A Randomized Cross-Over Trial Comparing the Effect of Intramuscular Versus Intranasal Naloxone Reversal of Intravenous Fentanyl on Odor Detection in Working Dogs

Fentanyl is a potent opioid used clinically as a pain medication and anesthetic but has recently seen a sharp rise as an illicit street drug. The potency of fentanyl means mucous membrane exposure to a small amount of the drug can expose first responders, including working canines, to accidental overdose. Naloxone, a fast-acting opioid antagonist administered intranasally (IN) or intramuscularly (IM) is currently carried by emergency personnel in the case of accidental exposure in both humans and canines. Despite the fact that law enforcement relies heavily on the olfactory abilities of canine officers, the effects of fentanyl exposure and subsequent reversal by naloxone on the olfactory performance of canines are unknown. In a block-randomized, crossover trial, we tested the effects of IN and IM naloxone on the abilities of working dogs to recognize the odor of Universal Detection Calibrant (UDC) prior to, and two, 24, and 48 h after intravenous fentanyl sedation and naloxone reversal. No detectable influence of fentanyl sedation and naloxone reversal on the dogs’ olfactory abilities was detected. We also found no difference in olfactory abilities when dogs received IN or IM naloxone. Together, results suggest no evidence that exposure to intravenous fentanyl followed by naloxone reversal impairs canine olfactory ability under these conditions

Systematic Cu-63 NQR studies of the stripe phase in La(1.6-x)Nd(0.4)Sr(x)CuO(4) for 0.07 <= x <= 0.25

We demonstrate that the integrated intensity of Cu-63 nuclear quadrupole resonance (NQR) in La(1.6-x)Nd(0.4)Sr(x)CuO(4) decreases dramatically below the charge-stripe ordering temperature T(charge). Comparison with neutron and X-ray scattering indicates that the wipeout fraction F(T) (i.e. the missing fraction of the integrated intensity of the NQR signal) represents the charge-stripe order parameter. The systematic study reveals bulk charge-stripe order throughout the superconducting region 0.07 <= x <= 0.25. As a function of the reduced temperature t = T/T(charge), the temperature dependence of F(t) is sharpest for the hole concentration x=1/8, indicating that x=1/8 is the optimum concentration for stripe formation.Comment: 10 pages of text and captions, 11 figures in postscript. Final version, with new data in Fig.

Reconstructing the deep-branching relationships of the papilionoid legumes

Resolving the phylogenetic relationships of the deep nodes of papilionoid legumes (Papilionoideae) is essential to understanding the evolutionary history and diversification of this economically and ecologically important legume subfamily. The early-branching papilionoids include mostly Neotropical trees traditionally circumscribed in the tribes Sophoreae and Swartzieae. They are more highly diverse in floral morphology than other groups of Papilionoideae. For many years, phylogenetic analyses of the Papilionoideae could not clearly resolve the relation- ships of the early-branching lineages due to limited sampling. In the eight years since the publication of Legumes of the World, we have seen an extraordinary wealth of new molecular data for the study of Papilionoideae phylogeny, enabling increasingly greater resolution and many surprises. This study draws on recent molecular phylogenetic studies and a new comprehensive Bayesian phylogenetic analysis of 668 plastid matK sequences. The present matK phylogeny resolves the deep-branching relationships of the papilionoids with increased support for many clades, and suggests that taxonomic realignments of some genera and of numerous tribes are necessary. The potentially earliest-branching papilionoids fall within an ADA clade, which includes the recircumscribed monophyletic tribes Angylocalyceae, Dipterygeae, and Amburanae. The genera Aldina and Amphimas represent two of the nine main but as yet unresolved lineages comprising the large 50-kb inversion clade. The quinolizidine-alkaloid-accumulating Genistoid s.l. clade is expanded to include Dermatophyllum and a strongly supported and newly circumscribed tribe Ormosieae. Sophoreae and Swartzieae are dramatically reorganized so as to comprise mono-phyletic groups within the Core Genistoid clade and outside the 50-kb inversion clade, respectively. Acosmium is excluded from the Genistoids s.l. and strongly resolved within the newly circumscribed tribe Dalbergieae. By providing a better resolved phylogeny of the earliest-branching papilionoids, this study, in combination with other recent evidence, will lead to a more stable phylogenetic classification of the Papilionoideae.Web of Scienc

GiardiaDB and TrichDB : integrated genomic resources for the eukaryotic protist pathogens Giardia lamblia and Trichomonas vaginalis

© 2008 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License. The definitive version was published in Nucleic Acids Research 37 (2009): D526-D530, doi:10.1093/nar/gkn631.GiardiaDB (http://GiardiaDB.org) and TrichDB (http://TrichDB.org) house the genome databases for Giardia lamblia and Trichomonas vaginalis, respectively, and represent the latest additions to the EuPathDB (http://EuPathDB.org) family of functional genomic databases. GiardiaDB and TrichDB employ the same framework as other EuPathDB sites (CryptoDB, PlasmoDB and ToxoDB), supporting fully integrated and searchable databases. Genomic-scale data available via these resources may be queried based on BLAST searches, annotation keywords and gene ID searches, GO terms, sequence motifs and other protein characteristics. Functional queries may also be formulated, based on transcript and protein expression data from a variety of platforms. Phylogenetic relationships may also be interrogated. The ability to combine the results from independent queries, and to store queries and query results for future use facilitates complex, genome-wide mining of functional genomic data.Federal funds from the National Institute of Allergy and Infectious Diseases; Department of Health and Human Services, National Institutes of Health (HHSN266200400037C). Funding for open access charge: National Institutes of Health (HHSN266200400037C)

Variation in dermcidin expression in a range of primary human tumours and in hypoxic/oxidatively stressed human cell lines.

Dermcidin acts as a survival factor in a variety of cancer cell lines under hypoxia or oxidative stress. The aim of this study was to evaluate dermcidin expression in cell lines following simulation of tumour microenvironmental conditions and in a range of primary tumours. Tumour tissues were collected from patients with oesophageal (28 samples), gastric (20), pancreatic (five), bile duct (one) and prostatic (52) carcinomas as well as 30 benign tissue samples, for assessment of dermcidin mRNA levels using real-time PCR. Dermcidin expression was assessed in prostatic and pancreatic cancer cell lines, with and without induction of hypoxia or oxidative stress. Dermcidin mRNA expression was very low or absent in both unstressed and stressed prostate cell lines. None of the primary prostate tissue, benign or malignant, expressed dermcidin mRNA. Only two (4%) of the gastro-oesophageal cancer samples expressed moderate quantities of dermcidin mRNA. However, three (60%) of the pancreatic cancer samples and the single cholangiocarcinoma specimen had moderate/high levels of dermcidin expression. Of the two pancreatic cancer cell lines, one expressed dermcidin moderately but neither showed a response to hypoxia or oxidative stress. Expression of dermcidin in human primary tumours appears highly variable and is not induced substantially by hypoxia/oxidative stress in cell line model systems. The relationship of these findings to dermcidin protein levels and cell survival remains to be determined

Cu-63 NQR Measurement of Stripe Order Parameter in La(2-x)Sr(x)CuO(4)

We demonstrate that one can measure the charge-stripe order parameter in the hole-doped CuO(2) planes of La(1.875)Ba(0.125)CuO(4), La(1.48)Nd(0.4)Sr(0.12)CuO(4) and La(1.68)Eu(0.2)Sr(0.12)CuO(4) utilizing the wipeout effects of Cu-63 NQR. Application of the same approach to La(2-x)Sr(x)CuO(4) reveals the presence of similar stripe order for the entire underdoped superconducting regime 1/16 < x < 1/8.Comment: 4 pages in RevTex, 3 figures in postscript. Minor changes have been made to increase readability. This manuscript has been accepted for publication in Physical Review Letter

Mutability and Importance of a Hypermutable Cell Subpopulation that Produces Stress-Induced Mutants in Escherichia coli

In bacterial, yeast, and human cells, stress-induced mutation mechanisms are induced in growth-limiting environments and produce non-adaptive and adaptive mutations. These mechanisms may accelerate evolution specifically when cells are maladapted to their environments, i.e., when they are are stressed. One mechanism of stress-induced mutagenesis in Escherichia coli occurs by error-prone DNA double-strand break (DSB) repair. This mechanism was linked previously to a differentiated subpopulation of cells with a transiently elevated mutation rate, a hypermutable cell subpopulation (HMS). The HMS could be important, producing essentially all stress-induced mutants. Alternatively, the HMS was proposed to produce only a minority of stress-induced mutants, i.e., it was proposed to be peripheral. We characterize three aspects of the HMS. First, using improved mutation-detection methods, we estimate the number of mutations per genome of HMS-derived cells and find that it is compatible with fitness after the HMS state. This implies that these mutants are not necessarily an evolutionary dead end, and could contribute to adaptive evolution. Second, we show that stress-induced Lac+ mutants, with and without evidence of descent from the HMS, have similar Lac+ mutation sequences. This provides evidence that HMS-descended and most stress-induced mutants form via a common mechanism. Third, mutation-stimulating DSBs introduced via I-SceI endonuclease in vivo do not promote Lac+ mutation independently of the HMS. This and the previous finding support the hypothesis that the HMS underlies most stress-induced mutants, not just a minority of them, i.e., it is important. We consider a model in which HMS differentiation is controlled by stress responses. Differentiation of an HMS potentially limits the risks of mutagenesis in cell clones

Research in progress: report on the ICAIL 2017 doctoral consortium

This paper arose out of the 2017 international conference on AI and law doctoral consortium. There were five students who presented their Ph.D. work, and each of them has contributed a section to this paper. The paper offers a view of what topics are currently engaging students, and shows the diversity of their interests and influences

Imitators of exercise-induced bronchoconstriction

Exercise-induced bronchoconstriction (EIB) is described by transient narrowing of the airways after exercise. It occurs in approximately 10% of the general population, while athletes may show a higher prevalence, especially in cold weather and ice rink athletes. Diagnosis of EIB is often made on the basis of self-reported symptoms without objective lung function tests, however, the presence of EIB can not be accurately determined on the basis of symptoms and may be under-, over-, or misdiagnosed. The goal of this review is to describe other clinical entities that mimic asthma or EIB symptoms and can be confused with EIB

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders