A Two-Experiment Approach to Scaling in Biomechanics.

A new approach to scaled experimentation has recently appeared in the open literature where hitherto unknown similitude rules have been discovered. The impact of this discovery on biomechanics is the focus of this paper, where rules for one and two scaled experiments are assessed. Biomechanical experimentation is beset by problems that can hinder its successful implementation. Availability of resources, repeatability and variability of specimens, ethical compliance and cost are the most prominent. Physical modeling involving synthetic composite materials can be used to advantage and circumvent ethical concerns but is presently impeded by cost and the limited scope of standardized geometries. The increased flexibility of the new approach, combined with the application of substantially cheaper three-dimensional printed materials, is investigated here for bone biomechanical experiments consisting of mechanical tests for the validation of finite element models by means of digital image correlation. The microstructure of the scaled materials is analyzed using a laser confocal microscope followed by the construction and validation of numerical models by means of a Bland-Altman statistical analysis. Good agreement is obtained demonstrated with means under 18 microstrains (µÏµ) and limits of agreement below 83 µÏµ. Consequently, numerical results for the new similitude approach shows an average percentage error of 3.1% and 4.8% for the optimized results across all values. The two-scaled experiment approach results in a sevenfold improvement for the average difference values of strain when compared to the single-scaled experiment, so demonstrating the potential of the new approach.

Organic and inorganic equivalent models for analysis of red blood cell mechanical behaviour.

Experimental investigation into the mechanical response of red blood cells is presently impeded with the main impediments being the micro dimensions involved and ethical issues associated with in vivo testing. The widely employed alternative approach of computational modelling suffers from its own inherent limitations being reliant on precise constitutive and boundary information. Moreover, and somewhat critically, numerical computational models themselves are required to be validated by means of experimentation and hence suffer similar impediments. An alternative experimental approach is examined in this paper involving large-scale equivalent models manufactured principally from inorganic, and to lesser extent organic, materials. Although there presently exists no known method providing the means to investigate the mechanical response of red blood cells using scaled models simultaneously having different dimensions and materials, the present paper aims to develop a scaled framework based on the new finite-similitude theory that has appeared in the recent open literature. Computational models are employed to test the effectiveness of the proposed method, which in principle can provide experimental solution methods to a wide range of practical applications including the design of red-blood cell nanorobots and drug delivery systems. By means of experimentally validated numerical experiments under impact loading it is revealed that although exact prediction is not achieved good accuracy can nevertheless be obtained. Furthermore, it is demonstrated how the proposed approach for first time provides a means to relate models at different scales founded on different constitutive equations.

Zeroth-order finite similitude and scaling of complex geometries in biomechanical experimentation.

Scaled experimentation provides an alternative approach to full-scale biomechanical (and biological) testing but is known to suffer from scale effects, where the underlying system behaviour changes with scale. This phenomenon is arguably the overriding principal obstacle to the many advantages that scaled experimentation provides. These include reduced costs, materials and time, along with the eschewal of ethical compliance concerns with the application of substitute artificial materials as opposed to the use of hazardous biological agents. This paper examines the role scale effects play in biomechanical experimentation involving strain measurement and introduces a formulation that overtly captures scale dependencies arising from geometrical change. The basic idea underpinning the new scaling approach is the concept of space scaling, where a biomechanical experiment is scaled by the metaphysical mechanism of space contraction. The scaling approach is verified and validated with finite-element (FE) models and actual physical-trial experimentation using digital image correlation software applied to synthetic composite bone. The experimental design aspect of the approach allows for the selection of three-dimensional printing materials for trial-space analysis in a complex pelvis geometry. This aspect takes advantage of recent advancements in additive manufacturing technologies with the objective of countering behavioural distorting scale effects. Analysis is carried out using a laser confocal microscope to compare the trial and physical space materials and subsequently measured using surface roughness parameters. FE models were constructed for the left hemipelvis and results show similar strain patterns (average percentage error less than 10%) for two of the three trial-space material combinations. A Bland-Altman statistical analysis shows a good agreement between the FE models and physical experimentation and a good agreement between the physical-trial experimentation, providing good supporting evidence of the applicability of the new scaling approach in a wider range of experiments.

Off-axis dose distribution with stand-in and stand-off configurations for superficial radiotherapy treatments.

Current practice when delivering dose for superficial skin radiotherapy is to adjust the monitor units so that the prescribed dose is delivered to the central axis of the superficial unit applicator. Variations of source-to-surface distance due to patient's anatomy protruding into the applicator or extending away from the applicator require adjustments to the monitor units using the inverse square law. Off-axis dose distribution varies significantly from the central axis dose and is not currently being quantified. The dose falloff at the periphery of the field is not symmetrical in the anode-cathode axis due to the heel effect. This study was conducted to quantify the variation of dose across the surface being treated and model a simple geometric shape to estimate a patient's surface with stand-in and stand-off. Isodose plots and color-coded dose distribution maps were produced from scans of GAFChromic EBT-3 film irradiated by a Gulmay D3300 orthovoltage x-ray therapy system. It was clear that larger applicators show a greater dose falloff toward the periphery than smaller applicators. Larger applicators were found to have a lower percentage of points above 90% of central axis dose (SA90). Current clinical practice does not take this field variation into account. Stand-in can result in significant dose falloff off-axis depending on the depth and width of the protrusion, while stand-off can result in a flatter field due to the high-dose region near the central axis being further from the source than the peripheral regions. The central axis also received a 7% increased or decreased dose for stand-in or stand-off, respectively.

Scaling in biomechanical experimentation: a finite similitude approach.

Biological experimentation has many obstacles: resource limitations, unavailability of materials, manufacturing complexities and ethical compliance issues; any approach that resolves all or some of these is of some interest. The aim of this study is applying the recently discovered concept of finite similitude as a novel approach for the design of scaled biomechanical experiments supported with analysis using a commercial finite-element package and validated by means of image correlation software. The study of isotropic scaling of synthetic bones leads to the selection of three-dimensional (3D) printed materials for the trial-space materials. These materials conforming to the theory are analysed in finite-element models of a cylinder and femur geometries undergoing compression, tension, torsion and bending tests to assess the efficacy of the approach using reverse scaling of the approach. The finite-element results show similar strain patterns in the surface for the cylinder with a maximum difference of less than 10% and for the femur with a maximum difference of less than 4% across all tests. Finally, the trial-space, physical-trial experimentation using 3D printed materials for compression and bending testing provides a good agreement in a Bland-Altman statistical analysis, providing good supporting evidence for the practicality of the approach.

Budget impact model of Mydrane®, a new intracameral injectable used for intra-operative mydriasis, from a UK hospital perspective.

BACKGROUND: During cataract surgery, maintaining an adequate degree of mydriasis throughout the entire operation is critical to allow for visualisation of the capsulorhexis and the crystalline lens. Good anaesthesia is also essential for safe intraocular surgery. Mydrane® is a new injectable intracameral solution containing two mydriatics (tropicamide 0.02% and phenylephrine 0.31%) and one anaesthetic (lidocaine 1%) that was developed as an alternative to the conventional topical pre-operative mydriatics used in cataract surgery. This study aimed to estimate the budget impact across a one year time frame using Mydrane® instead of topical dilating eye drops, for a UK hospital performing 3,000 cataract operations a year. METHODS: A budget impact model (BIM) was developed to compare the economic outcomes associated with the use of Mydrane® versus topical drops (tropicamide 0.5% and phenylephrine 10%) in patients undergoing cataract surgery in a UK hospital. The outcomes of interest included costs and resource use (e.g. clinician time, mydriasis failures, operating room time, number of patients per vial of therapy etc.) associated with management of mydriasis in patients undergoing cataract surgery. All model inputs considered the UK hospital perspective without social or geographical variables. Deterministic sensitivity analyses were also performed to assess the model uncertainty. RESULTS: Introduction of Mydrane® is associated with a cost saving of £6,251 over 3,000 cataract surgeries in one year. The acquisition costs of the Mydrane® (£18,000 by year vs. £3,330 for eye drops) were balanced by substantial reductions in mainly nurses' costs and time, plus a smaller contribution from savings in surgeons' costs (£20,511) and lower costs associated with auxiliary dilation (£410 due to avoidance of additional dilation methods). Results of the sensitivity analyses confirmed the robustness of the model to the variation of inputs. Except for the duration of one session of eye drop instillation and the cost of Mydrane®, Mydrane® achieved an incremental cost gain compared to tropicamide/phenylephrine eye drops. CONCLUSIONS: Despite a higher acquisition cost of Mydrane®, the budget impact of Mydrane® on hospital budgets is neutral. Mydrane® offers a promising alternative to traditional regimes using eye drops, allowing for a better patient flow and optimisation of the surgery schedule with neutral budget impact.

Budget impact assessment of Aprokam® compared with unlicensed cefuroxime for prophylaxis of post-cataract surgery endophthalmitis.

BACKGROUND: Intracameral cefuroxime is recommended as prophylaxis against postoperative endophthalmitis (POE) following cataract surgery. Aprokam is the only licensed product for prophylaxis of POE, although unlicensed intracameral cefuroxime may be administered using pre-filled syringes (PFS), either prepared in hospital by reconstituting cefuroxime via serial dilution (prepared PFS), or commercially purchased (purchased PFS). This study aimed to estimate the potential budget impact of using Aprokam over unlicensed cefuroxime for intracameral administration. METHODS: A budget impact model (BIM) was developed from UK NHS hospital perspective to estimate the economic impact of adopting Aprokam compared with purchased PFS or prepared PFS for the prophylaxis of POE following cataract surgery over a 5-year time horizon. The BIM incorporated direct costs only, associated with the acquisition, delivery, storage, preparation, and administration of cefuroxime. Resource utilisation costs were also incorporated; resource utilisation was sourced from a panel survey of hospital pharmacists, surgeons, and theatre nurses who are involved in the delivery, storage, preparation, quality assurance, or administration of cefuroxime formulations. Unit costs were sourced from NHS sources; drug acquisition costs were sourced from BNF. The model base case used a hypothetical cohort comprising of 1000 surgeries in the first year and followed a 5.2 % annual increase each year. RESULTS: The model predicts Aprokam is cost saving compared with purchased PFS, with a modest increase compared prepared PFS over 5 years. There are total savings of £ 3490 with Aprokam compared with purchased PFS, driven by savings in staff costs that offset greater drug acquisition costs. Compared with prepared PFS, there are greater drug acquisition costs which drive an increased total cost over 5 years of £ 13,177 with Aprokam, although there are substantial savings in staff costs as well as consumables and equipment costs. CONCLUSIONS: The lower direct costs of using Aprokam compared with purchased PFS presents a strong argument for the adoption of Aprokam where purchased PFS is administered. The additional benefits of Aprokam include increased liability coverage and possible reduction in dilution errors and contaminations; as such, in hospitals where unlicensed prepared PFS is used, modest additional resources should be allocated to adoption of Aprokam.