The common TMEM173 HAQ, AQ alleles rescue CD4 T cellpenia, restore T-regs, and prevent SAVI (N153S) inflammatory disease in mice.

The significance of STING (encoded by the TMEM173 gene), in tissue inflammation and cancer immunotherapy has been increasingly recognized. Intriguingly, common human STING alleles R71H-G230A-R293Q (HAQ) and G230A-R293Q (AQ) are carried by ~60% of East Asians and ~40% of Africans, respectively. Here, we examine the modulatory effects of HAQ, AQ alleles on STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function human STING mutations. CD4 T cellpenia is evident in SAVI patients and mouse models. Using STING knock-in mice expressing common human STING alleles HAQ, AQ, and Q293, we found that HAQ, AQ, and Q293 splenocytes resist STING-mediated cell death ex vivo, establishing a critical role of STING residue 293 in cell death. The HAQ/SAVI(N153S) and AQ/SAVI(N153S) mice did not have CD4 T cellpenia. The HAQ/SAVI(N153S), AQ/SAVI(N153S) mice have more (~10-fold, ~20-fold, respectively) T-regs than WT/SAVI(N153S) mice. Remarkably, while they have comparable TBK1, IRF3, and NFκB activation as the WT/SAVI, the AQ/SAVI mice have no tissue inflammation, regular body weight, and normal lifespan. We propose that STING activation promotes tissue inflammation by depleting T-regs cells in vivo. Billions of modern humans have the dominant HAQ, AQ alleles. STING research and STING-targeting immunotherapy should consider TMEM173 heterogeneity in humans.

A novel method of determining the active drag profile in swimming via data manipulation of multiple tension force collection methods.

A novel method aimed at evaluating the active drag profile during front-crawl swimming is proposed. Fourteen full trials were conducted with each trial using a stationary load cell set-up and a commercial resistance trainer to record the tension force in a rope, caused by an athlete swimming. Seven different stroke cycles in each experiment were identified for resampling time dependent data into position dependent data. Active drag was then calculated by subtracting resistance trainer force data away from the stationary load cell force data. Mean active drag values across the stroke cycle were calculated for comparison with existing methods, with mean active drag values calculated between 76 and 140 N depending on the trial. Comparing results with established active drag methods, such as the Velocity Perturbation Method (VPM), shows agreement in the magnitude of the mean active drag forces. Repeatability was investigated using one athlete, repeating the load cell set-up experiment, indicating results collected could range by 88 N depending on stroke cycle position. Variation in results is likely due to inconsistencies in swimmer technique and power output, although further investigation is required. The method outlined is proposed as a representation of the active drag profile over a full stroke cycle.

Nicotine Exacerbates TAAD Formation Induced by Smooth Muscle-Specific Deletion of the TGF-ß Receptor 2.

Tobacco smoke is an established risk factor for thoracic aortic aneurysms and dissections (TAAD). However, little is known about its underlying mechanisms due to the lack of validated animal models. The present study developed a mouse model that may be utilized to investigate exacerbation of TAAD formation by mimetics of tobacco smoke. TAADs were created via inducible deletion of smooth muscle cell-specific Tgfbr2 receptors. Using this model, the first set of experiments evaluated the efficacy of nicotine salt (34.0 mg/kg/day), nicotine free base (NFB, 5.0 mg 90-day pellets), and cigarette smoke extract (0.1 ml/mouse/day). Compared with their respective control groups, only NFB pellets promoted TAAD dilation (23 ± 3% vs. 12 ± 2%, P = 0.014), and this efficacy was achieved at a cost of >50% acute mortality. Infusion of NFB with osmotic minipumps at extremely high, but nonlethal, doses (15.0 or 45.0 mg/kg/day) failed to accelerate TAAD dilation. Interestingly, costimulation with ß-aminopropionitrile (BAPN) promoted TAAD dilation and aortic rupture at dosages of 3.0 and 45.0 mg/kg/day, respectively, indicating that BAPN sensitizes the response of TAADs to NFB. In subsequent analyses, the detrimental effects of NFB were associated with clustering of macrophages, neutrophils, and T-cells in areas with structural destruction, enhanced matrix metalloproteinase- (MMP-) 2 production, and pathological angiogenesis with attenuated fibrosis in the adventitia. In conclusion, modeling nicotine exacerbation of TAAD formation requires optimization of chemical form, route of delivery, and dosage of the drug as well as the pathologic complexity of TAADs. Under the optimized conditions of the present study, chronic inflammation and adventitial mal-remodeling serve as critical pathways through which NFB exacerbates TAAD formation.

Characterisation and constitutive modelling of biaxially stretched poly(L-lactic acid) sheet for application in coronary stents.

A poly(L-lactic acid) stent is exposed to a variety of processing techniques, temperatures and environmental conditions during its lifecycle, from the manufacturing process, to crimping through to deployment within the body. The effect of the biaxial stretching procedure and the effects of temperature and extension rate (post-processing) on the mechanical response of poly(L-lactic acid) are hereby investigated, and a constitutive model calibrated against experimental data is proposed. Dumb-bell specimens were punched from biaxially stretched sheets subjected to different processing histories, and tested under uniaxial tension at various temperatures (20, 37 and 55 °C) and extension rates (1, 5 and 10 mm/min). A Design of Experiments methodology was employed to identify the parameters that had the most significant effect on the mechanical response of the polymer. Results show that the elastic modulus and yield strength of the stretched sheets are strongly dependent on the aspect ratio of the biaxial deformation, along with the temperature during uniaxial deformation (post-processing). In contrast, these mechanical properties were not heavily dependent on extension rate (post-processing). A transversely isotropic, elastic-plastic constitutive model for finite element implementation is proposed, with the intention that it may be used as a design tool for developing high stiffness, thin-strut polymeric stents that contend with the performance of their metallic counterparts.

Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer.

BACKGROUND: In early-stage pancreatic cancer, there are currently no biomarkers to guide selection of therapeutic options. This prospective biomarker trial evaluated the feasibility and potential clinical utility of circulating tumor DNA (ctDNA) analysis to inform adjuvant therapy decision making. MATERIALS AND METHODS: Patients considered by the multidisciplinary team to have resectable pancreatic adenocarcinoma were enrolled. Pre- and post-operative samples for ctDNA analysis were collected. PCR-based-SafeSeqS assays were used to identify mutations at codon 12, 13 and 61 of KRAS in the primary pancreatic tumor and to detect ctDNA. Results of ctDNA analysis were correlated with CA19-9, recurrence-free and overall survival (OS). Patient management was per standard of care, blinded to ctDNA data. RESULTS: Of 112 patients consented pre-operatively, 81 (72%) underwent resection. KRAS mutations were identified in 91% (38/42) of available tumor samples. Of available plasma samples (N = 42), KRAS mutated ctDNA was detected in 62% (23/37) pre-operative and 37% (13/35) post-operative cases. At a median follow-up of 38.4 months, ctDNA detection in the pre-operative setting was associated with inferior recurrence-free survival (RFS) [hazard ratio (HR) 4.1; P = 0.002)] and OS (HR 4.1; P = 0.015). Detectable ctDNA following curative intent resection was associated with inferior RFS (HR 5.4; P < 0.0001) and OS (HR 4.0; P = 0.003). Recurrence occurred in 13/13 (100%) patients with detectable ctDNA post-operatively, including in seven that received gemcitabine-based adjuvant chemotherapy. CONCLUSION: ctDNA studies in localized pancreatic cancer are challenging, with a substantial number of patients not able to undergo resection, not having sufficient tumor tissue for analysis or not completing per protocol sample collection. ctDNA analysis, pre- and/or post-surgery, is a promising prognostic marker. Studies of ctDNA guided therapy are justified, including of treatment intensification strategies for patients with detectable ctDNA post-operatively who appear at very high risk of recurrence despite gemcitabine-based adjuvant therapy.

Processing-property relationships of biaxially stretched poly(L-lactic acid) sheet for application in coronary stents.

The development of coronary stents from poly(L-lactic acid) requires knowledge of its mechanical properties and the effects of manufacturing processes on those properties. The effects of the biaxial stretching procedure on the mechanical and microstructural properties of poly(L-lactic acid) are hereby investigated. The mechanical properties were evaluated before and after biaxial stretching, with a Design of Experiments methodology employed to identify processing parameters that had the most significant effect on the elastic modulus and yield strength of the biaxially stretched sheets. Microstructural characterisation was performed using differential scanning calorimetry to evaluate crystallinity and thermal transitions of the biaxially stretched sheets. The results show that the mechanical properties of the stretched sheets are highly dependent on the extent of stretch ratio applied during processing; however, neither the elastic modulus nor yield strength are directly attributable to crystallinity, but are affected by the degree of amorphous orientation. The results of this study have the potential to be applied in the design of high stiffness, thin-strut polymeric expandable scaffolds for the application of coronary stents.

Dual endothelin-1 receptor antagonism attenuates platelet-mediated derangements of blood coagulation in Eisenmenger syndrome.

Essentials Eisenmenger syndrome is characterised by thrombotic and hemorrhagic risks of unclear aetiology. Calibrated automated thrombography was used to assess these coagulation derangements. Platelet activity supported abnormalities in procoagulant and anticoagulant pathway function. Endothelin-1 antagonism appeared to ameliorate these derangements. SUMMARY: Aims The mechanisms underlying the competing thrombotic and hemorrhagic risks in Eisenmenger syndrome are poorly understood. We aimed to characterize derangements of blood coagulation and to assess the effect of dual endothelin-1 receptor antagonism in modulating hemostasis in this rare disorder. Methods In a 10-month recruitment period at a tertiary cardiology referral center, during which time there were over 14 000 outpatient consultations, consecutive subjects with Eisenmenger syndrome being considered for macitentan therapy (n = 9) and healthy volunteers (n = 9) were recruited. Plasma thrombin generation in platelet-rich and platelet-poor plasma was assessed by calibrated automated thrombography prior to and following therapy. Results Median peak plasma thrombin generation was higher in platelet-rich plasma obtained from Eisenmenger syndrome subjects relative to controls (median peak thrombin [25th-75th percentile]: 228.3 [206.5-258.6] nm vs. 169.9 [164.3-215.8] nm), suggesting a critical mechanistic role for platelets in supporting abnormal hypercoagulability in Eisenmenger syndrome. Abnormal enhanced sensitivity to the anticoagulant activity of activated protein C was also observed in platelet-rich plasma in Eisenmenger syndrome, suggesting that derangements of platelet activity may influence the activity of anticoagulant pathways in a manner that might promote bleeding in this disease state. Following 6 months of macitentan therapy, attenuations in the derangements in both procoagulant and anticoagulant pathways were observed. Conclusions Abnormal platelet activity contributes to derangements in procoagulant and anticoagulant pathways in Eisenmenger syndrome. Therapies targeting the underlying vascular pathology appear to ameliorate these derangements and may represent a novel strategy for the management of the competing prothrombotic and hemorrhagic tendencies in this disorder.

Effect of combined flexion and external rotation on measurements of the proximal femur from anteroposterior pelvic radiographs.

INTRODUCTION: Fixed flexion and external rotation contractures are common in patients with hip osteoarthritis and, in particular, before total hip replacement (THR). We aimed to answer the following question: how does combined flexion and external rotation of the femur influence the radiographic assessment of (1) femoral offset (FO) (2) neck-shaft angle (NSA) and (3) distance (parallel to the femoral axis) from greater trochanter to femoral head center (GT-FHC)? HYPOTHESIS: Combined flexion and external rotation impact the accuracy of two-dimensional (2D) proximal femur measurements. MATERIALS AND METHODS: Three-dimensional (3D) CT segmentations of the right femur from 30 male and 42 female subjects were acquired and used to build a statistical shape model. A cohort (n=100; M:F=50:50) of shapes was generated using the model. Each 3D femur was subjected to external rotation (0°-50°) followed by flexion (0°-50°) in 10° increments. Simulated radiographs of each femur in these orientations were produced. Measurements of FO, NSA and GT-FHC were automatically taken on the 2D images. RESULTS: Combined rotations influenced the measurement of FO (p<0.05), NSA (p<0.001), and GT-FHC (p<0.001). Femoral offset was affected predominantly by external rotation (19.8±2.6mm [12.2 to 26.1mm] underestimated at 50°); added flexion in combined rotations only slightly impacted measurement error (20.7±3.1mm [13.2 to 28.8mm] underestimated at 50° combined). Neck-shaft angle was reduced with flexion when external rotation was low (9.5±2.1° [4.4 to 14.2°] underestimated at 0° external and 50° flexion) and increased with flexion when external rotation was high (24.4±3.9° [15.7 to 31.9°] overestimated at 50° external and 50° flexion). Femoral head center was above GT by 17.0±3.4mm [3.9 to 22.1mm] at 50° external and 50° flexion. In contrast, in neutral rotation, FHC was 12.2±3.4mm [3.9 to 22.1mm] below GT. DISCUSSION: This investigation adds to current understanding of the effect of femoral orientation on preoperative planning measurements through the study of combined rotations (as opposed to single-axis). Planning measurements are shown to be significantly affected by flexion, external rotation, and their interaction. LEVEL OF EVIDENCE: IV Biomechanical study.

Exploring the perspectives of 10-, 11-, and 12-year-old primary school students on physical activity engagement-"'Cause you can't just be sitting at a desk all the time!"

BACKGROUND: Research indicates that 91% of Canadian children are not engaging in enough physical activity (PA) to achieve health benefits. Physical education (PE) classes have been identified as a way to improve child health by facilitating engagement in movement-based activities. The daily physical activity (DPA) initiative was created with similar intentions and requires that students participate in at least 20 min of PA daily via PE classes and/or during instructional time for other subjects. Despite recommendations that 150 min of exercise/play be incurred weekly through either avenue, nearly half of Canadian schools fail to achieve this goal. The disconnect between PA-related school policies and low reported participation rates suggests that additional research is warranted. The purpose of this study was to explore the perspectives of primary students regarding the facilitators, barriers, and recommendations for PA engagement at their schools. METHODS: Researchers conducted nine group interviews with 53 children aged 10-12, representing six primary schools in Northwestern Ontario using a semi-structured interview format. Sessions were analysed using inductive content analysis. RESULTS: Participants discussed several facilitators of PA including enjoying activities (alleviating boredom and participating with others), accomplishment (skill building and enhanced self-image), and benefits in the classroom (thinking clearly and enhanced readiness to learn). Barriers to PA participation included school rules and culture (PA/PE restrictions, heavy workload, and "no work, no PA"), personal struggles (physical challenges and varied skill levels), and technology (being addictive and a replacement for being active). Recommendations for enhancing engagement that were outlined by the children centred around PE and daily physical activity (increase opportunities and involve students in planning/delivery) and recess-based themes (decrease focus on safety and make equipment more available). CONCLUSION: These student perspectives and related recommendations may be beneficial for administrators and teachers in similar contexts who are seeking to enhance PA engagement among students with the goal of improving child health.

Critical review: Injectability of calcium phosphate pastes and cements.

Calcium phosphate cements (CPC) have seen clinical success in many dental and orthopaedic applications in recent years. The properties of CPC essential for clinical success are reviewed in this article, which includes properties of the set cement (e.g. bioresorbability, biocompatibility, porosity and mechanical properties) and unset cement (e.g. setting time, cohesion, flow properties and ease of delivery to the surgical site). Emphasis is on the delivery of calcium phosphate (CaP) pastes and CPC, in particular the occurrence of separation of the liquid and solid components of the pastes and cements during injection; and established methods to reduce this phase separation. In addition a review of phase separation mechanisms observed during the extrusion of other biphasic paste systems and the theoretical models used to describe these mechanisms are discussed. STATEMENT OF SIGNIFICANCE: Occurrence of phase separation of calcium phosphate pastes and cements during injection limits their full exploitation as a bone substitute in minimally invasive surgical applications. Due to lack of theoretical understanding of the phase separation mechanism(s), optimisation of an injectable CPC that satisfies clinical requirements has proven difficult. However, phase separation of pastes during delivery has been the focus across several research fields. Therefore in addition to a review of methods to reduce phase separation of CPC and the associated constraints, a review of phase separation mechanisms observed during extrusion of other pastes and the theoretical models used to describe these mechanisms is presented. It is anticipated this review will benefit future attempts to develop injectable calcium phosphate based systems.

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Systematic review with network meta-analysis: pharmacological prophylaxis against post-ERCP pancreatitis.

BACKGROUND: The efficacy of many pharmacological agents for preventing post-ERCP pancreatitis (PEP) has been evaluated in randomised controlled trials (RCTs), but it is unclear which agent(s) should be used in clinical practice. Network meta-analyses of RCTs are used to simultaneously compare several agents to determine their relative efficacy and identify priority agents for comparison in future RCTs. AIM: To evaluate pharmacological agents for the prevention of PEP by conducting a network meta-analysis of RCTs. METHODS: We searched MEDLINE, EMBASE and Cochrane Library databases for RCTs that evaluated the efficacy of agents for preventing PEP. RCTs were simultaneously analysed using random-effects network meta-analysis under the Bayesian framework to identify the best agents. The efficacy of agents was ordered according to the probability of being ranked as any of the top three best performing agents. RESULTS: The network meta-analysis included 99 RCTs evaluating 16 agents in 25 313 patients. Topical epinephrine (adrenaline) was the most efficacious agent with 85.9% probability of ranking among the top three agents, followed by nafamostat (51.4%), antibiotics (44.5%) and NSAIDs (42.8%). However, in a sensitivity analysis including only rectal NSAIDs, NSAIDs moved from fourth rank to second (58.1%). Patients receiving topical epinephrine, compared with placebo, had a 75% reduced risk of PEP (OR 0.25, 95% probability interval 0.06-0.66). CONCLUSIONS: Topical epinephrine and rectal NSAIDs are the most efficacious agents for preventing post-ERCP pancreatitis, based on existing RCTs. Combinations of these agents, which act on different steps in the pathogenesis of post-ERCP pancreatitis, should be evaluated in future trials.

How can cells sense the elasticity of a substrate? An analysis using a cell tensegrity model.

A eukaryotic cell attaches and spreads on substrates, whether it is the extracellular matrix naturally produced by the cell itself, or artificial materials, such as tissue-engineered scaffolds. Attachment and spreading require the cell to apply forces in the nN range to the substrate via adhesion sites, and these forces are balanced by the elastic response of the substrate. This mechanical interaction is one determinant of cell morphology and, ultimately, cell phenotype. In this paper we use a finite element model of a cell, with a tensegrity structure to model the cytoskeleton of actin filaments and microtubules, to explore the way cells sense the stiffness of the substrate and thereby adapt to it. To support the computational results, an analytical 1D model is developed for comparison. We find that (i) the tensegrity hypothesis of the cytoskeleton is sufficient to explain the matrix-elasticity sensing, (ii) cell sensitivity is not constant but has a bell-shaped distribution over the physiological matrix-elasticity range, and (iii) the position of the sensitivity peak over the matrix-elasticity range depends on the cytoskeletal structure and in particular on the F-actin organisation. Our model suggests that F-actin reorganisation observed in mesenchymal stem cells (MSCs) in response to change of matrix elasticity is a structural-remodelling process that shifts the sensitivity peak towards the new value of matrix elasticity. This finding discloses a potential regulatory role of scaffold stiffness for cell differentiation.

Computer simulating a clinical trial of a load-bearing implant: an example of an intramedullary prosthesis.

Computational modelling is becoming ever more important for obtaining regulatory approval for new medical devices. An accepted approach is to infer performance in a population from an analysis conducted for an idealised or 'average' patient; we present here a method for predicting the performance of an orthopaedic implant when released into a population--effectively simulating a clinical trial. Specifically we hypothesise that an analysis based on a method for predicting the performance in a population will lead to different conclusions than an analysis based on an idealised or 'average' patient. To test this hypothesis we use a finite element model of an intramedullary implant in a bone whose size and remodelling activity is different for each individual in the population. We compare the performance of a low Young's modulus implant (E=20 GPa) to one with a higher Young's modulus (200 GPa). Cyclic loading is applied and failure is assumed when the migration of the implant relative to the bone exceeds a threshold magnitude. The analysis for an idealised of 'average' patient predicts that the lower modulus device survives longer whereas the analysis simulating a clinical trial predicts no statistically-significant tendency (p=0.77) for the low modulus device to perform better. It is concluded that population-based simulations of implant performance-simulating a clinical trial-present a very valuable opportunity for more realistic computational pre-clinical testing of medical devices.

Verification and implementation of a modified split Hopkinson pressure bar technique for characterizing biological tissue and soft biosimulant materials under dynamic shear loading.

Modeling human body response to dynamic loading events and developing biofidelic human surrogate systems require accurate material properties over a range of loading rates for various human organ tissues. This work describes a technique for measuring the shear properties of soft biomaterials at high rates of strain (100-1000 s(-1)) using a modified split Hopkinson pressure bar (SHPB). Establishing a uniform state of stress in the sample is a fundamental requirement for this type of high-rate testing. Input pulse shaping was utilized to tailor and control the ramping of the incident loading pulse such that a uniform stress state could be maintained within the specimen from the start of the test. Direct experimental verification of the stress uniformity in the sample was obtained via comparison of the force measured by piezoelectric quartz force gages on both the input and the output sides of the shear specimen. The technique was demonstrated for shear loading of silicone gel biosimulant materials and porcine brain tissue. Finite element simulations were utilized to further investigate the effect of pulse shaping on the loading rate and rise time. Simulations also provided a means for visualization of the degree of shear stress and strain uniformity in the specimen during an experiment. The presented technique can be applied to verify stress uniformity and ensure high quality data when measuring the dynamic shear modulus of soft biological simulants and tissue.

Knowledge, attitudes and beliefs towards injury prevention: a population-based telephone survey.

Public knowledge and beliefs about injury prevention are currently poorly understood. A total of 1030 residents in the State of Queensland, Australia, responded to questions about injury prevention in or around the home, on the roads, in or on the water, at work, deliberate injury and responsibility for preventing deliberate injury allowing for comparison with reported injury prevalence data. Overall, the youngest members of society were identified as being the most vulnerable to deliberate injury with young adults accounting for 59% of responses aligning with reported data. However, younger adults failed to indicate an awareness of their own vulnerability to deliberate injury in alcohol environments even though 61% of older respondents were aware of this trend. Older respondents were the least inclined to agree that they could make a difference to their own safety in or around the home but were more inclined to agree that they could make a difference to their own safety at work. The results are discussed with a view to using improved awareness of public beliefs about injury to identify barriers to the uptake of injury prevention strategies (e.g. low perceived injury risk) as well as areas where injury prevention strategies may receive public support.

A method to reconstruct patient-specific proximal femur surface models from planar pre-operative radiographs.

Three-dimensional reconstruction from volumetric medical images (e.g. CT, MRI) is a well-established technology used in patient-specific modelling. However, there are many cases where only 2D (planar) images may be available, e.g. if radiation dose must be limited or if retrospective data is being used from periods when 3D data was not available. This study aims to address such cases by proposing an automated method to create 3D surface models from planar radiographs. The method consists of (i) contour extraction from the radiograph using an Active Contour (Snake) algorithm, (ii) selection of a closest matching 3D model from a library of generic models, and (iii) warping the selected generic model to improve correlation with the extracted contour. This method proved to be fully automated, rapid and robust on a given set of radiographs. Measured mean surface distance error values were low when comparing models reconstructed from matching pairs of CT scans and planar X-rays (2.57-3.74mm) and within ranges of similar studies. Benefits of the method are that it requires a single radiographic image to perform the surface reconstruction task and it is fully automated. Mechanical simulations of loaded bone with different levels of reconstruction accuracy showed that an error in predicted strain fields grows proportionally to the error level in geometric precision. In conclusion, models generated by the proposed technique are deemed acceptable to perform realistic patient-specific simulations when 3D data sources are unavailable.