A method to improve the brazing between YSZ and Ti6Al4V by femtosecond laser surface machining is introduced. The highest strength of ~150 MPa (which is 95.2% higher than that of the flat YSZ/Ti6Al4V joint) is achieved when the processing speed is 200 μm/s. To understand the strengthen mechanism of the surface machining on the joint strength, image based models, based on the observed microstructure, have been used to probe the stress distribution in the joint. It is found that through surface machining on the ceramic, the residual stress distribution in ceramic becomes nonlinear. Upon shear testing, for the joint with a flat interface, the failure happens in the reaction layer and the out of plane stress in this layer is found to be tensile, which acts as the driving force for the crack generation and propagation. But for the joint with a rumpled interface, the compressive out of plane stress at the boundary of the grooves in the reaction layer could inhibit the propagation of the cracks. Finally, by surface machining on the ceramic, the maximum shear stress in the reaction layer is decreased, which could also help to improve the reliability of the joint. In these applications, the ceramic is often bonded with metals to realise its functional or mechanical applications. Active brazing5 is a practical method to join ceramics or join ceramics to metals, in which reactive elements such as Ti, Zr and Hf are incorporated into the brazing alloys to modify the chemistry of the ceramic surface and to improve the wettability and adhesion of the brazing alloy on ceramics. Numerous research8 has been carried out to investigate the active brazing between ceramics and metals and two main challenges are often encountered. The first one is the control of the reaction between the brazing alloy and the ceramics to avoid the excessive formation of brittle reaction products at the interface. This problem can often be properly solved by modifying the composition of the brazing alloy and using the optimised brazing parameters10. The other challenge is the residual stress generated from the mismatch of the coefficient of thermal expansion (CTE) between the ceramic and the metal. The residual stress is detrimental to the reliability of the joint and sometimes can directly lead to the failure of the joint. A considerable amount of literature has been published on strategies to relax the residual stress in ceramic/metal brazing joint. Three most commonly used methods are: (i) by applying a soft and ductile interlayer such as copper foil11, foam12 and niobium foil13 which could release the residual stress in the joint via plastic deformation. This method is considered to be of limited success because the soft interlayer usually has relatively low melting temperature and the addition of the interlayer will inevitably be detrimental to the high temperature mechanical properties of the joint14. (ii) By applying an interlayer with a CTE value between the two substrates, which could form a gradient structure in the joint and moderate the residual stress distribution15 and (iii) by incorporating secondary phases which usually have a low CTE17 into the brazing alloy to tailor the CTE of the brazing alloy. For the last two methods, the additional interlayer or secondary phases must be compatible in both CTE and chemical composition with the material system in the brazing joint. However, sometimes it can be quite challenging to find proper candidates. Thus it is desirable to develop a novel method to optimise the residual stress distribution in ceramic/metal brazing joint.Yttria stabilised zirconia (YSZ) is a ceramic material widely used as thermal barrier coatings18. Improved mechanical keying through a rough interface profile is widely used in ceramic/metal systems to increase the interface adhesion and the lifetimes of the components19. It was found that this undulate interface could have a considerable influence on the residual stress distribution across the coating20. Thus it is expected that a well-designed rumpled interface for a brazing joint may also be able to optimise the residual stress distribution and benefit the bonding quality. Some research has been carried out to modify the surface morphology of ceramic prior to brazing. Xiong et al.21 machined a series of rectangular grooves on the surface of C/C composite material and then brazed it with Ti6Al4V alloy. It was predicted by FE (Finite Element) models that the residual stress distribution in the joint was modified and the shear strength of the joint was found to be increased. Shen et al.22 and Hernandez et al.23 machined the surface of C/C and Cf/SiC composite materials by hole drilling before brazing and achieved strengthened joint with Ni-based superalloy and titanium alloy. However, the depth of the patterns machined usually ranges from several hundred microns to several millimetres, which might be detrimental to the mechanical properties of the substrates. Femtosecond laser has become one of the most promising methods for patterning the surface of ceramics26 and metals29 because it could create relatively shallow grooves with little thermal damage. Yang et al.30 carried out surface machining on alumina surface via femtosecond laser and the achieved grooves were less than 100 μm deep. The strength of the joint with stainless steel is about 2.7 times higher than that with a flat interface. The effect of the laser power on the joint strength was investigated and the optimised laser power was found to be 0.3 W. Unfortunately, the effect of the machining speed which is an important parameter for laser machining31 on the microstructure and mechanical property of the joint was not discussed. The authors also predict the residual stress distribution along the interface by FE models and found it was altered by the surface machining. This result, however, has failed to present the residual stress distribution in the ceramic substrate near the interface and the reaction layer adjacent to the ceramic where the actual failure usually happens. And up to now, no research is available on the effect of surface machining of YSZ on the residual stress distribution in the interface area.Residual stress is the driving force for the failure of the ceramic coatingset al.32 developed an analytical model to calculate the residual stress distribution as a function of depth in the brazing joint. It was predicted when the CTE of ceramic is smaller than that of the metal, the residual stress is compressive in the ceramic and increases from the surface to the interface. FE models have also been utilised to investigate the residual stress distribution in brazing joints between ceramic and metals such as Si3N4/Invar33, BN/AISI 1045 steel34, alumina/Kovar35 and zirconia/cast iron36. The results generally show that the residual stress in ceramic is compressive. However, all the previous research has only been restricted to using artificial or simplified models which regard the brazing seam as a homogeneous layer and all the interfaces are flat. In reality, brazing joints usually have a complex microstructure which consists of various phases with undulated morphology5, which could have great influence on the residual stress distribution. Unfortunately, no previous study has taken the morphology of the phases into consideration when investigating the residual stress distribution in the joint.Residual stress has a pivotal role in the reliability of the brazing joint and a considerable number of research has been carried out to model its distribution in the joint. Iancu 37 and porous materials39. Therefore, it is expected that the residual stress distribution in a brazing joint could be modelled using a similar approach.Image based modelling is a method which incorporates real microstructure of material into FE models. This method has been successfully applied to investigate the residual stress distribution in materials with relatively complex microstructure such as thermal barrier coatings (TBC)In this study, a new method to modify the residual stress distribution in a YSZ/Ti6Al4V alloy brazing joint and to improve the joining quality via femtosecond laser surface machining is introduced. The effect of the machined surface morphology on the microstructure and the mechanical properties of the joint are studied. The effect of the surface machining on the residual stress distribution and stress distribution during shear testing in the brazing joint is investigated by image based models based on the observed microstructure of the joint.The surface morphologies of YSZ after machining by femtosecond laser with different processing speeds are shown in Fig. 40.From Fig. 41. Thus in this paper, the previously investigated microstructure of the joint which is YSZ/TiO + Ti3Cu3O/Ag/TiCu2/TiCu/Ti2Cu/α + β Ti/Ti6Al4V is applied for further discussion. It can be seen that the surface machining process will not change the phase composition in the joint and mainly affect the interface morphology of the joint.The typical microstructure of the surface machined YSZ/Ti6Al4V joint brazed at 870 °C for 10 min and the corresponding element maps are shown in Fig. 42. Thus it can be inferred that to achieve a defect free joint, the machining speed should be higher than 100 μm/s. It is also noted that the width of the brazing seam decreases with the increasing of the groove depth. This is because part of the brazing filler needs to fill up the grooves and less brazing filler is left in the brazing seam.The microstructure of the joints achieved using the YSZ after surface machining with different machining speed as the substrates are shown in Fig. 43, which is considered to have a significant influence on the strength of the joint. Thus shear testing was carried out to investigate the effect of the surface machining on the strength of the joint. The direction of load is perpendicular to the direction of the grooves as shown in Fig. F) is applied to calculate the strength of the joint (τ), which is achieved by formula (1).A is the area of the nominal joined surface, which is 4 mm × 4 mm = 16 mm2 in this research.The interface morphology has a close relationship with the residual stress distribution near the interface41. The hardness distribution across the joint is shown in Fig. As shown in Fig. 44 or calculated using Jmatpro software.It can be seen that the surface machining could dramatically improve the shear strength of the joint but it has no large effect on the phase composition and the fracture position. The only feature it affects in the joint is the interface morphology which has a great influence on the residual stress distribution after brazing and stress distribution during the shear test near the interface region. Thus image based FE models are set up to study the effect of the surface machining on these two features. Figure 35, which increases from the surface to the interface in a uniform trend. However, the residual stress distribution near the rumpled interface shows significant differences. The residual stress is compressive, which first increases from the surface to the interface, then decreases and increases again to the interface, resulting in a “jump” feature in the residual stress trend. This phenomenon is similar to the residual stress distribution as a function of depth in thermal barrier coatings with a rumpled interface45. This residual stress trend indicates that despite a maximum residual stress value appears at the interface of the joint, there is another maximum residual stress value about 800–900 μm away from the interface. This phenomenon could be correlated to the morphology of the failed sample shown in Fig. In general, the failure of a layered structure such as the ceramic/metal joint and ceramic coatings consists of the following procedures: the generation of the cracks, the propagation and the connection of the generated cracks, and then the actual failure happens. These procedures are closely related to the residual stress distribution in the joint. Thus to understand the mechanism of improvement of the reliability of the YSZ/Ti6Al4V brazing joint by the surface machining on the YSZ substrate, the residual stress distribution in the joint was firstly investigated via FE modelling. The modelled residual stress distribution in the YSZ substrate and the reaction layer which is the failure position of the joint is shown in Fig. 46, some brazing joint between ceramic and metal may fail directly after the cooling procedure, where the crack leading to failure initiates from the edge of the ceramic near the interface. This modelling result corresponds well with this observation. YSZ is a kind of ceramic with relatively high fracture toughness and thus this kind of failure mode was not observed in our experiment. For the models which take the rumpled interface into consideration  may happen during the cooling process. To investigate the effect of the plastic deformation on the residual stress distribution in the joint, we set the yielding strength of silver as 85 MPa and the modelled result is shown in Fig. 48. Thus, hardness mapping measurements are carried out in the interface region of the YSZ substrate for the joint with rumpled and flat interface to validate the simulation results. It can be seen from Fig. It has been reported that the compressive stress could lead to a higher measured hardness and tensile stress results in a lower measured hardnessAs discussed above, the strength of the joint can be improved by carrying out surface machining on YSZ before brazing it with metal and the actual strength of the joint was measured by shear testing. So one more step which is the process of the shear test is added to the model after the cooling procedure. A displacement of 0.02 mm to the X-positive direction is applied on the Ti6Al4V substrate while the displacement in the X direction of the YSZ right edge and its rotation around the Z axis are fixed as zero to simulate the shear testing process in our experiment. The predicted stress distribution in YSZ after surface machining is shown in Fig. While the out of plane stress Fig.  of the cThe fracture of the joint was found to happen in the reaction layer. Thus to understand the mechanism for the improvement of the joint strength via surface machining on the YSZ substrate, the stress distribution in the reaction layer during the shear test is studied and the results are shown in Fig. 41. When the surface of the YSZ is machined by femtosecond laser, the out of plane stress in the reaction layer upon shear testing is greatly altered, which is shown in Fig. As shown in Fig. 49, upon shear testing, during which the value of shear stress keeps increasing, the failure could also be possibly generated by the shear stress. So the shear stress inside the reaction layer (where the failure happens) during the shear testing is predicted using the FE method. The result is shown in Fig. Even though ceramics are more resistant to shear stress than tensile stress−3 Pa at 870° for 5 min. The cooling rate was set as 10 °C/min to inhibit the possible cracking.The ceramic used in this study was 3 mol% YSZ with the size of 4 mm × 4 mm × 4 mm, and the Ti6Al4V alloy was machined into 10 mm × 6 mm × 3 mm pieces before the brazing procedure. The composition of the brazing filler is Ag-28Cu (wt%) and it was sandwiched between the ceramic and the metal. The thickness of the brazing filler was 50 μm and the size of which was 4 mm × 4 mm to fit the ceramic. The brazing process was carried out in a vacuum furnace under a vacuum lower than 2 × 10The surface machining of the YSZ was carried out in an air atmosphere using a Yb:KGW laser system , emitting at a wavelength of 1030 nm. The pulse energy was 200 μJ and the repetition rate was set as 1 kHz. The sample was mounted on a computer driven stage which could move in X and Y directions and help pinpoint the laser spot to the desired position on the surface of YSZ. The schematic depicting the geometry of the surface machining is shown in Fig. After brazing, the samples were mounted in resin, cross sectioned by the diamond cutting wheel, ground and polished to 1 μm finish. Before observation, the surface of the sample was coated by ~20 nm thick gold coating. The morphology of the machined YSZ surface and the microstructure of the joint were observed by SEM (Quanta 200) coupled with an EDS detector.50 in the Fiji software51 and Avizo Lite 9.0 software . Then the segmented images were imported into OOF252 to generate a mesh for FE model calculation. The meshing was carried out in an adaptive mesh generation approach which could adjust the element size depending on the microstructural features (mainly interface). The mesh was then exported as INP files and imported into an FE solver (Abaqus 6.13) to calculate the residual stress distribution. To investigate the effect of the surface machining on the residual stress distribution in the YSZ/Ti6Al4V joint, the uneven interface in the original segmented image was smeared out using the lasso tool in Avizo 9.0, and a flat interface which has a reaction layer with the same thickness was placed at the original position. Then this image was exported, meshed and the obtained model was solved. The predicted stress distribution was compared with that achieved using the actual microstructure to determine the effect of the surface machining on the stress distribution in a YSZ/Ti6Al4V joint.The achieved microstructure of the joint by SEM was saved as tiff files, and then these images were segmented using the trainable Weka segmentation pluginThe strength of the joint was evaluated by shear testing, which was carried out on a universal mechanical testing machine. The loading speed was 0.5 mm/min and for each test, at least 5 samples were used. The hardness evolution through the interfaces was measured using nanoindentation. The hardness in a matrix of 5 × 20 across the interface was measured and since the width of the brazing seam is small (<100 μm), to improve the resolution of the measurement, the matrix had an angle of 45° to the interface counterclockwise. The penetration depth of the indenter was fixed at 1000 nm and the distance between each indenter was 15 μm.Grooves can be successfully manufactured on the surface of the YSZ substrate using a femtosecond laser. The processing speed has no large effect on the width of the machined grooves, but with the decreasing of the processing speed, the depth of the machined grooves increase. The brazing alloy could fill up the grooves when the machining speed is no less than 200 μm/s and when the processing speed is lowered to 100 μm/s, defects can be observed at the sharp corner of grooves. Despite the interfacial morphology, the surface machining is found not to affect the microstructure of the joint and shear strength of the joint first increases with the processing speed and then decreases. The highest joining strength of 103 MPa is achieved when the processing speed is 200 μm/s which is about 95.2% higher than that using the flat YSZ as the substrate.According to image based modelling, the in plane residual stress in both the surface machined and flat YSZ substrate are compressive. The residual stress in the flat ceramic is increasing from surface to the interface in a uniform trend, while the residual stress in the surface machined first increases from the surface to the interface, decreases a little and then increases again to the interface. This results in a “jump” feature in the residual stress trend. Out of plane tensile residual stress concentration regions can be observed at the corner of the ceramic near the interface, while the surface machining could eliminate these tensile stress concentration regions. The in plane residual stress in the reaction layer for both the flat and the rumpled interface joint are tensile. The out of plane residual stress in the flat reaction layer is tensile and for the rumpled reaction layer, the residual stress at the concave is tensile while the residual stress becomes compressive at the boundary of the grooves.Upon shear testing, the in plane stress in the YSZ substrate for both the flat and the rumpled interface become unsymmetrical. The tensile out of plane stress in the YSZ can be found in both cases. For the joint with a rumpled interface, compressive stress is presented beside the region with tensile stress. The in plane stress in the reaction layer is tensile during shear testing for both the flat and the rumpled interface. The out of plane stress in the reaction layer is tensile in the joint with a flat interface which could drive the propagation of the cracks. The stress in the reaction layer at the concave of the rumpled interface during shear testing is tensile which may be the driving force for the generation for the cracks, but the propagation of the cracks will be inhibited by the compressive out of plane stress at the boundary of the grooves. The maximum shear stress in the reaction layer can be deceased by the surface machining of the YSZ substrate, which also increases the reliability of the joint.In this paper, a novel method to improve the bonding between YSZ and Ti6Al4V alloy is developed by surface micromachining on the YSZ substrate via femtosecond laser, the effect of the processing speed on the microstructure and mechanical property of the joint is investigated, the influence of the surface machining on the residual stress distribution after brazing and the stress distribution in the joint upon shear testing was predicted using image based modelling. Several conclusions have been drawn from this study:


The NVVC/NHJ publication prizes are named after one of the founding fathers of Dutch Cardiology, professor D. Durrer 1918–1984) who was the chair of the department of Cardiology at the former Wilhelmina Gasthuis in Amsterdam. He was an outstanding pioneer in the field of electrophysiology with classical works on the electric activation of the heart in the 1960s and 1970s [918–1984 The Netherlands Heart Journal, the official journal of the Netherlands Society of Cardiology (NVVC), awarded the Durrer prizes to two outstanding NHJ articles published in 2018. These articles are selected based upon their originality and scientific quality as well as the number of citations. The two articles were selected out of a total of 123 articles published in the NHJ 2018.The first article entitled ‘Extracorporeal life support in cardiogenic shock: indications and management in current practice’ is a review of veno-arterial extracorporeal life support (VA-ECLS). This device is increasingly being used as a cardiac and circulatory support modality with the ability to provide immediate stabilisation in patients with otherwise refractory cardiogenic shock . This reThe other selected article is entitled ‘Nationwide claims data validated for quality assessments in acute myocardial infarction in the Netherlands’ . In the The first authors of these articles received an educational grant, provided by the NVVC, at the Annual Spring Meeting of the NVVC held at the Postillion Convention Centre WTC in Rotterdam, the Netherlands, on 11 and 12 April 2019. The NHJ would like to congratulate the authors with these awards and thank them for submitting their excellent work to our journal. The editorial board of the NHJ hopes that the Durrer prizes act as a stimulus for authors to send their best paper to our journal.


Interprofessional education (IPE) is now recognized as an important initiative to prepare the next generation of health providers. Although IPE has been embraced by many institutions, faculty development still remains an issue. In this manuscript, the authors share their story of one attempt to educate a variety of health science faculty on IPE in what was perceived as an approachable venue. The story of its epic failure and lessons learned will be shared to help others avoid similar pitfalls. Since interprofessional education (IPE) and collaborative practice has emerged as a key hot topic and is now infused in the accreditation guidelines for many health professions, faculty development in this area is an evident need. Faculty development for IPE has been identified as critical to the successful implementation of both interprofessional education and practice , 2. In fAs an academic institution with significant complexities including eight health professions programs, multiple health sciences schools and colleges and an academic health partner that retains physician employment, the issue of faculty development for IPE seemed almost impossible at our institution. As the IPE leadership team identified the need for a standardized course on topics related to IPE for all early learners across our health sciences programs, the team, a group of faculty members leading IPE at the institution, identified that an online self-paced course promotes the levelling for students prior to engaging in IPE activities. The student course was developed and implemented with success serving almost 1,000 students in its first year. Overall, feedback from the course was positive and it is now entering its third year.It seemed only natural to create a companion course to this approach for faculty and clinicians. Our team also wanted faculty and clinicians to have a similar interprofessional education to our students. Making them complementary served to ensure our faculty could reinforce and support the student experience. The institution had the benefit of holding an academic Joint Accreditation to provide continuing education across the health professions. With a new academic health partner, it seemed a prime opportunity to create a course both for faculty and clinician learners. In order to promote buy-in and offer a benefit to faculty and clinicians, the team pursed continuing education for the online IPE faculty development course from the Joint Accredited program. Due to the structure and intensity of the course, it was identified as offering 8 continuing education credits and could be a fit for healthcare professions across the spectrum.The team rolled out the course identifying its benefits, similar to those the students identified including 1) the course is self-paced allowing learners to sit down and engage at their own pace; 2) the course provides a general overview of information on how to collaborate on a healthcare team geared towards multiple health professions; and 3) clinicians and faculty would receive 8 continuing education credits at no cost. All of these factors seemed to our team to be motivators for faculty and clinicians to take the course. Prior to the course release, an opportunity for peer review was offered to faculty and clinicians. Overall, around 40 faculty and staff provided feedback on the peer review and adjustments were made to the course based on this feedback. We then developed an informational email and easy sign-up infrastructure followed by an invitation for faculty and clinicians to take the course.The team distributed the course to faculty and clinicians hoping to mirror the success of the student course. In addition to offering the course to faculty, the team encouraged the Deans and leadership of the schools and colleges to send out the course with a due date for completion. The course was distributed and the team had high hopes, proud of the product that had been produced and believing it would help faculty become more proficient in IPE.Unfortunately, the team’s perceptions of our educational tool were completely wrong. In our minds, we had developed an educational tool that filled a gap for faculty and clinicians where they could earn credits and be better prepared for teaching students. The course’s self-paced nature and ease of access in the institution’s learning management system all seemed like benefits to our team.Yet, on the course roll out, participation was minimal and dismal. First, many faculty balked at the idea of even needing to learn about IPE and the notion of them benefitting from education on the topic. Complaints rolled in about the enrolment process, course’s length, online format and content, despite being offered for free to all health professions faculty and clinicians in the health system. In the student course, complaints of this nature were minimal, if nonexistent.Even the opportunity to earn 8 continuing education credits was not an enabler. The only health profession that participated with any depth was nursing because their Dean saw the inherent value and required course participation by a deadline. This same Dean also confirmed faculty participation and sent reminders for course completion. Our team observed a cultural shift after the Nursing faculty completed the course with more buy-in for the IPE student course and multiple faculty reaching out for resources to develop IPE activities. Although other Deans encouraged participation, it was minimal from other health professions. In addition, faculty members and clinicians treated the course creators as the ‘IPE police’ always making excuses to team members as to why they had not participated and freely complaining about the course. Often our team found this aspect surprising as our perspective was to create a resource to help faculty and clinicians be more informed on IPE and the intent was not to hold them to some sort of formal accountability.Overall, our team made a general assumption that what students perceived as valuable, faculty and clinicians would also value. Our perceptions that developing something accessible and with continuing education credits would be well received was incorrect. In our minds, we were developing an educational resource that would allow flexibility and help faculty support their own professional development. We were truly unaware that faculty, themselves, had spent little time in the learning management system as learners. We did not realize that many viewed IPE as frivolous or the latest healthcare fad and did not feel they needed professional development in this area. After our efforts to ensure an accessible course with credit for faculty and clinicians, we truly were shocked by the negative response and feedback we received across the health professions.An unintended consequence of putting the course on our IPE website was that more external stakeholders interested in IPE participated in the course. The external stakeholders were individuals at other institutions searching for IPE faculty development and finding our course through an internet search. The positive feedback from external stakeholders further confirmed our beliefs that the course had value and we turned our attention to these individuals to generate revenue for IPE. Although an unintended consequence, this outcome reassured the team that all the hard work and the efforts to assign continuing education was worth it.Overall, upon further reflection, our team has identified four core lessons learned from this experience: 1) an educational success for one group can be a failure in another group; 2) increased cooperation occurs when accountability is built in or the faculty development is made a requirement; 3) champions are critical along with early adopters in leadership; and 4) what your team values as important is not necessarily what others value. Elaborating on each of these, we provide our reflections on this failed experiment on IPE faculty development.Due to the experience and feedback from students in their version of the course, the team assumed that faculty and clinicians would align with the same benefits. Although we are very aware that students have different accountability measures than faculty and clinicians, our team thought that faculty and clinicians would appreciate the content and delivery method in a similar way to the students. In the student course evaluation, students reported constructively on the ease of the course and the benefits of its self-paced nature. Due to the overwhelmingly positive response from students, our team was surprised at the negative response from faculty and clinicians in the course delivery model. Our failure here was the simple assumption that what would benefit students would also be perceived as beneficial by faculty and clinicians. It demonstrated our lack of recognition of the culture of the faculty buy-in for IPE. We learned that we needed to expand our concept of learners along with considering a unique delivery catered towards each audience rather than a blanketed approach.Our team discovered that faculty and clinicians did not have an inherent desire to gain knowledge in IPE. Without a clear tie to their current faculty or clinical role or a clear incentive or requirement, faculty and clinicians were not going to complete the course. Besides nursing, where the course is required, those from other professions who completed the course found value and recognized a need to learn about IPE. Essentially, mostly early adopters engaged in the course, those already recognizing a value for IPE. Overall, IPE has struggled with its perceived distance and impact on clinical practice . The lacTo get the course developed and implemented, champions are critical. The need for champions for IPE has been clearly documented as critical to success , 8. The Early adopters are also important. Suter and colleagues  identifiPerhaps our biggest mistake was assuming that our passions for IPE were shared by others. Our own ethnocentrism blinded us to the real culture of the institution towards IPE. Each member of our team is admittedly a champion for IPE and immersed in its value. Perhaps we thought we were preaching to the choir and lacked the recognition of the true culture of the institution at the time. In a way interprofessionalism is controversial and we neglected to think about how our faculty development efforts would stir up the many cultural nuances that occur in collaboration among health professions. This concept has been echoed in the literature and our team was naïve to the cultural implications of IPE faculty development due to our closeness and passion to the topic , 12. ThrThe moral of the story is that leaders in IPE should obtain a pulse of the culture of the institution and ask not just champions and early adopters about the best approaches for IPE faculty development. Proceeding forward with assumptions that the student experience will mirror the faculty development process puts a team at risk for failure. Leaders in IPE faculty development should recognize their institution’s culture and expect both early adopters and laggards.


The studies are carried out at constant hematocrit and volumetric flow rate. We find that when the diameter of the capillary is smaller than that of the RBC, the flow rate of the RBCs is lowered as the concentration of BSA is increased while the reverse is true when the diameter is comparable to that of the RBC. We confirm that this is a consequence of altered CMS of the RBCs from their reorientation dynamics in an Optical Tweezer. We find that a treatment with 0.50mg/ml BSA mimics the situation for RBCs extracted from a healthy individual while concentrations higher than 0.50mg/ml elevate the RBC CMS across a range expected for individuals with a condition of hyperglycemia. Using a simple theoretical model of the RBC deformation process at the entry of a narrow channel, we extract the RBC membrane bending modulus from their flow rate.Human red blood cells (RBCs) need to deform in order to pass through capillaries in human vasculature with diameter smaller than that of the RBC. An altered RBC cell membrane stiffness (CMS), thereby, is likely to have consequences on their flow rate. RBC CMS is known to be affected by several commonly encountered disease conditions. This study was carried out to investigate whether an increase in RBC CMS, to the extent seen in such commonly encountered medical conditions, affects the RBC flow rate through channels with diameters comparable to that of the RBC. To do this, we use RBCs extracted from a healthy individual with no known medical conditions and treated with various concentrations of Bovine Serum Albumin (BSA). We study their flow through polycarbonate membranes with pores of diameter 5 The most important function of RBCs is to carry oxygen to various parts of the body. The viscoelastic properties of RBCs are of extreme importance here as RBCs, in their lifespan of approximately 120 days [Human blood consists of plasma, red blood cells (RBCs), white blood cells (WBCs) and platelets. RBCs form the major cellular component of blood with a ratio of RBC volume to the total volume of blood  of approximately 45% . RBCs ca120 days , 4.The deformation process that an RBC undergoes at the entrance of a narrow capillary, finally enabling passage through it, is a gradual process . Each RBStudies on viscoelastic properties of RBCs involve either observing the response of an RBC subjected to a well calibrated deforming stress or an analysis of the detailed observation of a process where RBC deformations occur. These have been widely reported in literature and involve a wide variety of techniques based on micro pipette aspiration –13, optiApart from the difficulties in settling on an appropriate experimental method that satisfies the criterion outlined above, there are even greater difficulties if RBCs with altered CMS are sourced from individuals with medical conditions known to affect RBC CMS. Donors affected with a particular medical condition need to be free of all other medical disorders which could have an impact on the RBC CMS in order to be able to establish a connection between the extent of the disorder and its consequences due to altered micro circulation in the human vasculature. Using such RBCs for the testing or calibration of any alternate measurement process of RBC CMS is thereby also not advisable. A necessary first step in this direction, then, would be to arrive at some artificial means of elevating the CMS of RBCs extracted from healthy individuals with no known medical conditions, in a controlled manner. The method of altering the CMS should preferably be such that it would be possible to mimic any RBC CMS associated with a medical disorder by varying a single parameter in a continuous manner.Our aim here is to study the effect of RBC CMS elevation to the extent seen in commonly encountered human disease conditions on the flow in channels of sizes commonly encountered in human micro vasculature and we use treatment with Bovine Serum Albumin (BSA) as the means of bringing about the required change. BSA is a serum albumin protein that is extracted from bovine blood. The use of BSA for preparation of RBC samples is widely quoted in literature. BSA is generally used in in-vitro studies of RBCs to enable a retention of the normal bi-concave shape and to prevent adhesion to glass slides , 32. TheNa2HPO4 (0.356g) and KH2PO4 (0.054g)) of pH 7.4 was prepared using a standard protocol and used for the experiments. The pH of PBS prepared was checked at regular intervals. If there was any change, care was taken to restore the pH to 7.4. Note that for a comparative study to be valid, it is important that the same solution of PBS is used to carry out all experiments. This is because minor variations in the osmolarity of the PBS could have an effect on the measurements [Phosphate Buffer Saline or PBS (200ml of deionized water with NaCl (1.602g), KCl (0.040g), urements . The susAll methods were carried out in accordance with the relevant guidelines and regulations of the World Medical Association Declaration of Helsinki. The proposal for this study, as well as subsequent progress reports, have been examined and approved by the Board of Studies and the Ph.D. Review Committee of Department of Physics, Bangalore University, Bangalore. The experiments were conducted with the informed consent of all participants.Four healthy individuals in the age group of 25–50 years with no known medical conditions participated in blood donation for experiments. However, the data used for analysis and shown here are with the blood samples obtained from the same individual . There were no significant changes observed in the trends of primary results for all individuals in both micropore filtration as well as reorientation experiments.All the experiments were carried out within four to five hours of the time of blood extraction. This was done to avoid any ambiguity in the interpretation of results that could arise due to CMS changes linked with storage time of the RBCs.BD Vacutainer) and centrifuged at 900 rpm for 10 minutes. The plasma and the top white layer containing WBCs and platelets were discarded. RBCs thus obtained were washed with PBS and about 200μl of RBCs were added to 3800μl of PBS+(x)BSA to obtain b(x)RBCs. This particular ratio ensures a 5% hematocrit level. We thus obtain b(x)RBCs for x = 0.50, 0.70, 1.00, 1.18 and 1.35. Note that BSA concentrations less than 0.50mg/ml were not used for flow experiments. It was observed that for a hematocrit level of 5% the biconcave shape could not be retained for all RBCs at BSA concentrations less than 0.50mg/ml.5ml of venous blood was drawn from a healthy volunteer with no history of any chronic medical conditions. This was transferred from the collection syringe to commercially available blood collection tubes coated with Ethylenediaminetetraacetic acid (EDTA)  with pores that are ion-track etched. The pores are of circular cross section with a well-defined uniform diameter throughout their length and run straight and perpendicular to the plane of the filter paper [μm (less than RBC diameter) and (ii) 8μm (≈ RBC diameter) for the experiment  and placed on a custom made aluminium stand fitted with height adjustment screws. About 4ml of the desired blood sample was loaded into a 5ml syringe and mounted on the syringe pump (Chemyx Fusion 200). The syringe was connected to the inlet of the filter holder and the outlet was connected to a micro centrifuge tube with a transparent tube procured from commercially available blood transfusion kits  and the output (Nout) stages, Nout being the average count of all the output samples collected for a particular BSA concentration. While Nin values are obtained to ascertain that the flow experiments for all b(x)RBCs have been done under identical input conditions, the effect of altered RBC CMS on the flow rate is in the value of Nout.The cell concentration at the input and output stage of the experiment were obtained using manual counting on a hemocytometer (Neubauer chamber). About 10μl of blood was drawn from a person with no known medical conditions using finger prick method. EDTA at a concentration of 1.8mg/ml was added to this to prevent agglomeration. The end product was further diluted with about 1ml of normal PBS of pH 7.4. The set of experiments carried out with these were taken as the control (nRBC).50μl of blood was drawn from the same individual and transferred into a centrifuge tube with EDTA (at the same concentration as used for nRBC sample preparation). It was diluted with normal PBS and centrifuged for 10 minutes at 900 rpm. The supernatant was then removed and suspended in a tube containing PBS+(x) BSA. The sample was labelled as b(x)RBC. In each of the samples, the RBCs were maintained at a hematocrit level of 5%. In each case, about 300μl of PBS+(x)BSA and 20μl of b(x)RBCs were loaded into a sample well that was made by gluing an O ring of diameter 0.8cm and thickness 1mm on a glass slide. The well was covered with a smaller cover slip to make it air tight.For the preparation of b(x)RBCs , 100et al [tre, defined as the time taken by an RBC which is initially with the plane of its disc perpendicular to the beam propagation direction (flat orientation) to rotate by 90° and acquire an edge-on orientation to the same, depends on the laser power as well as the RBC CMS [A detailed description of the optical tweezer set up used for this experiment can be found in Parthasarathi et al , however RBC CMS . Note thtre, was extracted from an analysis of the video recordings and an average tre was found for each laser power used, with the standard deviation being taken as the error in tre.Video recordings of the reorientation process in the tweezer were carried out at the rate of 16 fps using a CCD camera . The power at the sample plane was varied from 0.002W to 0.040W in steps of 0.002W. Powers higher than 0.040W were avoided as permanent damage to the RBCs at high laser power is inevitable. At each power, reorientation process of the control and 7 sets of b(x)RBCs were recorded and stored for further analysis. For each type of RBC, the reorientation process was recorded for at least ten different RBCs at each laser power. The time of reorientation, μm with a standard deviation of 0.5-0.9μm  of nRBCs is estimated to be ≈10−4 in the active region , 0.87 in 5μm pore and 0.62 in 8μm pore where Ca is given byη being the viscosity of the fluid, l = 2.78μm, the radius of a sphere of volume equal to that of an RBC (90fL) [Es, the RBC membrane shear modulus (≈ 4μN/m) [RBCs do not show any detectable change in their size distribution with the BSA concentration they are treated with see . At all ≈ 4μN/m) . It is k≈ 4μN/m) .For reasons detailed above, the fact that the RBC suspension is pumped continuously at a constant flow rate with a constant hematocrit of 5% at the input stage and that care is taken to both not re use the filter papers as well as not run the flow for more than four minutes at a stretch, the chances of RBCs blocking the pores during the course of the experiment is very minimal. Thereby a reduction in the number of channels during the process of filtration is unlikely. Any change in the number of RBCs collected per unit time at the output stage can be, thereby, attributed to a change in their rate of transfer from the input to the output stage and not because of blocked pores or RBC loss due to lysis.N*, from Nout using Aactive is the area of the active region. The filter holder used for the experiment has an inlet of inner radius 0.2cm giving us an active area Aactive = 12.56mm2. Npore is the number of pores per unit area of the filter paper and Q is the volumetric flow rate. As we use a Q of 400μl/minute here, N*, corresponds to the number of RBCs that have passed through a single pore in one minute.To enable a comparison in the flow rate of various bRBCs, we first determine the number of RBCs that have passed through the filter paper per unit time per pore, N* decreases with increasing BSA concentration for the 5μm filter paper  from the N* values determined from the flow experiment. We obtain the average filtration time in seconds using the expression T = 60/N*. Note that this is indeed an average time required for deformation and passage of an RBC through a channel measured from a large throughput process (the filtration time is averaged over at least 500 million RBCs). All variations arising from changes in velocity of the suspension fluid at the pore entry because of radial location of a pore or approach time of individual RBCs which might entail a simultaneous process of passage / deformation of two different RBCs with respect to the same channel are averaged over. The values thus obtained are tabulated in Td)) and the average time taken to travel through the channel length to exit the filter paper at the outlet stage ).The basic idea is to determine the average time required by the RBCs to deform enough to be able to pass through a channel that has a diameter smaller than that of the RBC and to then correlate this with the RBC CMS. To do this, one has to be able to determine an average filtration time per RBC  will be the passage time itself (Tp8μm), as the deformation time Td8μm will be zero and we can easily obtain the passage velocity of RBCs in the 8μm diameter channel by simply dividing the filter paper thickness with Tμm8. The variation of passage velocity with BSA concentration for the 8μm diameter channel is shown in For the case of the 8U) using an equation of motion of RBCs in fluid flow where the forces acting on the RBC are the drag force and force due to kinematic pressure of the fluid  such that the deformed RBC radius is 0.25μm less than a. Using h, we determine the final curvature the RBC surface has to acquire. The deformation energy (εdef) is then the energy required to effect the required curvature change of the RBC membrane.We describe here a simple theoretical model of the deformation an RBC undergoes to enable passage through a channel with a diameter smaller than it’s own. Given the axial symmetry of the situation when an RBC is required to deform in order to gain entry into a narrow channel, we assume that the deformed RBC shape will also conform to this symmetry. We thereby assume the simplest possible symmetric shape of a paraboloid for it. Further, we impose a constraint that the surface area of the RBC remains constant throughout the entire process of deformation as the energy required for membrane surface area expansion is large when compared to the membrane bending energy of RBCs . With thh commensurate with a constraint of constant volume and find that it is consistently higher for all channel radii (a) when compared to the case of the constraint of constant surface area. This will imply a higher final curvature for the deformed RBC which will in turn imply higher deformation energy. In our analysis, we use the constraint of constant surface area as it is more energetically favourable within the limits of our model for the deformation process. We simplify further, by assuming the undeformed RBC to be a cylindrical disk with a diameter of 7.5μm and height 2.022μm  is given byK is the dynamic pressure i.e, kinetic energy carried by fluid per unit volume. The total energy per unit time available at the cross sectional area of an RBC that is stationary at the entrance of a narrow channel can be obtained asvmax is the fluid velocity at a location on the axial line of the narrow channel where the deformation of the RBC takes place.If we calculate the energy incident per unit time at the channel entrance per unit RBC surface area, we can find out how the energy builds up with time when an RBC blocks the entrance to a narrow channel. Energy incident at the RBC surface per unit time  is shown in et al [tre. If we were to assume the RBC to be a perfect rigid body, the variation in tre with laser power would follow a 1/P relation. Assuming that the behaviour at the lowest powers is most like that of a rigid body, we extract from the variation of tre at the lowest laser powers used, a term (α) that modifies the rotational drag of a perfectly rigid cylindrical disc to that of a perfectly rigid RBC shaped object . Beyond Pd, the RBC is found to require more time for the reorientation process than that predicted for the rigid body. We fit a straight line through the values of tre beyond Pd and use this to predict the excess time required by the RBC compared to its perfectly rigid counterpart. We then use this excess time to estimate the excess energy ΔE, which is the amount of energy utilized in the RBC reorientation process that is in excess of that required for a rigid body with dimensions and rotational drag coefficient identical to the undeformed RBC. Variation of ΔE as a function of P is shown in Variation of the time of reorientation, in et al , a briefject see . We thenα, is factored out from ΔE RBCs are reported in To enable a comparison between the CMS of the different RBCs, the rotational drag modification term, m ΔE see . It can  RBC CMS . The varEmax for the control is found to be within reasonable limits of that determined for normal RBCs [Emax that is greater than that obtained for the control and comparable to the values obtained for RBCs extracted from individuals with an established condition of hyperglycemia (hRBC) reported in [Emax is found to increase with the increase in BSA concentration beyond 0.50mg/ml RBCs are identical to that of normal RBCs. Thereby, we assume that the CMS of b(0.5)RBC is identical to that of nRBC and assign a value of 2X10−19 J reported for normal RBCs [Eb for b(0.5)RBC. Then using vmax. This velocity will remain the same for the case of all bRBCs as it depends on the fluid flow conditions which are maintained identical throughout. From the simulation of flow conditions in filtration through a 5μm channel diameter filter paper . S5 Appendix: Extraction of bending modulus of bRBCs from their flow rate in narrow channels: A condensed scheme.(PDF)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.S2 Figz = 15μm.The pore entrance is located at (TIF)Click here for additional data file.S1 Image(ZIP)Click here for additional data file.S2 Image(ZIP)Click here for additional data file.S1 Review(ZIP)Click here for additional data file.S1 Video(ZIP)Click here for additional data file.S2 Video(ZIP)Click here for additional data file.S3 Video(ZIP)Click here for additional data file.


CO2 emitted by cars and the average commuting time. We confirm these analytical predictions on 25 major urban areas in the world, and our results suggest that urban density is not the most relevant variable controlling car-related quantities but rather are the city’s area size and the density of public transport. Mitigating the traffic (and its effect such as CO2 emissions) can then be obtained by reducing the urbanized area size or, more realistically, by improving either the public transport density or its access. In particular, increasing the population density is a good idea only if it also increases the fraction of individuals having access to public transport.Car traffic in urban systems has been studied intensely in past decades but models are either limited to a specific aspect of traffic or applied to a specific region. Despite the importance and urgency of the problem we have a poor theoretical understanding of the parameters controlling urban car use and congestion. Here, we combine economical and transport ingredients into a statistical physics approach and propose a generic model that predicts for different cities the share of car drivers, the  As most humans now live in urban areas and two-third of the world population will live in cities by 2050 , understOn the other hand, car traffic has been studied at various granularities—and mostly at the theoretical level of a single lane—with various tools ranging from agent-based modelling , cex and work at location y such that the quantityW(y) is the typical wage earned at location y, CR(x) is the rent cost at x, and G is the generalized transportation cost to go from x to y. There is also a similar equation for the profit of companies (that they want to maximize) and that we do not need here: we assume that employment is located at a unique center y = 0 and that wages and rent costs are of the same order for all individuals. Most large cities are polycentric [x is given and random—residence choice is obviously a complex problem and replacing a complex quantity by a random one is a typical assumption made in the statistical physics of complex systems. Within these assumptions, we obtain a simplified Fujita-Ogawa model where we focus on the mode choice: individuals have already a home and work at the CBD, and the problem is about choosing a transport mode. Within these assumptions, the maximization of Z implies the minimization of the transport cost G: max Z ⇒ min G. Thus, individuals simply tend to choose the mode that minimizes their commuting costs to go the office located at 0. In this perspective, we assume that individuals change more frequently their jobs than their homes. More generally, the Fujita Ogawa model gives a density that results of the interplay between residential and commuting costs and due to our simplifications, the density is now an exogenous quantity.According to the classical urban ecomomics model of Fujita and Ogawa , individycentric , 25 withp of the population has access  to mass rapid transit such as the subway or elevated rail (we neglect buses or tramways here) whereas a share 1 − p of the population has no choice but to commute by car . In other words, p is the probability to have access to the MRT . All the assumptions used in this model are of course approximations to the reality but we claim here that our model captures the essence of the traffic in large urban areas phenomenon. Starting with a model containing all these various parameters would actually be not tractable and would hide the critical ingredients.p of individuals that have a choice between car and MRT will choose the transport mode with the lowest generalized cost which takes into account both monetary costs and trip duration , and we neglect spatial correlations between the densities of public transport and residence or population, which is an important assumption that certainly needs to be refined in future studies. The fraction  example , 27).Cc is the daily cost of a car, vc and vm are respectively the car and MRT velocities, c is the road capacity of the city, f the walking plus waiting time for transit, r the distance between home and the central business district, T the total car traffic, and μ the exponent that characterizes the sensitivity to traffic. The quantity V is the value of time defined in transport economics as the money amount that a traveler is willing to pay in order to save one hour of time. It is an increasing function of income and is bounded by the hourly wage. We assume here that driving is faster than riding public transport (vc > vm) but is more expensive. Once an individual has chosen a mode he sticks to it and will not reconsider his choice even if the traffic evolves. In other words, we assume here that individual habits have a longer time scale than traffic dynamics.For cars, we include congestion described by the Bureau of Public Roads function  to choose the car. The function F is in general smooth and satisfies F(−∞) = 1 and F(+∞) = 0 and we consider here the simplest case where F(x > 0) = 0 and F(x < 0) = 1. An individual located at x with access to the MRT will then choose to use the car if Gcar < GMRT which implies a condition on the value of time of the form V < Vm(r) where Vm(r) depends on the parameters of the system and on the distance to the center r and readsGcar = GMRT between generalized costs of car and MRT leads to the critical distance given byA is the area size of the city) is the largest extent of the city. This critical distance evolves as traffic increases —individuals favor driving to avoid lengthy journeys, and the richer they are, the smallest this distance.Individual mobility is then governed by comparing these costs  example ), given ncreases , translad = L, gives the critical maximal traffic T* for which driving is less beneficial in the whole agglomeration:Writing p share of individuals far from MRT stations, and the second term to the fraction 1 − η of individuals that have access to the MRT and are living further from the center than d. This equation is valid for T < T* and for T > T* we have η = 1. By considering statistically isotropic cities with population density ρ(r) (r is the distance to the CDB), we obtainWhen population increases, car traffic has essentially two sources: first, individuals may not have access to the MRT and second, if they have access to it, they might be too far and will prefer to take the car. This can be summarized by the following differential equation for the variation of car traffic T when P variesd and to solve the differential equation r and a simple choice is ρ(r) = ρ0exp(−r/r0) and we then obtain at dominant order in T/Ca = (Cc/V − f)/(1/vm − 1/vc). We note here that in the uniform density case ρ(r) = ρ0, we obtain η = πd2/A and b is a function of the exogenous parameters We have to plug in this expression together with d > L the only source of car traffic comes from individuals who do not have access to the mass rapid transit, which leads to dT/dP = 1 − p implyingT < T* and therefore does not impact our conclusions.This result p), we compute the critical levels T* and P*. We note that for all these cities the definition of p is the same: it is the share of individuals living within 1km from a MRT station. For reasonable values of time [T* = 0 and all have T* ≪ P (T* ranges from 0 to 50% of P). Cases where T* = 0 mean that even at zero traffic the critical distance d is larger than the typical size of the city L. This depends a bit on the value of time but in most cases we do observe small values of T* indicating that cities are mostly in the saturated regime where the MRT is always more advantageous than the car. Public transports are so economical (compared to cars) that people living near rapid transit stations are highly likely to ride them. Thus, traffic does not appear as a determinant parameter in individual mobility choices as it concerns mostly individuals who have no choice but to drive and who suffer from onerous commuting costs and unavoidable time-consuming trips as traffic increases. We note here that correlations between the neighborhoods with low MRT density  where individuals have expensive commuting costs and their revenue is an interesting field of study and appears as an important source of urban segregation [T*, P* ≪ P, we obtain the simple prediction that p is the probability to leave in the vicinity of a MRT station but that doesn’t imply the use of this transport mode. We compare the empirical car modal shares Compiling data from 25 megacities in the world see  for whic of time , 30, mosregation . Since wCO2 case for which we obtained data. We make the simplest assumption where these emissions are proportional to the total time spent on roads. The quantity of CO2 emitted for a driver residing at x is then given by T = (1 − p)P. We assumed that the sum ∑iri is of the form g encodes the geometrical aspect of car mobility in the city, including the spatial distribution of residences and activities, and the transport infrastructure. Its estimation probably requires a more detailed, specific calculation but the important aspect here is the scaling with 2 emitted by car and per capita is given byc is usually not empirically accessible). It is interesting to note that 2 emissions on 2 emissions and areas such as New York which appears to be one of the largest transport CO2 emitter in the world [2 emissions. Most importantly, we identify urban sprawl  in contrast with the naive Newman-Kenworthy assumption where increasing the density leads to a decrease of CO2 emissions.Our model also provides a prediction for the transport-related gas emissions and we will focus on the database  . We comhe world . This reenworthy  could hac  may not be a good remedy, as we identified drivers with individuals with no other solution. Worse, by making their trips longer, diminishing c indirectly contributes to higher emissions and pollution as well as potentially socially segregating situations.We also note thatτc averaged over the population the following expressiong is a geographical factor that encodes the spatial complexity of trips. The comparison with the data displays relatively large fluctuations, but our analysis seems to capture the main trend and the one-parameter fit over g using our expression g ≈ 0.203. We note that for a uniform distribution of residences, a simple calculation leads to r to the center as ρ(r) = ρ0(1 − r/L), we obtain g obtained by the fit is in between these two theoretical estimates. However, polycentrism and more generally the spatial organization of the city and its infrastructure certainly play an important role here and our model can only provide a first approximation to the average commuting time.Finally, we can also estime the average commuting time , polycentrism, the transport network structure, fuel price and tax, dynamic road pricing, etc. but our main point was to fill a gap for understanding traffic in urban areas by proposing a parsimonious model with the smallest number of parameters and the largest number of predictions in agreement with data. Given the simplicity of this model we cannot expect a perfect agreement with data for various and different cities, but it seems that this approach captures correctly all the trends and identifies correctly the critical factors for car traffic. This seems to be a basic requirement before adding other factors and increasing the complexity of the model. Also, it seems at this stage necessary to first encourage the measure and sharing of data such as the density of public transport in order to propose further tests of our theoretical framework.We presented a parsimonious and generic model for the car traffic and its consequences in large cities, and tested it against empirical data for 25 large cities in the world. This approach illustrates how a combination of statistical physics, economical ingredients and empirical validation can lead to a robust understanding of systems as complex as cities. In particular, this approach is in contrast with the commonly accepted idea that urban density is pivotal, and our aim here was to capture the essence of the urban mobility phenomenon and to obtain analytical results for the car traffic and the quantity of emitted n the US ), or to The definition of a metropolitan area varies from one country to another but we aimed at assembling a statistically coherent set of agglomerations. Populations and areas were collated from Wikipedia data on metropolitan statistical areas in accordance with national definitions.p is taken from transit accessibility reports [2 emissions from [Various indicators were compiled from diverse sources: the quantity  reports –41. A co reports , CO2 emions from , 48–51, ons from –60.Values of time were assessed by taking half of the hourly wage after tax for each city , 30.Congestion delays were taken from the TomTom index , except τ by c ∼ P/τμ1/ with the value μ = 2 that we used for all cities.The road capacity was computed from the congestion delay vm and vc and the costs Cc and f we choose the same values for all cities. For vm wikipedia data [vm ≈ 30km/h. The free flow car velocity vc also depends a bit on the city and varies from 30 km/h (without congestion effect) in European cities such as Paris to 56 km/h in some american cities [vc ≈ 40 km/h.For the velocities dia data  displaysn cities . We deciCc, we used a cost simulator [Cc ≈ 15 USD per trip.For imulator  which gif we counted on average 10 minutes to reach the station, 10 minutes to reach the office and 10 minutes for transit for a total of about f ≈ 30 minutes. This value can certainly be improved but it is difficult to get and we expect it not to vary too much (at least not over more than one order of magnitude).For We studied 25 metropolitan areas from Europe, America, Asia and Australia. The number of cities was limited by the availability of data on MRT accessibility and reliable modal share estimates. All the data is freely available and we list here their sources. We also provide a file together with this submission with all the data used in this study see .The defg is a geographical factor. We therefore obtain for the one-trip commuting time τc averaged over the population the following expressiong ≈ 0.203. We note that for a uniform distribution of residences, a simple calculation leads to r to the center as ρ(r) = ρ0(1 − r/L), we obtain g obtained by the fit is in between these two theoretical estimates. From geff’ for each city and compare it to the average value g. This quantity geff (and the ratio η = geff/g) encodes both the complexity of the population and activity densities, and of the transportation infrastructure. For our set of cities, the average ratio is of order 1.37 and we observe outliers with small values such as Barcelona (η = 0.04), Seoul (η = 0.62), and large ones . Most of the cities (76%) have however here a ratio η larger than 1 which implies that our model underestimates in general the commuting distance. Many local effects can explain the variations observed in the commuting distance: the existence of polycentricity could reduce the commuting distance , but other factors such as poor transportation infrastructures  could have the opposite effect of increasing this quantity. In general we expect that the transport network structure will have an important impact, especially if it is very anisotropic in space. The determination of the commuting distance for each city probably implies to take into account a large number of specific details, but our analysis shows that it is consistent to assume that the order of magnitude of this quantity is The commuting time for MRT users is given by S1 DatasetThis file contains all data used in this paper (in a format.xlsx).(XLSX)Click here for additional data file.


Journal of Orthopaedic Research. Published by Wiley Periodicals, Inc. J Orthop Res 37:1537–1545, 2019.An important reason for poor functional outcome of Total Knee Arthroplasty is inadequate soft tissue balancing. Custom‐made cutting guides or computer‐aided surgical navigation make possible to accurately achieve what is planned; the challenge is to perform a pre‐operative planning that properly accounts for soft‐tissue balancing. The first step in the development of a patient‐specific computer model that can predict during pre‐operative planning the post‐operative soft‐tissue balancing is a better understanding of the role that cutting heights and angles have on the balancing of the soft tissues after TKA as the patient perform the more common daily tasks. In the present study, we conducted a sensitivity analysis of the ligament elongations during level walking due to TKA as a function of position and orientation of the cutting guides, by means of a validated patient‐specific dynamic model of the post‐TKA knee biomechanics. The results suggest a considerable sensitivity of the collateral ligaments elongation to the surgical variables, and in particular to the varus‐valgus angles of both tibia and femur. This complete elongation map can be used as a baseline for the development of reduced‐order models to be integrated in pre‐operative planning environments. © 2019 The Authors  Total Knee Arthroplasty (TKA) is a surgical procedure aimed to replace the damaged surfaces of the knee joint with artificial components. The increasing number of osteoarthritis patients due to the progressive aging of the population boosted the demand of total knee replacement surgeries, which now present in most clinical studies a success rate of 90% or better, when measured in term of revisions.Achieving an optimal balance between stability and mobility requires both an accurate pre‐operative planning , and an accurate execution . In principle, both computer‐aided surgical navigation and patient‐specific instrumentation such as custom‐made cutting guides should ensure accurate execution, but in spite of this both technologies have contradictory reports in terms of clinical outcome.In principle, patient‐specific inverse multibody dynamics computer models could be used for this purpose. However, such models require as input the full 3D kinematics of the movement. Even if pre‐operative acquisition of the patient's gait was routinely possible, since patients compensate post‐operatively for any functional alteration by adjusting their kinematics and kinetics, such measurements would not be informative. Thus, the pre‐operative prediction of the functional outcome must necessarily rely on reduced‐order models that do not need full kinematics as input.A first step toward the development of such reduced‐order models is the better understanding of the role that cutting heights and angles have on the balancing of the soft tissues after TKA as the patient perform the more common daily tasks. Such investigation, conducted on a TKA patient once the rehabilitation is completed and the post‐operative neuromuscular control during level waking has stabilized, would provide a baseline accuracy against which any reduced‐order models could be compared. Such sensitivity analysis could not be conducted experimentally, as the same patient cannot be operated multiple times; however, this would be possible using a validated patient‐specific computer model of the musculoskeletal dynamics during level waking.The aim of the present study is to conduct a sensitivity analysis of the ligament elongations during level walking due to TKA as a function of position and orientation of the cutting guides, by means of a validated patient‐specific dynamic model of the post‐TKA knee biomechanics.,The experimental data used in this study come from the third “Grand Challenge Competition to Predict In Vivo Knee Loads” data,eTibia) capable of recording and transmitting via telemetry the instantaneous knee resultant force. The dataset includes pre‐operative MRI, post‐operative CT, geometries of the lower limb bones and of the total knee prosthesis, strength data measured with a BIODEX isokinetic dynamometer, motion analysis data for level‐walking including EMG signals from 15 lower‐limb muscles, and the eTibia recordings, synchronized with gait and EMG data. The six‐component generalized force vector the eTibia provide can be decomposed in two compartmental force Fmedial and Flateral, using a simple regression equation.The data were obtained from a female subject , who received in her left knee a posterior cruciate‐retaining total knee replacement prosthesis  and the Medial Collateral Ligament (MCL) were included in the lower limb model. The estimation of the ligaments origins and insertions were computed on the preoperative CT scan following a validated procedure.Knee ligaments were modeled as one‐bundle non‐linear springs, according to ref.Last, in order to replace the dynamic contribution related to the missing torso and contralateral leg, coordinate actuators acting to the 6 degrees of freedom of the pelvis respect to the ground were added to the model.The resulting model was used to track four separate gait cycles recorded experimentally, using a standard global optimization algorithm.R2). The computed knee joint reaction forces were also compared using the magnitude and the timing of their two typical main peaks and the similarity of their shape.Once the patient‐specific model was completed, we conducted a systematic verification and validation study on it. The OpenSim software is extensively benchmarked . The inverse dynamics solution of our model was verified for conservation of momentum (RMSE < 0.1%). A number of previous studies showed for very similar models the moderate sensitivity to inputs uncertainty.The orientation in the frontal plane of the varus‐valgus femur cutting plane;the orientation in the frontal plane of the varus‐valgus tibia cutting plane;the orientation in the frontal plane of the internal‐external rotation femur cutting plane;the orientation in the sagittal plane of the posterior slope of the tibial cutting plane;gap between the femoral and tibial cutting planes.Once the biomechanical alignment with the hip and ankle centers is achieved,Varus‐valgus femur cutting plane: From −3° to 3°, with a step of 1°;Varus‐valgus tibia cutting plane: From −3° to 3°, with a step of 1°;External rotation femur condyle cutting plane: From 0° to 6°, with a step of 1°;Posterior slope tibial cutting plane: From 3° to 5°, with a step of 1°;Gap between cut planes: From 18 to 28 mm, with a step of 2 mm.Solving repeatedly the model each time modeling different values for these surgical variables allowed a systematic exploration of how sensitive the elongation of the knee collateral ligaments is to changes in the gap distance and in orientation of the cutting planes. The following values where used:These surgical parameters are those most commonly controlled by the surgeons in various TKA pre‐operative planning tools to define the position of the femoral and tibial components on the bones. A sensitivity analysis was conducted throughout four normal gait cycles, by varying each surgical parameter independently.In the patient under examination here, the postoperative geometries of the bones were already shaped to simulate the actual TKA surgery and the prosthetic implants were already placed on the subject. The surgical procedure adopted comprised one cut on the tibia and five cuts on the femur: (1) distal cut (2) anterior and posterior femur cuts (3) anterior and posterior chamfer cuts.A number of studiesThe knee contact force predicted by our model and that measured by the instrumented implant over the four gait cycles and similar in amplitude and timing Fig. .The total force measured by the instrumented prosthesis reported two peaks throughout the full gait cycle, with the first peak of 2.0 BW occurring at the beginning of the stance, and a second peak of 2.6 BW occurring toward the end of the gait cycle. The model showed an excellent accuracy showing a difference of 0.1 BW when compared to the prosthesis data for both peaks , with a Root Mean Square Error (RMSE) of 0.35 BW ± 0.05 BW.The timing was also found in good agreement, as the predicted peak force was shifted by less than 4% of the gait cycle duration, from the measured one. The computed joint contact forces were highly correlated to those measured experimentally  and 60.4 mm (+2% longer than preoperative length). The gap between the femoral cut and the tibial cut in the neutral postoperative position, considered as the thickness of the prosthetic implant, was 26 mm.When the surgical variables were modified, the pre‐operative length of the two collateral ligaments changed considerably. The full sensitivity to femur and tibia varus‐valgus as a function of the gap is reported in Figure As expected the post‐operative elongation of collateral ligaments is quite sensitive to the varus‐valgus angle. The MCL is most sensitive, and any gap of 26 mm or greater stretches it beyond the 10% limit. In comparison, the LCL seems less sensitive, reaching the limit only for a gap of 28 mm and a varus angle of 3°. The effect of tibial slope and femoral rotation was less marked, and the MCL reached the limit only for gaps of 28 mm.The aim of the present study was to conduct a sensitivity analysis of the knee ligament elongations during level walking due to TKA as a function of position and orientation of the cutting guides, by means of a validated patient‐specific dynamic model of the post‐TKA knee biomechanics.R2 = 0.88) the knee contact forces measured during level walking. The 2012 Grand Challenge, where the data of the patient we analyzed here we used, had two winners.R2 = 0.82) and the unblinded prediction  have accuracies very close to those reported here. A crude error propagation analysis we made assuming static equilibrium suggests that this uncertainty in the knee contact force can bias the prediction of ligaments elongation of less than 1%, making the results of this study clinically relevant.The patient‐specific model predicted with good accuracy . The effect of all these is accounted in the predictive accuracy of the model, in this particular case expressed in term of accuracy in predicting the knee contact forces measured by the instrumented implant. But probably the most important limitation derives from the assumption that in no case the surgery would alter the gait kinematics; in other words, we assume the compensation strategies are effective in retaining a “normal” kinematics after surgery. Of course, this is true up to a point, and for some extreme value in the rage of surgical parameters explored this is quite unlikely.A more specific limitation is that we assumed that the balance of all soft tissues wrapping the implanted knee could be reduced to the balance of the two collateral ligaments. The method we used here work very well also for the cruciate ligaments, when the implant design preserves any (which is not the case for implant examined here). In principle, the method we usedA more structural limitation of this study is that we did not focus our attention of the effect surgical variables on the patellar tracking and the elongation of the patellar tendon, which is a well‐known functional complication for TKA. While the methods used here could in principle be used also to explore this aspect, this was considered beyond the scope of this study.All the conclusions we reached in this study are valid only for this patient, and cannot be extended to any population, without further studies on a much larger cohort.The method used in this study, which can be implemented whenever gait analysis and imaging data are available, can be used to evaluate the post‐operative soft tissue balance while performing daily life activities such as level walking. This could be useful, for example, for a patient with functional limitations to understand if these can be attributed to ineffective soft tissue balancing.Because of delicate balance between kinematics, dynamics, and soft tissue balancing, this detailed analysis is possible only post‐operatively, when the actual functional kinematics can be measured on the individual patient. If soft tissue balancing needs to be predicted during walking pre‐operatively, reduced‐order models that do not require a detailed lower limb kinematics as input need to be developed. This study can provide an excellent baseline to estimate the impact that order reduction can have on the predictive accuracy of the new solutions.In conclusion the elongation of the knee ligaments was found to be sensitive to the surgical parameters that define the positioning of the femoral and tibial components. The elongations were computed within a full‐order dynamic simulation, which accounted for all forces transmitted, and that could be validated because of the availability of telemetric knee force recordings. As such they provide an ideal baseline for the development and validation of reduced‐order models to be embedded in surgical planning simulators.Marco Viceconti wrote this paper and supervised the PhD project from which this works derives. Daniele Ascani was the PhD student who run that project and did most of the modelling work and revised the manuscript. Claudia Mazzà co‐supervised the project and revised the manuscript. All authors have read and approved the final submitted manuscript.