Difficulties Encountered in Projecting Canada’s Aboriginal Population

Abstract not availabl

A Look at Technology Use Across the Country: State Implementation of AT Practices for Infants and Toddlers

EI professionals from across the country recently participated in the Tots-n-Tech’s (TnT) Assistive Technology (AT) Program Self-Assessment. Part C Coordinators designated agency and program directors, regional coordinators, or other relevant people in their states to respond to the on-line self assessment of AT practices. The self-assessment is designed to provide a picture of how well recommended AT practices are implemented within state communities. Information from all respondents is combined to provide state-wide and regional views of how programs are doing in making AT available for infants and toddlers with disabilities or delayed development

Does life satisfaction reduce risk of incident hypertension and stroke? Evidence from the Whitehall II cohort

Background: Previous studies showed life satisfaction is related to reduced risk of coronary heart disease and diabetes, but its association with other cardiometabolic endpoints including hypertension and stroke remains unexplored. This study examined life satisfaction's prospective association with incident hypertension and stroke in middle-aged adults. Methods: At baseline (1985–1988), 6225 healthy British civil servants aged 35–55 from the Whitehall II cohort completed the validated Satisfaction with Life Scale and provided information regarding sociodemographics, a range of health-related factors, and psychological distress. Incident hypertension was ascertained according to clinic-derived measures of systolic or diastolic blood pressure of ≥140/90 mmHg, respectively, or self-reports of either physician-diagnosed hypertension or hypertensive medication use. Incident stroke and transient ischemic attack (TIA) were ascertained by self-reported physician diagnosis. Follow-up assessments occurred every 2–5 years through 2017. Cox proportional hazards regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) of hypertension and stroke/TIA risk separately. Results: Over a 31-year follow-up, 2703 cases of hypertension and 370 cases of stroke/TIA occurred. Life satisfaction was not related to risk of developing hypertension but was associated with 12% decreased risk of stroke/TIA after controlling for sociodemographics, health status, and health behaviors (HRper 1-SD = 0.88; 95%CI = 0.79–0.98). However, the association was attenuated after adjustment for psychological distress. Conclusions: No robust associations were found between life satisfaction and incident hypertension and stroke/TIA, respectively, after accounting for well-established risk factors and psychological distress. More research is needed to understand why associations of life satisfaction with cardiometabolic health seem to vary across endpoints

Visual hypo and hypergnosia as exemplars of poles of psychic tonus in the occipital lobes: Multiple case analyses

Abstract. The "psychic tonus" model or PT

Wind Retrieval Algorithms for the IWRAP and HIWRAP Airborne Doppler Radars with Applications to Hurricanes

Algorithms for the retrieval of atmospheric winds in precipitating systems from downward-pointing, conically-scanning airborne Doppler radars are presented. The focus in the paper is on two radars: the Imaging Wind and Rain Airborne Profiler(IWRAP) and the High-altitude IWRAP (HIWRAP). The IWRAP is a dual-frequency (Cand Ku band), multi-beam (incidence angles of 30 50) system that flies on the NOAAWP-3D aircraft at altitudes of 2-4 km. The HIWRAP is a dual-frequency (Ku and Kaband), dual-beam (incidence angles of 30 and 40) system that flies on the NASA Global Hawk aircraft at altitudes of 18-20 km. Retrievals of the three Cartesian wind components over the entire radar sampling volume are described, which can be determined using either a traditional least squares or variational solution procedure. The random errors in the retrievals are evaluated using both an error propagation analysis and a numerical simulation of a hurricane. These analyses show that the vertical and along-track wind errors have strong across-track dependence with values of 0.25 m s-1 at nadir to 2.0 m s-1 and 1.0 m s-1 at the swath edges, respectively. The across-track wind errors also have across-track structure and are on average, 3.0 3.5 m s-1 or 10 of the hurricane wind speed. For typical rotated figure four flight patterns through hurricanes, the zonal and meridional wind speed errors are 2 3 m s-1.Examples of measured data retrievals from IWRAP during an eyewall replacement cycle in Hurricane Isabel (2003) and from HIWRAP during the development of Tropical Storm Matthew (2010) are shown

Heparin Isomeric Oligosaccharide Separation Using Volatile Salt Strong Anion Exchange Chromatography

The complexity of heparin and heparan sulfate saccharides makes their purification, including many isomeric structures, very challenging and is a bottleneck for structure–activity studies. High-resolution separations have been achieved by strong anion exchange (SAX) chromatography on Propac PA1 and cetyltrimethylammonium (CTA)-C18 silica columns; however, these entail subsequent desalting methodologies and consequent sample losses and are incompatible with orthogonal chromatography methodologies and, in particular, mass spectrometry. Here, we present the CTA-SAX purification of heparin oligosaccharides using volatile salt (VS) buffer. In VSCTA-SAX, the use of ammonium bicarbonate buffer for elution improves resolution through both weaker dissociation and conformational coordination of the ammonium across the sulfate groups. Using ion mobility mass spectrometry, we demonstrate that isomeric structures have different structural conformations, which makes chromatographic separation achievable. Resolution of such structures is improved compared to standard SAX methods, and in addition, VSCTA-SAX provides an orthogonal method to isolate saccharides with higher purity. Because ammonium bicarbonate is used, the samples can be evaporated rather than desalted, preventing substantial sample loss and allowing more effective subsequent analysis by electrospray mass spectrometry. We conclude that VSCTA-SAX is a powerful new tool that helps address the difficult challenge of heparin/heparan sulfate saccharide separation and will enhance structure–activity studies

Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells. © 2010 MacTavish et al

Variations in the Peritrophic Matrix Composition of Heparan Sulphate from the Tsetse Fly, Glossina morsitans morsitans

Tsetse flies are the principal insect vectors of African trypanosomes—sleeping sickness in humans and Nagana in cattle. One of the tsetse fly species, Glossina morsitans morsitans, is host to the parasite, Trypanosoma brucei, a major cause of African trypanosomiasis. Precise details of the life cycle have yet to be established, but the parasite life cycle involves crossing the insect peritrophic matrix (PM). The PM consists of the polysaccharide chitin, several hundred proteins, and both glycosamino- and galactosaminoglycan (GAG) polysaccharides. Owing to the technical challenges of detecting small amounts of GAG polysaccharides, their conclusive identification and composition have not been possible until now. Following removal of PMs from the insects and the application of heparinases (bacterial lyase enzymes that are specific for heparan sulphate (HS) GAG polysaccharides), dot blots with a HS-specific antibody showed heparan sulphate proteoglycans (HSPGs) to be present, consistent with Glossina morsitans morsitans genome analysis, as well as the likely expression of the HSPGs syndecan and perlecan. Exhaustive HS digestion with heparinases, fluorescent labeling of the resulting disaccharides with BODIPY fluorophore, and separation by strong anion exchange chromatography then demonstrated the presence of HS for the first time and provided the disaccharide composition. There were no significant differences in the type of disaccharide species present between genders or between ages (24 vs. 48 h post emergence), although the HS from female flies was more heavily sulphated overall. Significant differences, which may relate to differences in infection between genders or ages, were evident, however, in overall levels of 2-O-sulphation between sexes and, for females, between 24 and 48 h post-emergence, implying a change in expression or activity for the 2-O-sulphotransferase enzyme. The presence of significant quantities of disaccharides containing the monosaccharide GlcNAc6S contrasts with previous findings in Drosophila melanogaster and suggests subtle differences in HS fine structure between species of the Diptera

Mantle redox state drives outgassing chemistry and atmospheric composition of rocky planets

Volcanic degassing of planetary interiors has important implications for their corresponding atmospheres. The oxidation state of rocky interiors affects the volatile partitioning during mantle melting and subsequent volatile speciation near the surface. Here we show that the mantle redox state is central to the chemical composition of atmospheres while factors such as planetary mass, thermal state, and age mainly affect the degassing rate. We further demonstrate that mantle oxygen fugacity has an effect on atmospheric thickness and that volcanic degassing is most efficient for planets between 2 and 4 Earth masses. We show that outgassing of reduced systems is dominated by strongly reduced gases such as H2, with only smaller fractions of moderately reduced/oxidised gases (CO, H2O). Overall, a reducing scenario leads to a lower atmospheric pressure at the surface and to a larger atmospheric thickness compared to an oxidised system. Atmosphere predictions based on interior redox scenarios can be compared to observations of atmospheres of rocky exoplanets, potentially broadening our knowledge on the diversity of exoplanetary redox states

Electronic sculpting of ligand-GPCR subtype selectivity:the case of angiotensin II

GPCR subtypes possess distinct functional and pharmacological profiles, and thus development of subtype-selective ligands has immense therapeutic potential. This is especially the case for the angiotensin receptor subtypes AT1R and AT2R, where a functional negative control has been described and AT2R activation highlighted as an important cancer drug target. We describe a strategy to fine-tune ligand selectivity for the AT2R/AT1R subtypes through electronic control of ligand aromatic-prolyl interactions. Through this strategy an AT2R high affinity (<i>K</i>_i = 3 nM) agonist analogue that exerted 18,000-fold higher selectivity for AT2R versus AT1R was obtained. We show that this compound is a negative regulator of AT1R signaling since it is able to inhibit MCF-7 breast carcinoma cellular proliferation in the low nanomolar range