Participant-Specific Modelling of the Proximal Femur during Lateral Falls: A Mechanistic Evaluation of Risk Factors

Falls among older adults are a common occurrence with the potential to result in substantial injury. Hip fractures are among the most frequent and devastating fall induced injuries, resulting in increased morbidity and mortality, as well as significant socioeconomic costs. From a mechanistic perspective, the risk of a hip fracture during a fall is dictated by the ratio between the impact loading and the ability of the femur to withstand such loads. Investigations of clinical fracture risk factors have generally focused on the latter, neglecting the influence of these factors on impact dynamics. Experimental fall simulations provide a means to investigate factors modulating impact dynamics; however, these studies are limited to the skin surface with limited ability to draw conclusions on femoral loading and fracture risk. Investigations into the mechanical basis of clinical risk factors (sensitive to both loading and femur morphology) could provide insights to inform the development of protective devices and increase the accuracy of screening tools. Therefore, the purpose of this thesis was to evaluate the influence of previously identified hip fracture risk factors on impact characteristics during lateral falls and how the application of these loading conditions influence femoral neck stresses and fracture risk. Specifically, the influence of fall simulation paradigm (FSP: a surrogate for fall type), sex, and trochanteric soft tissue thickness (TSTT) were evaluated through coupling of experimental impact dynamics with participant-specific proximal femur models. Healthy young males and females, encompassing a wide range of body compositions underwent a series of fall simulation paradigms. These paradigms varied in fall trajectory and impact configuration, ranging from highly controlled vertical drops (pelvis release) to releases more representative of falls observed in older adults (kneeling and squat releases). Peak impact force magnitude and localization over the proximal femur, as well as orientation and point of application with respect to the femur were extracted (Chapters 3 and 4). A subset of the participants subsequently underwent dual energy X-ray absorptiometry (DXA) imaging, enabling participant-specific modelling and tissue level analysis - driven by experimental loading conditions (reginal force magnitude, orientation, and point of application; Chapter 5). FSP significantly influenced skin surface loading conditions, as well as femoral neck stresses and fracture risk. Compared to kneeling and squat, pelvis release elicited lower peak force magnitude; however, this force was applied closer to and was more concentrated over the greater trochanter. Despite the differences in force distribution, kneeling and squat release still elicited greater force directed over the proximal femur compared to pelvis release. Beyond force magnitude and distribution, these FSP varied significantly in impact vector orientation with respect to the femur. Kneeling release was associated with the most perpendicular loading vector, while squat release elicited the most distally directed vector in the frontal plane. In the anterior-posterior plane, pelvis release was directed posteriorly, while kneeling and squat release were directed anteriorly. Observed difference in skin surface loading conditions across FSP interacted with underlying femoral geometry to influence stress generation and fracture risk. Compressive stress at the superior-lateral femoral neck was greatest in kneeling release, while tensile stress at the inferior-medial femoral neck was greatest in squat release (driven by proportion of force resulting in axial compression vs. bending stress). While no differences in femoral neck fracture risk were observed between kneeling and squat release, kneeling release may elicit a greater risk of local compressive failure in the superior femoral neck. At the skin surface, sex and TSTT significantly influenced impact dynamics; however, underlying differences in femur morphology influenced the translation of these loading conditions to femoral neck stresses and fracture risk. Compared to females, males exhibited greater impact force magnitude, which was applied closer to and was more concentrated over the greater trochanter of the proximal femur. This increased loading in males was mitigated by differences in femur morphology (greater resistance to bending and shear stress generation, as well as strength), resulting in no differences in femoral neck stresses or fracture risk. The increased risk of hip fracture in females may be explained by age related changes in femur morphology, as well as sex-differences in the circumstances of falls. High-TSTT individuals exhibited greater impact force magnitude; however, these loads were applied further from and less focally over the greater trochanter compared to low-TSTT individuals. Combined, no differences were observed in the amount of force directed over the proximal femur across TSTT. Despite similar loading conditions, low-TSTT individuals elicited greater femoral neck stresses and fracture risk compared to their high-TSTT counterparts, driven by differences in underlying femur morphology (reduced resistance to bending and shear stress generation). The protective influence of TSTT to redistribute impact force peripherally away from the greater trochanter appears to play an important role in fracture risk. When global impact force was utilized instead of local force during modelling, no differences in femoral stresses or fracture risk were observed across TSTT. In summary, this thesis combined two previously exclusive approaches (experimental fall simulations and tissue level modelling) to gain novel insights into the influence of FSP, sex, and TSTT on femoral neck stresses and fracture risk. Through a participant-specific multi-level approach, this analysis was sensitive to both impact dynamics and underlying femoral geometry. FSP influenced fracture risk, as well as the location and magnitude of peak femoral stresses. Inclusion of muscle activation in future versions of the current approach may inform ‘safe-falling’ strategies, designed to reduce fracture risk. The current results support epidemiological findings suggesting TSTT is a protective factor against hip fracture; however, sex differences in fracture risk are likely driven by age related changes in femur morphology not included in this analysis. Based on the apparent importance to fracture risk, future work should aim to quantify the translation of skin surface pressure distributions to impact energy delivered to the proximal femur

The influence of increased passive stiffness of the trunk and hips on balance control during reactive stepping

The final publication is available at Elsevier via https://doi.org/10.1016/j.gaitpost.2019.05.018. © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Background Age-related changes, which include increased trunk and hip stiffness, negatively influence postural balance. While previous studies suggest no net-effect of trunk and hip stiffness on initial trip-recovery responses, no study to date has examined potential effects during the dynamic restabilisation phase following foot contact. Research question Does increased trunk and hip stiffness, in isolation from other ageing effects, negatively influence balance during the restabilisation phase of reactive stepping. Methods Balance perturbations were applied using a tether-release paradigm, which required participants to react with a single-forward step. Sixteen young adults completed two blocks of testing: a baseline and an increased stiffness (corset) condition. Whole-body kinematics were utilized to estimate spatial step parameters, center of mass (COM), COM incongruity (peak - final position) and time to restabilisation, in anteroposterior (AP) and mediolateral (ML) directions. Results In the corset condition, peak COM displacement was increased in both directions (p  0.233). Increased passive stiffness also increased the magnitude and variability of peak shear ground reaction force, COM incongruity, and time to restabilisation in the ML (but not AP) direction (p < 0.027). Significance In contrast to previous literature, increased stiffness resulted in greater peak COM displacement in both directions. Our results suggest increased trunk and hip stiffness have detrimental effects on dynamic stability following a reactive step, particularly in the ML direction. Observed increases in magnitude and variability of COM incongruity suggest the likelihood of a sufficiently large loss of ML stability - requiring additional steps - was increased by stiffening of the hips and trunk. The current findings suggest interventions aiming to mobilize the trunk and hips, in conjunction with strengthening, could improve balance and reduce the risk of falls.This research was funded in part by grants from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-03636), the Canadian Foundation for Innovation (Grant #25351) and the Ontario Ministry of Research and Innovation (Grant #25351 and ER14-10-236)

Do agri-environment schemes result in improved water quality?

Welsh Government. Grant Number: 183/2007/0

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Jones_JI_et_al_data from Do agri-environment schemes result in improved water quality_Journal of Applied Ecology.xlsx

Data describing physico-chemical parameters, modelled pollutant concentrations and biological condition of 80 catchments in Wales defined by proportion of catchment under available agri-environment schemes

Data from: Do agri-environment schemes result in improved water quality?

Improved water quality, through a reduction in diffuse pollution from agricultural sources, is an expected benefit of agri-environment schemes, but this has yet to be demonstrated in practice. Here, we evaluate the impact of Welsh agri-environment schemes on water quality and freshwater ecosystem condition through a combined monitoring and modelling framework. To determine the influence of the agri-environment schemes on ecosystem condition, spatially independent catchments dominated by a single scheme (>40% of catchment) were compared to control catchments dominated (>70%) by agricultural land that was not part of any scheme. Biological indicators of water quality were monitored at the outfall of each catchment and a spatially explicit modelling framework of diffuse pollutant emissions applied to each of the 80 catchments. Direct comparison (scheme/non-scheme) was unable to identify any significant effect of agri-environment scheme participation. However, derived biological indicators that reflected organic pollution, eutrophication and pesticide run-off were strongly correlated with modelled concentrations of corresponding diffuse pollutants, thus providing a ground-truth for the models. Scenarios that assessed the correct counterfactuals (i.e. the influence of scheme entry on pollutant output) were developed for the whole of Wales. The models indicated an important effect of scheme entry on water quality, but this effect was not evenly distributed across the landscape. Synthesis and applications. Our results indicate that agri-environment schemes can deliver improvements in water quality, through a reduction in diffuse pollution from agricultural sources. However, it is not easy to demonstrate scheme effectiveness; the combination of field survey and modelling used here provides a framework for addressing these difficulties. A spatially targeted approach for agri-environment scheme options to protect water resources from diffuse pollution is likely to be most effective at delivering water quality improvements

A 2021 Horizon Scan of Emerging Global Biological Conservation Issues.

We present the results from our 12th annual horizon scan of issues likely to impact biological conservation in the future. From a list of 97 topics, our global panel of 25 scientists and practitioners identified the top 15 issues that we believe society may urgently need to address. These issues are either novel in the biological conservation sector or represent a substantial positive or negative step-change in impact at global or regional level. Six issues, such as coral reef deoxygenation and changes in polar coastal productivity, affect marine or coastal ecosystems and seven relate to human and ecosystem-level responses to climate change. Identification of potential forthcoming issues for biological conservation may enable increased preparedness by researchers, practitioners, and decision-makers

Environmental Morale and Motivation

This chapter discusses the role of environmental morale and environmental motivation in individual behavior from the point of view of economics and psychology. It deals with the fundamental public good problem, and presents empirical (laboratory and field) evidence on how the cooperation problem can be overcome. Four different theoretical approaches are distinguished according to how individuals’ underlying environmental motivation is modeled. Specifically, we look at the interaction between environmental policy and environmental morale through the lens of cognitive evaluation theory (also known as crowding theory)