The relationship of spirituality, self-transcendence, and social support to morale in chronically ill elderly was the focus of this research study. The research was based upon a developmental framework of aging. Individuals answered questionnaires regarding their perspectives on the above variables to determine how significantly the variables related to feelings of morale. Findings revealed that self-transcendence and social support were significantly correlated with morale in this population. No significant relationship between spirituality and morale was found. Self-transcendence and social support together accounted for 45% of the variance in predicting morale in the chronically ill elderly. Findings also revealed existing relationships between spirituality and gender, education level and social support, and length of illness and social support.

CBL proteins are E3 ubiquitin ligases and adaptor proteins. The mammalian homologs – CBL, CBL-B and CBL-3 show broad tissue expression; accordingly, the CBL proteins play roles in multiple cell types. We have investigated the function of the CBL-B protein in hematopoietic cells and fibroblasts. The causative agent of chronic myeloid leukemia (CML) is BCR-ABL. This oncogenic fusion down-modulates CBL-B protein levels, suggesting that CBL-B regulates either the development or progression of CML. To assess the involvement of CBL-B in CML, bone marrow transduction and transplantation (BMT) studies were performed. Recipients of BCR-ABL-infected CBL-B(-/-) cells succumbed to a CML-like myeloproliferative disease with a longer latency than the wild-type recipients. Peripheral blood white blood cell numbers were reduced, as were splenic weights. Yet despite the reduced leukemic burden, granulocyte numbers were amplified throughout the animals. As well, CBLB(-/-) bone marrow (BM) cells possessed defective BM homing capabilities. From these results we concluded that CBL-B negatively regulates granulopoiesis and that prolonged latency in our CBL-B(-/-) BMT animals was a function of perturbed homing.To develop an in vitro model to study CBL-B function we established mouse embryonic fibroblasts (MEFs) deficient in CBL-B expression. Transduction of the wild-type and CBL-B-deficient MEFs with BCR-ABL did not confer transformation; nevertheless, the role of CBL-B in fibroblasts was evaluated. The CBL-B(-/-) MEFs showed enhanced chemotactic migration toward serum in both Transwell migration and time-lapse video microscopy studies. The biochemical response to serum was extensively evaluated leading to the development of a model. We predict that CBL-B deficiency either: (a) augments GRB2-associated binding protein 2 (GAB2) phosphorylation leading to enhanced extracellular signal-regulated kinase (ERK) and protein kinase B (PKB / Akt) signaling, or (b) alleviates negative control of Vav3 resulting in stimulation of Rho effectors. In either case, our results reveal a negative regulatory role for CBL-B in fibroblast migration. The two studies detailed herein expand our knowledge of CBL-B function. They strongly suggest that CBL-B can modulate granulocyte proliferation and point toward a role for CBL-B in the motility of numerous cell types.

Despite recent research advances, there are still several common medical conditions whose underlying mechanisms are poorly understood. In conditions with few or diffuse physical findings, it can be difficult to diagnose and determine the state of the condition and its effects on working ability or performance, and the health care practitioners have to rely on the patient’s self-reports. Identification of objective measurements that are sensitive enough to aid in diagnosis or determination of the state of these conditions would thus be valuable. Psychophysiological measurements are generally non-invasive and have the potential to serve as such diagnostic or prognostic tools. In this thesis, psychophysiological reactions to different stressors were recorded in two selected medical conditions; namely motion sickness and chronic trapezius myalgia (musculoskeletal pain). These subjective conditions are unpleasant, unwanted and apparently serve no survival purpose. It is therefore important to elucidate any physical findings associated with them to, eventually, find new means to prevent the development of these conditions or to ameliorate symptoms. The overall aim of the thesis was to explore the development of psychophysiological responses to stressors in relation to performance and subjective reports in healthy individuals and in women with chronic trapezius myalgia. More in detail, the purpose was to identify psychophysiological responses that could provide information about the mechanisms behind, or serve as candidates for characterization of motion sickness and chronic trapezius myalgia, respectively. Responses to motion sickness, triggered by optokinetic stimulation, were studied in healthy individuals, whereas responses to repetitive low-force work and psychosocial stress were studied in women with chronic trapezius myalgia and in pain-free controls. In both medical conditions, the psychophysiological responses were accompanied by subjective reports. The effects of motion sickness on two different aspects of memory performance were tested during exposure to optokinetic stimulation. In the studies of chronic trapezius myalgia, psychophysiological responses were also related to health status, i.e., being a patient or a pain-free control and measurements of pain intensity, psychological symptoms, sleep-related problems and quality of life. The psychophysiological responses to optokinetic stimulation were inconclusive. Moderate levels of motion sickness did not affect memory performance, whereas decreased short term memory performance was seen in subjects reporting high levels of motion sickness. The autonomic responses and stress hormone secretion in response to low-force repetitive work and psychosocial stress in the chronic trapezius myalgia group were similar to those of the pain-free controls. However, muscle activity in the trapezius muscle was generally higher in the chronic trapezius myalgia group. There were indications of negative psychological states being related to a slower response and lower circadian variations of stress hormone secretion. With the present methods, it was possible to measure general stress responses but none of the measurements showed sufficient specificity to serve as predictors or indicators of motion sickness and chronic musculoskeletal pain, respectively. Summarizing, I cannot objectively measure how you feel; I still have to rely on your description of your condition.

In this research, two studies were conducted in order to examine the psychological, social, somatic and educational effects of chronic traumatic experience on Palestinian children over the six years of the Al-Aqsa Intifada (2000-2006). Firstly, a quantitative study was conducted which aimed to explore the long-term effects of war and occupation on the Palestinian children in the Gaza Strip. The sample consisted of 1,137 children aged between ten and 18 years randomly selected from all parts of the Gaza Strip to participate in the study. The participants completed a Checklist of Traumatic Experiences (CTE), a Symptoms of Post Traumatic Stress Disorder Scale (SPTSDS), a Network of Psycho-Social Support (NPSS) and a Personality Assessment Questionnaire (PAQ). This study found that every child in Palestine is likely to have been exposed to at least three traumatic events. Importantly, this study also found that 41% of the participants suffered from Post-Traumatic Stress Disorders (PTSD). This indicates that there are potentially more than 300,000 children in the Gaza Strip in need of psychological, social,and medical services in the areas of rehabilitation and therapeutic treatment. The study revealed that the support of family, friends, relatives, teachers, and spiritual leaders can be of great help. In addition to this, positive traits of personality can reduce the effects of PTSD. Secondly, a qualitative study aimed to explore, in more depth, the moderating factors relating to Palestinian children who have been exposed to chronic traumatic experiences, particularly the children who show low levels of PTSD. The sample consisted of six children interviewed in Arabic by using a semi-structured interview. They were aged between 13-18 years. The participants were selected according to the amount of traumatic events and level of PTSD experienced by the children who took part in the first study. This study found that the moderating factors and levels of influence which protected them from developing PTSD are positive personality traits and ideological commitment, psychosocial support, entertainment and adaptation or acclimatization. This research concluded that having a normal childhood in Palestine is unlikely in the current circumstances and the future psychological well-being of Palestinian children is at risk of being compromised by on-going traumatic experiences.

Background: In recent years Acceptance and Commitment Therapy (ACT) has gained increasing status as a promising approach to treating chronic pain physical functioning and psychological well-being. The basic premise of ACT as applied to chronic pain is that while pain hurts, it is the struggle with pain that causes suffering. This approach aims to restore effective and adaptive functioning for an individual within a context of continuing pain so that the individual can live a more vital and meaningful life. There is a growing empirical support for the effectiveness of ACT however research has relied on self-reported quantitative outcomes, focused on addressing changes in pain intensity and the physical and psychological impact of chronic pain. There appears to be a gap in the literature on the exploration of the experience of attending an ACT programme for chronic pain from the patient’s perspective. Aim: This study sought to explore the experience of attending an ACT programme for chronic pain within an outpatient NHS hospital setting. Furthermore the study sought to explore the modulating factors influencing clients learning and understanding of the construct of acceptance from the perspective of the participants. Additionally, the experience of attending a group based ACT intervention was explored. Methodology: A qualitative methodology was chosen for the project. The study used a purposive sample of twelve participants, who had all attended the Luton & Dunstable Hospital ACT 8 week outpatient programme for chronic pain. The participants were interviewed through the use of a semi structured interviews, and the transcripts were transcribed and then analysed using Thematic Analysis. Identified themes were further organised using the tool of Thematic Network Analysis. Results: Three global themes emerged from the analysis of the data. The first global theme encompassed the participant’s pre-programme expectations and this theme highlighted the participant’s feelings of hope and hopelessness prior to attending the programme. The second global theme demonstrated the on-going process of living with chronic pain and highlighted the benefits and barriers to adopting and ACT based approach to chronic pain. Finally the third global theme addressed the experience of a group based intervention and included the positive and negative aspects of this experience for the participants. Clinical Implications & Conclusion: Based on the results of this study a number of clinical implications were highlighted in relation to the future development of ACT programmes for chronic pain. These included suggestions in relation to engaging participants in such programmes. Notably, timing issues, validation of physical symptoms, and consideration of the potential barriers to acceptance and understanding of the benefits of adopting and ACT group based pain management approach were discussed.

Alzheimer's disease is the most common form (~60-80%) of dementia, currently affecting approximately half a million people in the UK and ~30 million people worldwide. The autosomal dominant form of AD represents a small proportion (~1-2%) of AD cases and is genetically well characterised. The vast majority of AD cases that show symptoms later in life (>65 years of age) are genetically complex. This type of AD, also known as late onset Alzheimer's disease (LOAD) disease, is still highly heritable with an estimated heritability of up to 76% (Gatz et al., 2006). Unfortunately, there is no cure for this devastating disease. Investigating genetic factors influencing the risk of LOAD is imperative for development of effective therapeutic treatments and more accurate diagnosis. A cross-platform comparison of four Genome-wide association studies (GWAS) was performed in an effort to identify novel genetic associations with LOAD (Chapter 3). A TRIM15 SNP rs929156 demonstrated significant evidence of association with LOAD with a p-value approaching genome-wide significance (p = 8.77 x 10-8) and an odds ratio that showed consistent effect on risk (OR = 1.1, p = 0.03). Within this chapter, a bio-informatic program to automate the process of GWAS meta-analysis taking into account linkage disequilibrium (LD) is also presented. Subsequently two fragments of the TRIM15 gene (including both 5’ and 3’ end flanking regions) were sequenced using the ABI SOLiDTM next generation sequencing technology. This was a pilot study using a DNA pooling strategy to determine whether this region harbours multiple rare variants which are associated with the disease (Chapter 4). Lastly, a candidate gene study combined with whole genome analysis was performed in an effort to search for genetic variants influencing human ageing using LOAD GWAS data (Chapter 5).

The current literature highlights the significant role of psychological factors including cognitive (pain related thoughts and beliefs) and acceptance components (pain willingness, activity engagement, psychological inflexibility) in the management of chronic pain. The research is however in the preliminary stages in terms of investigating the specific relationships that exist between these psychological processes in their ability to predict adjustment to pain. This study aims to extend the current findings by investigating the relationships between several cognitive and acceptance components in their ability to predict emotional and physical adjustment in the context of chronic pain. The hypotheses that cognitive and acceptance components mediate the relationship between pain severity and pain adjustment, and also that acceptance mediates the relationship between cognitive components and pain adjustment will be tested. Method The study employed a cross-sectional survey-based design, including 214 chronic pain patients recruited from an NHS pain clinic. Participants completed a series of self-report questionnaires measuring pain severity, fear of movement beliefs, pain self-efficacy beliefs, pain catstrophising, acceptance and psychological flexibility, pain disability, and depression and anxiety. Structural Equation Modeling was used in order to conduct path analyses, investigating the complex relationships between these variables in predicting physical and emotional adjustment to chronic pain. Results The results from a Confirmatory Factor Analysis indicated that a three factor model comprising pain, cognitive and acceptance components as separate latent variables had a poor fit and therefore could not be used in further analysis. The results of path analyses showed that pain self-efficacy was the only variable to have a strong mediating influence between pain and physical adjustment. Findings also supported a nested path model demonstrating that acceptance, catastrophising and self-efficacy were mediators between pain and emotional adjustment, and that acceptance was also a mediator for pain catastrophising and a partial mediator for pain self-efficacy in their relationship with emotional adjustment. Conclusions The importance of pain self-efficacy specifically in predicting physical adjustment to pain is highlighted. A more complex model however is required to explain emotional adjustment, with acceptance playing a more prominent role in comparison with other variables. The findings also provide support for both Cognitive and Acceptance-based interventions in improving adjustment to living with chronic pain. Given the preliminary nature of these findings, further research employing similar statistical methods are required to provide further support.

Intact white matter is critical for normal cognitive function. In traumatic brain injury (TBI), chronic cerebral hypoperfusion and Alzheimer’s disease (AD) damage to white matter is associated with cognitive impairment. However, these conditions are associated with grey matter damage or with other pathological states and the contribution of white matter damage in isolation to their pathogenesis is not known. Furthermore, TBI is a risk factor for AD and cerebral hypoperfusion is an early feature of AD. It is hypothesised that white matter damage following TBI or chronic cerebral hypoperfusion will be associated with cognitive deficits and that white matter changes after injury contribute to AD pathogenesis. To investigate this, this thesis examined the contribution of white matter damage to cognitive deficits after TBI and chronic cerebral hypoperfusion and furthermore, investigated the role of white matter damage in the relationship between TBI and AD. Three studies addressed these aims. In the first, mild TBI was induced in wild-type mice and the effects on axons, myelin and neuronal cell bodies examined at time points from 4 hours to 6 weeks after injury. Spatial reference learning and memory was tested at 3 and 6 weeks after injury. Injured mice showed axonal damage in the cingulum, close to the injury site in the hours after injury and at 6 weeks, damage in the thalamus and external capsule were apparent. Injured and sham animals had comparable levels of neuronal damage and no change was observed in myelin. Injured animals showed impaired spatial reference learning at 3 weeks after injury, demonstrating that selective axonal damage is sufficient to impair cognition. In the second study mild TBI was induced in a transgenic mouse model of AD and the effects on white matter pathology and AD-related proteins examined 24 hours after injury. There was a significant increase in axonal damage in the cingulum and external capsule and parallel accumulations of amyloid were observed in these regions. There were no changes in tau or in overall levels of AD-related proteins. This suggests that axonal damage may have a role in mediating the link between TBI and AD. The third study used a model of chronic cerebral hypoperfusion in wild type mice and investigated white matter changes after one and two months of hypoperfusion as well as a comprehensive assessment of learning and memory. Chronic cerebral hypoperfusion resulted in diffuse myelin damage in the absence of ischaemic neuronal damage at both 1 and 2 months after induction of hypoperfusion. Hypoperfused animals also showed minimal axonal damage and microglial activation. Cognitive testing revealed a selective impairment in spatial working memory but not spatial reference or episodic memory in hypoperfused animals, showing that modest reductions in blood flow have effects on white matter sufficient to cause cognitive impairment. These results demonstrate that selective damage to white matter components can have a long-term impact on cognitive function as well as on the development of AD. This suggests that minimisation of axonal damage after TBI is a target for reducing subsequent risk of AD and that repair or prevention of white matter damage is a promising strategy for rescuing cognitive function in individuals who have experienced mild TBI or chronic cerebral hypoperfusion.

Chronic illness affects nearly half of all American adults, yet this experience is often regarded as socially normative for older adults. In this study, I examined chronic illness onset early in the life course and its effects on mastery, a person’s self-perception as capable of coping with and managing life’s circumstances, and depressive symptoms as informed by the life course perspective and the stress process model. Using multilevel modeling of American Changing Lives Survey (ACLS) data, I examined the following questions: What is the relationship between early onset chronic illness and mastery? Second, what is the relationship between early onset chronic illness and depressive symptoms? Does mastery mediate the relationship between early onset chronic illness and depressive symptoms? Is early onset chronic illness (24-35) more strongly associated with decreased mastery and increased depressive symptoms than illness onset at the more socially normative life stages of mid-life (36-64) and late-life (65 years and older)? Lastly, does mastery mediate or moderate the relationship between timing of illness onset and depressive symptoms? Through this study, I aim to contribute to sociological knowledge of whether and how chronic illness impacts mastery and depression among young adults. I argue that ill-timed chronic illness impacts young adults’ sense of control over their lives, which has enduring psychological and social consequences. Findings support that healthy and chronically ill young adults do not significantly differ on mastery, but ill young adults report significantly higher depressive symptoms than healthy same age peers. Mastery moderates the effects of timing of illness onset on depressive symptoms with older adults reaping greater benefit from mastery against depressive symptoms than young adults with early onset illness. These findings suggest that early onset chronic illness positions people at greater risk for poor mental health outcomes and that the chronic illness experience and its effects are not uniform across the life course. Consequently, work in this area must consider age as an important context in which the life event of chronic illness onset occurs.

Bakgrund: Långvarig smärta definieras som smärta som inte har gått över på 3-6 månader. Smärta är en individuell upplevelse som inte kan mätas objektivt, utan den som upplever vet själv hur intensiv den är och smärtans duration. Syfte: Syftet med denna litteraturstudie var att beskriva patienters upplevelser av att leva med långvariga smärta ur ett psykosocialt perspektiv. Syftet var också att beskriva vilka datainsamlingsmetoder de vetenskapliga artiklarna har använt sig av. Metod: Föreliggande litteraturstudie har en deskriptiv design. Föreliggande litteraturstudies resultat baseras på 12 kvalitativa vetenskapliga artiklar som har sökts fram genom databaserna CINAHL och PubMed. Huvudresultat: Sammanställningen av de inkluderade artiklarna visade på upplevelser av känslomässig påverkan på patienternas liv som ett kraftigt lidande och negativa tankar inför framtiden. Smärta upplevdes också ge sociala begränsningar i arbetslivet, förlust av identitet samt sociala relationer. Patienterna upplevde ett negativt bemötande från sjukvårdspersonalen. Slutsats: Upplevelser av smärta påverkade patienterna psykiskt och socialt. Smärta har resulterat till känslomässig påverkan och lett till sociala begränsningar i både arbetslivet och relationen till familj, vänner och barn. Upplevelsen av sjukvårdspersonalens bemötande upplevdes negativt av patienterna, där smärtan inte togs på allvar. Detta i sin tur påverkade de att få någon behandling eller mediciner. Författaren till föreliggande litteraturstudie menar att utifrån föreliggande litteraturstudies resultat finns brister hos sjukvårdpersonalen, detta i sin tur kan vara till hjälp att öka sjukvårdens kunskaper om dessa patienters upplevelser av långvarig smärta samt att kunna bemöta de på ett värdigt och respektfullt sätt. Det är viktigt att tro på patienters smärta och kunna sträcka de hjälpande hand. / Background: Chronic pain is defined as pain that has not gone over 3-6 months. Pain is an individual experience that cannot be objectively measured, but that experience knows how intense it is, and pain duration. Aim: The aim of this literature review was to describe patient's experiences of living with chronic pain from a psychosocial perspective. The aim was also to describe the data collection methods of scientific articles have used. Method: This literature review has a descriptive design. This literature review study's results are based on 12 scientific articles that have been found through the database CINAHL and PubMed. Result: The compilation of the included articles led to perceptions of emotional impact on patients' lives as a major suffering and negative thoughts about the future. Pain was felt also that the social constraints of working life, loss of identity and social relationships. Patients experienced a negative attitude of medical staff. Conclusion: Experiences of pain affect patients psychologically and socially. Pain has led to the emotional impact and led to social constraints in both working life and relationship to family, friends and children. Experience of healthcare professionals experienced negative treatment of patients where the pain is not taken seriously. This in turn affected the receive any treatment or medication. The author of this literature review means that based on present literature studies results are deficiencies in health care, this in turn may help to increase medical knowledge of these patients experience chronic pain as well as to cope with the in a dignified and respectful manner, believing the pain and to extend helping hand to patients