Pain-induced distress and its alleviation using butorphanol after ovariohysterectomy of bitches : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Clinical Science at Massey University

Content removed due to copyright restrictions: Appendix D: Fox, S. M., Mellor, D. J., Firth, E. C., Hodge, H., & Lawoko, C. R. O. (1994). Changes in plasma cortisol concentrations before, during and after analgesia, anaesthesia and anaesthesia plus ovariohysterectomy in bitches. Research in Veterinary Science, 57(1), 110-118Ovariohysterectomy is the most frequently performed surgical procedure in companion animal veterinary practice. It is regarded by many as being quite benign; however, questioning of that premise prompted this investigation. There were no satisfactory data available to determine how benign or noxious this procedure might be, yet this query is of considerable clinical importance. There exists the further vagary of assessment for pain-relief measures, whether associated with surgery or injury. Great value would lie in establishing a routinely available criterion for pain assessment. The present work was therefore undertaken to examine this area of clinical relevance and to establish a model for further study of postsurgical pain-induced distress and its alleviation. Most previous studies in this area had omitted Satisfactory control or baseline animals in that the anaesthetic or analgesic treatments were rarely, if ever, applied to animals that were not also subjected to surgery. Accordingly, the following nine treatments were made: Control, Anaesthesia, Analgesia, Analgesia plus Anaesthesia, Anaesthesia plus Analgesia at intubation, Anaesthesia plus Analgesia at extubation, Anaesthesia plus Surgery, Analgesia plus Anaesthesia plus Surgery, and Anaesthesia plus Surgery plus Analgesia. These were designed so that, with the inclusion of surgery, all the major variations in treatment were independently examined. The parameters used to evaluate the extent of pain-induced distress were changes in plasma cortisol concentration and behaviour. Cortisol is a well established physiological parameter of distress, and behaviour is a cue used by most clinicians. Butorphanol was selected as the analgesic of choice in this investigation based upon its wide use, margin of safety, across-species efficacy, versatility in route of administration, long shelf-life, competitive pricing, and freedom from the requirement for documented use by controlling authorities. The following conclusions were drawn from the cortisol data. Psychogenic stimuli in conscious control bitches were responsible for a transient rise in Cortisol concentrations not seen in anaesthetised dogs which were unconscious. Butorphanol elicited a large cortisol response, attributable to dysphoria, which was again prevented by anaesthetic administration. As judged by cortisol response there was no apparent benefit of preoperative butorphanol administered intravenously 30 minutes prior to or at the time of anaesthetic induction. However, there was an earlier decline in cortisol concentration when butorphanol was given at extubation and this was interpreted to reflect an earlier decrease in postoperative pain-induced distress. The study commenced with 166 behavioural parameters (interactive and noninteractive) from which it was found that 76 occurred at insufficient frequencies as to be valuable as indices of postoperative pain-induced distress. Among the discriminating behaviours, noninteractive parameters characteristic of the nonanalgesic surgery group were drawing the rear limbs up into a pike position, lip licking, cage circling, incision licking, vomition, and 'look back' (flank gazing), while the only characteristic interactive behaviour was an extended neck. Vocalisation was associated with the dysphoria of analgesia rather than pain-induced distress. The major contributions of this research were: (1) establishing ovariohysterectomy as a model of pain-induced distress to examine the benefit of various pain-control strategies, (2) elimination of a number of commonly seen behaviours and identification of useful behaviours for identifying pain-induced distress, (3) clarification of the responses to control and 'base-comparison' treatments with regard to both cortisol and behavioural responses, (4) identification of specific pain-induced behaviours, (5) derivation of a mathematical function representing a numerical expression for the clinical intuition of the subjective impression of pain experience in dogs, and (6) identifying behaviours that can be used by the clinician to indicate the presence or absence of pain-induced distress following ovariohysterectomy. Results suggest that the ovariohysterectomy is associated with sufficient pain-induced distress to warrant the associated use of analgesia

Strength of Cold-Formed Steel Jamb Stud-To-Track Connections

The North American Standard for Cold-Formed Steel Framing - Wall Stud Design, AISI S211-07, provides a design expression for web crippling at the end reaction of the single stud-to-track connection. The subject of this report is an experimental investigation that was carried out at the University of Waterloo to establish a similar design expression for multiple jamb stud members. It is anticipated that the AISI Committee on Framing Standards will consider the results of this study in the development of future standards and the Cold-Formed Steel Engineers Institute in the development of design aids. The American Iron and Steel Institute and Steel Framing Alliance wish to express their appreciation to the researchers and project sponsors for this report

Nowhere to Run; Nowhere to Hide: The Reality of Being a Law Library Director in Times of Great Opportunity and Significant Challenges

This is an edited version of remarks presented at \u27Nowhere to Run, Nowhere to Hide\u27: The Reality of Being a Law Library Director in Times of Great Opportunity and Significant Challenges, January 5, 2015, at the Association of American Law Schools Annual Meeting, Washington, D.C

Altered Gene Expression in Blood and Sputum in COPD Frequent Exacerbators in the ECLIPSE Cohort

Patients with chronic obstructive pulmonary disease (COPD) who are defined as frequent exacerbators suffer with 2 or more exacerbations every year. The molecular mechanisms responsible for this phenotype are poorly understood. We investigated gene expression profile patterns associated with frequent exacerbations in sputum and blood cells in a well-characterised cohort. Samples from subjects from the ECLIPSE COPD cohort were used; sputum and blood samples from 138 subjects were used for microarray gene expression analysis, while blood samples from 438 subjects were used for polymerase chain reaction (PCR) testing. Using microarray, 150 genes were differentially expressed in blood (>±1.5 fold change, p≤0.01) between frequent compared to non-exacerbators. In sputum cells, only 6 genes were differentially expressed. The differentially regulated genes in blood included downregulation of those involved in lymphocyte signalling and upregulation of pro-apoptotic signalling genes. Multivariate analysis of the microarray data followed by confirmatory PCR analysis identified 3 genes that predicted frequent exacerbations; B3GNT, LAF4 and ARHGEF10. The sensitivity and specificity of these 3 genes to predict the frequent exacerbator phenotype was 88% and 33% respectively. There are alterations in systemic immune function associated with frequent exacerbations; down-regulation of lymphocyte function and a shift towards pro-apoptosis mechanisms are apparent in patients with frequent exacerbations

Short Duration Waveforms Recorded Extracellularly from Freely Moving Rats are Representative of Axonal Activity

While extracellular somatic action potentials from freely moving rats have been well characterized, axonal activity has not. We report direct extracellular tetrode recordings of putative axons whose principal feature is a short duration waveform (SDW) with an average peak-trough length less than 179 μs. While SDW recordings using tetrodes have previously been treated as questionable or classified as cells, we hypothesize that they are representative of axonal activity. These waveforms have significantly shorter duration than somatic action potentials, are triphasic and are therefore similar to classic descriptions of microelectrode recordings in white matter and of in vitro action potential propagation along axons. We describe SDWs recorded from pure white-matter tracts including the alveus and corpus callosum. Recordings of several SDWs in the alveus exhibit grid-like firing patterns suggesting these axons carry spatial information from entorhinal cortical neurons. Finally, we locally injected the GABAA agonist Muscimol into layer CA1 of the hippocampus while simultaneously recording somatic activity and SDWs on the same tetrodes. The persistent activity of SDWs during Muscimol inactivation of somatic action potentials indicates that SDWs are representative of action potential propagation along axons projecting from more distal somata. This characterization is important as it illustrates the dangers of exclusively using spike duration as the sole determinant of unit type, particularly in the case of interneurons whose peak-trough times overlap with SDWs. It may also allow future studies to explore how axonal projections from disparate brain regions integrate spatial information in the hippocampus, and provide a basis for studying the effects of pharmaceutical agents on signal transmission in axons, and ultimately to aid in defining the potential role of axons in cognition

The future of human nature: a symposium on the promises and challenges of the revolutions in genomics and computer science, April 10, 11, and 12, 2003

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's Symposium on the Promises and Challenges of the Revolutions in Genomics and Computer Science took place during April 10, 11, and 12, 2003. Co-organized by Charles DeLisi and Kenneth Lewes; sponsored by Boston University, the Frederick S. Pardee Center for the Study of the Longer-Range Future.This conference focused on scientific and technological advances in genetics, computer science, and their convergence during the next 35 to 250 years. In particular, it focused on directed evolution, the futures it allows, the shape of society in those futures, and the robustness of human nature against technological change at the level of individuals, groups, and societies. It is taken as a premise that biotechnology and computer science will mature and will reinforce one another. During the period of interest, human cloning, germ-line genetic engineering, and an array of reproductive technologies will become feasible and safe. Early in this period, we can reasonably expect the processing power of a laptop computer to exceed the collective processing power of every human brain on the planet; later in the period human/machine interfaces will begin to emerge. Whether such technologies will take hold is not known. But if they do, human evolution is likely to proceed at a greatly accelerated rate; human nature as we know it may change markedly, if it does not disappear altogether, and new intelligent species may well be created

Right ventricular outflow tract velocity time integral-to-pulmonary artery systolic pressure ratio: a non-invasive metric of pulmonary arterial compliance differs across the spectrum of pulmonary hypertension.

Pulmonary arterial compliance (PAC), invasively assessed by the ratio of stroke volume to pulmonary arterial (PA) pulse pressure, is a sensitive marker of right ventricular (RV)-PA coupling that differs across the spectrum of pulmonary hypertension (PH) and is predictive of outcomes. We assessed whether the echocardiographically derived ratio of RV outflow tract velocity time integral to PA systolic pressure (RVOT-VTI/PASP) (a) correlates with invasive PAC, (b) discriminates heart failure with preserved ejection-associated PH (HFpEF-PH) from pulmonary arterial hypertension (PAH), and (c) is associated with functional capacity. We performed a retrospective cohort study of patients with PAH (n = 70) and HFpEF-PH (n = 86), which was further dichotomized by diastolic pressure gradient (DPG) into isolated post-capillary PH (DPG \u3c 7 mmHg; Ipc-PH, n = 54), and combined post- and pre-capillary PH (DPG ≥ 7 mm Hg; Cpc-PH, n = 32). Of the 156 patients, 146 had measurable RVOT-VTI or PASP and were included in further analysis. RVOT-VTI/PASP correlated with invasive PAC overall (ρ = 0.61, P \u3c 0.001) and for the PAH (ρ = 0.38, P = 0.002) and HFpEF-PH (ρ = 0.63, P \u3c 0.001) groups individually. RVOT-VTI/PASP differed significantly across the PH spectrum (PAH: 0.13 [0.010-0.25] vs. Cpc-PH: 0.20 [0.12-0.25] vs. Ipc-PH: 0.35 [0.22-0.44]; P \u3c 0.001), distinguished HFpEF-PH from PAH (AUC = 0.72, 95% CI = 0.63-0.81) and Cpc-PH from Ipc-PH (AUC = 0.78, 95% CI = 0.68-0.88), and remained independently predictive of 6-min walk distance after multivariate analysis (standardized β-coefficient = 27.7, 95% CI = 9.2-46.3; P = 0.004). Echocardiographic RVOT-VTI/PASP is a novel non-invasive metric of PAC that differs across the spectrum of PH. It distinguishes the degree of pre-capillary disease within HFpEF-PH and is predictive of functional capacity

Effect of topical imiquimod as primary treatment for lentigo maligna: the LIMIT-1 study

Background: Topical imiquimod is sometimes used for lentigo maligna (LM) in situ melanoma instead of surgery, but frequency of cure is uncertain. Pathological complete regression (pCR) is a logical surrogate marker for cure after imiquimod, although residual LM and atypical melanocytic hyperplasia may not be reliably distinguished. A trial comparing imiquimod vs. surgery might be justified by a high imiquimod pCR rate.  Objectives: Primary: to estimate the pCR rate for LM following imiquimod. Secondary: to assess the accuracy of prediction of pCR, using clinical complete regression (cCR) plus negative post-treatment biopsies, tolerability, resource use, patients' preferences and induced melanoma immunity.  Methods: This was a single-arm phase II trial of 60 imiquimod applications over 12 weeks for LM then radical resection. A pCR rate ≥ 25 out of 33 would reliably discriminate between pCR rates < 60% and ≥ 85%. Clinical response was assessed and biopsies taken after imiquimod. Patients recorded adverse events in diaries. Patient preference was measured after surgery using a standard gamble tool.  Results: The pCR rate was 10 of 27 (37%, 95% confidence interval 19-58%). The rate of cCR plus negative biopsies was 12 of 28, of whom seven of 11 had pCR on subsequent surgery. The median dose intensity was 86·7%. Of the 16 surveyed patients, eight preferred primary imiquimod over surgery if the cure rate for imiquimod was 80%, and four of 16 if it was ≤ 40%.  Conclusions: The pCR rate was insufficient to justify phase III investigation of imiquimod vs.  Surgery: Clinical complete response and negative targeted biopsies left uncertainty regarding pathological clearance. Some patients would trade less aggressive treatment of LM against efficacy

The future of human nature: a symposium on the promises and challenges of the revolutions in genomics and computer science, April 10, 11, and 12, 2003

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's Symposium on the Promises and Challenges of the Revolutions in Genomics and Computer Science took place during April 10, 11, and 12, 2003. Co-organized by Charles DeLisi and Kenneth Lewes; sponsored by Boston University, the Frederick S. Pardee Center for the Study of the Longer-Range Future.This conference focused on scientific and technological advances in genetics, computer science, and their convergence during the next 35 to 250 years. In particular, it focused on directed evolution, the futures it allows, the shape of society in those futures, and the robustness of human nature against technological change at the level of individuals, groups, and societies. It is taken as a premise that biotechnology and computer science will mature and will reinforce one another. During the period of interest, human cloning, germ-line genetic engineering, and an array of reproductive technologies will become feasible and safe. Early in this period, we can reasonably expect the processing power of a laptop computer to exceed the collective processing power of every human brain on the planet; later in the period human/machine interfaces will begin to emerge. Whether such technologies will take hold is not known. But if they do, human evolution is likely to proceed at a greatly accelerated rate; human nature as we know it may change markedly, if it does not disappear altogether, and new intelligent species may well be created