The effects of environmental stress on the physiology of growth in rainbow trout, Salmo gairderi Richardson

There is little doubt that both mammalian and teleost growth hormones can accelerate growth and increase food conversion efficiency in all commonly-reared species of salmonid fish. In those vertebrates that have been closely studied (predominantly mammals), the pituitary hormone somatotropin (GH or growth hormone) is a prime determinant of somatic growth. The hormone stimulates protein biosynthesis and tissue growth, enhances lipid utilization and lipid release from the adipose tissues (a protein-sparing effect) and suppresses the peripheral utilization of glucose. The present study is a prerequisite for future work on growth hormone physiology in salmonids and should contribute to our understanding of the mechanisms of growth suppression in stressed fish. Plasma growth hormone (GH) levels were measured in rainbow trout using a radioimmunoassay developed against chinook salmon growth hormone

A comparison of some methods for detection of safety signals in randomised controlled trials

The occurrence, severity and duration of patient adverse events are routinely recorded during randomised controlled clinical trials. This data may be used by a trial’s Data Safety Monitoring Committee to make decisions regarding the safety of treatments and in some cases may lead to the discontinuation of a trial if real safety issues are detected. Consequently the analysis of this data is a very important part of the conduct of any trial. There are many different types of adverse event and the statistical analysis of this data must take into account multiple comparison issues when performing statistical tests. Unadjusted tests may lead to large numbers of false positive results, but simple adjustments are generally too conservative and risk compromising the power to detect important treatment differences. Mathematically there are a number of different approaches to analysing safety data with general error controlling procedures, recurrent event analysis, survival analysis and other direct modelling approaches (both Bayesian and Frequentist) all being used. Recently a variety of classical (Mehrotra and Adewale, 2012) and Bayesian (Berry and Berry, 2004; DuMouchel, 2010) methods have been proposed to address this problem. These methods use possible relationships or groupings of the adverse events. We implement and compare by way of a simulation study of grouped data some of these more recent approaches to adverse event analysis and investigate if the use of a common underlying model which involves groupings of adverse events by body-system or System Organ Class is useful in detecting adverse events associated with treatments. All of the group methods detect more correct significant effects than the Benjamini-Hochberg or Bonferroni procedures for this type of data. In particular the body-system as described by Berry and Berry (2004) looks to be a worthwhile structure to consider for use when modelling adverse event data

Role of extracellular matrix in vascular smooth muscle cell behaviour and the identification of novel markers of cell phenotype.

Increased synthesis and deposition of extracellular matrix proteins in the blood vessel wall are implicated in vascular disorders such as atherosclerosis, restenosis and hypertension. (Liau and Chan 1989). The increase in extracellular matrix proteins can be mostly attributed to smooth muscle cells (SMC’s) within vascular lesions (Mecham et al 1987). It is presumed that modulation of SMC’s from their normally quiescent, contractile phenotype to a proliferative synthetic phenotype results in increased synthesis of extracellular matrix proteins. Studies have also demonstrated that signals elicited from the extracellular matrix (ECM) may play a role in the regulation of this SMC phenotypic modulation (Yamamoto et al 1993; Hedin et al 1988). The mechanism by which ECM can alter the phenotypic state of SMC’s is not well understood but clearly involves the induction of intracellular signals as a consequence of ECM ligand - cell surface integrin binding. These signals must subsequently exert downstream molecular events altering gene expression and ultimately cell phenotype. The research project presented in this thesis examined the influence various extracellular matrix substrates have on vascular SMC behaviour in vitro. Initial observations demonstrated that SMC’s cultured on different matrix substrates exhibit distinct morphological growth patterns. Functional differences in SMC proliferation and migration rates were also observed in response to seeding on different ECM surfaces.Analysis of the expression levels of known SMC phenotypic protein markers between SMC’s cultured on different matrix substrates did not reveal any significant differences in protein expression. Slight upregulation of Myosin Light Chain Kinase (MLCK)-210 kd isoform was observed in SMC’s cultured on cellular fibronectin, Collagen III and Vitronectin substrates. The Meta-vinculin protein was upregulated in SMC’s cultured on fibronectin coated substrates.In order to identify altered gene expression patterns induced by ECM adhesion, SMC populations cultured on fibronectin coated plastic and SMC’s grown on uncoated plastic were selected for analysis by the differential display technique. Differential display is a recently developed PCR based technique that allows the identification of differentially expressed genes between related cell populations (Liang and Pardee 1992). Much effort was spent optimising the differential display procedure to overcome such limitations as primer redundancy and high false positive selection rates. However, as a result of the persistence of false positives only one gene, meta-vinculin was confirmed as being differentially expressed between SMC populations cultured on fibronectin coated and uncoated tissue culture plastic surfaces.It was concluded that the failure to identify a significant number of fibronectin modulated genes was probably a result of limitations in the differential display procedure as carried out in this study, and may also possibly be due to the existence of only very minor differences in phenotype between SMC’s grown on plastic with or without fibronectin precoating

Siblings of children with disabilities: The Needs and adjustment of today\u27s nondisabled siblings

This study examined the adjustment of nondisabled siblings of children with a disability. Factors such as family income and characteristics of the nondisabled child as they relate to psychological, behavioral, and academic functioning, and parents\u27 perceptions regarding the needs of nondisabled siblings were explored. Specific attention was given to determining parents\u27 interest in sibling support groups. Study participants consisted of 65 parents who had at least one child between the ages of 5 and 21 with a disability and at least one nondisabled child between. the ages of 5 and 18. The primary caregiver was asked to complete a 22 question Sibling Needs Assessment Survey as well as the rate the behavior of the nondisabled sibling on the Behavior Evaluation Scale-2 Home Version. Significant main effects were found for age and sex of the nondisabled sibling with respect to academic difficulties. More academic difficulties were reported when the nondisabled sibling was older than the child with a disability. In addition, males were rated as having significantly higher problems with school performance than, females. Family income was not found to have a significant effect on the psychological, behavioral, or academic functioning of the nondisabled siblings

An Electrochemical Investigation into the Corrosion Protection Properties of Coatings for the Active Metal Copper

In the research presented in this thesis, corrosion protection films were synthesised and characterised. The films were based on polypyrrole (PPy) coatings doped with combinations of tartrate, oxalate and dodecylbenzene sulfonate (DBS) along with the incorporation of multiwalled carbon nanotubes (MWCNT), and viologen films adsorbed at copper. The corrosion protective properties of these films were studied and compared to the uncoated copper substrate. They were assessed and studied using a combination of cyclic voltammetry, polarisation curves, Tafel analysis, open-circuit potential measurements and electrochemical impedance spectroscopy. Polypyrrole films were successfully deposited at copper from a 0.10 mol dm-3 oxalate solution at a pH of 8.0 and a 0.10 mol dm-3 tartrate solution at a pH of 7.0 to generate PPy- Tartrate and PPy-Oxalate films on copper. SEM micrographs confirmed that the polymers were homogeneous, defect and crack-free. In addition, bi-layers comprising PPy-Tartrate/PPy- Oxalate and PPy-Oxalate/PPy-Tartrate were successfully formed at the copper interface. The bi-layer provided the better corrosion protective coatings. Higher breakdown potentials were observed with the bi-layer. In an attempt to further improve the corrosion protective properties of the bi-layer coatings, MWCNT, were incorporated into the polymer films. The MWCNT were successfully dispersed using DBS. The concentration ratio of the MWCNT to DBS was important in forming a stable and well dispersed solution. This was achieved using 0.05 mol dm-3 DBS and 0.02 mg MWCNT. The MWCNT-modified polypyrrole films were deposited as bi-layers and multi-layers and showed excellent corrosion protection for copper. The PPy- Tartrate/PPy-DBS bi-layer films also showed potential as a corrosion protective coating. An alternative approach was then considered. The electrochemical deposition of three viologens, methyl viologen (MV), benzyl viologen (BV) and ethyl viologen (EV) at copper in the presence of a 0.10 mol dm-3 NaCl supporting electrolyte was studied. The formation of the viologen films was achieved by cycling the copper electrode from -0.20 to 1.00 V vs. SCE at a scan rate of 1 mV s-1. For comparison, the copper was cycled under the same conditions in the 0.10 mol dm-3 NaCl solution, but in the absence of the viologens. Significant dissolution of the copper was observed in the absence of the viologens. However, considerably lower currents were measured in the presence of the viologens, indicating a reduction in the rate of dissolution and the formation of a protective film

Detection of safety signals in randomised controlled trials

The occurrence, severity, and duration of patient adverse events are routinely recorded during randomised clinical trials. This data is used by a trial's Data Monitoring Committee to make decisions regarding the safety of a treatment and may lead to the alteration or discontinuation of a trial if real safety issues are detected. There are many different types of adverse event and the statistical analysis of this data, particularly with regard to hypothesis testing, must take into account potential multiple comparison issues.;Unadjusted hypothesis tests may lead to large numbers of false positive results, but simple adjustments are generally too conservative. In addition, the anticipated effect sizes of adverse events in clinical trials are generally small and consequently the power to detect such effects is low.;A number of recent classical and Bayesian methods, which use groupings of adverse events, have been proposed to address this problem. We illustrate and compare a number of these approaches, and investigate if their use of a common underlying model, which involves groupings of adverse events by body-system or System Organ Class, is useful in detecting adverse events associated with treatments.;For data where this type of grouped approach is appropriate, the methods considered are shown to correctly flag more adverse event effects than standard approaches, while maintaining control of the overall error rate.;While controlling for multiple types of adverse event, these proposed methods do not take into account event timings or patient exposure time, and are more suited to end of trial analysis. In order to address the desire for the early detection of safety issues in clinical trials a number of Bayesian methods are introduced to analyse the accumulation of adverse events as the trial progresses, taking into account event timing, patient time in study, and body-system.;These methods are suitable for use at interim trial safety analyses. The models which performed best were those that had a common body-system dependence over the duration of the trial.The occurrence, severity, and duration of patient adverse events are routinely recorded during randomised clinical trials. This data is used by a trial's Data Monitoring Committee to make decisions regarding the safety of a treatment and may lead to the alteration or discontinuation of a trial if real safety issues are detected. There are many different types of adverse event and the statistical analysis of this data, particularly with regard to hypothesis testing, must take into account potential multiple comparison issues.;Unadjusted hypothesis tests may lead to large numbers of false positive results, but simple adjustments are generally too conservative. In addition, the anticipated effect sizes of adverse events in clinical trials are generally small and consequently the power to detect such effects is low.;A number of recent classical and Bayesian methods, which use groupings of adverse events, have been proposed to address this problem. We illustrate and compare a number of these approaches, and investigate if their use of a common underlying model, which involves groupings of adverse events by body-system or System Organ Class, is useful in detecting adverse events associated with treatments.;For data where this type of grouped approach is appropriate, the methods considered are shown to correctly flag more adverse event effects than standard approaches, while maintaining control of the overall error rate.;While controlling for multiple types of adverse event, these proposed methods do not take into account event timings or patient exposure time, and are more suited to end of trial analysis. In order to address the desire for the early detection of safety issues in clinical trials a number of Bayesian methods are introduced to analyse the accumulation of adverse events as the trial progresses, taking into account event timing, patient time in study, and body-system.;These methods are suitable for use at interim trial safety analyses. The models which performed best were those that had a common body-system dependence over the duration of the trial

Life after diagnosis : the social experience of adolescents diagnosed with attention-deficit/hyperactivity disorder and how they manage their lives

Attention-Deficit/Hyperactivity Disorder is the most frequently diagnosed developmental disorder in school-age children in Western Australia today. It concerns and frustrates the children and adolescents who are diagnosed with the disorder, their parents, teachers and the general community. In spite of the plethora of research associated with AD/HD, dissension abounds in the community, literature and the media over its diagnosis and the best treatment and response to the disorder. Notwithstanding the body of research very little is known about adolescents\u27 experiences, opinions, needs and problems associated with the disorder as research and treatment regimes are currently determined by adults. The research on which this dissertation is based uses the grounded theory method for data collection and analysis to gain insights into the social experience of a small group of Western Australian adolescents diagnosed with AD/HD receiving stimulant medication treatment In doing so this research extends current research becoming the first grounded theory study with adolescents with AD/HD in Western Australia The issues examined in my research focus on the adolescents perception of the impact of their diagnosis and stimulant medication use on their social environment and how they manage their lives. A substantive theory emerged that explains the social problem faced by these adolescents and the complex basic social-psychological process by which they endeavour to resolve the difficulties that they face so as to be able to manage their lives. The discussion includes extracts from the data and literature to demonstrate how the substantive theory Reaching for the Light emerged from my research and the social theories that determine how adolescents view their world. The theory Reaching for the Light is composed of four levels of process; seeking solutions, transforming, scaffolding and potentialising and two near core categories (balancing and fortressing) interrelating as they pass through stages. Walking with this small group of adolescents in order to present their worldview of the impact of AD/HD and stimulant medication, rather than that of adults, was both challenging and fascinating particularly taking into account the different cultural perceptions that exist between adults and adolescents. For those with ADIHD social condemnation relating to their diagnosis and stimulant medication treatment is the general rule so that the adolescents fear labeling and marginalisation. Being aware of the participants\u27 fears I, therefore, lock care to ensure their anonymity at all times. My research presents a new picture of how adolescents with AD/HD are able to manage their lives and shows the importance of involving adolescents in decisions about themselves and how positive, patient and constructive social interaction from the adults in their lives can assist them. It emerged from the data that where support and social experience are negative low self-esteem increased the probability of risk-taking behaviour associated with stimulant medication and attempted suicide. This dissertation that focuses on the social experience of a small group of adolescents with ADIHD is oriented around the belief that with effective support these adolescents are able to manage their lives

A Bayesian hierarchical approach for multiple outcomes in routinely collected healthcare data

Clinical trials are the standard approach for evaluating new treatments, but may lack the power to assess rare outcomes. Trial results are also necessarily restricted to the population considered in the study. The availability of routinely collected healthcare data provides a source of information on the performance of treatments beyond that offered by clinical trials, but the analysis of this type of data presents a number of challenges. Hierarchical methods, which take advantage of known relationships between clinical outcomes, while accounting for bias, may be a suitable statistical approach for the analysis of this data. A study of direct oral anticoagulants in Scotland is discussed and used to motivate a modeling approach. A Bayesian hierarchical model, which allows a stratification of the population into clusters with similar characteristics, is proposed and applied to the direct oral anticoagulant study data. A simulation study is used to assess its performance in terms of outcome detection and error rates