Simon Fraser University Institutional Repository

    The Economic Burden of Prematurity in Canada

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    Background Preterm birth is a major risk factor for morbidity and mortality among infants worldwide, and imposes considerable burden on health, education and social services, as well as on families and caregivers. Morbidity and mortality resulting from preterm birth is highest among early (< 28 weeks gestational age) and moderate (28–32 weeks) preterm infants, relative to late preterm infants (33–36 weeks). However, substantial societal burden is associated with late prematurity due to the larger number of late preterm infants relative to early and moderate preterm infants. Methods The aim in this study was to characterize the burden of premature birth in Canada for early, moderate, and late premature infants, including resource utilization, direct medical costs, parental out-of-pocket costs, education costs, and mortality, using a validated and published decision model from the UK, and adapting it to a Canadian setting based on analysis of administrative, population-based data from Québec. Results Two-year survival was estimated at 56.0% for early preterm infants, 92.8% for moderate preterm infants, and 98.4% for late preterm infants. Per infant resource utilization consistently decreased with age. For moderately preterm infants, hospital days ranged from 1.6 at age two to 0.09 at age ten. Cost per infant over the first ten years of life was estimated to be 67,467forearlypreterminfants,67,467 for early preterm infants, 52,796 for moderate preterm infants, and id="mce_marker"0,010 for late preterm infants. Based on population sizes this corresponds to total national costs of id="mce_marker"23.3 million for early preterm infants, 255.6millionformoderatepreterminfants,255.6 million for moderate preterm infants, 208.2 million for late preterm infants, and $587.1 million for all infants. Conclusion Premature birth results in significant infant morbidity, mortality, healthcare utilization and costs in Canada. A comprehensive decision-model based on analysis of a Canadian population-based administrative data source suggested that the greatest national-level burden is associated with moderate preterm infants due to both a large cost per infant and population size while the highest individual-level burden is in early preterm infants and the largest total population size is in late preterm infants. Although the highest medical costs are incurred during the neonatal period, greater resource utilization and costs extend into childhood

    Early Immune Adaptation in HIV-1 Revealed By Population-Level Approaches

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    Background The reproducible nature of HIV-1 escape from HLA-restricted CD8+ T-cell responses allows the identification of HLA-associated viral polymorphisms “at the population level” – that is, via analysis of cross-sectional, linked HLA/HIV-1 genotypes by statistical association. However, elucidating their timing of selection traditionally requires detailed longitudinal studies, which are challenging to undertake on a large scale. We investigate whether the extent and relative timecourse of immune-driven HIV adaptation can be inferred via comparative cross-sectional analysis of independent early and chronic infection cohorts. Results Similarly-powered datasets of linked HLA/HIV-1 genotypes from individuals with early (median < 3 months) and chronic untreated HIV-1 subtype B infection, matched for size (N > 200/dataset), HLA class I and HIV-1 Gag/Pol/Nef diversity, were established. These datasets were first used to define a list of 162 known HLA-associated polymorphisms detectable at the population level in cohorts of the present size and host/viral genetic composition. Of these 162 known HLA-associated polymorphisms, 15% (occurring at 14 Gag, Pol and Nef codons) were already detectable via statistical association in the early infection dataset at p ≤ 0.01 (q < 0.2) – identifying them as the most consistently rapidly escaping sites in HIV-1. Among these were known rapidly-escaping sites (e.g. B*57-Gag-T242N) and others not previously appreciated to be reproducibly rapidly selected (e.g. A*31:01-associated adaptations at Gag codons 397, 401 and 403). Escape prevalence in early infection correlated strongly with first-year escape rates (Pearson’s R = 0.68, p = 0.0001), supporting cross-sectional parameters as reliable indicators of longitudinally-derived measures. Comparative analysis of early and chronic datasets revealed that, on average, the prevalence of HLA-associated polymorphisms more than doubles between these two infection stages in persons harboring the relevant HLA (p < 0.0001, consistent with frequent and reproducible escape), but remains relatively stable in persons lacking the HLA (p = 0.15, consistent with slow reversion). Published HLA-specific Hazard Ratios for progression to AIDS correlated positively with average escape prevalence in early infection (Pearson’s R = 0.53, p = 0.028), consistent with high early within-host HIV-1 adaptation (via rapid escape and/or frequent polymorphism transmission) as a correlate of progression. Conclusion Cross-sectional host/viral genotype datasets represent an underutilized resource to identify reproducible early pathways of HIV-1 adaptation and identify correlates of protective immunity

    The northern Cache Creek terrane: record of Middle Triassic arc activity and Jurassic-Cretaceous terrane imbrication

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    The northern termination of the Cache Creek terrane in the Cordillera contains oceanic crustal lithologies including subalkaline mafic intrusive rocks with an arc geochemical signature, mafic volcanics with arc to back-arc signatures, and an arc-flanking volcaniclastic succession informally termed the Michie formation. This formation contains unimodal zircon populations with U-Pb dates of 245.85 ± 0.07 and 244.64 ± 0.08 Ma. These dates differ from the dominant detrital zircon age population of ca. 190 Ma found in the adjacent Whitehorse trough, but are similar to igneous crystallization ages of the Kutcho arc of northern British Columbia. Two main faults record oppositely verging deformational events: 1) The Judas Mountain thrust, a west-verging structure that emplaced Cache Creek terrane rocks above Stikinia and the Whitehorse trough, and 2) the Mount Michie thrust, an east-verging second phase structure that imbricated Stikinia and Whitehorse trough rocks onto and replaced them over the Cache Creek terrane

    Neonatal Pain-Related Stress Predicts Cortical Thickness at Age 7 Years in Children Born Very Preterm

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    Background Altered brain development is evident in children born very preterm (24–32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age. Methods 42 right-handed children born very preterm (24–32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling. Results After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes. Conclusions In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors

    A Multicentre, Pragmatic, Parallel Group, Randomised Controlled Trial to Compare the Clinical and Cost-Effectiveness of Three Physiotherapy-Led Exercise Interventions for Knee Osteoarthritis in Older Adults: The BEEP Trial Protocol (ISRCTN: 93634563)

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    Background Exercise is consistently recommended for older adults with knee pain related to osteoarthritis. However, the effects from exercise are typically small and short-term, likely linked to insufficient individualisation of the exercise programme and limited attention to supporting exercise adherence over time. The BEEP randomised trial aims to improve patients’ short and long-term outcomes from exercise. It will test the overall effectiveness and cost-effectiveness of two physiotherapy-led exercise interventions (Individually Tailored Exercise and Targeted Exercise Adherence) to improve the individual tailoring of, and adherence to exercise, compared with usual physiotherapy care. Methods/design Based on the learning from a pilot study (ISRCTN 23294263), the BEEP trial is a multi-centre, pragmatic, parallel group, individually randomised controlled trial, with embedded longitudinal qualitative interviews. 500 adults in primary care, aged 45 years and over with knee pain will be randomised to 1 of 3 treatment groups delivered by fully trained physiotherapists in up to 6 NHS services. These are: Usual Physiotherapy Care (control group consisting of up to 4 treatment sessions of advice and exercise), Individually Tailored Exercise (an individualised, supervised and progressed lower-limb exercise programme) or Targeted Exercise Adherence (supporting patients to adhere to exercise and to engage in general physical activity over the longer-term). The primary outcomes are pain and function as measured by the Western Ontario and McMaster Osteoarthritis index. A comprehensive range of secondary outcomes are also included. Outcomes are measured at 3, 6 (primary outcome time-point), 9, 18 and 36 months. Data on adverse events will also be collected. Semi-structured, qualitative interviews with a subsample of 30 participants (10 from each treatment group) will be undertaken at two time-points (end of treatment and 12 to 18 months later) and analysed thematically. Discussion This trial will contribute to the evidence base for management of older adults with knee pain attributable to osteoarthritis in primary care. The findings will have important implications for healthcare commissioners, general practitioners and physiotherapy service providers and it will inform future education of healthcare practitioners. It may also serve to delay or prevent some individuals from becoming surgical candidates

    Testing the Weak-Form Market Efficiency Hypothesis for Canadian and Chinese Stock

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    The main empirical test methods for Weak-form efficiency market hypothesis can be divided into two categories: one is to test the randomness of stock prices; the other is to test the invalidity of technical analysis, which testing the predictability of earnings. This study mainly focused on the first category.To examining the hypothesis whether Canadian and Chinese stock markets are efficient in the weak form, two types of test are conducted. They are parametric and non-parametric tests. For Non-parametric test, we implement the Runs test and Kolmogrov–Smirnov goodness of fit test. For parametric test, autocorrelation (LBQ test), variance ratio and ARMA model have been chosen. The empirical analysis in this study uses daily closing prices of indices from Shanghai Stock Exchange (SSE) and Toronto Stock Exchange (TSX). To avoiding the biases of choosing testing period, we implemented the same tests among different sample periods for each market.The overall testing results are mixed from sample period to sample period for both markets. In general, for the early testing period, almost all testing techniques generate unfavoured results against the weak-form efficient market hypothesis (EMH) for both TSX and SSE. Several testing results based on more recent sample periods align with the assumption under the EMH, but it is still early to claim that either the Canadian or the Chinese stock market hasbecome the weak form efficient. More comprehensive testing results and analysis can be found under section 5 and 6

    VIX AND VIX FUTURES: A TOOL OF RISK REDUCTION AND DOWNSIDE PROTECTION FOR HEDGE FUNDS

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    We analyze VIX, VIX futures and hedge funds. VIX is a measure of the implied volatility of S&P 500 index options. VIX futures performance is measured by the S&P 500 VIX Mid-Term Futures Index and the CBOE VIX Premium Strategy Index. Credit Suisse Hedge Fund Index and Hedge Fund Research Indices represent hedge funds performance. In our project, we expand Dash and Moran (2005) by expanding the end period of survey from December 2004 to May 2014 and including two hedge fund databases, Credit Suisse and Hedge Fund Research. In addition, we conduct analyses on both VIX index and VIX futures indices, which are not included in the Dash and Moran (2005). Not only we check the addition of VIX index or VIX futures indices to hedge fund portfolios for risk reduction or downside protection, but also our analysis pays more attention to the period of 2008 financial crisis. We find that broad-based hedge fund indices and most narrow hedge fund indices are negatively and asymmetrically correlated with VIX. Addition of VIX index as well as VIX futures indices protects hedge fund portfolios from major drawdowns and helps reduce risk

    A sustainable identity: The creativity of an everyday designer

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    In this paper we explore sustainability in interaction design by reframing concepts of user identity and use in a domestic setting. Building on our own work on everyday design and Blevis’s Sustainable Interaction Design principles, we present examples from an ethnographic study of families in their homes which illustrate design-in-use: the creative and sustainable ways people appropriate and adapt designed artifacts. We claim that adopting a conception of the user as a creative everyday designer generates a new set of design principles that promote sustainable interaction design

    Plant Selection for Ethnobotanical Uses on the Amalfi Coast (Southern Italy)

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    Background Many ethnobotanical studies have investigated selection criteria for medicinal and non-medicinal plants. In this paper we test several statistical methods using different ethnobotanical datasets in order to 1) define to which extent the nature of the datasets can affect the interpretation of results; 2) determine if the selection for different plant uses is based on phylogeny, or other selection criteria. Methods We considered three different ethnobotanical datasets: two datasets of medicinal plants and a dataset of non-medicinal plants (handicraft production, domestic and agro-pastoral practices) and two floras of the Amalfi Coast. We performed residual analysis from linear regression, the binomial test and the Bayesian approach for calculating under-used and over-used plant families within ethnobotanical datasets. Percentages of agreement were calculated to compare the results of the analyses. We also analyzed the relationship between plant selection and phylogeny, chorology, life form and habitat using the chi-square test. Pearson’s residuals for each of the significant chi-square analyses were examined for investigating alternative hypotheses of plant selection criteria. Results The three statistical analysis methods differed within the same dataset, and between different datasets and floras, but with some similarities. In the two medicinal datasets, only Lamiaceae was identified in both floras as an over-used family by all three statistical methods. All statistical methods in one flora agreed that Malvaceae was over-used and Poaceae under-used, but this was not found to be consistent with results of the second flora in which one statistical result was non-significant. All other families had some discrepancy in significance across methods, or floras. Significant over- or under-use was observed in only a minority of cases. The chi-square analyses were significant for phylogeny, life form and habitat. Pearson’s residuals indicated a non-random selection of woody species for non-medicinal uses and an under-use of plants of temperate forests for medicinal uses. Conclusions Our study showed that selection criteria for plant uses (including medicinal) are not always based on phylogeny. The comparison of different statistical methods (regression, binomial and Bayesian) under different conditions led to the conclusion that the most conservative results are obtained using regression analysis
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