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BACKGROUND: N-methyl-2-pyrrolidone (NMP) is an epigenetically active chemical fragment and organic solvent with numerous applications including use as a drug-delivery vehicle. Previously considered biologically inert, NMP demonstrates immunomodulatory and anti-myeloma properties that are partly explained by acetyllysine mimetic properties and non-specific bromodomain inhibition. We therefore evaluated orally administered NMP in a phase 1 dose-escalation trial to establish its maximum tolerated dose (MTD) in patients with relapsed/refractory multiple myeloma (RR-MM). Secondary endpoints were safety, pharmacokinetics (PK), overall response rate and immunological biomarkers of activity. RESULTS: Thirteen patients received NMP at starting doses between 50 and 400 mg daily. Intra-patient dose escalation occurred in five patients, with one attaining the ceiling protocolised dose of 1 g daily. Median number of monthly cycles commenced was three (range 1-20). Grade 3-4 adverse events (AEs) were reported in seven (54%; 95% CI 25-81%) patients. Most common AEs (> 30% of patients) of any grade were nausea and musculoskeletal pain. The only dose limiting toxicity (DLT) was diarrhoea in a patient receiving 200 mg NMP (overall DLT rate 8%; 95% CI 0-36%). Hence, the MTD was not defined. Median progression-free and overall survival were 57 (range 29-539) days and 33 (95% CI 9.7- > 44) months, respectively. The best response of stable disease (SD) was achieved in nine patients (69%; 95% CI 39-91%). PK analysis demonstrated proportional dose-concentrations up to 400 mg daily, with a more linear relationship above 500 mg. Maximum plasma concentrations (Cmax) of 16.7 mg/L at the 800 mg dose were below those predicted to inhibit BET-bromodomains. Peripheral blood immune-profiling demonstrated maintenance of natural killer (NK) cells, and a gene expression signature suggestive of enhanced T, B and NK cell functions; a subject with prolonged exposure manifested sustained recovery of B and

Endometrial cancer is the most diagnosed gynecological malignancy. Despite numerous scientific advances, the incidence and mortality rate of endometrial cancer continues to rise. Emerging evidence suggests a putative role of the (pro)renin receptor ((P)RR), in the ontogenesis of endometrial cancer. The (P)RR is implicated in breast cancer and pancreatic carcinoma pathophysiology by virtue of its role in proliferation, angiogenesis, fibrosis, migration and invasion. Thus, we aimed to investigate the functional role of the (P)RR in human endometrial cancer. We employed an siRNA-mediated knockdown approach to abrogate (P)RR expression in the endometrial epithelial cell lines; Ishikawa, AN3CA and HEC-1-A and examined cellular proliferation and viability. We also carried out a sophisticated proteomic screen to explore potential pathways via which the (P)RR is acting in endometrial cancer physiology. These data confirmed that the (P)RR is critical for endometrial cancer development, contributing to both its proliferative capacity and in the maintenance of cell viability. This is likely mediated through proteins such as MGA, SLC4A7, SLC7A11 or DHRS2, which were reduced following (P)RR knockdown. These putative protein interactions/pathways, which rely on the presence of the (P)RR, are likely to contribute to endometrial cancer progression and could therefore, represent several novel therapeutic targets for endometrial cancer.

Infection of humans with SARS-CoV-2 virus causes a disease known colloquially as "COVID-19" with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE-2 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28 days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and/or taste, fatigue, cough, aching pain, "brain fog," insomnia, shortness of breath, and tachycardia) after 12 weeks and are diagnosed with a syndrome named "LONG COVID." Longitudinal clinical studies in a group of subjects who were infected with SARS-CoV-2 have been compared to a non-infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self-report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively. It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid-derived 2-like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re-purposing studies in "LONG COVID" subjects experiencing insomnia, depression, fatigue, and "brain fog" but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin.

OBJECTIVE: To identify points for improvements within the health system where Aboriginal and Torres Strait Islander cancer patients may experience a lack of continuity in their cancer care. The optimal care pathway for Aboriginal and Torres Strait Islander people with cancer (OCP) framework was utilised as a tool in this work. METHODS: Semi-structured interviews were conducted with health professionals at the primary health care (PHC) and hospital setting. Data were categorised into six steps using the OCP framework. RESULTS: This study identified multiple time-points in the cancer pathways that could be strengthened to increase the continuity of cancer care for these patients. In addition, the provision of person-centred care and adequate education tailored to patients' and health professionals' needs can help minimise the likelihood of patients experiencing a lack of continuity in their cancer care. Participants were recruited from an urban hospital (n = 9) and from six Aboriginal Community Controlled Health Services (n = 17) across geographical locations in Queensland. The provision of culturally competent care, effective communication, coordination and collaboration between services along the cancer pathway from prevention and early diagnosis through to end-of-life care were highlighted as important to enhance care continuity for Indigenous Australians. CONCLUSION: The implementation of recommendations outlined in the OCP framework may help with improving cancer care continuity for Indigenous patients with cancer. SUMMARY: Aboriginal and Torres Strait Islander people can sometimes find cancer care pathways complex and difficult to navigate. This study identified points in the cancer pathways that could be strengthened to increase the continuity of cancer care for these patients which could potentially lead to improved outcomes.

The 2019 meeting of the Society for Reproductive Biology (SRB) provided a platform for the dissemination of new knowledge and innovations to improve reproductive health in humans, enhance animal breeding efficiency and understand the effect of the environment on reproductive processes. The effects of environment and lifestyle on fertility and animal behaviour are emerging as the most important modern issues facing reproductive health. Here, we summarise key highlights from recent work on endocrine-disrupting chemicals and diet- and lifestyle-induced metabolic changes and how these factors affect reproduction. This is particularly important to discuss in the context of potential effects on the reproductive potential that may be imparted to future generations of humans and animals. In addition to key summaries of new work in the male and female reproductive tract and on the health of the placenta, for the first time the SRB meeting included a workshop on endometriosis. This was an important opportunity for researchers, healthcare professionals and patient advocates to unite and provide critical updates on efforts to reduce the effect of this chronic disease and to improve the welfare of the women it affects. These new findings and directions are captured in this review.

AIM: To explore health professionals' perspectives on communication, continuity and between-service coordination for improving cancer care for Indigenous people in Queensland. METHODS: Semi-structured interviews were conducted in a purposive sample of primary health care (PHC) services in Queensland with Indigenous and non-Indigenous health professionals who had experience caring for Indigenous cancer patients in the PHC and hospital setting. The World Health Organisation integrated people-centred health services framework was used to analyse the interview data. RESULTS: Seventeen health staff from six Aboriginal Community Controlled Services and nine health professionals from one tertiary hospital participated in this study. PHC sites were in urban, regional and rural settings and the hospital was in a major city. Analysis of the data suggests that timely communication and information exchange, collaborative approaches, streamlined processes, flexible care delivery, and patient-centred care and support were crucial in improving the continuity and coordination of care between the PHC service and the treating hospital. CONCLUSION: Communication, collaboration and care coordination are integral in the provision of quality cancer care for Indigenous Australians. It is recommended that health policy and funding be designed to incorporate these aspects across services and settings as a strategy to improve cancer outcomes for Indigenous people in Queensland.

Cancer medicine is a challenging field with an increasing range of promising therapies and combinations. Increasingly, personalised medicine shows promise to improve cancer outcomes – response, symptom control, survival and cure. However, optimal dosing is an under‐appreciated aspect of personalised anticancer therapy, with few clinical trials addressing this specific issue. This position paper aims to inform various health professionals about the principles that guide anticancer drug dose selection and modifications. We discuss the available evidence base for personalised dosing, as well as the professional judgement required by experienced oncology physicians to determine the most appropriate dose for each patient. We provide nine steps to guide clinicians and trainees in this process, based on: pharmacology of each agent (absorption, distribution, metabolism, elimination and mechanism of action); scientific evidence for recommended doses; professional knowledge of patients' unique phenotype (adiposity, comorbidities, etc.); previous drug tolerance; individual dose adjustment in combination therapy; communication and documentation, with the added need for ongoing monitoring and adjustment. We strongly propose professional education and future research towards optimal dosing.

[This corrects the article DOI: 10.5334/ijic.5456.].

With cannabis medicines now obtaining legal status in many international jurisdictions (generally on the authorisation of a medical professional), a rapid increase in consumer demand for access to cannabis as a therapeutic option in the treatment and management of a range of indications is being noted. Despite this accessibility, knowledge on optimal use is lacking. Further drug development and clinical trials at regulatory standards are necessary both if a better understanding of the efficacy of cannabis medicines, optimal product formulation and indication-specific dosing is needed and to ensure the broader quality and safety of cannabis medicines in the clinical setting.To enable this, clinical, academic and public calls for the undertaking of rigorous clinical trials to establish an evidence base for the therapeutic use of cannabis medicines have been made internationally. While this commitment to undertake human studies with cannabis medicines is welcomed, it has highlighted unique challenges, notably in the review stages of ethics and governance. This often results in lengthy delays to approval by Human Research Ethics Committees (herein 'HREC', Australia's nomenclature for Institutional Review Boards) and trial commencement. A principal concern in these cases is that in contrast to clinical trials using other more conventional pharmaceutical products, trials of cannabis medicines in humans often involve the use of an investigational product prior to some (or any) of the preclinical and pharmaceutical safety issues being established. This paucity of data around product safety, potential drug interactions, continuity of supply, shelf life and product storage results in apprehension by HRECs and governance bodies to endorse trials using cannabis medicines.This manuscript draws from the experiences of Australian researchers and staff involved in clinical trials of cannabis medicines to describe some of the common difficulties that may be faced in the HREC approva

Aim:To explore health professionals' perspectives on communication, continuity and between-service coordination for improving cancer care for Indigenous people in Queensland. Methods:Semi-structured interviews were conducted in a purposive sample of primary health care (PHC) services in Queensland with Indigenous and non-Indigenous health professionals who had experience caring for Indigenous cancer patients in the PHC and hospital setting. The World Health Organisation integrated people-centred health services framework was used to analyse the interview data. Results:Seventeen health staff from six Aboriginal Community Controlled Services and nine health professionals from one tertiary hospital participated in this study. PHC sites were in urban, regional and rural settings and the hospital was in a major city. Analysis of the data suggests that timely communication and information exchange, collaborative approaches, streamlined processes, flexible care delivery, and patient-centred care and support were crucial in improving the continuity and coordination of care between the PHC service and the treating hospital. Conclusion:Communication, collaboration and care coordination are integral in the provision of quality cancer care for Indigenous Australians. It is recommended that health policy and funding be designed to incorporate these aspects across services and settings as a strategy to improve cancer outcomes for Indigenous people in Queensland.

BACKGROUND:Disparity in outcomes between Indigenous and non-Indigenous people after cancer diagnosis is multifactorial, including lower cancer screening participation, later diagnosis, reduced access and uptake of cancer treatment, higher rate of comorbidities, and barriers accessing the health system. Little is known about cancer survivorship experiences. OBJECTIVE:The aim of this study was to explore Indigenous Australian cancer survivor's perspectives of cancer survivorship. METHODS:Indigenous people who completed cancer treatment 6 months to 5 years before fieldwork were recruited from a tertiary hospital and remote primary health service for this qualitative study. Data collection was guided by yarning methods, a culturally appropriate method emphasizing storytelling. Data were interpreted using a social constructionist framework. RESULTS:Thirteen women and 6 men were interviewed. Participants' past experiences contributed to their specific identity as survivors. Participants described factors affecting a positive transition from cancer patient to cancer survivor and the importance of ongoing family support in helping to manage survivorship. Finally, participants described a range of community support they received and provided to others and how this improved their cancer survivorship. CONCLUSION:Although a range of experiences are presented, this study provides evidence that the survivorship perspectives of Indigenous cancer survivors may be, in part, shared by non-Indigenous cancer survivors. IMPLICATIONS FOR PRACTICE:Acknowledging Indigenous cancer survivors' past experiences and how these influence their overall well-being is important for providing patient-centered and culturally appropriate care. Nurses and other healthcare professionals may use this knowledge to foster a range of coping strategies to assist Indigenous cancer survivors to live well.

Artificially generated radiofrequency-electromagnetic energy (RF-EME) is now ubiquitous in our environment owing to the utilization of mobile phone and Wi-Fi based communication devices. While several studies have revealed that RF-EME is capable of eliciting biological stress, particularly in the context of the male reproductive system, the mechanistic basis of this biophysical interaction remains largely unresolved. To extend these studies, here we exposed unrestrained male mice to RF-EME generated via a dedicated waveguide (905 MHz, 2.2 W/kg) for 12 h per day for a period of 1, 3 or 5 weeks. The testes of exposed mice exhibited no evidence of gross histological change or elevated stress, irrespective of the RF-EME exposure regimen. By contrast, 5 weeks of RF-EME exposure adversely impacted the vitality and motility profiles of mature epididymal spermatozoa. These spermatozoa also experienced increased mitochondrial generation of reactive oxygen species after 1 week of exposure, with elevated DNA oxidation and fragmentation across all exposure periods. Notwithstanding these lesions, RF-EME exposure did not impair the fertilization competence of spermatozoa nor their ability to support early embryonic development. This study supports the utility of male germ cells as sensitive tools with which to assess the biological impacts of whole-body RF-EME exposure.

© 2019 Nixon et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc. Competition to achieve paternity has contributed to the development of a multitude of elaborate male reproductive strategies. In one of the most well-studied examples, the spermatozoa of all mammalian species must undergo a series of physiological changes, termed capacitation, in the female reproductive tract before realizing their potential to fertilize an ovum. However, the evolutionary origin and adaptive advantage afforded by capacitation remains obscure. Here, we report the use of comparative and quantitative proteomics to explore the biological significance of capacitation in an ancient reptilian species, the Australian saltwater crocodile (Crocodylus porosus). Our data reveal that exposure of crocodile spermatozoa to capacitation stimuli elicits a cascade of physiological responses that are analogous to those implicated in the functional activation of their mammalian counterparts. Indeed, among a total of 1119 proteins identified in this study, we detected 126 that were differentially phosphorylated ( 1.2 fold-change) in capacitated versus noncapacitated crocodile spermatozoa. Notably, this subset of phosphorylated proteins shared substantial evolutionary overlap with those documented in mammalian spermatozoa, and included key elements of signal transduction, metabolic and cellular remodeling pathways. Unlike mammalian sperm, however, we noted a distinct bias for differential phosphorylation of serine (as opposed to tyrosine) residues, with this amino acid featuring as the target for 80% of all changes detected in capacitated spermatozoa. Overall, these results indicate that the phenomenon of sperm capacitation is unlikely to be restricted to mammals and provide a framework for understanding the molecular changes in sperm physiology necessary for fertilization.

© La Trobe University 2018. Indigenous Australians diagnosed with cancer experience higher mortality and lower survival rates compared to non-Indigenous Australians. Reasons are multifaceted and complex. Knowledge about Indigenous cancer survivors' perspectives of positive cancer survivorship is a gap in research evidence. The study explored cancer survivorship perspectives of Indigenous cancer survivors, their support people and healthcare workers with a view to developing recommendations for cancer survivorship. Indigenous Australians who completed cancer treatment in the previous 6 months to 5 years, their support people and primary healthcare workers were recruited from primary healthcare centres and a large tertiary Queensland hospital. Semi-structured interviews and focus groups were conducted with written and informed consent obtained prior. Participants emphasised key action areas and recommendations to enhance cancer survivorship, namely: establishing a community cancer advocate and peer support program, availability and use of a cancer-specific Indigenous primary healthcare worker and hospital-based Indigenous patient navigator, as well as adoption of question prompt lists and cancer survivorship care plans. Existing research suggests significant benefits from implementing the key recommendations identified in this study. Greater support and commitment across health sectors and funding bodies is needed to promote institutional change and health system development.

BACKGROUND: Aboriginal and Torres Strait Islander Australians have poorer cancer outcomes and experience 30% higher mortality rates compared to non-Indigenous Australians. Primary health care (PHC) services are increasingly being recognized as pivotal in improving Indigenous cancer patient outcomes. It is currently unknown whether patient information systems and practices in PHC settings accurately record Indigenous and cancer status. Being able to identify Indigenous cancer patients accessing services in PHC settings is the first step in improving outcomes. METHODS: Aboriginal Medical Centres, mainstream (non-Indigenous specific), and government-operated centers in Queensland were contacted and data were collected by telephone during the period from 2014 to 2016. Participants were asked to (i) identify the number of patients diagnosed with cancer attending the service in the previous year; (ii) identify the Indigenous status of these patients and if this information was available; and (iii) advise how this information was obtained. RESULTS: Ten primary health care centers (PHCCs) across Queensland participated in this study. Four centers were located in regional areas, three in remote areas and three in major cities. All participating centers reported ability to identify Indigenous cancer patients attending their service and utilizing electronic Patient Care Information Systems (PCIS) to manage their records; however, not all centers were able to identify Indigenous cancer patients in this way. Indigenous cancer patients were identified by PHCCs using PCIS (n = 8), searching paper records (n = 1), and combination of PCIS and staff recall (n = 1). Six different types of PCIS were being utilized by participating centers. There was no standardized way to identify Indigenous cancer patients across centers. Health service information systems, search functions and capacities of systems, and staff skill in extracting data using PCIS varied between centers. CONCLUSION: It

Muscle moment arms are used widely in biomechanical analyses. Often they are measured in 2D or at a series of static joint positions. In the present study we demonstrate a simple MRI method for measuring muscle moment arms dynamically in 3D from a single range-of-motion cycle. We demonstrate this method in the Achilles tendon for comparison with other methods, and validate the method using a custom apparatus. The method involves registration of high-resolution joint geometry from MRI scans of the stationary joint with low-resolution geometries from ultrafast MRI scans of the slowly moving joint. Tibio-talar helical axes and 3D Achilles tendon moment arms were calculated throughout passive rotation for 10 adult subjects, and compared with recently published data. A simple validation was conducted by comparing MRI measurements with direct physical measurements made on a phantom. The moment arms measured using our method and those of others were similar and there was good agreement between physical measurements (mean 41.0. mm) and MRI measurements (mean 39.5. mm) made on the phantom. This new method can accurately measure muscle moment arms from a single range-of-motion cycle without the need to control rotation rate or gate the scanning. Supplementary data includes custom software to assist implementation.

This study examined the effects of Tai Chi, a low-impact mind-body movement therapy, on severity of depression, anxiety, and stress symptoms in centrally obese people with elevated depression symptoms. In total, 213 participants were randomized to a 24-week Tai Chi intervention program or a wait-list control group. Assessments were conducted at baseline and 12 and 24 weeks. Outcomes were severity of depression, anxiety, and stress symptoms, leg strength, central obesity, and other measures of metabolic symptom. There were statistically significant between-group differences in favor of the Tai Chi group in depression (mean difference = -5.6 units, P < 0.001), anxiety (-2.3 units, P < 0.01), and stress (-3.6 units, P < 0.001) symptom scores and leg strength (1.1 units, P < 0.001) at 12 weeks. These changes were further improved or maintained in the Tai Chi group relative to the control group during the second 12 weeks of follow-up. Tai Chi appears to be beneficial for reducing severity of depression, anxiety, and stress and leg strength in centrally obese people with depression symptoms. More studies with longer follow-up are needed to confirm the findings. This trial is registered with ACTRN12613000010796.

The amount of hoof slip at the moment of impact can cause musculoskeletal injuries to the horse. Risk of injury is influenced by surface properties, however there is limited understanding of the effect on hoof slip during jump landing. The objectives of this study were to compare hoof slip on two different surfaces and investigate relationships between hoof slip and surface properties. A contact mat and hoof reference marker were designed and validated, the former to indicate the moment of impact and the latter to provide a visible reference marker on the lateral hoof wall. The leading right forelimb of six horses was recorded during jump landing on two different surfaces. Five trials, plus one where the forelimb landed on a contact mat were recorded at 500 Hz using a calibrated high speed camera positioned perpendicular to landing. Surface traction, hardness and penetration were measured between horses. Horizontal displacement of the hoof reference marker was plotted and smoothed with a Butterworth filter at 25 Hz cut off. Hoof slip was measured from impact to mid-stance. Data were analysed using ANOVA and Pearson correlations. A significant difference in hoof slip (10% wax=4.9 ± 2.1 cm and, 3% wax=7.4 ± 3.6 cm) was found between the two surfaces (P<0.01). In addition, hoof slip was correlated with all surface measurements (hardness, traction and penetrability) on the 10% wax surface, but none on the 3% wax surface. Wax content appears to influence hoof slip during jump landing as greater hoof slip was measured on a 3% wax surface and variability on this surface was greater for the group. The results suggest that wax content influenced surface properties and on the 3% wax surface the greater variability in hardness and traction influenced the consistency with which the horses jumped upon it.

Introduction: In this study we compared passive mechanical properties of gastrocnemius muscle-tendon units, muscle fascicles, and tendons in control subjects and people with ankle contractures after spinal cord injury. Methods:: Passive gastrocnemius length-tension curves were derived from passive ankle torque-angle data obtained from 20 spinal cord injured subjects with ankle contractures and 30 control subjects. Ultrasound images of muscle fascicles were used to partition length-tension curves into fascicular and tendinous components. Results:: Spinal cord injured subjects had stiffer gastrocnemius muscle-tendon units (stiffness index: 74.8 ± 27.0 m -1) than control subjects (54.4 ± 17.7 m -1) (P = 0.004). Muscle-tendon slack lengths, as well as slack lengths and changes in length of fascicles and tendons, were similar in the two groups. Conclusions:: People with ankle contractures after spinal cord injury have stiff gastrocnemius muscle-tendon units. It is not clear whether this reflects changes in properties of muscle fascicles or tendons. copy; 2012 Wiley Periodicals, Inc..

Objective: To investigate the mechanisms of contracture after stroke by comparing passive mechanical properties of gastrocnemius muscle-tendon units, muscle fascicles, and tendons in people with ankle contracture after stroke with control participants. Design: Cross-sectional study. Setting: Laboratory in a research institution. Participants: A convenience sample of people with ankle contracture after stroke (n=20) and able-bodied control subjects (n=30). Interventions: Not applicable. Main Outcome Measures: Stiffness and lengths of gastrocnemius muscle-tendon units, lengths of muscle fascicles, and tendons at specific tensions. Results: At a tension of 100N, the gastrocnemius muscle-tendon unit was significantly shorter in participants with stroke (mean, 436mm) than in able-bodied control participants (mean, 444mm; difference, 8mm; 95% confidence interval [CI], 0.2-15mm; P=.04). Muscle fascicles were also shorter in the stroke group (mean, 44mm) than in the control group (mean, 50mm; difference, 6mm; 95% CI, 1-12mm; P=.03). There were no significant differences between groups in the mean stiffness or length of the muscle-tendon units and fascicles at low tension, or in the mean length of the tendons at any tension. Conclusions: People with ankle contracture after stroke have shorter gastrocnemius muscle-tendon units and muscle fascicles than control participants at high tension. This difference is not apparent at low tension. © 2012 American Congress of Rehabilitation Medicine.

Diabetes therapies based on manipulation of the incretin system are now widely available, with millions of people receiving treatment. The incretin hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1 are released from endocrine cells in the small intestinal mucosa primarily in response to oral nutrient ingestion. They have various effects, but those most relevant to metabolic dysfunction include stimulation of insulin and suppression of glucagon secretion, with resultant reduction in fasting and postprandial glucose. Incretin secretion and/or action is impaired in type 2 diabetes, leading to development of strategies aimed at redressing this abnormality. These strategies include pharmacological inhibition of dipeptidyl peptidase-4, the enzyme responsible for the short half-life of endogenous incretins, and administration of long-acting dipeptidyl peptidase-4-resistant peptides that bind to and activate the glucagon-like peptide-1 receptor. In this review, we address aspects of incretin biology and pharmacotherapy with a view to highlighting potentially clinically relevant issues and areas of basic research that may impinge on these.

Foot strike can be difficult to determine using kinematics alone, particularly when studying equine activities on more compliant surfaces, so this study was done with the aim of developing and validating a method to determine foot strike on an arena surface that can be used in conjunction with kinematics alone, and of applying the method in the context of measuring foot strike during jump landing on an arena surface. A low-cost contact mat was developed. The timing of the contact mat switching ‘on’ was compared to the timing of a force platform onset of 20 N, load and loading rate at foot strike. Two groups of 25 participants were used in two separate studies to validate the contact mat: the first measured the difference in timing with respect to two different activities (running and stepping down from a box), and the second measured the difference in timing with respect to 1- and 2-cm depths of an arena surface during running. In a third study, the mat was used to measure leading limb foot strike of six horses during jump landing, and these data were compared to kinematics from a palmar marker on the hoof wall. All data were recorded at 500 Hz. A consistent difference in delay was found between the mat and force platform onset, and as a result, no significant differences (P>0.05) in timing delay between different loading rates or depths were found. During jump landing, foot strike (determined from the mat) occurred after the vertical velocity minima and the acceleration maxima for the hoof marker, but it occurred before the point where the rate of vertical displacement began to reduce. In conclusion, further work is needed to enhance these techniques, but these preliminary results indicate that this method may be effective in determining foot strike for field-based applications.