Impacts of a Palliative Approach for Nursing (IPAN)

This practice-relevant nursing health services research initiative will address the questions:

  1. How and in which contexts can a palliative approach better meet the needs of patients with a life-limiting illness and their family members?
  2. How can a palliative approach guide the development of innovations in health care delivery systems to better support nursing practice and the health system in British Columbia?

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Evaluation of the Integration of Nurse Practitioners into the BC Healthcare System

The nurse practitioner (NP) role is new to BC and its impact has yet to be evaluated. The proposed multi-year study will evaluate a practice innovation – the integration of NPs into the BC healthcare system, and will establish a framework for sustainable ongoing evaluation of the impact of NP practice on those they serve and the health care system. The study process will be divided into three parts addressing the following broad questions:

  1. What changes result for patients, and what are the implications for the health care system when NPs become part of the care process?
  2. What is the impact of adding a NP to the functioning of collaborative health care teams?
  3. What are the practice settings and scope of practice of NPs working in BC?

The final work of the project team will be to use the study findings to develop an ongoing evaluation method for future data collection and evaluation of NPs’ practice and impact.

Evaluation of the Residential Program Care Delivery Model

CDM was launched in Fraser Health in July 2010, with plans to implement the model across all residential care beds in the Health Authority. The model consists of three inter-related aspects: staff mix, funding methodology and direct care hours. CDM sets a goal of reaching 3.36 direct care hours per resident per day across Fraser Health by targeting residents, their families and staff in residential care programs in FH-operated facilities. The evaluation project will examine Phase 1 of the implementation of CDM (July 2010 to January 2011) and will include monitoring funding indicators as well as quality of care indicators.

Evaluation of Neurogenesis and Synaptic Plasticity in the YAC128 Transgenic Mouse Model of Huntington's Disease

Currently, there are no therapeutic options available to help regenerate lost brain tissue in patients with Huntington’s disease (HD). However, a large body of evidence suggests that the adult brain retains a limited ability to generate new neurons (a process called neurogenesis), and that adult neuronal stem cells that underlie this process may be a possible endogenous source of healthy neurons for the treatment of certain neurodegenerative diseases including HD. Significant strides are being made in understanding how neural stem cells could be used in regenerative transplant therapies in a number of pathologies. However, whether a “”diseased”” brain has the capacity to sustain regenerative therapy remains unclear. Jessica Simpson is studying how HD affects two populations of endogenously active neuronal stem cells. These stem cells normally give rise to new neurons through out life, so they offer an endogenous indicator of how HD is affecting the brains capacity to regenerate. In addition, she will be testing whether non-invasive therapies aimed at restoring adult neurogenesis and synaptic plasticity (i.e. voluntary physical exercise), might be beneficial in reversing some of the cognitive as well as neuropathological and motor deficits seen in HD mouse models. Adult neurogenesis and synaptic plasticity are thought to be involved in cognitive function, namely learning and memory, in the normal adult brain. Her studies will improve our existing knowledge of how adult neurogenesis and synaptic plasticity are affected in the HD brain and thereby improve our knowledge of the pathogenic mechanisms triggered by HD at the neuronal level. Ms. Simpson’s research may lead to the development of restorative therapeutic strategies that recruit endogenous stem cells into degenerated areas of the brain. Such strategies might also be useful for the treatment of other neurodegenerative diseases characterized by the loss of specific neuronal populations such as Parkinson’s disease. Moreover, the results from this study could potentially contribute to the growing body of evidence suggesting that the use of non-invasive therapeutic strategies, such as voluntary physical exercise and environmental enrichment, provide benefit in the treatment of neurodegenerative conditions such as Alzheimer’s disease.

Neural Mechanisms of Reward Learning and Cognitive Control in Children with Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder (ADHD), is characterized by its behavioural manifestations including difficulties with attention, hyperactivity and impulsivity. It is one of the most common childhood disorders with a prevalence rate of three to seven percent of school-aged children. ADHD carries a significant impact not only on children diagnosed with this disorder, but also on their families, schools, communities and the health care system. Numerous theories of ADHD have focused on deficits in executive functions, specifically cognitive control and the inability to inhibit inappropriate behaviours. Neuropsychological and neuroimaging studies in children with ADHD support a theory of frontal-subcortical dysfunction: specifically, a dysfunction in the midbrain dopamine (DA) system that may result in an impaired midbrain DA system and reinforcement learning, or the ability to learn to modify behaviour on the basis of rewarding and punishing stimuli in the environment. Furthermore, recent developments in reinforcement learning theory indicate that the midbrain DA system carries Reward Prediction Error (RPE) signals. Carmen Lukie is investigating how a midbrain DA system for reinforcement learning may be impaired in children with ADHD. This study follows on from her earlier research which showed that children with ADHD are particularly sensitive to the saliency of rewards. Specifically, she found that RPE signals in children with ADHD are modulated by the context in which feedback is given, and differs from what is observed in typically developing children. The current study will replicate this finding, while correcting for the limitations of the earlier study. Ultimately, the results of this research could lead to the development of novel, more effective behavioural and pharmacological treatments. Further, the research may expand to include individuals with substance abuse, pathological gambling, conduct and borderline personality disorders.

Small molecules with affinity for S100A7, a tumorigenic protein in breast cancer

Biochemical events in humans are influenced and triggered by cell signalling pathways and their associated feedback loops. Changes and mutations to members of these signalling pathways can cause cancer to develop. Trouble can also occur when alternative pathways are triggered or when built-in negative feedback (“”shut off””), loops are not triggered. In the case of cancer, the observed uncontrolled cell growth results in tumours that can eventually metastasize and send diseased cells throughout the body resulting in an aggressive, invasive cancer. Before the aggressive stage of cancer is reached, the disease often goes through stages of progressively worsening cancers. In breast cancer, Ductal Carcinoma In Situ (DCIS), is one such stage prior to invasive disease. With DCIS, the cancer is contained to a duct and has not yet spread to other areas of the breast or body. Research at the BC Cancer Agency’s Deeley Research Centre has revealed two proteins, S100A7 and Jab1, involved in a pathway associated with the transition from DCIS to invasive breast cancer. There is compelling evidence to suggest that if the interaction between S100A7 and Jab1 were prevented or disrupted, the critical signalling pathways would not be triggered and the progress of invasive breast cancer would be stopped. Amanda Whiting is researching the effects of blocking the interactions between S100A7 and Jab1 by using small, drug-like molecules. In particular, Ms. Whiting’s research uses the molecule 2,6-ANS, as the basis for modifications to improve binding to S100A7 and decrease binding to other important body proteins. Her research will provide an expanded understanding of small molecule binding requirements and, in turn, allow for appropriate modifications to the compounds. Moreover, her work explores a potential new target for breast cancer therapy using small molecule inhibitors to disrupt a cancer-associated protein-protein interaction.

A structure-function analysis of the exo-beta-D-N-acetylglucosaminidase StrH, an important Streptococcus pneumoniae virulence factor.

Streptococcus pneumoniae is a common bacterium that can cause serious infections like acute respiratory disease (pneumonia), infections of the brain and central nervous system (meningitis), blood infections (septicaemia, sometimes leading to sepsis), and ear infections (otitis media). This organism is one of the leading causes of death from infectious disease across the globe. In addition to showing a lethal synergism with the influenza virus, many strains of S. pneumoniae are rapidly becoming resistant to antibiotics and some strains have even been dubbed “”superbugs. From the practical perspective of combating S. pneumonia, there is a clear need to better understand how it makes us sick. Numerous studies have revealed that the ability of this germ to cause disease strongly depends on it attacking the sugars present in its host’s tissues. Dr. Pluvinage’s work focuses on one protein that performs this type of function, a large enzyme called StrH, which is necessary for S. pneumoniae to infect its most commonly targeted human organs, the lungs and the ears. StrH is responsible for removing an abundant sugar (N-acetylglucosamine) from the surface of host cells and the protective sugar layers found in mucus. Though the activity of StrH is known, precisely how it performs its job is not. Consequently, Dr. Pluvinage is working to characterize the protein’s complex, three-dimensional structure in order to better understand the protein’s function. The results of this research will provide a foundation for generating new small molecular inhibitors that might allow for the effective treatment of infections caused by S. pneumoniae “superbugs”.

Examining the link between cognitive deficits in the elderly and suboptimal activity of the locus coeruleus-norepinephrine system

A working brain produces electrical activity that can be recorded at the scalp. An event-related potential (ERP) is a characteristic electrophysiological response to any specific category of stimulus or event. The P300 is an ERP associated with stimuli that must be attended. It has been suggested that the P300 may be a manifestation of functioning in the locus coeruleus – norepinephrine system (LC-NE system), a neuromodulatory system that is associated with arousal , vigilance and attention. A link has been suggested between cognitive deficits in the elderly and suboptimal activity in the LC-NE system. Christopher Warren is attempting to demonstrate the link between the P300 and the LC-NE system, and describe the related changes in the brain that occur with age. He is assessing the performance of elderly participants on a specific attentional task, while simultaneously recording the electrophysiological activity of their brain using electroencephalograph recording equipment. The data will be compared with a control group of younger participants. Chris is looking for specific, key differences in electrophysiological activity and behavioural performance between elderly participants and controls, which will support the link between the LC-NE system and the P300, and will allow inference as to how the LC-NE system is behaving in the elderly participants.. Chris’s results will describe, and possibly implicate suboptimal function of the LC-NE system in cognitive decline with age. This research has direct implications for understanding the cognitive decline associated with healthy aging, potentially describing the function and malfunction of the LC-NE system in aging populations. It could also generate a model that could be applied to understanding LC-NE function in people with attention deficit/hyperactivity disorder, dementia, schizophrenia, or traumatic brain injury. A comprehensive theory of the LC-NE system could inform the development of clinical strategies and tools to help elderly citizens effectively work around attention-related cognitive deficits that occur with age

Regulation of the Jun Transcription Factors in B Lymphocytes by the NEDD4 Family E3 Ubiquitin Ligase, Itch

Ubiquitin is a small protein found in all cells containing a nucleus. A key function for this protein is ubiquitylation, the process by which ubiquitin attaches to target proteins to “mark” them for degradation (breaking down) and removal from the cell. Ubiquitylation is an important process for maintaining proper levels of cellular proteins and removing mis-folded proteins to ensure proper cellular function and to prevent disease. E3 Ub ligases are important regulators of the ubiquitylation process because they select the specific proteins (substrates) that are to be degraded. Itch is an E3 Ub ligase that is important in the immune system, as mice deficient in Itch (Itchy mice) develop a fatal autoimmune-like disease. The Jun transcription factors, c-Jun and JunB, are found to be deregulated in the T cells of these mice, and this is believed to contribute to the disease. These proteins are also important for the proper function of B cells and their deregulation has been implicated in some B cell cancers, such as Hodgkin lymphoma. Joel Pearson is determining whether Itch also regulates the Jun proteins in B cells, and how this may contribute to the autoimmune-like disease of Itchy mice. He is also investigating whether Itch regulates the Jun proteins in B and T cell lymphomas where these proteins are expressed at unusually high levels. His hypothesis is that Itch is an important regulator of the Jun proteins in B cells. Furthermore, he believes that Itch is also an important regulator of the Jun proteins in B and T cell lymphomas where these proteins are over-expressed. Understanding how the Jun proteins are regulated in these cells is important for understanding how the autoimmune-like disease of Itch-deficient mice may arise. Deregulation of the Jun proteins also contributes to the pathogenesis of some types of B and T cell lymphomas. Because of this, understanding how they are regulated is important for understanding how these cancers arise and persist. It could also lead to the development of novel ways to treat these cancers.

Polysubstance use: psychosocial functions of combined use of alcohol and psychostimulants

Much of the research that informs current understandings of drug and alcohol use and addictive behaviour is based on studies that concentrate on a single substance type. This narrow focus is in distinct contrast to actual patterns of use and related harms: most Canadians with substance use problems use more than one substance (polysubstance use), often on the same occasion, and their behaviours and health outcomes may be strongly shaped by this combination. Health policies and programs are usually developed, implemented and evaluated one substance or behaviour at a time, without consideration of possible consequences for other substance use and addiction outcomes. In the current research literature there is a lack of information regarding polysubstance use. This includes when, in what order, and in what quantities people use substances, why they choose to use simultaneously, and the risk behaviours (e.g. sexual behaviour, spending behaviours) associated with simultaneous polysubstance use. Kristina Brache is exploring the patterns of use, the settings and the motivations associated with combined use of alcohol and psychostimulants (cocaine, amphetamines). She is conducting a series of in-depth interviews and self-administered surveys of 150-200 substance-using individuals in a treatment setting. Understanding the use of multiple substances can inform prevention and intervention strategies to reduce harm or risk to individuals using multiple substances. Ultimately, this research could improve health and health delivery systems by informing policy, programs and treatment about combined drug use in this population of interest.