Full ethics approval for all the work contained in this thesis was received form the research ethics committee of the Royal College of Surgeons in Ireland.

Initial work on developing mechanical tests was performed in the Bioengineering Laboratory in the School of Electrical and Mechanical Engineering in University College Dublin, under the supervision of Mr. Luke Curley and Dr. David Fitzpatrick (Head of School of Engineering,UCD).

Storage and preparation of cadaveric tissues was carried out in the Smurfit Building, Beaumont Hospital under the supervision of Mr. Hannan Mullett (Consultant Orthopaedic Surgeon, Beaumont Hospital) and Prof. A.D.K. Hill (Professor of Surgery, RCSI).

Biomechanical testing of cadaveric specimens was carried out in the Bioengineering Laboratory in Trinity College Dublin, under the supervision of Mr. Peter O’Reilly and Prof. Patrick Prendergast (Professor of Bioengineering, TCD).

All radiological studies of cadaveric tissues were performed at the Sports Surgery Clinic, Dublin, under the supervision of Dr. Frank McGrath (Consultant Radiologist).

Computational modelling was carried out in both the School of Mechanical Engineering UCD and the Department of Mechanical Engineering, National University of Ireland, Galway, under the supervision of both Dr. David Fitzpatrick (Head of School of Engineering, UCD) and Dr. Patrick McGarry (Lecturer in Mechanical Engineering, NUIG).

A total of 41 patients aged 55 to 75 years with arthroscopically or radiographically confirmed moderate to severe knee OA were randomised to a 6-week home RT program, a 6-week NMES program or a control group receiving standard care. The RT group performed quadriceps femoris strengthening exercises 3 times per week, while the NMES group used a portable garment stimulator for 20 minutes 5 times per week at the maximum intensity comfortably tolerated.

Outcomes were assessed at baseline, post-intervention and 6 weeks post-intervention. The primary outcome measure was self-reported disability, measured using the Short Form Health Survey (SF-36) score and the Western Ontario McMaster Universities Arthritis (WOMAC) index. Secondary outcome measures were functional capacity (25m walk test, chair rise test, stair climb test), peak isometric and isokinetic quadriceps torque, quadriceps CSA, and expression of MHC isoforms, muscle atrophy F-box (MAFbx) and muscle RING finger-1 (MuRF).

There was no significant change in any of the outcome measures in the control group. Compared to baseline, SF-36 scores, functional capacity and CSA increased significantly in the NMES and RT groups post-intervention. WOMAC scores increased significantly in the NMES group. Isometric peak torque did not change in any group. Adherence was 91% and 83% in the NMES and RT groups respectively (p=0.324). There were no between-group or withingroup differences in MHC isoforms, MAFbx and MuRF. At 6-week follow-up, functional improvements were maintained for both training groups, while most of the health score gains were lost.

Home-based NMES is an acceptable alternative to exercise therapy in the management of knee OA, especially for patients who have difficulty complying with an exercise program.

The solution to improve novice surgeon's attentional capacity is to pre-trained pertinent operative skills in a controlled setting using simulator technology. EYESi phacoemulsification simulator offers high fidelity rendition of intra-ocular microsurgical environment. Novice surgeons can practice on the simulator until proficiency level is achieved.

The aim of this project is to design and validate didactic and skill training curriculum for cataract surgery. The didactic curriculum employs 3-dimentional animations in order to explain complex surgical procedures. The proficiency level for skill training is set based on the simulator performance of ten expert cataract surgeons. A structured proficiency based simulator curriculum is designed and validated with randomized control trialin this study.

- Therselben, 1790

Although anthropometric work on the clavicle by Broca dates as far back as 1869 according to Voisin¹, the role of the clavicle has been described more than 200 years ago by Therselben. While one study stated that the clavicle is the most frequently fractured bone of the human skeleton², data collected in Malmo, Sweden between 1952 and 1987 showed that fractures of the clavicle only accounted for 4% of all fractures, but that this represented 35% of all fractures in the shoulder region³. Other studies have shown similar results, estimating that clavicular fractures account for 5 to 10% of all fractures^4,5, and 44% of all injuries to the shoulder girdle⁶.

According to Wheeless' Online Textbook of Orthopaedics, fractures to the middle third are the most common in adults and children, accounting for account for 80% while fractures to the lateral third are seen in 15% with the remaining 5% affecting the medial third. Numerous studies have verified this, statingthat 80% of clavicular fractures occur in the middle third, 10 to 18% in the lateral third and 2 to 10% in the medial third ^7,8,9,10,11. This can be explained by a number of facts. Firstly, that the narrowest part of the clavicle is at the meeting point of the sternal convexity and the acromial concavity, which is the location of the majority of clavicle fractures². Second of all, there is a significant decrease in bone density at the transition from middle to lateral thirds of the clavicle, explaining the increased frequency of fractures occurring in the middle and lateral thirds². It has also been previously shown that the mid-portion of the clavicle is the thinnest and narrowest part of the bone and represents a transitional region of the bone, both in curvature and cross-sectional anatomy, making it a mechanically weak area that is most likely to fracture¹².

In terms of location, the sternoclavicular and acromioclavicular joints hold the clavicle in its anatomical position with the latter having been described as a 'keystone' link between the scapula and clavicle¹³. Its integrity plays an important role in the movement of the shoulder girdle. The construct of the ACJ makes it a very strong joint able to tolerate a significant amount of force before disruption. This explains that in comparison to clavicular fractures, injuries to the ACJ account for approximately only 12% of those to the shoulder girdle seen in clinical practice¹⁴. Much higher incidences are seen in contact sports. In rugby, ACJ injuries have been shown to account for 32% of shoulder injuries¹⁵ and in American football they are the most common injury to the shoulder¹⁶. Even in non-contact sports such as recreational skiing, about 20% of injuries to the shoulder girdle involve the ACJ¹⁷. With the majority of injuries to the ACJ seen in young males, the same applies to fractures of the clavicle¹⁸.

The main aim in treating fractures of the clavicle is to provide comfort and pain relief. Management options for both ACJ injuries as well as fractures of the clavicle vary widely, spanning from conservative treatment to fixation requiring surgical intervention with the latter including a variety of options from minimally invasive techniques¹⁹ to the application of a fixation plate. Whenever a fixation implant is to be selected, several factors drive the decision. The fit on bone of any fixation plate has a direct impact on the strength of the construct. However, current clavicular implants overlook the variations in geometry of the bone. In 2007, a paper describing the anatomy of the clavicle stated that gender specific anatomical features should be taken into consideration when performing intramedullary fixation of the clavicle². While the length, diameters and curvature of the clavicles measured were based on 196 embalmed specimens, cortical bone thickness and the medullary canal diameter were determined using only 10 fresh specimens. In a more recent article, it has been reported that cortical bone thickness and bone shape of the clavicle have large effects on bone responses until failure and on fracture location²⁰. This study emphasized the need for geometrical personalization of clavicle models in order to consider various age, gender and shape discrepancies. However, the radiological aspect of this study was based only on six clavicles with the biomechanical testing based on 18 clavicles from nine subjects with a mean age of 78. From a clinical standpoint, a larger number and much younger population should be studied, considering that fractures to the clavicle are most commonly seen in the twenties although comminuted fractures may be more common in the third and forth decades.

The relationship between clavicular length restoration post-fracture and functional outcome remains controversial. Some studies have concluded no observable reduction in shoulder function ^21,22,23, while others have stressed the importance of restoration of clavicular length post-fracture ^24,25. Previous literature has also stated that up to 30% of patients treated non-operatively develop unsatisfactory outcomes clinically, radiologically, and subjectively because of bony shortening, malunion, poor alignment or deforrnity ^24,25,26,27. In another study of outcome after closed treatment of the fractured clavicle, the majority of patients were not satisfied with the cosmetic deformity and 40% complained of impaired function²⁸. Although most fractures of the clavicle have a good prognosis and can be managed conservatively, the role of surgical intervention and its importance must not be forgotten.

In the literature, some studies focused on clavicle tests ^20,29,30,31, while others focused on geometry ^2,12,20,32. However, these studies had very small sample sizes as previously stated. As plate and intramedullary fixation are accepted and widely used methods of treatment, a study analyzing the shape and looking into the necessity for modifying modern implants in order to optimize fixation based on personalized bony geometry has much clinical relevance with regard to the management of clavicular fractures. One recent study set out to characterize variations in clavicular anatomy and determine the clinical applicability of an anatomic precontoured clavicular plate designed for fracture fixation³³. However, the authors themselves stated that their main limitation was that it was a two-dimensional analysis of plate fit rather than a three-dimensional analysis. By noting the shortcomings of the abovementioned studies, this thesis focuses on the anatomy of the clavicle and the analysis and application of it to the design of currently available clavicle fixation plates in both a systematic and structured manner.

The objective of this work was to determine how the addition of a calcium phosphate mineral phase to a collagen-based scaffold, designed for use in bone tissue engineering, affects the in-vitro and in-vivo scaffold degradation characteristics in addition to the rate of tissue healing as assessed by new bone formation and host immune response in a rat calvarial model.

In vitro analysis of the collagen calcium phosphate (CCP) scaffolds revealed minimal degradation and loss of mechanical properties over time in a non enzymatic degradation media, these results were similar to those of pure collagen (collagen) and collagen glycosaminogylcan (CollGAG) scaffolds. However, in a bacterial collagenases media the mineralised CCP scaffolds were relatively resistant to degradation compared to the collagen and CollGAG scaffolds.

The CollGAG and CCP scaffolds were then implanted into a 7mm trans-osseouscritically sized defect created in the calvarium of Wistar rats. Half of each group were pre-cultured with mesenchymal stem cells (MSC). Animals were sacrificed at 4 and 8 weeks post implantation. Quantitative histomorphometry identified significantly better rates of new bone formation in non MSC seeded scaffolds, with superior results for the mineralised collagen scaffold at 8 weeks (37.24%V13.15%, p<0.05). Scaffolds pre cultured with MSCs showed an accumulation of fibrous tissue at the periphery of the scaffold.

In the knowledge that macrophages play an important role in fracture healing and that this fibrous tissue surrounding the MSC seeded scaffolds appeared inflammatory in nature, immunohistochemical staining was performed to confirm the presence of macrophages (CD68) and to phenotype the macrophage response (CD163, CCR7). A marked macrophage response to the MSC seeded scaffolds, with only a moderate response to non seeded irnplants.was seen. Whilst all scaffold types demonstrated an M2 (immunomodulatory and tissue remodelling) macrophage phenotype response the location of this response was confined to the scaffold periphery in the MSC seeded group as opposed to areas of new bone formation in the non seeded group.

In conclusion this thesis demonstrates quantitatively superior new bone formation in non MSC seeded mineralised (CCP) collagen scaffolds. Aside from increasing the scaffolds mechanical properties the addition of a mineral phase also retards scaffold degradation. Furthermore, an appropriate macrophage response is necessary for successful bone deposition in collagen scaffolds and appears hindered by current tissue engineering approaches.

Several factors were shown to influence stability in compression. Axial stiffness was mainly influenced by the working length. On omission of the two innermost screws near the fracture site, axial stiffness decreased by 39%. Construct stability was also affected by the distance from the plate to the bone. Axial stiffness of the construct decreased by increasing the boneplate distance.

Increasing the post-fixation fracture angle and the fracture translation reduced construct stability, whereas fracture gap had no effect on construct stability when no bone contact occurred during loading.

Stress analysis of the LCP demonstrated that the maximum von Mises stresses were found in the innermost screws at the screw-head junction. Screw stresses decreased significantly with the removal of the two innermost screws.

When the stresses in the plate were isolated, the maximum von Mises stresses were concentrated at the outer edges of the two outermost empty screw holes. Maximum plate stresses also decreased with the removal of the two innermost screws, a pair at a time. Reduction in stresses was more pronounced when the first pair of innermost screws were removed.

Stress concentrations were localized to a point or a specific region of the implant. The majority of stresses were below the yield stress and would nothave led to permanent deformation. Despite this, these stress concentrations can indicate where fatigue failure might occur.

Removal of the distal cement plug in revision hip arthroplasty is a technically challenging procedure. Its location makes it difficult to visualise and this can lead to perforation or fracture of the surrounding bone during removal of the plug.

The primary aim of this work was to design a drill guide device that would guide a drill bit along a pre-determined path through the centre of the cement plug. This would then ensure its safe removal and thus decrease the risk of perforation or fracture of the surrounding bone. The design chosen was a pre-drilled femoral prosthesis. This prosthesis was then tested on a series of synthetic bones and cadaveric specimens. The two most common implants used in primary THA, Chamley and Exeter, were tested.

There were two other components to the study. Firstly, a radiographic assessment of all RHAs performed at Cappagh hospital over a one-year period was undertaken. Secondly, an experiment to assess the cutting forces experienced as the drill bit passes through the cement was designed. This was in an attempt to determine the most favourable drill bit characteristics for cement drilling.

In recent years, aberrant expression of growth factor receptor systems and dysregulation of downstream cell signaling molecules has been reported in a wide range of epithelial tumours including oral cancer. The insulin-like growth factor (IGF) system is well documented to have a critical role in growth and development and is implicated in tumourigenesis and progression. The IGF system consists of two ligands, IGF-I and IGF-II and six types of high-affinity IGF binding proteins, IGFBP-1 to -6. Both IGF-I and -11 mediate their biological effects via a cell membrane-bound receptor, IGF-1R. Over-expression of IGF-I, IGF-II and IGF-IR, or combinations of these, has been noted in a wide variety of carcinomas and is thought to modulate tumour cell motility, adhesion as well as influence angiogenesis.

The role of IGF in the development of oral carcinomas is less clear. The aim of this study was to investigate the expression, and roles, of components of the IGF system in OSCC ex vivo and in vitro. Firstly, the relationship between serum levels of IGF-I and its binding proteins in patients with oral cancer was studied. Blood samples were taken and the plasma was analysed. Cancer patients had low levels of IGF-I, but high levels of IGFBP-1 and -2 compared to control patients. Secondly, we decided to characterise IGF-I, IGF-II, and IGF-1R by investigating their expression and function in human oral epithelial cancer cell lines and normal cells maintained in short-term culture. Tumour cells over-expressed IGF-II and IGF-1 R genes and protein compared to normal cells, as determined by western blotting, immunocytochemistry and DNA manipulation techniques. This pattern of over-expression was also observed in oral biopsy material taken from oral cancer patients, as detected by northem blotting and immunohistology. Thirdly, the importance between increased IGF-1 R expression and malignant transformation was studied by looking at IGF signaling mechanisms in normal oral epithelial cells. We found that IGF-I and -11 rescued apoptotic cells via a P13-K signaling pathway, not MAPK.

Data from this study lends further evidence to the significance of IGF proteins in the development in OSCC.

The RCSl E-Portfolio offers students a secure, personal online learning space to store coursework, achievements and other documents relevant to their education. Since portfolio building is both demanding and time consuming,face validity is intuitively desirable. Our findings confirmed the EPortfolio is face valid compared to the traditional paper logbook and its benefit is transferable to medical students at all stages of undergraduate education. Its superiority over the paper logbook was particularly evidenced by the fact that E-Portfolio users were statistically more likely to refer to their data in the future than their logbook counterparts.

It has previously been reported in the literature that web-based portfolios have a motivating effect on students, a finding corroborated by our results. Graduate entry students using the E-Portfolio submitted significantly more assignments and recorded more clinical competencies than their logbook counterparts. Furthermore, almost 20% of students In the IC3 group submitted more E-Portfolio assignments than they were required to do.

Assessment is intrinsically important in the implementation of a successful EPortfolio. We correctly hypothesised that E-Portfolio assessment would reflect performance in high-stakes examinations. In addition, students in both the GEP and IC3 groups acknowledged the benefit of feedback received on case assignments. In the sub-intern group, feedback was not provided. As a result, almost half of the sub-interns specifically cited the lack of feedback as a negative feature of the E-Portfolio. The user satisfaction level in this group was significantly lower than in the other groups assessed. We concluded that the lack of assessment contributed to this finding.

On evaluating alternative methods of assessment, our findings indicated that while the E-Portfolio promotes self-assessment, there was no correlation between student assessment and tutor assessment. Standardised feedback on the performance of a suture task, on the other hand, was shown to be both effective and efficient and has the potential to significantly reduce resource implications of formal assessment by tutors.