Canine Olfactory Thresholds to Amyl Acetate in a Biomedical Detection Scenario

Dogs’ abilities to respond to concentrations of odorant molecules are generally deemed superior to electronic sensors. This sensitivity has been used traditionally in many areas; but is a more recent innovation within the medical field. As a bio-detection sensor for human diseases such as cancer and infections, dogs often need to detect volatile organic compounds in bodily fluids such as urine and blood. Although the limits of olfactory sensitivity in dogs have been studied since the 1960s, there is a gap in our knowledge concerning these limits in relation to the concentration of odorants presented in a fluid phase. Therefore the aim of this study was to estimate olfactory detection thresholds to an inert substance, amyl acetate presented in a liquid phase. Ten dogs were trained in a “Go/No go” single scent-detection task using an eight-choice carousel apparatus. They were trained to respond to the presence of solutions of amyl acetate diluted to varying degrees in mineral oil by sitting in front of the positive sample, and not responding to the seven other control samples. Training and testing took place in an indoor room with the same handler throughout using a food reward. After 30 weeks of training, using a forward chaining technique, dogs were tested for their sensitivity. The handler did not assist the dog during the search and was blind to the concentration of amyl acetate tested and the position of the target in the carousel. The global olfactory threshold trend for each dog was estimated by fitting a least-squares logistic curve to the association between the proportion of true positives and amyl acetate concentration. Results show an olfactory detection threshold for fluid mixtures ranging from 40 parts per billion to 1.5 parts per trillion. There was considerable inter-dog difference in sensitivity, even though all dogs were trained in the same way and worked without the assistance of the handler. This variation highlights factors to be considered in future work assessing olfactory detection performance by dogs

A Switch in Hepatic Cortisol Metabolism across the Spectrum of Non Alcoholic Fatty Liver Disease

Context: Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of liver disease ranging from reversible hepatic steatosis, to non alcoholic steato-hepatitis (NASH) and cirrhosis. The potential role of glucocorticoids (GC) in the pathogenesis of NAFLD is highlighted in patients with GC excess, Cushing's syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol (F) from inactive cortisone (E) (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1), or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR). Objective and Methods: In vitro studies defined 11β-HSD1 expression in normal and NASH liver samples. We then characterised hepatic cortisol metabolism in 16 patients with histologically proven NAFLD compared to 32 obese controls using gas chromatographic analysis of 24 hour urine collection and plasma cortisol generation profile following oral cortisone. Results: In patients with steatosis 5αR activity was increased, with a decrease in hepatic 11β-HSD1 activity. Total cortisol metabolites were increased in this group consistent with increased GC production rate. In contrast, in patients with NASH, 11β-HSD1 activity was increased both in comparison to patients with steatosis, and controls. Endorsing these findings, 11β-HSD1 mRNA and immunostaining was markedly increased in NASH patients in peri septal hepatocytes and within CD68 positive macrophages within inflamed cirrhotic septa. Conclusion: Patients with hepatic steatosis have increased clearance and decreased hepatic regeneration of cortisol and we propose that this may represent a protective mechanism to decrease local GC availability to preserve hepatic metabolic phenotype. With progression to NASH, increased 11β-HSD1 activity and consequent cortisol regeneration may serve to limit hepatic inflammation

Expert considerations and consensus for using dogs to detect human SARS-CoV-2-infections

Funding Information: This Open Access publication was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 491094227 “Open Access Publication Funding” and the University of Veterinary Medicine Hannover, Foundation.Peer reviewe

The global pharmacy workforce: a systematic review of the literature

The importance of health workforce provision has gained significance and is now considered one of the most pressing issues worldwide, across all health professions. Against this background, the objectives of the work presented here were to systematically explore and identify contemporary issues surrounding expansion of the global pharmacy workforce in order to assist the International Pharmaceutical Federation working group on the workforce

Has Motivational Interviewing fallen into its own Premature Focus Trap?

Since the initial conception of the behaviour change method Motivational Interviewing, there has been a shift evident in epistemological, methodological and practical applications, from an inductive, process and practitioner-focussed approach to that which is more deductive, research-outcome, and confirmatory-focussed. This paper highlights the conceptual and practical problems of adopting this approach, including the consequences of assessing the what (deductive outcome-focussed) at the expense of the how (inductively process-focussed). We encourage a return to an inductive, practitioner and client-focussed MI approach and propose the use of Computer Assisted Qualitative Data Analysis Systems such as NVivo in research initiatives to support this aim

Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

Virally suppressed HIV-positive individuals on combination antiretroviral therapy who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality. The increased mortality was seen across different patient groups and for all causes of deat

Using Qualitative Evidence in Decision Making for Health and Social Interventions: An Approach to Assess Confidence in Findings from Qualitative Evidence Syntheses (GRADE-CERQual)

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Public Library of Science via the DOI in this record.Simon Lewin and colleagues present a methodology for increasing transparency and confidence in qualitative research synthesis.This work was supported by funding from the Department of Reproductive Health and Research, WHO (www.who.int/reproductivehealth/about_us/en/) and Norad (Norwegian Agency for Development Cooperation: www.norad.no) to the Norwegian Knowledge Centre for the Health Services. Additional funding for several of the pilot reviews was provided by the Alliance for Health Policy and Systems Research (www.who.int/alliance-hpsr/en/). We also received funding for elements of this work through the Cochrane supported "Methodological Investigation of Cochrane reviews of Complex Interventions" (MICCI) project (www.cochrane.org). SL is supported by funding from the South African Medical Research Council (www.mrc.ac.za). The funders had no role in study design, data collection and analysis, preparation of the manuscript or the decision to publish

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant