712 research outputs found
An assessment of the welfare of non-human primates used in neuroscience research
The Animals (Scientific Procedures) Act 1986 governs the use of animals in scientific research in the UK. Embedded within this is a requirement to implement the 3Rs: replacement, reduction, and refinement; a key mechanism for minimising the pain, suffering, distress, and lasting harm of research models. To adhere fully to these principles, it is imperative to assess animal welfare. Non-human primates (NHP) human similarities make them both an essential biomedical research model and a species particularly vulnerable to welfare challenges. This thesis investigates non-invasive, objective methods of welfare assessment and applies them alongside neuroscience research to monitor the welfare of rhesus macaques (Macaca mulatta).
Accelerometers monitored changes in activity levels following general anaesthesia (GA) and revealed a decline in activity for 5.7 days following GA alone. Additionally, 2.6 days of activity decline were observed after surgery under GA, followed by an activity increase, suggesting post-operative behavioural change. Additionally, accelerometers were used to create a rule-based model for automated behavioural assessment. This model groups macaque activity into 5 species-typical behavioural categories with an overall 69% accuracy.
Physiological welfare parameters were assessed by detecting cortisol in faeces and hair. Faecal cortisol levels were significantly elevated for several days following GA, with a longer and more profound increase after surgery. Hair samples are a valuable measure of chronic stress and cumulative experience, facilitating longitudinal cortisol assessment without influence from transient stressors. Hair cortisol levels were significantly elevated post-surgery and, in some cases, following social disruption.
A customised, neck-based ECG was designed to monitor heart rate variability. The ECG was trialled on anaesthetised and restrained NHPs, dogs, and sheep. Proof of concept was achieved, with R-waves detectable in all species.
Overall, this thesis demonstrates how welfare and neuroscience research can be conducted in parallel for a better understanding of the life-time experience of animal models. This is an essential step towards implementing refinements and improving welfare, which may ultimately improve public perception and help to form the evidence-base required to inform and drive policy change
Using Hybrid Agent-Based Systems to Model Spatially-Influenced Retail Markets
One emerging area of agent-based modelling is retail markets; however, there are problems with modelling such systems. The vast size of such markets makes individual-level modelling, for example of customers, difficult and this is particularly true where the markets are spatially complex. There is an emerging recognition that the power of agent-based systems is enhanced when integrated with other AI-based and conventional approaches. The resulting hybrid models are powerful tools that combine the flexibility of the agent-based methodology with the strengths of more traditional modelling. Such combinations allow us to consider agent-based modelling of such large-scale and complex retail markets. In particular, this paper examines the application of a hybrid agent-based model to a retail petrol market. An agent model was constructed and experiments were conducted to determine whether the trends and patterns of the retail petrol market could be replicated. Consumer behaviour was incorporated by the inclusion of a spatial interaction (SI) model and a network component. The model is shown to reproduce the spatial patterns seen in the real market, as well as well known behaviours of the market such as the "rocket and feathers" effect. In addition the model was successful at predicting the long term profitability of individual retailers. The results show that agent-based modelling has the ability to improve on existing approaches to modelling retail markets.Agents, Spatial Interaction Model, Retail Markets, Networks
Page Ranking Systems: Axiomatisation and Experimentation
Ranking a set of objects based on the relationships between them is fundamental for use with search engines, e-commerce websites and in the field of bibliometrics. Two of the most prominent search ranking algorithms are PageRank and SALSA (Stochastic Approach to Link-Structure Analysis).
In this thesis, we further explore the connections between page ranking algorithms and the theory of social choice, providing a basis for theoretical assessment of a weighted version of PageRank and we create and assess a new page ranking al- gorithm, combining ideas from both PageRank and SALSA which we call Query- Independent SALSA.
We justify the use of weighted PageRank from a theoretical perspective by providing a set of axioms which characterize the algorithm. We provide a tighter bound for our derivation than that of Altman et al and show that each of our axioms are independent.
We describe a query-independent version of SALSA, using ideas from the PageRank algorithm and test this on a real-world subgraph of the web graph. We find that our new algorithm, Query-Independent Stochastic Approach to Link-Structure Analysis (QISALSA) slightly outperforms PageRank on two measures and under-performs on one measure. We suggest that the approach of combining aspects of both algo-rithms may be less eective than precomputational methods for query-dependent algorithms
Mechanisms of neurokinin₁ receptor action in the dorsal horn of the spinal cord
This study addressed the role of neurokinin] (NKi) receptors in nociceptive transmission and
their participation in a series of events involving glycine and NMDA receptor-mediated
effects on spinal neurones. Using an in vivo electrophysiology protocol utilising ionophoresis
and extracellular recording from laminae III-V dorsal horn neurones of anaesthetised rats,
the mechanisms of these interactions were assessed.
The functions of the inflammatory cytokine leukaemia inhibitory factor (LIF) were also
considered. Injury-induced alterations in the spinal expression pattern of this factor and the
consequences of these changes to neuropeptide and excitatory amino acid expression were
measured using in situ hybridisation.1. The involvement of NK] receptors in spinal pain transmission may be dependent upon
the duration and intensity of the nociceptive stimulus. Since activation of spinal NK]
receptors leads to increases in the concentration of glycine in the dorsal horn, the role of the
inhibitory glycine receptor as a regulator of NKj receptor function was investigated.
Ionophoretic application of GR82334, a selective NK] receptor antagonist did not alter
activity evoked by cutaneous applications of mustard oil. Flowever in the presence of the
glycine antagonists strychnine or phenylbenzene-co-phosphono- a-amino acid (PMBA),
GR82334 displayed inhibitory properties. Therefore inhibitory glycine receptors may mask
the contribution made by NK] receptors to nociceptive processing. This is discussed with
reference to the role of NK] receptors during brief nociceptive transmission.2. NK] receptors can contribute to the processing of sustained nociceptive stimuli by
modulating excitatory amino acid-mediated transmission, particularly through potentiation of
NMDA receptor activity. Experiments were carried out to investigate the possible role of the
glycine site of the NMDA receptor (GlyNMDA) and of protein kinase C (PKC) activation to
the NK]/NMDA interaction.Ionophoresis of the NMDA receptor agonist 1 -aminocyclobutane-m-1,3-dicarboxylic acid
(ACBD) produced a sustained increase in the firing rate of dorsal horn neurones that was
facilitated by the NK] agonist acetyl-[Arg6,Sar9,Met(02)11]-SP6-ii (Sar9-SP). GlyNMDA site
antagonists 2-carboxy-4,6-dichloro-(lH)-indole-3-propanoic acid (MDL 29951), 7-chloro-3-
(cyclopropylcarbonyl)-4-hydroxy-2(lH)-quinoline (L701,252), 5,7-dinitroquinaxoline-2,3-
dione (MNQX) and 7-chlorothiokynurenic acid (7-CTK) or PKC inhibitors, chelerythrine
and GF109203X significantly reduced this facilitation whilst having no effect on activity
driven by ACBD alone. Like the NK] receptor agonist, a selective GlyNMDA site agonist 1-
aminocyclopropanecarboxylic acid (ACPC) also caused facilitation of ACBD-evoked
activity and this was inhibited by the GlyNMDA site antagonist L701,252 in a similar manner.
These data suggest that NKi receptors facilitate NMDA receptor by potentiating the positive
influence of the GlyNMDA site. This may be bought about by the NKi receptor-induced
glycine release and/or by a PKC mediated increase in the sensitivity of the GlyNMDA site.
This demonstrates that co-transmitters released from fine primary afferent fibres may interact
postsynaptically to alter central hyperexcitability, particularly that associated with more
prolonged noxious events.3. LIF is a neuroactive cytokine that is associated with peripheral nerve injury. Using in situ
hybridisation, the present study has examined the distribution of LIF mRNA in the spinal
cord, normally or following peripheral inflammation or nerve injury and determined the
consequences of intrathecally applied LIF on spinal expression of NK, receptor and the high
affinity glutamate transporter, EAAT2.In control animals, dorsal horn expression of LIF was high in superficial laminae I-II with
only light expression in the deeper laminae III-V and in the ventral horn. Both peripheral
inflammation and neuropathy significantly increased levels of LIF mRNA in the dorsal horn
and this was most evident in the lateral parts of laminae I and II.
NKi and EAAT2 expression was normally associated with cells in laminae I-II, IV-V and
ventral horn motorneurones. Intrathecal LIF administration significantly increased this
expression for all three mRNAs and resulted in dense hybridisation throughout the dorsal
horn.These results show that LIF is normally expressed in the spinal cord in a specific laminar
pattern that increases dramatically following peripheral inflammation or nerve damage.
Furthermore, LIF upregulates the expression of NKi receptors and EAAT2 transporters
indicating that it may be a critical regulator of the central changes that occur following
peripheral injury.Interactions within the spinal cord may underlie the plasticity of the dorsal horn in sensory
processing. This has been discussed with reference to the regulation of short-term co¬
operation between NIG and NMDA receptors by glycine and to long-term modifications of
peptide and excitatory amino acid neurotransmission by altered LIF gene expression
Military Law - Service Discharge - Judicial Review of Discharge Classifications
In 1954 petitioners were discharged from the Army in form other than honorable. Petitioner Harmon had previously been questioned by Army officials regarding alleged Communist affiliations. Since most of the charges against him were based on conduct antedating his induction into the Army and since his military record had been excellent, petitioner Harmon was informed that he would not be discharged as disloyal or subversive pursuant to Army regulations, but would be retained in his then present grade, assigned nonsensitive duties, and given a discharge at the end of his career appropriate to the character of the service he had rendered. Issuance of Directive 5210.9 shortly thereafter by the Secretary of Defense, which applied to military personnel the criteria of the civilian security program, resulted in review of petitioner Harmon\u27s case and his discharge as undesirable. While the record is not clear, petitioner Abramowitz apparently was discharged as undesirable under similar circumstances. After exhausting administrative remedies, petitioners brought suit seeking a declaration that their discharges were void and an order that the discharges be changed to honorable. Concluding that it lacked jurisdiction to review the action, the district court entered summary judgment in favor of the Secretary of the Army, and the court of appeals affirmed. On certiorari to the United States Supreme Court, held, reversed, one justice dissenting. In a per curiam opinion the Court ruled that the district court had jurisdiction to determine whether the Secretary of the Army had exceeded his statutory authority in basing the discharge classification on conduct antedating induction, and petitioners had standing to bring this action. On the merits, the secretary may consider only a soldier\u27s military record; hence the secretary\u27s action was in excess of his statutory authority and the case should be remanded to the district court for relief to petitioners. Harmon v. Brucker, 355 U.S. 579 (1958)
Municipal Corporations - Contracts - Ratification and Estoppel in Contracts Made By Unauthorized Agent
Plaintiff\u27s infant daughter, admitted to Newark City Hospital as an emergency case, received hospitalization and medical treatment worth 100 for any subscriber-patient would constitute payment in full to the city. The city accepted the $100 check paid by the Plan as billed by the hospital for the care of the child. In order to facilitate settlement with the person whose alleged negligence had caused his daughter\u27s injuries, by removing the city\u27s hospital lien for the balance of the charges for treatment, plaintiff sued for a declaratory judgment absolving him of any liability to the city. The real contest having evolved between the city and the Plan, the trial court rendered judgment for the Plan ordering cancellation of the lien. On certification to the New Jersey Supreme Court, held, affirmed, one justice dissenting without opinion. Even assuming that the medical director was without authorization to consummate the agreement, the city is bound by its subsequent course of conduct which impliedly ratified the contract, and is also estopped to deny its validity. Johnson v. Hospital Service Plan of N.J., (N.J. 1957) 135 A. (2d) 483
Civil Procedure - Process - Immunity from Service of Nonresident Entering State to Discuss Settlement of a Dispute
Defendant, a resident of Idaho, leased a service station in Idaho from plaintiff, a Utah corporation. Plaintiff\u27s attorney travelled to Idaho to attempt settlement of difficulties which had arisen concerning the lease. When the Idaho negotiations failed, plaintiff invited defendant to make further attempts at settlement in Utah. Defendant accepted the proposal and, when the Utah negotiations proved unfruitful, defendant was served with process in Utah at plaintiff\u27s request. It was undisputed that defendant went to Utah solely to effect settlement, returning directly to Idaho after cessation of negotiations. On appeal from the trial court\u27s denial of defendant\u27s motion to quash service, held, reversed, one judge dissenting. Actual fraudulent intent in inducing a defendant to enter a state is not necessary to invalidate service of process on such defendant. When defendant was invited into the state to discuss settlement of a dispute and came for that sole purpose, he was not subject to service of civil process in the absence of notice by the party extending the invitation that he would be served with process if the attempted settlement failed. Western States Refining Co. v. Berry, (Utah 1957) 313 P. (2d) 480
Frontline Justice: The Evolution and Reform of Summary Trials in the Canadian Armed Forces by Pascal Lévesque
The security of Canada and the safety of its inhabitants depend on the readiness of the Armed Forces. To maintain this readiness, service members are subject to special disciplinary standards and penal processes that ordinary courts are ill-suited to handle. A separate military justice system—which exists parallel to the civilian criminal justice system—imposes these distinct standards and enforces swift, stern discipline
Building cities from slime mould, agents and quantum field theory
Managing the unprecedented growth of cities whilst ensuring that they are sustainable, healthy and equitable places to live, presents significant challenges. Our current thinking conceptualise cities as being driven by processes from the bottom-up, with an emphasis on the role that individual decisions and behaviour play. Multiagent systems, and agent-based modelling in particular, are ideal frameworks for the analysis of such systems. However, identifying the important drivers within an urban system, translating key behaviours from data into rules, quantifying uncertainty and running models in real time all present significant challenges. We discuss how innovations in a diverse range of fields are influencing empirical agent-based models, and how models designed for the simplest biological systems might transform the ways that we understand and manage real cities
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