indicate pockets of high and low particle counts that are not uncommon in the region. These perturbations are difficult to observe by satellite and very difficult to model. Indeed, the Navy Aerosol Analysis and Prediction System (NAAPS) simulations captured longer period aerosol events quite well but largely failed to capture the timing of high-frequency phenomena. Ultimately, the research findings of these cruises demonstrate the real world challenges of satellite-based missions, significant aerosol life cycle questions such as those the future Aerosol/Clouds/Ecosystems (ACE) will investigate, and the importance of small-scale phenomena such as sea breezes, squall lines, and nucleation events embedded within SWM patterns in dominating aerosol life cycle and potential relationships to clouds

A MULTIDISCIPLINARY APPROACH TO INFORMATION SYSTEMS RESEARCH

Information Systems Working Papers Serie