Geodesic flow on the ellipsoid with equal semi-axes

The equations for the geodesic flow on the ellipsoid are well known, and were first solved by Jacobi in 1838 by separating the variables of the Hamilton–Jacobi equation. In 1979 Moser showed that the equations for the geodesic flow on the general ellipsoid with distinct semi-axes are Liouville-integrable, and described a set of integrals which weren't known classically. These integrals break down in the case of coinciding semi-axes. After reviewing the properties of the geodesic flow on the three-dimensional ellipsoid with distinct semi-axes, the three-dimensional ellipsoid with the two middle semi-axes being equal, corresponding to a Hamiltonian invariant under rotations, is investigated, using the tools of singular reduction and invariant theory. The system is Liouville-integrable and thus the invariant manifolds corresponding to regular points of the energy momentum map are 3-dimensional tori. An analysis of the critical points of the energy momentum map gives the bifurcation diagram. The fibres of the critical values of the energy momentum map are found, and an analysis is carried out of the action variables. The obstruction to the existence of single valued globally smooth action variables is monodromy. [Continues.

Asymmetric addition reactions using chiral diamine derived catalysts

This thesis details the use of chiral diamine derived catalysts in asymmetric addition reactions. Three separate projects are outlined within. The first project involved the investigation of dibenz[c,e]azepinium salt 113 as a catalyst for the aldol reaction. The catalyst was synthesised in 4 steps from commercially available 1R,2R-diaminocyclohexane in 74% overall yield. It was found to be an efficient catalyst in the aldol reaction of cyclic ketones with a range of aromatic aldehydes, giving high yields, diastereo- and enantioselectivities. This catalyst was also found to be effective when acyclic ketones were used, in which case the major diastereoisomer produced was no longer an anti-aldol but a the syn-aldol. A catalytic cycle for these reactions is proposed, with the stereochemical outcome of these reactions being further investigated by computational calculations. The second project investigated the use of chiral primary amine catalysts in the conjugate addition of N-heterocycles to α,β-unsaturated ketones. It was found that commercially available 1R,2R-diaminocyclohexane 114 was an efficient and enantioselective catalyst for the addition of pyrazoles to α,β-unsaturated ketones. Through comparison with the performance of related catalyst structures we propose a catalytic cycle in which 114 forms bonds with both the α,β-unsaturated ketone and the incoming pyrazole. Alternative chiral amines derived from camphor sulfonic acid were investigated as catalysts for the conjugate addition reaction; these proved to be relatively poor catalysts giving the product with a low enantiomeric excess. Finally, an investigation into intramolecular N-conjugate additions was performed. We found that 9-epi-9-amino-9-deoxyquinine derived squaramide 355 was a highly enantioselective catalyst for the intramolecular cyclisation of sulfonamides to α,β-unsaturated ketones. Best results were seen with α,β-unsaturated ketones conjugated to an aryl group, however squaramide 355 also proved to be an enantioselective catalyst for the cyclisation of methyl ketone and ester conjugated alkenes. In the latter two cases higher temperatures and catalyst loadings were required. In conjunction with molecular modelling studies we propose a catalytic cycle that accounts for the observed stereochemistry

Detecting heat stress in dairy cattle using neck-mounted activity collars

Collar based activity sensors are in common use as a means of detecting oestrus to optimise farm fertility and hence productivity. More recently the same acceleration-derived signals have been processed to detect the time spent ruminating and eating which together give an insight into animal welfare. Here the use of neck-mounted accelerometers to provide a quantifiable measure of the time period that an individual animal exhibits signs of heat stress is reported. Heat stress has a significant impact on both animal welfare and productivity. Cattle studied during elevated temperatures were found to exhibit signs of exaggerated breathing motions, an indicator of heat stress, for 8 hours on average per day. This exceeds the time that cattle spend feeding and is similar to daily rumination times which could impact on both animal welfare and production. No similar cases were recorded on the cooler conditions of a Scottish winter. The approach offers a cost effective measure of heat stress and a potential tool to quantify its impact more generally

Review of diagnostic testing of mastitis

[Abstract not available

Systolic blood pressure reduction during the first 24 h in acute heart failure admission: friend or foe?

Aims: Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes. Methods and results: We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last time-point available (72 h), using linear regression, and with 30- and 180-day outcomes, using Cox regression, in 1257 patients in the VERITAS study. After multivariable adjustment for baseline SBP, greater SBP decrease at 24 h from randomization was associated with greater creatinine increase at 72 h and greater risk for 30-day all-cause death, worsening heart failure (HF) or HF readmission. The hazard ratio (HR) for each 1 mmHg decrease in SBP at 24 h for 30-day death, worsening HF or HF rehospitalization was 1.01 [95% confidence interval (CI) 1.00–1.02; P = 0.021]. Similarly, the HR for each 1 mmHg decrease in SBP at 24 h for 180-day all-cause mortality was 1.01 (95% CI 1.00–1.03; P = 0.038). The associations between SBP decrease and outcomes did not differ by tezosentan treatment group, although tezosentan treatment was associated with a greater SBP decrease at 24 h. Conclusions: In the current post hoc analysis, SBP decrease during the first 24 h was associated with increased renal impairment and adverse outcomes at 30 and 180 days. Caution, with special attention to blood pressure monitoring, should be exercised when vasodilating agents are given to AHF patients

Predictors and associations with outcomes of length of hospital stay in patients with acute heart failure: results from VERITAS

Background: The length of hospital stay (LOS) is important in patients admitted for acute heart failure (AHF) because it prolongs an unpleasant experience for the patients and adds substantially to health care costs. Methods and Results: We examined the association between LOS and baseline characteristics, 10-day post-discharge HF readmission, and 90-day post-discharge mortality in 1347 patients with AHF enrolled in the VERITAS program. Longer LOS was associated with greater HF severity and disease burden at baseline; however, most of the variability of LOS could not be explained by these factors. LOS was associated with a higher HF risk of both HF readmission (odds ratio for 1-day increase: 1.08; 95% confidence interval [CI] 1.01–1.16; P = .019) and 90-day mortality (hazard ratio for 1-day increase: 1.05; 95% CI 1.02–1.07; P < .001), although these associations are partially explained by concurrent end-organ damage and worsening heart failure during the first days of admission. Conclusions: In patients who have been admitted for AHF, longer length of hospital stay is associated with a higher rate of short-term mortality. Clinical Trial Registration: VERITAS-1 and -2: Clinicaltrials.gov identifiers NCT00525707 and NCT00524433

Classification of cattle behaviour using convolutional neural networks

The monitoring of cattle behaviour through sensor systems is gaining importance in the improvement of animal health, fertility and management of large herds. Commercial farms commonly implement accelerometer-based systems to monitor the time an animal spends ruminating, eating and overall activity which informs farmers on the health and fertility status of individual cattle. Ill or injured cattle feed and ruminate less, so tracking the duration and frequency of these states provide key indicators of animal health. Activity is used as a metric for the detection of oestrus (heat) which promotes more efficient fertilisation of dairy and beef cattle, reducing operating costs and increasing profits for farmers. The aim of the study was to determine the feasibility of enhancing the accuracy of estimating multiple classifications derived from acceleration-based activity collars can through Convolutional Neural Networks (CNN). CNN models are typically used to classify objects within images, but have been demonstrated to be effective at classifying time-series data across different domains. To evaluate their effectiveness for cattle behaviours classifications, acceleration data was collected from 18 cows across 3 farms using neck-mounted collars which provided 3-axis acceleration values at 10Hz sampling frequency. Each cow was equipped with pressure sensor halters which provided ground truth data of the animal behavioural state, also at 10Hz sampling frequency. The ground truth from the halter allowed the CNN model to be trained to predict a number of key cattle behaviours. The model was then tested on separate data to assess performance. The CNN was able to classify the 3 activity states (rumination, eating and other) with an overall F1 score of 82% compared to reported collar classifications with an overall F1 score of 72%

Rolofylline, an adenosine A1−receptor antagonist, in acute heart failure

Background: Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1−receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure. Methods: We conducted a multicenter, double-blind, placebo-controlled trial involving patients hospitalized for acute heart failure with impaired renal function. Within 24 hours after presentation, 2033 patients were randomly assigned, in a 2:1 ratio, to receive daily intravenous rolofylline (30 mg) or placebo for up to 3 days. The primary end point was treatment success, treatment failure, or no change in the patient’s clinical condition; this end point was defined according to survival, heart-failure status, and changes in renal function. Secondary end points were the post-treatment development of persistent renal impairment and the 60-day rate of death or readmission for cardiovascular or renal causes. Results: Rolofylline, as compared with placebo, did not provide a benefit with respect to the primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P=0.35). Persistent renal impairment developed in 15.0% of patients in the rolofylline group and in 13.7% of patients in the placebo group (P=0.44). By 60 days, death or readmission for cardiovascular or renal causes had occurred in similar proportions of patients assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P=0.86). Adverse-event rates were similar overall; however, only patients in the rolofylline group had seizures, a known potential adverse effect of A1-receptor antagonists. Conclusions: Rolofylline did not have a favorable effect with respect to the primary clinical composite end point, nor did it improve renal function or 60-day outcomes. It does not show promise in the treatment of acute heart failure with renal dysfunction. (Funded by NovaCardia, a subsidiary of Merck; ClinicalTrials.gov numbers, NCT00328692 and NCT00354458.