On the Efficient Design and Testing of Dependable Systems Software

Modern computing systems that enable increasingly smart and complex applications permeate our daily lives. We strive for a fully connected and automated world to simplify our lives and increase comfort by offloading tasks to smart devices and systems. We have become dependent on the complex and ever growing ecosystem of software that drives the innovations of our smart technologies. With this dependence on complex software systems arises the question whether these systems are dependable, i.e., whether we can actually trust them to perform their intended functions. As software is developed by human beings, it must be expected to contain faults, and we need strategies and techniques to minimize both their number and the severity of their impact that scale with the increase in software complexity. Common approaches to achieve dependable operation include fault acceptance and fault avoidance strategies. The former gracefully handle faults when they occur during operation, e.g., by isolating and restarting faulty components, whereas the latter try to remove faults before system deployment, e.g., by applying correctness testing and software fault injection (SFI) techniques. On this background, this thesis aims at improving the efficiency of fault isolation for operating system kernel components, which are especially critical for dependable operation, as well as at improving the efficiency of dynamic testing activities to cope with the increasing complexity of software. Using the widely used Linux kernel, we demonstrate that partial fault isolation techniques for kernel software components can be enhanced with dynamic runtime profiles to strike a balance between the expected overheads imposed by the isolation mechanism and the achieved degree of isolation according to user requirements. With the increase in software complexity, comprehensive correctness and robustness assessments using testing and SFI require a substantially increasing number of individual tests whose execution requires a considerable amount of time. We study, considering different levels of the software stack, if modern parallel hardware can be employed to mitigate this increase. In particular, we demonstrate that SFI tests can benefit from parallel execution if such tests are carefully designed and conducted. We furthermore introduce a novel SFI framework to efficiently conduct such experiments. Moreover, we investigate if existing test suites for correctness testing can already benefit from parallel execution and provide an approach that offers a migration path for test suites that have not originally been designed for parallel execution

The impact of nature of onset of pain and posttraumatic stress on adjustment to chronic pain and treatment outcome

Despite the demonstrated efficacy of cognitive-behavioural therapy for chronic pain, recent research has attempted to identify predictors of treatment outcome in order to improve the effectiveness of such treatments. This research has indicated that variables such as the nature of the onset of the pain and psychopathology are associated with poor adjustment to chronic pain. Accordingly, these variables might also be predictive of poor response to treatment. Individuals who experience a sudden onset of pain following an injury or accident, particularly when the instigating event is experienced as psychologically traumatic, may present for treatment with high levels of distress, including symptoms consistent with a posttraumatic stress response. The impact of this type of onset of pain and posttraumatic stress symptoms on adjustment to chronic pain and treatment outcome is the focus of this thesis. Three studies were conducted to clarify and extend earlier research findings in this area. Using 536 patients referred for treatment in a tertiary referral pain management centre, the first study examined the psychometric properties of a widely used self-report measure of posttraumatic stress symptoms (the PTSD Checklist, or PCL), modified for use in a chronic pain sample. This study provided preliminary support for the suitability of the PCL as a self-report measure of Posttraumatic Stress Disorder (PTSD) symptoms in chronic pain patients. However, the study also highlighted a number of issues with the use of self-report measures of posttraumatic stress symptoms in chronic pain patient samples. In particular, PCL items enquiring about symptoms which are a common aspect of the chronic pain experience (e.g. irritability, sleep problems) appeared to contribute to high mean scores on the PCL Avoidance and Arousal subscales. Furthermore, application of diagnostic cut-off scores and an algorithm recommended for the PCL in other trauma groups suggested that a much larger proportion of the sample was identified as potentially meeting diagnostic criteria for PTSD than would have been expected from previous research. The second study utilised the modified PCL to investigate the impact of different types of onset of pain (e.g. traumatic onset) and posttraumatic stress symptoms on adjustment to chronic pain in a sample of 196 chronic pain patients referred to the same centre. For patients who experienced the onset of pain related to a specific event, two independent experts in the field of PTSD determined whether these events satisfied the definition of a traumatic event according to DSM-IV diagnostic criteria. Adjustment was assessed through a number of validated measures of mood, disability, pain experience, and pain-related cognitions. Contrary to expectations, comparisons between patients who had experienced different types of onset of pain revealed few significant differences between them. That is, analyses comparing patients presenting with accident-related pain, or pain related to other specific events, to patients who had experienced spontaneous or insidious onset of pain revealed no significant differences between the groups on measures of pain severity, pain-related disability, and symptoms of affective distress after adjustment for age, pain duration, and compensation status. Similarly, comparisons between patients who had experienced a potentially traumatic onset of pain with those who had experienced a non-traumatic or spontaneous or insidious onset of pain also revealed no significant differences on the aforementioned variables. In contrast, compensation status, age, and a number of cognitive variables were significant predictors of pain severity, pain-related disability, and depression. The final study investigated the impact of type of pain onset and posttraumatic stress symptoms on response to a multidisciplinary cognitive-behavioural pain management program. Unlike the previous study, this treatment outcome study revealed a number of differences between onset groups. Most notably, patients who had experienced an insidious or spontaneous onset of pain reported greater improvements in pain severity and maintained these improvements more effectively over a one month period than patients who had experienced pain in the context of an accident or other specific incident. There was also limited evidence that improvements in depression favoured patients who had experienced an insidious or spontaneous and non-traumatic onset of pain. Consistent with this, posttraumatic stress symptoms were a significant predictor of treatment outcome, with higher levels of symptoms being associated with smaller improvements in pain-related disability and distress. Notably, this study also revealed that certain cognitive variables (i.e. catastrophising, self-efficacy, and fear-avoidance beliefs) were also significant predictors of treatment outcome, consistent with previous findings in the pain literature. This provided some perspective on the relative roles of both PTSD symptoms and cognitive variables in adjustment to persisting pain and treatment response. These findings were all consistent with expectations and with previous research. Implications for future research and for the assessment and treatment of chronic pain patients who present with posttraumatic stress symptoms are discussed

The impact of nature of onset of pain and posttraumatic stress on adjustment to chronic pain and treatment outcome

Despite the demonstrated efficacy of cognitive-behavioural therapy for chronic pain, recent research has attempted to identify predictors of treatment outcome in order to improve the effectiveness of such treatments. This research has indicated that variables such as the nature of the onset of the pain and psychopathology are associated with poor adjustment to chronic pain. Accordingly, these variables might also be predictive of poor response to treatment. Individuals who experience a sudden onset of pain following an injury or accident, particularly when the instigating event is experienced as psychologically traumatic, may present for treatment with high levels of distress, including symptoms consistent with a posttraumatic stress response. The impact of this type of onset of pain and posttraumatic stress symptoms on adjustment to chronic pain and treatment outcome is the focus of this thesis. Three studies were conducted to clarify and extend earlier research findings in this area. Using 536 patients referred for treatment in a tertiary referral pain management centre, the first study examined the psychometric properties of a widely used self-report measure of posttraumatic stress symptoms (the PTSD Checklist, or PCL), modified for use in a chronic pain sample. This study provided preliminary support for the suitability of the PCL as a self-report measure of Posttraumatic Stress Disorder (PTSD) symptoms in chronic pain patients. However, the study also highlighted a number of issues with the use of self-report measures of posttraumatic stress symptoms in chronic pain patient samples. In particular, PCL items enquiring about symptoms which are a common aspect of the chronic pain experience (e.g. irritability, sleep problems) appeared to contribute to high mean scores on the PCL Avoidance and Arousal subscales. Furthermore, application of diagnostic cut-off scores and an algorithm recommended for the PCL in other trauma groups suggested that a much larger proportion of the sample was identified as potentially meeting diagnostic criteria for PTSD than would have been expected from previous research. The second study utilised the modified PCL to investigate the impact of different types of onset of pain (e.g. traumatic onset) and posttraumatic stress symptoms on adjustment to chronic pain in a sample of 196 chronic pain patients referred to the same centre. For patients who experienced the onset of pain related to a specific event, two independent experts in the field of PTSD determined whether these events satisfied the definition of a traumatic event according to DSM-IV diagnostic criteria. Adjustment was assessed through a number of validated measures of mood, disability, pain experience, and pain-related cognitions. Contrary to expectations, comparisons between patients who had experienced different types of onset of pain revealed few significant differences between them. That is, analyses comparing patients presenting with accident-related pain, or pain related to other specific events, to patients who had experienced spontaneous or insidious onset of pain revealed no significant differences between the groups on measures of pain severity, pain-related disability, and symptoms of affective distress after adjustment for age, pain duration, and compensation status. Similarly, comparisons between patients who had experienced a potentially traumatic onset of pain with those who had experienced a non-traumatic or spontaneous or insidious onset of pain also revealed no significant differences on the aforementioned variables. In contrast, compensation status, age, and a number of cognitive variables were significant predictors of pain severity, pain-related disability, and depression. The final study investigated the impact of type of pain onset and posttraumatic stress symptoms on response to a multidisciplinary cognitive-behavioural pain management program. Unlike the previous study, this treatment outcome study revealed a number of differences between onset groups. Most notably, patients who had experienced an insidious or spontaneous onset of pain reported greater improvements in pain severity and maintained these improvements more effectively over a one month period than patients who had experienced pain in the context of an accident or other specific incident. There was also limited evidence that improvements in depression favoured patients who had experienced an insidious or spontaneous and non-traumatic onset of pain. Consistent with this, posttraumatic stress symptoms were a significant predictor of treatment outcome, with higher levels of symptoms being associated with smaller improvements in pain-related disability and distress. Notably, this study also revealed that certain cognitive variables (i.e. catastrophising, self-efficacy, and fear-avoidance beliefs) were also significant predictors of treatment outcome, consistent with previous findings in the pain literature. This provided some perspective on the relative roles of both PTSD symptoms and cognitive variables in adjustment to persisting pain and treatment response. These findings were all consistent with expectations and with previous research. Implications for future research and for the assessment and treatment of chronic pain patients who present with posttraumatic stress symptoms are discussed

Promoting a Lay Led Self-Care Approach to Managing Persistent Pain.

This research project explored the impact of introducing a lay led self-management approach known as the Expert Patient Programme (EPP) at patients' initial referral stage to a pain management clinic in a secondary care setting. It involved a randomised controlled trial and employed a mixed method approach permitting triangulation of data with a longitudinal design. Sixty-three patients (Control group n=33, Intervention group n=30) with persistent non-malignant musculo-skeletal pain conditions referred to a District General Hospital (DGH) Pain Clinic , agreed to take part and provided data for the research. The intervention was usual care and an invitation to attend a lay led self-management programme known as the Expert Patients Programme (EPP). This consisted of six 2 hour per week programmes led by lay tutors. The Control group received only usual care, data being collected at baseline, 3-6 months and 10-14 months. The primary hypothesis was to determine if the early introduction of a selfmanagement approach alongside medical treatments could influence and encourage participants to adopt self-management approaches to managing their persistent pain. The primary outcome, readiness to take action to self-manage persistent pain symptoms was measured by the Pain Stages of Change Questionnaire (PSOCQ). Secondary outcomes of Acceptance, Pain and Interference were measured by applying the Chronic Pain Acceptance Questionnaire (CPAQ), and Brief Pain Inventory (BPI). The Qualitative data was gathered using focus groups. The results identified significant promotion through the Stages of Change process accompanied by improvements in Pain and Interference levels for the Intervention groups' data at 10-14 months; no significant changes were found in the Control group. Improvements in the Intervention group were related to a synergistic effect of offering a self-management approach in parallel with a medical model approach and participants taking actions to relinquish their Sick Role. This study is the first to suggest an association between the Stages of Change process and the Sick Role. Results provide evidence that improvements seen in the Intervention group were associated with progress through the Stages of Change and linked with participants adopting self-management approaches and relinquishing their Sick Role; this allowed them to take on a more appropriate role described as the Persistent Condition Role (PCR)

Encountering Pain: Hearing, seeing, speaking

What is persistent pain? How do we communicate pain, not only in words but in visual images and gesture? How do we respond to the pain of another, and can we do it better? Can explaining how pain works help us handle it? This unique compilation of voices addresses these and bigger questions. Defined as having lasted over three months, persistent pain changes the brain and nervous system so pain no longer warns of danger: it seems to be a fault in the system. It is a major cause of disability globally, but it remains difficult to communicate, a problem both to those with pain and those who try to help. Language struggles to bridge the gap, and it raises ethical challenges in its management unlike those of other common conditions. Encountering Pain shares leading research into the potential value of visual images and non-verbal forms of communication as means of improving clinician–patient interaction. It is divided into four sections: hearing, seeing, speaking, and a final series of contributions on the future for persistent pain. The chapters are accompanied by vivid photographs co-created with those who live with pain. The volume integrates the voices of leading scientists, academics and contemporary artists with poetry and poignant personal testimonies to provide a manual for understanding the meanings of pain, for healthcare professionals, pain patients, students, academics and artists. The voices and experiences of those living with pain are central, providing tools for discussion and future research, shifting register between creative, academic and personal contributions from diverse cultures and weaving them together to offer new understanding, knowledge and hope

Mechanochemical ablation in the treatment of superficial venous incompetence

BackgroundThe routine management of venous incompetence has undergone considerable changes in the last two decades led by the introduction of minimally invasive endovenous techniques. At the heart of these changes has been a drive to offer patients effective symptomatic relief whilst minimising disruption to patient quality of life and periprocedural pain. Endovenous thermal ablation (EVTA) has been the main mode of treatment in this minimally invasive era, however, non-thermal methods are challenging this established order and include mechanochemical ablation (MOCA) which is an exciting new technique that combines liquid sclerotherapy with mechanical damage to vessel intima.AimsThe studies contained within this thesis aim to assess the evidence supporting the use of MOCA for the treatment of venous incompetence, to independently validate these results, to optimise a strategy of performing MOCA, and to test the efficacy and clinical effectiveness of MOCA against EVTA.MethodsStudy 1 is a systematic review of the current literature of MOCA, focusing on objective assessment of clinical success including duplex ultrasound (DUS) measurements and health related patient reported outcomes (PROMS). Study 2 is a cohort study of symptomatic patients with superficial venous incompetence (SVI), treated with MOCA and 1.5% Sodium tetradecyl sulphate (STS). Outcomes included clinical examination, DUS, health related PROMS at baseline and weeks 1,6,26 and 52. Study 3 compares the approach of treating varicose tributaries with phlebectomy at the time of performing MOCA (MOCAP) against sequential treatment of tributary varicosities at a later date (MOCAS). A similar outcomes assessment and follow up strategy to study 2 was adopted. Study 4 takes forward the results of the previous studies and compares endovenous laser ablation (EVLA) to MOCA in a randomised controlled study comparing the clinical and technical outcomes of each intervention at baseline and weeks 1,6,26 and 52.ResultsStudy 1: MOCA is a safe and effective method of treating SVI in the short-term, however, the evidence for the longevity of its results beyond 6 months is poor. Moreover, the data on anatomical occlusion rates is questionable and may not match those of EVTA.Study 2: Thirty-two patients were recruited to the study. Complete target vein occlusion at one year was achieved in 21 (75%) patients. Six patients (21.4%) required secondary procedures, of which three had axial EVLA and three required ambulatory phlebectomy with perforator ligation. There was a significant improvement in the median (interquartile range) Venous Clinical Severity Score (VCSS) from baseline 6 (5–8) to a score of 1 (0–2) at one year (p<0.001). There was also a significant improvement in health-related quality of life (HRQoL), both generic (p<0.001) and disease specific (p<0.001). One patient (3.1%) had a post-procedural non-fatal pulmonary embolus.Study 3: Fifty patients underwent MOCAP and 33 patients MOCAS. The two groups were comparable at baseline. MOCAP was associated with lower (better) AVVQ scores at six weeks (3.4 (0.5–6.0) vs. 6.1 (1.8–12.1); p=0.009) and at six months (1.6 (0.0–4.5) vs. 3.34 (1.8–8.4); p=0.009) but by one year the difference was no longer statistically significant (1.81 (0.0–4.5) vs. 3.81 (0.2–5.3); p=0.099). MOCAP was associated with longer procedural duration (45 min (36–56) vs. 30 min (25–37); p<0.001) and higher maximal periprocedural pain (31 (21–59) vs. 18 (7–25); p<0.001). VCSS at all time points was lower in MOCAP group compared to MOCAS (0 (0–1) vs. 1 (0–3); p<0.001). MOCAP was associated with fewer episodes of clinically significant thrombophlebitis (6 of 50 (12%) vs. 10 of 33 (30%); p=0.039) and lower numbers of secondary procedures (2 (4%) vs. 6 (18%); p=0.032)Study 4: One hundred and fifty patients were randomised equally between MOCA and EVLA. Both groups reported low intraprocedural pain scores; on a 100 mm visual analogue scale, pain during axial EVLA was 22 (9-44) compared to 15 (9-29) during MOCA; p=0.210. At 1 year, duplex derived anatomical occlusion rates after EVLA were 63/69 (91%) compared to 53/69 (77%) in the MOCA group; p=0.020. Both groups experienced significant improvement in VCSS and AVVQ after treatment, without a significant difference between groups. Median VCSS improved from 6 (5-8) to 0 (0-1) at one year; p<0.001. Median AVVQ improved from 13.8 (10.0-17.7) to 2.0 (0.0-4.9); p<0.001. One patient in the MOCA group experienced DVT.ConclusionMOCA with 1.5% STS is safe, effective and leads to significant improvement in patient health related quality of life (HRQoL) outcomes up to 1 year follow up. However, the anatomical occlusion rates achieved with MOCA are lower than has been previously reported in the literature and do not match EVLA results. Patient HRQoL gains are better when MOCA is combined with concomitant phlebectomy of varicose tributaries and using this approach HRQoL gains following MOCA are equivalent to those achieved by EVLA. Long-term follow up is needed however to ascertain the effect of the increased recanalisation following MOCA on disease recurrence and progression

Evidence-based guidelines and secondary meta-analysis for the use of transcranial direct current stimulation in neurological and psychiatric disorders

Background: Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. Objective: We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson’s disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. Methods: Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. Results: Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson’s disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). Conclusion: All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs