A helping hand: roles for accessory cells in the sense of touch across species.

During touch, mechanical forces are converted into electrochemical signals by tactile organs made of neurons, accessory cells, and their shared extracellular spaces. Accessory cells, including Merkel cells, keratinocytes, lamellar cells, and glia, play an important role in the sensation of touch. In some cases, these cells are intrinsically mechanosensitive; however, other roles include the release of chemical messengers, the chemical modification of spaces that are shared with neurons, and the tuning of neural sensitivity by direct physical contact. Despite great progress in the last decade, the precise roles of these cells in the sense of touch remains unclear. Here we review the known and hypothesized contributions of several accessory cells to touch by incorporating research from multiple organisms including C. elegans, D. melanogaster, mammals, avian models, and plants. Several broad parallels are identified including the regulation of extracellular ions and the release of neuromodulators by accessory cells, as well as the emerging potential physical contact between accessory cells and sensory neurons via tethers. Our broader perspective incorporates the importance of accessory cells to the understanding of human touch and pain, as well as to animal touch and its molecular underpinnings, which are underrepresented among the animal welfare literature. A greater understanding of touch, which must include a role for accessory cells, is also relevant to emergent technical applications including prosthetics, virtual reality, and robotics.

Assessing bicycle-vehicle conflicts at urban intersections utilizing a VR integrated simulation approach.

Animosity between drivers and cyclists has existed on urban road networks for many years. Conflicts between these two groups of road users are exceptionally high in the shared right-of-way environments. Benchmarking methods of conflict assessments are mostly based on statistical analysis with limited data sources. The actual crash data would be valuable to understand the features of bike-car collisions, however the available data are spatially and temporally sparse. To this end, this paper proposes a simulation-based bicycle-vehicle conflict data generation and assessment approach. The proposed approach uses a three-dimensional visualization and virtual reality platform, integrating traffic microsimulation to reproduce a naturalistic driving/cycling-enabled experimental environment. The simulation platform is validated to reflect the human-resembled driving/cycling behaviors under different infrastructure designs. Comparative experiments are carried out on bicycle-vehicle interactions under different conditions, with data collected from a total of 960 scenarios. Based on the results of the surrogate safety assessment model (SSAM), the obtained key insights include: (1) scenarios of a high conflict probability do not lead to actual crashes, which suggests that the classic SSM-based measurements such as TTC or PET values may not sufficiently reflect real cyclist-driver interactions; (2) the major cause of conflicts is variation in vehicle acceleration, which suggests that drivers are considered to be the main party responsible for bicycle-vehicle conflict/crash occurrence; (3) the proposed approach is able to generate near-miss events and reproduce interaction patterns between cyclists and drivers, facilitating experiments and data collections which would be typically unavailable for this type of study.

Optimizing the Cell Painting assay for image-based profiling.

In image-based profiling, software extracts thousands of morphological features of cells from multi-channel fluorescence microscopy images, yielding single-cell profiles that can be used for basic research and drug discovery. Powerful applications have been proven, including clustering chemical and genetic perturbations on the basis of their similar morphological impact, identifying disease phenotypes by observing differences in profiles between healthy and diseased cells and predicting assay outcomes by using machine learning, among many others. Here, we provide an updated protocol for the most popular assay for image-based profiling, Cell Painting. Introduced in 2013, it uses six stains imaged in five channels and labels eight diverse components of the cell: DNA, cytoplasmic RNA, nucleoli, actin, Golgi apparatus, plasma membrane, endoplasmic reticulum and mitochondria. The original protocol was updated in 2016 on the basis of several years' experience running it at two sites, after optimizing it by visual stain quality. Here, we describe the work of the Joint Undertaking for Morphological Profiling Cell Painting Consortium, to improve upon the assay via quantitative optimization by measuring the assay's ability to detect morphological phenotypes and group similar perturbations together. The assay gives very robust outputs despite various changes to the protocol, and two vendors' dyes work equivalently well. We present Cell Painting version 3, in which some steps are simplified and several stain concentrations can be reduced, saving costs. Cell culture and image acquisition take 1-2 weeks for typically sized batches of ≤20 plates; feature extraction and data analysis take an additional 1-2 weeks.This protocol is an update to Nat. Protoc. 11, 1757-1774 (2016): https://doi.org/10.1038/nprot.2016.105.

The role of safety in modal choice and shift: A transport expert perspective in the state of Victoria (Australia).

BACKGROUND: Previous research showed differences in the exposure to risk from using different modes of transport and that modal choice can significantly impact road safety outcomes. Though, a modal shift to a safer mode is not commonly discussed as part of road safety strategies. AIM: This study aimed to explore the perspectives of transport policymakers about the role of safety in modal choice and if it can be one of the main factors for modal choice and shift. METHOD: Seven semi-structured interviews were conducted with transport experts from government (n = 5) and private (n = 2) organisations in the state of Victoria. Interview transcripts were analysed using a thematic approach to identify the key perspectives of the experts. RESULTS: Overall, the analyses indicated uncertainty of the ability to use safety in modal choice as a road safety strategy and identified two main issues; 1) the perceived limited role that safety plays in people's modal choice, and 2) that safety is perceived to be a barrier to modal choice and modal shift towards public and active travel. Experts suggested that when considering transport modes other factors such as convenience, availability, speed, cost, trip purpose and income are more influential than safety in modal choice. They also suggested that safety might play a role within the chosen mode, but not in choosing between modes, such as considering safety features when purchasing a car after deciding to drive a car. It was also stated that safety could act as a barrier preventing people from choosing sustainable transport modes of public transport and active travel. CONCLUSIONS: Theoretically, it is argued that safety and mobility cannot be traded against each other, and that mobility becomes a function of safety, not vice-versa. However, our findings indicated that the transport experts did not believe that safety is the main factor in the modal choice process. Transport experts believed users choose their mode of transport mainly to achieve mobility benefits without necessarily considering how safe is their choice as a differentiator factor. While the shift to a safer mode of transport would help improve road safety outcomes, further investigations are needed to inform how can we influence the consideration of safety as the main factor in modal choice and removing barriers to using the relatively safest available mode of transport.

Surface crossing and energy flow in many-dimensional quantum systems.

Energy flow in molecules, like the dynamics of other many-dimensional finite systems, involves quantum transport across a dense network of near-resonant states. For molecules in their electronic ground state, the network is ordinarily provided by anharmonic vibrational Fermi resonances. Surface crossing between different electronic states provides another route to chaotic motion and energy redistribution. We show that nonadiabatic coupling between electronic energy surfaces facilitates vibrational energy flow and, conversely, anharmonic vibrational couplings facilitate nonadiabatic electronic state mixing. A generalization of the Logan-Wolynes theory of quantum energy flow in many-dimensional Fermi resonance systems to the two-surface case gives a phase diagram describing the boundary between localized quantum dynamics and global energy flow. We explore these predictions and test them using a model inspired by the problem of electronic excitation energy transfer in the photosynthetic reaction center. Using an explicit numerical solution of the time-dependent Schrödinger equation for this ten-dimensional model, we find quite good agreement with the expectations from the approximate analytical theory.

Intentions and willingness to engage in risky driving behaviour among high school adolescents: evaluating the bstreetsmart road safety programme.

OBJECTIVE: To investigate the impact of a road safety programme on adolescents' willingness to engage in risky behaviour as probationary drivers, adjusted for covariates of interest. METHOD: The bstreetsmart is a road safety programme delivered to around 25 000 adolescent students annually in New South Wales. Using a smartphone-based app, student and teacher participation incentives, students were surveyed before and after programme attendance. Mixed-methods linear regression analysed pre/post-modified Behaviour of Young Novice Driver (BYNDS_M) scores. RESULTS: 2360 and 1260 students completed pre-event and post-event surveys, respectively. Post-event BYNDS_M scores were around three points lower than pre-event scores (-2.99, 95% CI -3.418 to -2.466), indicating reduced intention to engage in risky driving behaviours. Covariates associated with higher stated intentions of risky driving were exposure to risky driving as a passenger (1.21, 95% CI 0.622 to 2.011) and identifying as non-binary gender (2.48, 95% CI 1.879 to 4.085), adjusting for other predictors. CONCLUSIONS: Trauma-informed, reality-based injury prevention programmes can be effective in changing short-term stated intentions to engage in risky driving, among a pre-independent driving student population. The adolescent novice driver age group is historically challenging to engage, and injury prevention action must be multipronged to address the many factors influencing their behaviour.

Morphology and gene expression profiling provide complementary information for mapping cell state.

Morphological and gene expression profiling can cost-effectively capture thousands of features in thousands of samples across perturbations by disease, mutation, or drug treatments, but it is unclear to what extent the two modalities capture overlapping versus complementary information. Here, using both the L1000 and Cell Painting assays to profile gene expression and cell morphology, respectively, we perturb human A549 lung cancer cells with 1,327 small molecules from the Drug Repurposing Hub across six doses, providing a data resource including dose-response data from both assays. The two assays capture both shared and complementary information for mapping cell state. Cell Painting profiles from compound perturbations are more reproducible and show more diversity but measure fewer distinct groups of features. Applying unsupervised and supervised methods to predict compound mechanisms of action (MOAs) and gene targets, we find that the two assays not only provide a partially shared but also a complementary view of drug mechanisms. Given the numerous applications of profiling in biology, our analyses provide guidance for planning experiments that profile cells for detecting distinct cell types, disease phenotypes, and response to chemical or genetic perturbations.

Restraint Use for Child Occupants in Dubai, United Arab Emirates.

The overall objective of the current study was to investigate the behaviours and knowledge of parents/carers in relation to safe child occupant travel in the Emirate of Dubai in the United Arab Emirates (UAE). A community survey was completed by 786 participants who were responsible for the safety of 1614 children (aged 10 years and younger). The survey included questions related to the type, frequency and appropriateness of restraint use for their eldest child. Overall, 24 percent of participants reported that they 'never/almost never' restrained their eldest child while travelling in a motor vehicle, with this proportion increasing with child age. For example, though 89 percent of participants reported that they restrained their infants (<1 year) in an 'appropriate' restraint for their age, this rate was much lower for children aged between 5 and 7 years (10%). Overall, these findings suggest that a large proportion of child occupants, especially those aged five years and older, are not appropriately restrained in vehicles, and therefore are at an increased risk of death or serious injury in the event of a crash. Future research will validate this self-reported child restraint use data with objective data from observations of real-world child restraint use behaviour in the UAE.

Understanding users' characteristics in the selection of vehicle seating configurations and positions in fully automated vehicles.

OBJECTIVE: To understand which users' characteristics influence their preferences in the selection of vehicle seating configurations and positions across different traveling scenarios involving a fully automated vehicle (FAV). METHODS: Participants (n = 730) completed an online survey in which they were asked to imagine traveling in a FAV across three hypothetical scenarios. Participants were asked to select between five different seating configurations and four positions for each scenario and about their anthropometry and their driving/riding experience. Multinomial regression analyses were conducted to identify the factors that influenced users' preferences. RESULTS: FAV Configuration #3 (traditional light vehicle seating configuration) was the preferred seating configuration for 74% of the participants, followed by FAV #2 (in which the two seating rows face each other, 13%) in Scenario 1 (riding by oneself). Similar numbers were observed in Scenario 3 (riding with an unknown person). In Scenario 2 (riding with their partner), participants preferred FAV #2 (12.5%) and FAV #5 (in which the front seat passengers point toward a common point in the front, conventional rear seat configuration, 17.5%). Having close family was significant to choose the traditional vehicle configuration over other vehicle configurations, but only when the participants were driving by themselves. Having previously experienced motion sickness was significant to prefer a forward seating configuration when the trip was shared with partners. Belonging to a particular height or weight group was significantly associated with the preferred seat within the preferred FAV configuration (the driver's position in FAV #3; a rear-facing seat in FAV #2), although there was not a clear trend between increasing weight and/or height and preferring one seating position over the others. CONCLUSIONS: Previous work had shown differences in participants' preferences for seating configurations and positions depending on age, sex and country. While increasing the sample size, the current study analyses other factors that were associated with choosing one vehicle configuration and seating position over others. As these factors are directly related to the likelihood of sustaining injuries in the event of a crash, the current study provides important insights regarding the potential risk factors for FAV occupants.

Modelling injury severity of bicyclists in bicycle-car crashes at intersections.

Bicyclists are vulnerable road users as they are not protected during a road collision. Although numerous studies have been conducted to understand the parameters contributing to bicyclist's injury severity, most of these studies have focused on the relationship between crash severity and road, environmental, vehicle and human demographic parameters. No study has been found that investigated the relationship of bicyclist's injury severity with speed and mass of both vehicles, as well as other crash dynamics aspects. This study developed a modelling framework to investigate the effect of variables such as speed, mass and crash angle on bicyclist's injury severity in bicycle-car crashes at intersections. A combination of Newtonian Mechanics and statistical analysis was utilised to develop this theory. This modelling process followed a two-step approach. In the first step, Newtonian Mechanics was used to develop numerical models to estimate the impact force applied to the bicyclist. Variables affecting the associated impact forces were then identified. In the second step, a mixed binary logistic regression model was developed to estimate injury severity of a bicycle-vehicle crash as a function of mass of both vehicles, speed of both vehicles before and after the crash, restraint use and age of bicyclist. Transport Accident Commission (TAC) validated crash data was used to develop the model. The results of the numerical models showed that kinetic energy of the car before crash and kinetic energy of the bicycle after crash are important parameters affecting the injury severity of the cyclist in bicycle-vehicle crashes. The results of the mixed binary logistic regression model confirmed that the addition of kinetic energy of the car before crash and the kinetic energy of the bicycle post-crash had a statistically significant effect on injury severity of bicyclist. The results further showed that older bicyclists were involved in higher severity crashes and helmet-wearing reduced the injury severity of the bicyclist.

Aldehyde dehydrogenase 3a2 protects AML cells from oxidative death and the synthetic lethality of ferroptosis inducers.

Metabolic alterations in cancer represent convergent effects of oncogenic mutations. We hypothesized that a metabolism-restricted genetic screen, comparing normal primary mouse hematopoietic cells and their malignant counterparts in an ex vivo system mimicking the bone marrow microenvironment, would define distinctive vulnerabilities in acute myeloid leukemia (AML). Leukemic cells, but not their normal myeloid counterparts, depended on the aldehyde dehydrogenase 3a2 (Aldh3a2) enzyme that oxidizes long-chain aliphatic aldehydes to prevent cellular oxidative damage. Aldehydes are by-products of increased oxidative phosphorylation and nucleotide synthesis in cancer and are generated from lipid peroxides underlying the non-caspase-dependent form of cell death, ferroptosis. Leukemic cell dependence on Aldh3a2 was seen across multiple mouse and human myeloid leukemias. Aldh3a2 inhibition was synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition; GPX4 inhibition is a known trigger of ferroptosis that by itself minimally affects AML cells. Inhibiting Aldh3a2 provides a therapeutic opportunity and a unique synthetic lethality to exploit the distinctive metabolic state of malignant cells.

Localization on Certain Graphs with Strongly Correlated Disorder.

Many-body localization in interacting quantum systems can be cast as a disordered hopping problem on the underlying Fock-space graph. A crucial feature of the effective Fock-space disorder is that the Fock-space site energies are strongly correlated-maximally so for sites separated by a finite distance on the graph. Motivated by this, and to understand the effect of such correlations more fundamentally, we study Anderson localization on Cayley trees and random regular graphs, with maximally correlated disorder. Since such correlations suppress short distance fluctuations in the disorder potential, one might naively suppose they disfavor localization. We find however that there exists an Anderson transition, and indeed that localization is more robust in the sense that the critical disorder scales with graph connectivity K as sqrt[K], in marked contrast to KlnK in the uncorrelated case. This scaling is argued to be intimately connected to the stability of many-body localization. Our analysis centers on an exact recursive formulation for the local propagators as well as a self-consistent mean-field theory; with results corroborated using exact diagonalization.

Safer vehicles and technology for older adults.

Objective: The objective of this study was to address the uptake of safer vehicles and in-vehicle technologies among older adults through a better understanding of extent and use of safer vehicles and awareness/acceptance of new vehicle technologies.Methods: Data were collected from a sample of 501 active older drivers (those who drove at least once a week) through telephone surveys.Results: The sample included experienced and active drivers aged between 65 and 92 years (median 73 years). Though two-thirds indicated that safety was a priority in their vehicle choice, other factors such as reliability and vehicle make were more important. There was low awareness of driver assist safety features, particularly among the oldest drivers. Only one-quarter of drivers were receptive to paying extra for safety features, and there was no interest in paying more for driverless vehicles.Conclusions: The findings showed an overall low awareness and acceptance of in-vehicle safety features; however, where there was some awareness, there was greater interest in purchasing vehicles with safety features. More effort should be undertaken to develop and prioritize a set of recommendations to increase use of safe vehicles by older drivers.

Seating configuration and position preferences in fully automated vehicles.

Objective: This study aimed to understand seating configuration and position preferences in a fully automated vehicle (FAV) across 7 hypothetical traveling scenarios.Methods: Participants completed an online survey in which they were asked to imagine traveling in an FAV across 7 hypothetical traveling scenarios and asked to select 1 of 5 seating configurations and 1 of 4 seating positions for themselves and for any additional occupants. Furthermore, participants were asked to indicate any activities that they and any additional occupants would engage in and whether they would be willing to wear a different seat belt in an FAV while seated in a non-forward-facing mode or while reclined.Results: Five hundred and fifty-two participants (male = 50.5%; mean = 36.6 years, SD = 14.0 years) completed the online survey. Most participants resided in Australia (40.9%), Spain (16.5%), Sweden (15.6%), or Lebanon (19.4%). Most participants drove on a daily basis (60.0%), had driven between 5,000 and 15,000 km in the previous year (33.2%), and reported that they always or almost always wear a seat belt while traveling in a motor vehicle (98.2%). Across all scenarios, participants were most likely to prefer a conventional seating configuration (i.e., all seats facing forward; between 40.0 and 76.3%). In terms of seating position preferences, participants preferred seating position A (i.e., the conventional driver's seat; between 54.6 and 68.3%), regardless of with whom they were traveling. The most common activity while traveling alone was reading (25.0%). However, when traveling with other occupants, talking was the most common activity (41.0-63.0%), even with someone they did not know (31.0%). Most participants predicted that they would always or almost always wear a seat belt when traveling in an FAV (95.9%). Most participants also reported that they would be very willing or willing to wear a different seat belt configuration in an FAV while seated in a non-forward-facing mode or while reclined (73.8 and 80.7%, respectively).Conclusions: This study has provided valuable insight regarding seating configuration and position preferences in an FAV, as well as predicted activities and restraint use. Future research will use this information to simulate likely injury outcomes of these preferences in the event of a motor vehicle crash and provide a basis for the design of occupant protection systems for FAVs.

Do angiosperms with highly divergent mitochondrial genomes have altered mitochondrial function?

Angiosperm mitochondrial (mt) genes are generally slow-evolving, but multiple lineages have undergone dramatic accelerations in rates of nucleotide substitution and extreme changes in mt genome structure. While molecular evolution in these lineages has been investigated, very little is known about their mt function. Some studies have suggested altered respiration in individual taxa, although there are several reasons why mt variation might be neutral in others. Here, we develop a new protocol to characterize respiration in isolated plant mitochondria and apply it to species of Silene with mt genomes that are rapidly evolving, highly fragmented, and exceptionally large (~11 Mbp). This protocol, complemented with traditional measures of plant fitness, cytochrome c oxidase activity assays, and fluorescence microscopy, was also used to characterize inter- and intraspecific variation in mt function. Contributions of the individual "classic" OXPHOS complexes, the alternative oxidase, and external NADH dehydrogenases to overall mt respiratory flux were found to be similar to previously studied angiosperms with more typical mt genomes. Some differences in mt function could be explained by inter- and intraspecific variation. This study suggests that Silene species with peculiar mt genomes still show relatively normal mt respiration. This may be due to strong purifying selection on mt variants, coevolutionary responses in the nucleus, or a combination of both. Future experiments should explore such questions using a comparative framework and investigating other lineages with unusual mitogenomes.

Motor primitives are determined in early development and are then robustly conserved into adulthood.

Motor patterns in legged vertebrates show modularity in both young and adult animals, comprising motor synergies or primitives. Are such spinal modules observed in young mammals conserved into adulthood or altered? Conceivably, early circuit modules alter radically through experience and descending pathways' activity. We analyze lumbar motor patterns of intact adult rats and the same rats after spinal transection and compare these with adult rats spinal transected 5 days postnatally, before most motor experience, using only rats that never developed hind limb weight bearing. We use independent component analysis (ICA) to extract synergies from electromyography (EMG). ICA information-based methods identify both weakly active and strongly active synergies. We compare all spatial synergies and their activation/drive strengths as proxies of spinal modules and their underlying circuits. Remarkably, we find that spatial primitives/synergies of adult injured and neonatal injured rats differed insignificantly, despite different developmental histories. However, intact rats possess some synergies that differ significantly, although modestly, in spatial structure. Rats injured as adults were more similar in modularity to rats that had neonatal spinal transection than to themselves before injury. We surmise that spinal circuit modules for spatial synergy patterns may be determined early, before postnatal day 5 (P5), and remain largely unaltered by subsequent development or weight-bearing experience. An alternative explanation but equally important is that, after complete spinal transection, both neonatal and mature adult spinal cords rapidly converge to common synergy sets. This fundamental or convergent synergy circuitry, fully determined by P5, is revealed after spinal cord transection.

Simple probability distributions on a Fock-space lattice.

We consider some aspects of a standard model employed in studies of many-body localization: interacting spinless fermions with quenched disorder, for non-zero filling fraction, here on d-dimensional hypercubic lattices. The model may be recast as an equivalent tight-binding model on a 'Fock-space (FS) lattice' with an extensive local connectivity. In the thermodynamic limit exact results are obtained for the distributions of local FS coordination numbers, FS site-energies, and the density of many-body states. All such distributions are well captured by exact diagonalisation on the modest system sizes amenable to numerics. Care is however required in choosing the appropriate variance for the eigenvalue distribution, which has implications for reliable identification of mobility edges.

Cyclist exposure to the risk of car door collisions in mixed function activity centers: A study in Melbourne, Australia.

OBJECTIVE: The objective of this study is to describe key risks related to dooring collisions on roads in mixed function activity centers by examining video footage recorded onboard the bicycles of cyclists riding through this road environment. The study aims to enhance our understanding of the risk associated with cyclist door collisions on these roads and to provide a focus for future studies that aim to identify measures that enhance cyclist safety. METHOD: The study measured 4 key risk exposures (per hour and kilometer), namely, on-street parked cars and 3 conditions associated with parked cars being accessed or egressed: door opened (a) after the cyclist passes (give-way event); (b) in the path of the cyclist without collision (obstruction event); and (c) in the path of the cyclist with collision (collision event). Exposure to the risk factors was measured using video footage recorded onboard the bicycles of adult cyclists (n = 25) as they rode through this road environment. The average speed of cyclists was also estimated from these video data and related to the measures of exposure. RESULTS: The cycling experiences of the participants were observed over 3 h 58 min and 84.0 km. On average, the sample was exposed to 1,166 parked car events per hour (55 per kilometer), 6.9 give-way events per hour (0.3 per kilometer), 2.3 obstruction events per hour (0.1 per kilometer), and no collision events. There were 9 instances of obstruction events. In most cases, the cyclist was clearly visible (n = 7; 77.8%) and modified his or her position to avoid the door (n = 8; 88.9%). Moreover, the door was opened by the driver in nearly all cases (n = 8; 88.9%), primarily to exit the vehicle (n = 4; 44.4%) or enter the vehicle (n = 3; 33.3%). The average speed of cyclists was 22.7 km/h (SD = 4.1 km/h), and average speed tended to reduce as exposure to parked car events increased. CONCLUSION: Cyclists seldom interact with a vehicle occupant accessing or egressing a parked car, yet a concerning proportion of these interactions involve the occupant opening the door in the path of the cyclist, rather than waiting for the cyclist to pass. This suggests that there is still considerable need to identify measures that increase the likelihood that a vehicle occupant will look for cyclists before opening the car door, particularly in road environments where longer-term solutions such as physical separation are not readily achieved.

Exploring road design factors influencing tram road safety - Melbourne tram driver focus groups.

Melbourne, Australia has the largest tram/streetcar network in the world including the largest mixed traffic tram operating environment. Therefore, Melbourne tram drivers are responsible for controlling one of the heaviest vehicles on road ranging from shared tram lanes to exclusive tram lanes. In addition to different tram lane configurations, tram drivers need to follow different traffic signal phases at intersections including tram priority signals as well as need to serve passengers at various types of closely spaced tram stops. Despite all these challenges, no research has explored tram driver perceptions of the risk factors on different tram route road design configurations. Therefore, the aim of this study is to investigate how tram drivers' safety perceptions alter along various tram route sections, signal settings and stop configurations. A tram driver focus group approach was adopted for this research involving thirty tram drivers (4 female and 26 male drivers). The tram drivers' age ranged from 29 to 63 years, with an average age of 47.6 years (standard deviation of 10.1 years), and their experience of tram driving ranged from 1.17 to 31 years, with an average experience of 12.5 years (standard deviation of 10.2 years). The participating tram drivers perceived that the raised tram tracks and tramways with raised yellow curbing beside tracks are safer lane priority features on the Melbourne tram network compared to full-time, part-time and mixed traffic tram lanes. They regarded 'hook turns' as a safe form of tram signal priority treatment at intersections and platform tram stops as the safest tram stop design for all passengers among all other tram stop designs in Melbourne. Findings of this research could enhance the understanding of crash risk factors for different tram route features and thus can offer effective planning strategies for transit agencies to improve tram road safety.

Mining for osteogenic surface topographies: In silico design to in vivo osseo-integration.

Stem cells respond to the physicochemical parameters of the substrate on which they grow. Quantitative material activity relationships - the relationships between substrate parameters and the phenotypes they induce - have so far poorly predicted the success of bioactive implant surfaces. In this report, we screened a library of randomly selected designed surface topographies for those inducing osteogenic differentiation of bone marrow-derived mesenchymal stem cells. Cell shape features, surface design parameters, and osteogenic marker expression were strongly correlated in vitro. Furthermore, the surfaces with the highest osteogenic potential in vitro also demonstrated their osteogenic effect in vivo: these indeed strongly enhanced bone bonding in a rabbit femur model. Our work shows that by giving stem cells specific physicochemical parameters through designed surface topographies, differentiation of these cells can be dictated.