Chronic pain is a major health problem affecting more than 1.5 billion people worldwide. Specifically, neuropathic pain and chronic post-surgical pain are debilitating clinical conditions with few efficacious treatments, warranting development of novel therapeutics. Starting with the hypothesis that dysregulated translation regulation pathways may underlie these pain states, we demonstrated that there is a major reorganization of translation machinery in the peripheral nervous system of rats and mice, including enhanced mTOR and ERK activity and increased phosphorylation of mTOR and ERK downstream targets in these persistent pain states. We also hypothesized that activators of AMP-activated protein kinase (AMPK) may represent a novel treatment avenue for the treatment of neuropathic and incision-induced pain because AMPK activators inhibit ERK and mTOR signaling, two important pathways involved in the sensitization of peripheral nociceptors. The AMP activated protein kinase (AMPK) activators, metformin, resveratrol and A769662, inhibited translation regulation signaling pathways in sensory neurons, eIF4F complex formation, nascent protein synthesis in injured nerves and sodium channel-dependent excitability of sensory neurons resulting in a resolution of neuropathic allodynia. We have further demonstrated that local injection of resveratrol, metformin or A769662 and topical application of resveratrol, a potent AMPK activator, into the hindpaw following plantar incision dose-relatedly reverses incision-mediated mechanical hypersensitivity as well as hyperalgesic priming induced by incision. In addition, co-treatment with systemic metformin and local resveratrol at individually sub-efficacious doses at the time of incision blocked acute hypersensitivity and hyperalgesic priming suggesting potential super-additive effects of combined AMPK activator use. These results highlight the importance of signaling to translation control in peripheral sensitization of nociceptors and provide further evidence for activation of AMPK as a novel treatment avenue for acute and chronic pain states.

Background: The applications for rapid prototyping have expanded dramatically over the last 20 years. In recent years, additive manufacturing has been intensely investigated for surgical implants, tissue scaffolds, and organs. There is, however, scant literature to date that has investigated the viability of 3D printing of surgical instruments. Materials and Methods: Using a fused deposition manufacturing (FDM) printer, an army/ navy surgical retractor was replicated from polylactic acid (PLA) filament. The retractor was sterilized using standard FDA approved glutaraldehyde protocols, tested for bacteria by PCR, and stressed until fracture in order to determine if the printed instrument could tolerate force beyond the demands of an operating room. Results: Printing required roughly 90 minutes. The instrument tolerated 13.6 kg of tangential force before failure, both before and after exposure to the sterilant. Freshly extruded PLA from the printer was sterile and produced no PCR product. Each instrument weighed 16g and required only $0.46 of PLA. Conclusions: Our estimates place the cost per unit of a 3D printed retractor to be roughly 1/10th the cost of a stainless steel instrument. The PLA Army/ Navy is strong enough for the demands of the operating room. Freshly extruded PLA in a clean environment, such as an OR, would produce a sterile, ready to use instrument. Due to the unprecedented accessibility of 3D printing technology world wide, and the cost efficiency of these instruments, there are far reaching implications for surgery in some underserved and less developed parts of the world.

The surgical culture values certainty and confidence, and this was proposed to be a source of internal conflict for surgeons, particularly during times of stress and uncertainty. Surgeons previously described the need to manage their image during these times, putting on an external appearance that is inconsistent internally. As part of a larger program of research on surgical judgment and decision making, this study used a constructivist grounded theory approach to explore 15 general surgery trainees’ perceptions and experiences of impression management during moments of decision making. Residents described their perceived expectations in training, and the impression management strategies they used to appear as though they were meeting them in circumstances when they were not. Participants described those who did not meet these expectations as branded the ‘struggling resident’. Concerns about one’s impression had implications for residents’ evaluations, learning opportunities, decision making, and wellness.

The surgical culture values certainty and confidence, and this was proposed to be a source of internal conflict for surgeons, particularly during times of stress and uncertainty. Surgeons previously described the need to manage their image during these times, putting on an external appearance that is inconsistent internally. As part of a larger program of research on surgical judgment and decision making, this study used a constructivist grounded theory approach to explore 15 general surgery trainees’ perceptions and experiences of impression management during moments of decision making. Residents described their perceived expectations in training, and the impression management strategies they used to appear as though they were meeting them in circumstances when they were not. Participants described those who did not meet these expectations as branded the ‘struggling resident’. Concerns about one’s impression had implications for residents’ evaluations, learning opportunities, decision making, and wellness.

Background: How to optimally integrate simulation into a surgical training program is relatively unknown. We studied the effect of varying the practice schedule into either blocked or random patterns (termed contextual interference) on the long-term retention and transfer of surgical skills. Methods: 36 participants were randomized to practice 4 tasks from the Fundamental of Laparoscopic Surgery (FLS) program using one of three training schedules (blocked, random, no training). Skill was assessed using FLS scoring and hand-motion efficiency scores. Results: A positive benefit of training was seen over the controls for all 4 tasks (p<0.05). No difference was seen between the blocked and random groups in the amount of skill acquired, skill learned, or transfer of skill. Conclusion: The application of contextual interference was unable to differentiate between the blocked and random training groups. This could be due to the complexity of the tasks and/or the inexperience of the learners.

Cardiac surgery incisional pain can decrease inspiratory effort, alter normal respiratory mechanics, and increase the potential for post-operative pulmonary complications. Post-surgical atelectasis is the most frequent complication after coronary artery bypass grafting (CABG), ranging from 54% to 92%. All types of therapy such as an incentive spirometry (IS), deep breathing exercises (DBE) or continuous positive airway pressure (CPAP) have a valuable role to play in the prevention or the treatment of post-surgical atelectasis. However, the type of therapy that should be used is not completely clear yet. The present research aims to evaluate the benefit of early use of CPAP via mask therapy to treat or prevent post-surgical atelectasis after CABG, particularly in smokers and elderly patients, as compared to regular (IS) therapy. Also, it aims to evaluate the patients' and medical staff's experience about the use of the new method of CPAP via mask therapy. The present research was conducted at King Fahd Armed Forces Hospital in Saudi Arabia between March 2010 and December 2011. It used a mixed methods approach. The first two studies were intervention quantitative studies, which investigated the benefit of CPAP via mask therapy. The others were qualitative studies that evaluated the experience of patients and medical staff regarding CPAP therapy use.A total of 180 patients (male and female) (36 in each group) participated in the two quantitative studies. Ninety two participants (male and female) participated in the qualitative studies. The first quantitative study results showed an improvement in CPAP via mask therapy for half hours every two hours group measurements as compared to IS therapy groups. IC was increased significantly in the "CPAP every two hours group" as compared to control group (IS) (baseline mean for IS group 1.34L and "CPAP every two hours group" 1.42L, post- therapy mean 1.59L and 1.88L respectively, p= 0.037). In addition, when chest physiotherapy was added to the two regimens, the improvement of CPAP therapy measurements became more than IS therapy. Moreover, the patient’s acceptance rate for CPAP therapy every two hours was 93% and the medical staff acceptance rate was 86%. CPAP via mask therapy for half hour every two hours had better outcomes in treating or preventing post-surgical atelectasis after CABG, particularly in smokers and elderly patients. Adding chest physiotherapy led to even better outcomes. The use of the new method of CPAP therapy had high acceptance rate by the participants and medical staff.

Objective: Evaluation of surgical quality ensures consistency of care and facilitates improvements in the quality of care delivered. Methods: An overview of surgical quality measurement is presented. A system for monitoring thoracic morbidity and mortality (TM&M) at the Ottawa Hospital is introduced and evaluated. Results of a needs assessment survey on the involvement in thoracic surgical research and quality improvement initiatives are presented. Results: Structure, process, and outcomes reflect different viewpoints on how to evaluate surgical quality. The feasibility of the TM&M system is evaluated using descriptive and univariate statistics, while its inter-rater reliability is assessed amongst the Canadian Association of Thoracic Surgeons. Conclusions: Outcomes have been fundamental in the evaluation of surgical quality. TM&M classification system advocates for a practice of continuous quality improvement and provides standardized and reliable feedback on surgical outcomes. Results of the needs assessment have built a strong foundation of knowledge on prospective ways to enhance the monitoring of surgical quality.

Surgery precipitates a hypercoagulable state and has been shown to increase the development of cancer metastases in animal models, however mechanism(s) responsible for this are largely unknown. We hypothesize that the prometastatic effect of surgery may be secondary to postoperative hypercoagulable state. Surgical stress was induced in mice by partial hepatectomy or nephrectomy, preceded by intravenous injection of CT26-LacZ or B16F10-LacZ cells to establish pulmonary metastases with or without perioperative anticoagulation and their lung tumor cell emboli (TCE) were quantified. Fibrinogen and platelets were fluorescently labeled prior to surgical stress to evaluate TCE-associated fibrin and platelet clots. Surgery significantly increased metastases while anticoagulation with five different agents attenuated this effect. Fibrin and platelet clots were associated with TCE significantly more frequently in surgically stressed mice. Surgery promotes the formation of fibrin and platelet clots around TCE and this appears to be the mechanism for the increase in metastases seen following surgery.

The thesis focuses on a model that seeks to address patient scheduling step of the surgical scheduling process to determine the number of surgeries to perform in a given day. Specifically, provided a master schedule that provides a cyclic breakdown of total OR availability into specific daily allocations to each surgical specialty, we look to provide a scheduling policy for all surgeries that minimizes a combination of the lead time between patient request and surgery date, overtime in the ORs and congestion in the wards. We cast the problem of generating optimal control strategies into the framework of Markov Decision Process (MDP). The Approximate Dynamic Programming (ADP) approach has been employed to solving the model which would otherwise be intractable due to the size of the state space. We assess performance of resulting policy and quality of the driven policy through simulation and we provide our policy insights and conclusions.

Background: How to optimally integrate simulation into a surgical training program is relatively unknown. We studied the effect of varying the practice schedule into either blocked or random patterns (termed contextual interference) on the long-term retention and transfer of surgical skills. Methods: 36 participants were randomized to practice 4 tasks from the Fundamental of Laparoscopic Surgery (FLS) program using one of three training schedules (blocked, random, no training). Skill was assessed using FLS scoring and hand-motion efficiency scores. Results: A positive benefit of training was seen over the controls for all 4 tasks (p<0.05). No difference was seen between the blocked and random groups in the amount of skill acquired, skill learned, or transfer of skill. Conclusion: The application of contextual interference was unable to differentiate between the blocked and random training groups. This could be due to the complexity of the tasks and/or the inexperience of the learners.