Biomedical Physiology and Kinesiology, Department of

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"Body-In-The-Loop": Optimizing Device Parameters Using Measures of Instantaneous Energetic Cost

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2015
Abstract: 

This paper demonstrates methods for the online optimization of assistive robotic devices such as powered prostheses, orthoses and exoskeletons. Our algorithms estimate the value of a physiological objective in real-time (with a body “in-the-loop”) and use this information to identify optimal device parameters. To handle sensor data that are noisy and dynamically delayed, we rely on a combination of dynamic estimation and response surface identification. We evaluated three algorithms (Steady-State Cost Mapping, Instantaneous Cost Mapping, and Instantaneous Cost Gradient Search) with eight healthy human subjects. Steady-State Cost Mapping is an established technique that fits a cubic polynomial to averages of steady-state measures at different parameter settings. The optimal parameter value is determined from the polynomial fit. Using a continuous sweep over a range of parameters and taking into account measurement dynamics, Instantaneous Cost Mapping identifies a cubic polynomial more quickly. Instantaneous Cost Gradient Search uses a similar technique to iteratively approach the optimal parameter value using estimates of the local gradient. To evaluate these methods in a simple and repeatable way, we prescribed step frequency via a metronome and optimized this frequency to minimize metabolic energetic cost. This use of step frequency allows a comparison of our results to established techniques and enables others to replicate our methods. Our results show that all three methods achieve similar accuracy in estimating optimal step frequency. For all methods, the average error between the predicted minima and the subjects’ preferred step frequencies was less than 1% with a standard deviation between 4% and 5%. Using Instantaneous Cost Mapping, we were able to reduce subject walking-time from over an hour to less than 10 minutes. While, for a single parameter, the Instantaneous Cost Gradient Search is not much faster than Steady-State Cost Mapping, the Instantaneous Cost Gradient Search extends favorably to multi-dimensional parameter spaces.

Document type: 
Article
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Clinical Usefulness of Lipid Ratios to Identify Men and Women with Metabolic Syndrome: A Cross-Sectional Study

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014
Abstract: 

Background

Waist circumference, a metabolic syndrome (MetSy) criterion, is not routinely measured in clinical practice making early identification of individuals with MetSy challenging. It has been argued that ratios of commonly measured parameters such as lipids and lipoproteins may be an acceptable alternative for identifying individuals with MetSy. The objective of our study was to explore clinical utility of lipid ratios to identify men and women with MetSy; and to explore the association between lipid ratios and the number of MetSy components.

Methods

Men and women (N = 797) of Aboriginal, Chinese, European, and South Asian origin (35–60 years), recruited across ranges of body mass index (BMI), with no diagnosed cardiovascular disease (CVD) or on medications to treat CVD risk factors were assessed for anthropometrics, family history of CVD, MetSy components (waist circumference, blood pressure, glucose, triglycerides (TG), high-density-lipoprotein-cholesterol (HDL-C)), low-density-lipoprotein-cholesterol (LDL-C), nonHDL-C, and health-related behaviours.

Results

Mean levels of lipid ratios significantly increased with increasing number of MetSy components in men and women (p < 0.05). After adjustment for age, ethnicity, smoking, alcohol consumption, physical activity, family history of CVD and BMI, (and menopausal status in women), all lipid ratios were associated with the number of MetSy components in men and women (Poisson regression, p < 0.001). Compared to the rest of the lipid ratios (ROC curve analysis), TG/HDL-C was best able to discriminate between individuals with and without MetSy (AUC = 0.869 (95% CI: 0.830, 0.908) men; AUC = 0.872 (95% CI: 0.832, 0.912) women). The discriminatory power of TC/HDL-C and nonHDL-C/HDL-C to identify individuals with MetSY was the same (for both ratios, AUC = 0.793 (95% CI: 0.744, 0.842) men; 0.818 (95% CI: 0.772, 0.864) women). Additionally, LDL-C/HDL-C was a good marker for women (AUC = 0.759 (95% CI: 0.706, 0.812)), but not for men (AUC = 0.689 (95% CI: 0.631, 0.748)). Based on a multiethnic sample, we identified TG/HDL-C cut-off values of 1.62 in men and 1.18 in women that were best able to discriminate between men and women with and without MetSY.

Conclusions

Our results indicate that TG/HDL-C is a superior marker to identify men and women with MetSy compared to TC/HDL-C, LDL-C/HDL-C, and nonHDL-C/HDL-C.

Document type: 
Article
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An Educational Video to Promote Multi-Factorial Approaches For Fall and Injury Prevention in Long-Term Care Facilities

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014
Abstract: 

Background

Older adults living in long term care (LTC) settings are vulnerable to fall-related injuries. There is a need to develop and implement evidence-based approaches to address fall injury prevention in LTC. Knowledge translation (KT) interventions to support the uptake of evidence-based approaches to fall injury prevention in LTC need to be responsive to the learning needs of LTC staff and use mediums, such as videos, that are accessible and easy-to-use. This article describes the development of two unique educational videos to promote fall injury prevention in long-term care (LTC) settings. These videos are unique from other fall prevention videos in that they include video footage of real life falls captured in the LTC setting.

Methods

Two educational videos were developed (2012–2013) to support the uptake of findings from a study exploring the causes of falls based on video footage captured in LTC facilities. The videos were developed by: (1) conducting learning needs assessment in LTC settings via six focus groups (2) liaising with LTC settings to identify learning priorities through unstructured conversations; and (3) aligning the content with principles of adult learning theory.

Results

The videos included footage of falls, interviews with older adults and fall injury prevention experts. The videos present evidence-based fall injury prevention recommendations aligned to the needs of LTC staff and: (1) highlight recommendations deemed by LTC staff as most urgent (learner-centered learning); (2) highlight negative impacts of falls on older adults (encourage meaning-making); and, (3) prompt LTC staff to reflect on fall injury prevention practices (encourage critical reflection).

Conclusions

Educational videos are an important tool available to researchers seeking to translate evidence-based recommendations into LTC settings. Additional research is needed to determine their impact on practice.

Document type: 
Article
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Population-Based Incidence Trends of Oropharyngeal and Oral Cavity Cancers by Sex among the Poorest and Underprivileged Populations

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014
Abstract: 

Background

Oral cancer is an important health issue, with changing incidence in many countries. Oropharyngeal cancer (OPC, in tonsil and oropharygeal areas) is increasing, while oral cavity cancer (OCC, other sites in the mouth) is decreasing. There is the need to identify high risk groups and communities for further study and intervention. The objective of this study was to determine how the incidence of OPC and OCC varied by neighbourhood socioeconomic status (SES) in British Columbia (BC), including the magnitude of any inequalities and temporal trends.

Methods

ICDO-3 codes were used to identify OPC and OCC cases in the BC Cancer Registry from 1981–2010. Cases were categorized by postal codes into SES quintiles (q1-q5) using VANDIX, which is a census-based, multivariate weighted index based on neighbourhood average household income, housing tenure, educational attainment, employment and family structure. Age-standardized incidence rates were determined for OPC and OCC by sex and SES quintiles and temporal trends were then examined.

Results

Incidence rates are increasing in both men and women for OPC, and decreasing in men and increasing in women for OCC. This change is not linear or proportionate between different SES quintiles, for there is a sharp and dramatic increase in incidence according to the deprivation status of the neighbourhood. The highest incidence rates in men for both OPC and OCC were observed in the most deprived SES quintile (q5), at 1.7 times and 2.2 times higher, respectively, than men in the least deprived quintile (q1). For OPC, the age-adjusted incidence rates significantly increased in all SES quintiles with the highest increase observed in the most deprived quintile (q5). Likewise, the highest incidence rates for both OPC and OCC in women were observed in the most deprived SES quintile (q5), at 2.1 times and 1.8 times higher, respectively, than women in the least deprived quintile (q1).

Conclusion

We report on SES disparities in oral cancer, emphasizing the need for community-based interventions that address access to medical care and the distribution of educational and health promotion resources among the most SES deprived communities in British Columbia.

Document type: 
Article
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Associations between Socioeconomic, Parental and Home Environment Factors and Fruit and Vegetable Consumption of Children in Grades Five and Six in British Columbia, Canada

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014
Abstract: 

Background

Regular fruit and vegetable (FV) consumption has been associated with reduced chronic disease risk. Evidence from adults shows a social gradient in FV consumption. Evidence from pre-adolescent children varies and there is little Canadian data. This study assessed the FV intake of school children in British Columbia (BC), Canada to determine whether socio-economic status (SES), parental and the home environment factors were related to FV consumption.

Methods

As part of the BC School Fruit and Vegetable Nutrition Program, 773 British Columbia fifth-and sixth-grade school children (Mean age 11.3 years; range 10.3-12.5) and their parents were surveyed to determine FV consumption and overall dietary intake. Students completed a web-based 24-hour dietary food recall, and a student measure of socio-economic status (The Family Affluence Scale). Parents completed a self-administered survey about their education, income, home environment and perceptions of their neighbourhood and children’s eating habits. Correlations and multiple regression analyses were used to examine the association between SES, parental and home environment factors and FV consumption.

Results

Approximately 85.8% of children in this study failed to meet minimum Canadian guidelines for FV intake (6 servings). Parent income and education were not significantly associated with child FV consumption but were associated with each other, child-reported family affluence, neighbourhood environment, access to FV, and eating at the table or in front of the television. Significant positive associations were found between FV consumption and child-reported family affluence, meal-time habits, neighbourhood environment and parent perceptions of the healthiness of their child’s diet; however, these correlations were weak (ranging from .089-.115). Multiple regression analysis showed that only child-reported family affluence significantly predicted FV consumption (std-β = 0.096 95% CI = 0.01 to 0.27).

Conclusions

The majority of children in our study were not meeting guidelines for FV intake irrespective of SES, parent perceptions or home environment, making this a population wide concern. An almost trivial socio-economic gradient was observed for the child-reported SES measure only. These results are consistent with several other studies of children. Longitudinal research is needed to further explore individual and social factors associated with FV consumption in childhood and their development over time.

Document type: 
Article
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Population Attributable Fraction of type 2 Diabetes due to Physical Inactivity in Adults: A Systematic Review

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014
Abstract: 

Background

Physical inactivity is a global pandemic. The population attributable fraction (PAF) of type 2 diabetes mellitus (T2DM) associated with physical inactivity ranges from 3% to 40%. The purpose of this systematic review was to determine the best estimate of PAF for T2DM attributable to physical inactivity and absence of sport participation or exercise for men and women.

Methods

We conducted a systematic review that included a comprehensive search of MEDLINE, EMBASE, SportDiscus, and CINAHL (1946 to April 30 2013) limited by the terms adults and English. Two reviewers screened studies, extracted PAF related data and assessed the quality of the selected studies. We reconstructed 95% CIs for studies missing these data using a substitution method.

Results

Of the eight studies reporting PAF in T2DM, two studies included prospective cohort studies (3 total) and six were reviews. There were distinct variations in quality of defining and measuring physical inactivity, T2DM and adjusting for confounders. In the US, PAFs for absence of playing sport ranged from 13% (95% CI: 3, 22) in men and 29% (95% CI: 17, 41) in women. In Finland, PAFs for absence of exercise ranged from 3% (95% CI: -11, 16) in men to 7% (95% CI: -9, 20) in women.

Conclusions

The PAF of physical inactivity due to T2DM is substantial. Physical inactivity is a modifiable risk factor for T2DM. The contribution of physical inactivity to T2DM differs by sex; PAF also differs if physical inactivity is defined as the absence of ‘sport’ or absence of ‘exercise’.

Background:Physical inactivity is a global pandemic. The population attributable fraction (PAF) of type 2 diabetesmellitus (T2DM) associated with physical inactivity ranges from 3% to 40%. The purpose of this systematic reviewwas to determine the best estimate of PAF for T2DM attributable to physical inactivity and absence of sportparticipation or exercise for men and women.Methods:We conducted a systematic review that included a comprehensive search of MEDLINE, EMBASE,SportDiscus, and CINAHL (1946 to April 30 2013) limited by the terms adults and English. Two reviewers screenedstudies, extracted PAF related data and assessed the quality of the selected studies. We reconstructed 95% CIs forstudies missing these data using a substitution method.Results:Of the eight studies reporting PAF in T2DM, two studies included prospective cohort studies (3 total) andsix were reviews. There were distinct variations in quality of defining and measuring physical inactivity, T2DM andadjusting for confounders. In the US, PAFs for absence of playing sport ranged from 13% (95% CI: 3, 22) in men and29% (95% CI: 17, 41) in women. In Finland, PAFs for absence of exercise ranged from 3% (95% CI: -11, 16) in men to7% (95% CI: -9, 20) in women.Conclusions:The PAF of physical inactivity due to T2DM is substantial. Physical inactivity is a modifiable risk factorfor T2DM. The contribution of physical inactivity to T2DM differs by sex; PAF also differs if physical inactivity isdefined as the absence of‘sport’or absence of‘exercise’.

Document type: 
Article
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Sex- and Subtype-Specific Analysis of H2AFX Polymorphisms in Non-Hodgkin Lymphoma

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2013
Abstract: 

H2AFX encodes a histone variant involved in signaling sites of DNA damage and recruiting repair factors. Genetic variants in H2AFX may influence risk of non-Hodgkin lymphoma (NHL), a heterogeneous group of lymphoid tumors that are characterized by chromosomal translocations. We previously reported that rs2509049, a common variant in the promoter of H2AFX, was associated with risk for NHL in the British Columbia population. Here we report results for 13 single nucleotide polymorphisms (SNPs) in 100 Kb surrounding H2AFX in an expanded collection of 568 NHL cases and 547 controls. After correction for multiple testing, significant associations were present for mantle cell lymphoma (p=0.007 for rs604714) and all B-cell lymphomas (p=0.046 for rs2509049). Strong linkage disequilibrium in the 5 Kb upstream of H2AFX limited the ability to determine which specific SNP (rs2509049, rs7759, rs8551, rs643788, rs604714, or rs603826), if any, was responsible. There was a significant interaction between sex and rs2509049 in the all B-cell lymphomas group (p=0.002); a sex-stratified analysis revealed that the association was confined to females (p=0.001). Neither the overall nor the female-specific association with rs2509049 was replicated in any of four independent NHL sample sets. Meta-analysis of all five study populations (3,882 B-cell NHL cases and 3,718 controls) supported a weak association with B-cell lymphoma (OR=0.92, 95% CI=0.86-0.99, p=0.034), although this association was not significant after exclusion of the British Columbia data. Further research into the potential sex-specificity of the H2AFX-NHL association may identify a subset of NHL cases that are influenced by genotype at this locus.

Document type: 
Article
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Genetic Polymorphisms at TIMP3 Are Associated with Survival of Adenocarcinoma of the Gastroesophageal Junction

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2013
Abstract: 

The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients.

Document type: 
Article
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Non-Hodgkin Lymphoma Risk and Variants in Genes Controlling Lymphocyte Development

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2013
Abstract: 

Non-Hodgkin lymphomas (NHL) are a heterogeneous group of solid tumours of lymphoid cell origin. Three important aspects of lymphocyte development include immunity and inflammation, DNA repair, and programmed cell death. We have used a previously established case-control study of NHL to ask whether genetic variation in genes involved in these three important processes influences risk of this cancer. 118 genes in these three categories were tagged with single nucleotide polymorphisms (SNPs), which were tested for association with NHL and its subtypes. The main analysis used logistic regression (additive model) to estimate odds ratios in European-ancestry cases and controls. 599 SNPs and 1116 samples (569 cases and 547 controls) passed quality control measures and were included in analyses. Following multiple-testing correction, one SNP in MSH3, a mismatch repair gene, showed an association with diffuse large B-cell lymphoma (OR: 1.91; 95% CI: 1.41–2.59; uncorrected p = 0.00003; corrected p = 0.010). This association was not replicated in an independent European-ancestry sample set of 251 diffuse large B-cell lymphoma cases and 737 controls, indicating this result was likely a false positive. It is likely that moderate sample size, inter-subtype and other genetic heterogeneity, and small true effect sizes account for the lack of replicable findings.

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Article
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Myelosuppressive Conditioning Using Busulfan Enables Bone Marrow Cell Accumulation in the Spinal Cord of a Mouse Model of Amyotrophic Lateral Sclerosis

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2013
Abstract: 

Myeloablative preconditioning using irradiation is the most commonly used technique to generate rodents having chimeric bone marrow, employed for the study of bone marrow-derived cell accumulation in the healthy and diseased central nervous system. However, irradiation has been shown to alter the blood-brain barrier, potentially creating confounding artefacts. To better study the potential of bone marrow-derived cells to function as treatment vehicles for neurodegenerative diseases alternative preconditioning regimens must be developed. We treated transgenic mice that over-express human mutant superoxide dismutase 1, a model of amyotrophic lateral sclerosis, with busulfan to determine whether this commonly used chemotherapeutic leads to stable chimerism and promotes the entry of bone marrow-derived cells into spinal cord. Intraperitoneal treatment with busulfan at 60 mg/kg or 80 mg/kg followed by intravenous injection of green fluorescent protein-expressing bone marrow resulted in sustained levels of chimerism (~80%). Bone marrow-derived cells accumulated in the lumbar spinal cord of diseased mice at advanced stages of pathology at both doses, with limited numbers of bone marrow derived cells observed in the spinal cords of similarly treated, age-matched controls; the majority of bone marrow-derived cells in spinal cord immunolabelled for macrophage antigens. Comparatively, significantly greater numbers of bone marrow-derived cells were observed in lumbar spinal cord following irradiative myeloablation. These results demonstrate bone marrow-derived cell accumulation in diseased spinal cord is possible without irradiative preconditioning.

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Article
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