Ross Bowden

The applicability of electrical impedance tomography (EIT) in birds is unknown. This study aimed to evaluate the use of EIT in anaesthetised chickens in four recumbency positions. Four adult Hyline chickens were anaesthetised with isoflurane in oxygen, and intubated endotracheally for computed tomography (CT). A rubber belt was placed around the coelom caudal to the shoulder joint. A chicken-specific finite element (FE) model, which is essential to generate anatomically accurate functional EIT images for analysis, was constructed based on the CT images obtained at the belt level. Ten additional chickens were anaesthetised with the same protocol. An EIT electrode belt was placed at the same location. The chickens were breathing spontaneously and positioned in dorsal, ventral, right and left lateral recumbency in a randomised order. For each recumbency, raw EIT data were collected over 2 min after 13 min of stabilisation. The data were reconstructed into functional EIT images. EIT variables including tidal impedance variation (TIV), centre of ventilation right to left (CoVRL) and ventral to dorsal (CoVVD), right to left (RL) ratio, impedance change (ΔZ) and eight regional impedance changes including the dorsal, central-dorsal, central-ventral and ventral regions of the right and left regions were analysed. Four breathing patterns (BrP) were observed and categorised based on the expiratory curve. A linear mixed model was used to compare EIT variables between recumbencies. Fisher's exact test was used to compare the frequencies of breathing patterns for each recumbency. The ΔZ observed was synchronous to ventilation, and represented tidal volume of the cranial air sacs as confirmed by CT. Significant differences were found in CoVVD and regional impedance changes between dorsal and ventral recumbencies (P < 0.05), and in CoVRL, RL ratio and regional impedance changes between right and left recumbencies (P < 0.05), which suggested a tendency for the distribution of ventilation to shift towards non-dependent air sacs. No differences were found for TIV and respiratory rate between recumbencies. Recumbency had a significant effect on the frequencies of each of the four BrPs (P = 0.001). EIT can monitor the magnitude and distribution of ventilation of the cranial air sacs in different recumbencies in anaesthetised chickens.

Studies assessing animal pain in veterinary research are often performed primarily for the benefit of animals. Frequently, the goal of these studies is to determine whether the analgesic effect of a novel treatment is clinically meaningful, and therefore has the capacity to improve the welfare of treated animals. To determine the treatment effect of a potential analgesic, control groups are necessary to allow comparison. There are negative control groups (where pain is unattenuated) and positive control groups (where pain is attenuated). Arising out of animal welfare concerns, there is growing reluctance to use negative control groups in pain studies. But for studies where pain is experimentally induced, the absence of a negative control group removes the opportunity to demonstrate that the study methods could differentiate a positive control intervention from doing nothing at all. For studies that are controlled by a single comparison group, the capacity to distinguish treatment effects from experimental noise is more difficult; especially considering that pain studies often involve small sample sizes, small and variable treatment effects, systematic error and use pain assessment measures that are unreliable. Due to these limitations, and with a focus on farm animals, we argue that many pain studies would be enhanced by the simultaneous inclusion of positive and negative control groups. This would help provide study-specific definitions of pain and pain attenuation, thereby permitting more reliable estimates of treatment effects. Adoption of our suggested refinements could improve animal welfare outcomes for millions of animals globally.

Doxapram is marketed as a respiratory stimulant and is used by some veterinarians to help with neonatal apnoea, especially in puppies delivered by caesarean. There is a lack of consensus as to whether the drug is effective and data on its safety are limited. Doxapram was compared to placebo (saline) in newborn puppies in a randomized, double-blinded clinical trial using two outcome measures: 7-day mortality rate and repeated APGAR score measurements. Higher APGAR scores have been positively correlated with survival and other health outcomes in newborns. Puppies were delivered by caesarean and a baseline APGAR score was measured. This was immediately followed by a randomly allocated intralingual injection of either doxapram or isotonic saline (of the same volume). Injection volumes were determined by the weight of the puppy and each injection was administered within a minute of birth. The mean dose of doxapram administered was 10.65 mg/kg. APGAR scores were measured again at 2, 5, 10 and 20 min. One hundred and seventy-one puppies from 45 elective caesareans were recruited into this study. Five out of 85 puppies died after receiving saline and 7 out of 86 died after receiving doxapram. Adjusting for the baseline APGAR score, the age of the mother and whether the puppy was a brachycephalic breed, there was insufficient evidence to conclude a difference in the odds of 7-day survival for puppies that received doxapram compared to those that received saline (p = .634). Adjusting for the baseline APGAR score, the weight of the mother, the litter size, the mother's parity number, the weight of the puppy and whether the puppy was a brachycephalic breed, there was insufficient evidence to conclude a difference in the probability of a puppy having an APGAR score of ten (the maximum APGAR score) between those that received doxapram compared to those that received saline (p = .631). Being a brachycephalic breed was not associated with an increased odds of 7-day mortality (p = .156) but the effect of the baseline APGAR score on the probability of having an APGAR score of ten was higher for brachycephalic than non-brachycephalic breeds (p = .01). There was insufficient evidence that intralingual doxapram provided an advantage (or disadvantage) compared to intralingual saline when used routinely in puppies delivered by elective caesarean and that were not apnoeic.

The goals of this study were to determine whether mice would adapt to a low-calorie flavored water gel as their sole source of hydration and whether the addition of acetaminophen, tramadol, meloxicam, or buprenorphine to the gel would affect their intake. Water and gel intakes were measured during a 4-phase study, each of which lasted 1 wk: phase 1, standard water bottle only; phase 2, standard water bottle and a separate tube containing water gel; phase 3, water gel only; and phase 4, water gel containing an analgesic drug. Water consumption, corrected for body mass, was not different between male and female mice when water was available (phases 1 and 2). However, the total consumption of water and water gel was higher for females than males during phase 2, and female mice consumed more gel than males during phase 3. When male and female data were combined, total corrected water intake was not different among the first 3 phases of the study. Gel intake did not change significantly after the addition of acetaminophen, meloxicam, buprenorphine or tramadol as compared with untreated water gel. These data suggest that drugs presented in the low-calorie flavored water gel may be a viable alternative to injection or gavage for the administration of analgesic drugs.

Introduction/Aim: Mycobacterium avium complex pulmonary disease (MAC‐PD) rates are increasing worldwide, prompting a greater need for effective and well‐tolerated therapeutic options. First‐line therapy is standardized across international guidelines. However, there is a paucity of research into the significant proportion of patients who fail first‐line therapy, and in those with recurrent disease. This study aims to characterize patients with MAC‐PD who are being considered for second‐line therapy. Methods: An observational study was performed on patients aged 18 years or older with MAC‐PD who were seen in the Royal Perth Hospital respiratory outpatient clinic from 2010 onwards. Patients who failed or were intolerant of first‐line therapy, and those with recurrent disease, defined as early (<18 months) or late (≥18 months) were included. Patient demographics, microbiology, radiology and treatment regimens were obtained from hospital medical records. Results: Data on 26 patients have been collected so far. Mean age was 68.8(range 45‐91) years, 16(61.5%) female. At the time of the initial diagnosis of MAC‐PD, 10(38%) were current or former smokers, and 8(31%) had co‐morbid lung disease. 21(81%) presented with nodular bronchiectasis. 16(62%) were treated with standardized first‐line therapy, mean treatment time 15.8 (range 0‐27) months. 12(46%) patients developed late recurrence of MAD‐PD, 2(8%) early recurrence, 4(15%) were intolerant of first‐line therapy and 8(31%) failed first‐line treatment. 13(50%) patients commenced second‐line therapy with curative intent, 6(23%) on suppressive therapy and 7(27%) were not given therapy. Conclusion: Patients with MAC‐PD who are being considered for second‐line therapy represent a diverse population of patients with differing disease phenotypes. Therefore, further data is required to better understand the population, in order to design suitable interventional clinical trials. Additional patient data is currently being collected for this study. Following this, the plan is to assess second‐line therapy outcome data.

This thesis explores Joint Autoregressive Moving-Average (JARMA) models for independent replicated univariate time series with common ARMA coefficients whose innovations variances are either in common, unique to each series or vary with the series mean. The constraint of a common variance is also applied to vector ARMA processes. Interleaving is shown to represent replicated series with a common variance as one series from the same process. The time and frequency domain properties of interleaved replicated stationary and invertible processes are established. As an aid to identification, hypothesis tests for comparing series are reviewed and several new tests are presented and explored along with a graphical method for identification. Unconditional maximum likelihood estimates of the parameters of various JARMA processes are derived using the methods of joint likelihood and interleaving. The properties of the estimators are examined using simulation and asymptotics. Finally JARMA models are fitted to over 60 years of daily univariate and bivariate temperature data to estimate differences in level due to location and climate change.

Long-term historical daily temperatures are used in electricity forecasting to simulate the probability distribution of future demand but can be affected by changes in recording site and climate. This paper presents a method of adjusting for the effect of these changes on daily maximum and minimum temperatures. The adjustment technique accommodates the autocorrelated and bivariate nature of the temperature data which has not previously been taken into account. The data are from Perth, Western Australia, the main electricity demand centre for the South-West of Western Australia. The statistical modelling involves a multivariate extension of the univariate time series ‘interleaving method’, which allows fully efficient simultaneous estimation of the parameters of replicated Vector Autoregressive Moving Average processes. Temperatures at the most recent weather recording location in Perth are shown to be significantly lower compared to previous sites. There is also evidence of long-term heating due to climate change especially for minimum temperatures.

Long-term historical daily temperatures are used in electricity forecasting to simulate the probability distribution of future demand but can be affected by changes in recording site and climate. This paper presents a method of adjusting for the effect of these changes on daily maximum and minimum temperatures. The adjustment technique accommodates the autocorrelated and bivariate nature of the temperature data which has not previously been employed. The data is from Perth, Western Australia, the main electricity demand centre for the South-West (of Western Australia) Interconnected System. The statistical modelling involves a multivariate extension of the univariate time series “interleaving method”, which allows fully efficient simultaneous estimation of the parameters of replicated VARMA processes. Temperatures at the most recent weather recording location in Perth are shown to be significantly lower compared to previous sites. There is also evidence of long-term heating due to climate change especially for minimum temperatures.