The Utility of Content-Relativism

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Avatars as Proxies

Acknowledgements I am grateful to the referees for this journal who provided very helpful suggestions that greatly improved the paper.Peer reviewedPublisher PD

The No-Proposition View of Vagueness

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Nostalgia reconsidered

Open Access via the Jisc Wiley Agreement ACKNOWLEDGEMENTS I am grateful to the participants of the workshop Time in Aesthetic Experience at the University of Lancaster for helpful feedback on an earlier version of this paper. I am also grateful to an anonymous referee for this journal for insightful and helpful comments on the submission.Peer reviewedPublisher PD

Contextualism and the principle of tolerance

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Trusting Social Robots

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A fictional dualism model of social robots

Publisher Copyright: © 2021, The Author(s).Peer reviewedPublisher PD

The health system burden of chronic disease care: an estimation of provider costs of selected chronic diseases in Uganda.

OBJECTIVE: To explore the chronic disease services in Uganda: their level of utilisation, the total service costs and unit costs per visit. METHODS: Full financial and economic cost data were collected from 12 facilities in two districts, from the provider's perspective. A combination of ingredients-based and step-down allocation costing approaches was used. The diseases under study were diabetes, hypertension, chronic obstructive pulmonary disease (COPD), epilepsy and HIV infection. Data were collected through a review of facility records, direct observation and structured interviews with health workers. RESULTS: Provision of chronic care services was concentrated at higher-level facilities. Excluding drugs, the total costs for NCD care fell below 2% of total facility costs. Unit costs per visit varied widely, both across different levels of the health system, and between facilities of the same level. This variability was driven by differences in clinical and drug prescribing practices. CONCLUSION: Most patients reported directly to higher-level facilities, bypassing nearby peripheral facilities. NCD services in Uganda are underfunded particularly at peripheral facilities. There is a need to estimate the budget impact of improving NCD care and to standardise treatment guidelines

The geographic problem in cephalopod genomics

Publications describing genomes of various cephalopod species have recently proliferated. Some papers have involved large geographic distances between the collection locality of sequenced specimens and the type locality of the presumed species. However, cryptic species have been demonstrated in many cephalopods. Therefore, even if the sequenced specimen is very similar morphologically to the species in question, the likelihood that it is a member of the species in question decreases with increasing distance from the type locality. An associated problem is that many publications do not provide information adequate to determine the source locality for the genomic sequence. We reviewed a decade of literature on mitochondrial genomes of cephalopods and found a total of 43 publications containing 48 species within 23 genera. Of the 48 species, only 17 could be evaluated for our geographic question. Distances between sampling locality and type locality of the named species ranged from 0 nautical miles (sampled at type locality) to half-way around the world. Where data were present for distance calculation, the average for the 17 species was 3785 km (2044 nmi)

The use of plasma aldosterone and urinary sodium to potassium ratio as translatable quantitative biomarkers of mineralocorticoid receptor antagonism

<p>Abstract</p> <p>Background</p> <p>Accumulating evidence supports the role of the mineralocorticoid receptor (MR) in the pathogenesis of diabetic nephropathy. These findings have generated renewed interest in novel MR antagonists with improved selectivity against other nuclear hormone receptors and a potentially reduced risk of hyperkalemia. Characterization of novel MR antagonists warrants establishing translatable biomarkers of activity at the MR receptor. We assessed the translatability of urinary sodium to potassium ratio (Na⁺/K⁺) and plasma aldosterone as biomarkers of MR antagonism using eplerenone (Inspra^®), a commercially available MR antagonist. Further we utilized these biomarkers to demonstrate antagonism of MR by PF-03882845, a novel compound.</p> <p>Methods</p> <p>The effect of eplerenone and PF-03882845 on urinary Na⁺/K⁺and plasma aldosterone were characterized in Sprague-Dawley rats and spontaneously hypertensive rats (SHR). Additionally, the effect of eplerenone on these biomarkers was determined in healthy volunteers. Drug exposure-response data were modeled to evaluate the translatability of these biomarkers from rats to humans.</p> <p>Results</p> <p>In Sprague-Dawley rats, eplerenone elicited a rapid effect on urinary Na⁺/K⁺yielding an EC₅₀that was within 5-fold of the functional <it>in vitro </it>IC₅₀. More importantly, the effect of eplerenone on urinary Na⁺/K⁺in healthy volunteers yielded an EC₅₀that was within 2-fold of the EC₅₀generated in Sprague-Dawley rats. Similarly, the potency of PF-03882845 in elevating urinary Na⁺/K⁺in Sprague-Dawley rats was within 3-fold of its <it>in vitro </it>functional potency. The effect of MR antagonism on urinary Na⁺/K⁺was not sustained chronically; thus we studied the effect of the compounds on plasma aldosterone following chronic dosing in SHR. Modeling of drug exposure-response data for both eplerenone and PF-03882845 yielded EC₅₀values that were within 2-fold of that estimated from modeling of drug exposure with changes in urinary sodium and potassium excretion. Importantly, similar unbound concentrations of eplerenone in humans and SHR rats yielded the same magnitude of elevations in aldosterone, indicating a good translatability from rat to human.</p> <p>Conclusions</p> <p>Urinary Na⁺/K⁺and plasma aldosterone appear to be translatable biomarkers of MR antagonism following administration of single or multiple doses of compound, respectively.</p> <p>Trial Registration</p> <p>For clinical study reference EE3-96-02-004, this study was completed in 1996 and falls out scope for disclosure requirements.</p> <p>Clinical study reference A6141115: <url>http://clinicaltrials.gov</url>, <url>http://NIHclinicaltrails.gov</url>; NCTID: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00990223">NCT00990223</a></p