Foreign policy beliefs and support for Stephen Harper and the Conservative Party

Similar to other recent Canadian elections, foreign policy did not feature prominently in the 2011 federal election campaign. In fact, many doubt Canadian public opinion on international affairs is linked to the actions taken by recent Governments. In this paper, we examine Canadian public opinion toward a range of foreign policy issues and argue that the survey questions measure two latent dimensions —militarism and internationalism. Our survey evidence indicates the existence of an “issue public” which is prepared to endorse military action and is skeptical of human rights and overseas aid programs, and this group is far more supportive of Prime Minister Harper and the Conservative Party than other Canadians. The absence of an elite discussion, either among politicians or between media elites, about the direction of Canadian foreign policy does not prevent the Canadian voter from thinking coherently about questions pertaining to this issue domain and employing these beliefs to support or oppose political parties and their leaders

A Computational and Experimental Study of the Regulatory Mechanisms of the Complement System

The complement system is key to innate immunity and its activation is necessary for the clearance of bacteria and apoptotic cells. However, insufficient or excessive complement activation will lead to immune-related diseases. It is so far unknown how the complement activity is up- or down- regulated and what the associated pathophysiological mechanisms are. To quantitatively understand the modulatory mechanisms of the complement system, we built a computational model involving the enhancement and suppression mechanisms that regulate complement activity. Our model consists of a large system of Ordinary Differential Equations (ODEs) accompanied by a dynamic Bayesian network as a probabilistic approximation of the ODE dynamics. Applying Bayesian inference techniques, this approximation was used to perform parameter estimation and sensitivity analysis. Our combined computational and experimental study showed that the antimicrobial response is sensitive to changes in pH and calcium levels, which determines the strength of the crosstalk between CRP and L-ficolin. Our study also revealed differential regulatory effects of C4BP. While C4BP delays but does not decrease the classical complement activation, it attenuates but does not significantly delay the lectin pathway activation. We also found that the major inhibitory role of C4BP is to facilitate the decay of C3 convertase. In summary, the present work elucidates the regulatory mechanisms of the complement system and demonstrates how the bio-pathway machinery maintains the balance between activation and inhibition. The insights we have gained could contribute to the development of therapies targeting the complement system.Singapore. Ministry of Education (Grant T208B3109)Singapore. Agency for Science, Technology and Research (BMRC 08/1/21/19/574)Singapore-MIT Alliance (Computational and Systems Biology Flagship Project)Swedish Research Counci

Localization of P-gp (Abcb1) and Mrp2 (Abcc2) in Freshly Isolated Rat Hepatocytes

Freshly isolated hepatocytes are widely accepted as the “gold standard” for providing reliable data on drug uptake across the sinusoidal (basolateral) membrane. However, the suitability of freshly isolated hepatocytes in suspension to assess efflux by canalicular (apical) proteins or predict biliary excretion in the intact organ is unclear. After collagenase digestion, hepatocytes rapidly lose polarity, but localization of canalicular transport proteins in the first few hours after isolation has not been well characterized. In this study, immunostaining and confocal microscopy have provided, for the first time, a detailed examination of canalicular transport protein localization in freshly isolated rat hepatocytes fixed within 1 h of isolation and in cells cultured for 1 h. Organic anion transporting polypeptide 1a1 (Oatp1a1) was expressed in all hepatocytes and distributed evenly across the basolateral membrane; there was no evidence for colocalization of Oatp1a1 with P-glycoprotein (P-gp) or multidrug resistance-associated protein 2 (Mrp2). In contrast, P-gp and Mrp2 expression was lower than Oatp1a1 and confined to junctions between adjacent cells, intracellular compartments, and “legacy” network structures at or near the cell surface. P-gp and Mrp2 staining was more predominant in regions adjacent to former canalicular spaces, identified by zonula occludens-1 staining. Functional analysis of rat hepatocytes cultured for 1 h demonstrated that the fluorescent anion and Mrp2 substrate, 5-(and-6)-carboxy-2′,7′-dichlorofluorescein (CDF), accumulated in cellular compartments; compartmental accumulation of CDF was sensitive to (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-[[3-dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK571, Mrp inhibitor) and was not observed in hepatocytes isolated from Mrp2-deficient rats. Drug efflux from freshly isolated hepatocytes as an estimate of apical efflux/biliary excretion would give an inaccurate assessment of true apical elimination and, as such, should not be used to make in vivo extrapolations

Coalition Culls and Zoonotic Ontologies

Diseases which can pass between animals and humans (zoonoses) have been headline news several times in the last ten years. This paper looks at bovine tuberculosis (bTB) in the United Kingdom, which, although not a major health hazard for humans, has been problematic for farmers and the veterinary health institutions. At its current rate of spread, the disease will cost the authorities £1 billion in compensation to farmers for slaughtered animals and in administrative expenses over the next decade. The present Coalition government is planning to cull badgers in England because they are the principal wildlife reservoir of bTB and are said to pass infection to cattle. We argue in five stories that the heterogeneities of bTB help explain the difficulties in dealing with it. In our opinion, the present reductive set of policies would be improved by taking this ontological multiplicity into account

Ethnic difference of clinical vertebral fracture risk

Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. This study observed that Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians, but the vertebral fracture rates were higher, resulting in a high vertebral-to-hip fracture ratio. As a result, estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. Introduction: Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. The aim of this study was to report the incidence of clinical vertebral fractures among the Chinese and to compare the vertebral-to-hip fracture risk to other ethnic groups. Methods: Four thousand, three hundred eighty-six community-dwelling Southern Chinese subjects (2,302 women and 1,810 men) aged 50 or above were recruited in the Hong Kong Osteoporosis Study since 1995. Baseline demographic characteristics and medical history were obtained. Subjects were followed annually for fracture outcomes with a structured questionnaire and verified by the computerized patient information system of the Hospital Authority of the Hong Kong Government. Only non-traumatic incident hip fractures and clinical vertebral fractures that received medical attention were included in the analysis. The incidence rates of clinical vertebral fractures and hip fractures were determined and compared to the published data of Swedish Caucasian and Japanese populations. Results: The mean age at baseline was 62 ± 8.2 years for women and 68 ± 10.3 years for men. The average duration of follow-up was 4.0 ± 2.8 (range, 1 to 14) years for a total of 14,733 person-years for the whole cohort. The incidence rate for vertebral fracture was 194/100,000 person-years in men and 508/100,000 person-years in women, respectively. For subjects above the age of 65, the clinical vertebral fracture and hip fracture rates were 299/100,000 and 332/100,000 person-years, respectively, in men, and 594/100,000 and 379/100,000 person-years, respectively, in women. Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians. At the age of 65 or above, the hip fracture rates for Asian (Hong Kong Chinese and Japanese) men and women were less than half of that in Caucasians, but the vertebral fracture rate was higher in Asians, resulting in a high vertebral-to-hip fracture ratio. Conclusions: The incidences of vertebral and hip fractures, as well as the vertebral-to-hip fracture ratios vary in Asians and Caucasians. Estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Low handgrip strength is a predictor of osteoporotic fractures: cross-sectional and prospective evidence from the Hong Kong Osteoporosis Study

Handgrip strength (HGS) is a potentially useful objective parameter to predict fracture since it is an indicator of general muscle strength and is associated with fragility and propensity to fall. Our objective was to examine the association of HGS with fracture, to evaluate the accuracy of HGS in predicting incident fracture, and to identify subjects at risk of fracture. We analyzed a cross-sectional cohort with 2,793 subjects (1,217 men and 1,576 women aged 50–101 years) and a subset of 1,702 subjects which were followed for a total of 4,855 person-years. The primary outcome measures were prevalent fractures and incident major fragility fractures. Each standard deviation (SD) reduction in HGS was associated with a 1.24-fold increased odds for major clinical fractures even after adjustment for other clinical factors. A similar result was obtained in the prospective cohort with each SD reduction in HGS being associated with a 1.57-fold increased hazard ratio of fracture even after adjustment for clinical factors. A combination of HGS and femoral neck bone mineral density (FN BMD) T-score values (combined T-score), together with other clinical factors, had a better predictive power of incident fractures than FN BMD or HGS T-score alone with clinical factors. In addition, combined T-score has better sensitivity and specificity in predicting incidence fractures than FN BMD alone. This study is the first study to compare the predictive ability of HGS and BMD. We showed that HGS is an independent risk factor for major clinical fractures. Compared with using FN BMD T-score of −2.5 alone, HGS alone has a comparable predictive power to BMD, and the combined T-score may be useful to identify extra subjects at risk of clinical fractures with improved specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11357-011-9297-2) contains supplementary material, which is available to authorized users

The effects of publishing emergency department wait time on patient utilization patterns in a community with two emergency department sites: a retrospective, quasi-experiment design

BACKGROUND: Providing emergency department (ED) wait time information to the public has been suggested as a mechanism to reduce lengthy ED wait times (by enabling patients to select the ED site with shorter wait time), but the effects of such a program have not been evaluated. We evaluated the effects of such a program in a community with two ED sites. METHODS: Descriptive statistics for wait times of the two sites before and after the publication of wait time information were used to evaluate the effects of the publication of wait time information on wait times. Multivariate logistical regression was used to test whether or not individual patients used published wait time to decide which site to visit. RESULTS: We found that the rates of wait times exceeding 4 h, and the 95th percentile of wait times in the two sites decreased after the publication of wait time information, even though the average wait times experienced a slight increase. We also found that after controlling for other factors, the site with shorter wait time had a higher likelihood of being selected after the publication of wait time information, but there was no such relationship before the publication. CONCLUSIONS: These findings were consistent with the hypothesis that the publication of wait time information leads to patients selecting the site with shorter wait time. While publishing ED wait time information did not improve average wait time, it reduced the rates of lengthy wait times

Location of residence associated with the likelihood of patient visit to the preoperative assessment clinic

BACKGROUND: Outpatient preoperative assessment clinics were developed to provide an efficient assessment of surgical patients prior to surgery, and have demonstrated benefits to patients and the health care system. However, the centralization of preoperative assessment clinics may introduce geographical barriers to utilization that are dependent on where a patient lives with respect to the location of the preoperative assessment clinic. METHODS: The association between geographical distance from a patient's place of residence to the preoperative assessment clinic, and the likelihood of a patient visit to the clinic prior to surgery, was assessed for all patients undergoing surgery at a tertiary health care centre in a major Canadian city. The odds of attending the preoperative clinic were adjusted for patient characteristics and clinical factors. RESULTS: Patients were less likely to visit the preoperative assessment clinic prior to surgery as distance from the patient's place of residence to the clinic increased (adjusted OR = 0.52, 95% CI 0.44–0.63 for distances between 50–100 km, and OR = 0.26, 95% CI 0.21–0.31 for distances greater than 250 km). This 'distance decay' effect was remarkable for all surgical specialties. CONCLUSION: The present study demonstrates that the likelihood of a patient visiting the preoperative assessment clinic appears to depend on the geographical location of patients' residences. Patients who live closest to the clinic tend to be seen more often than patients who live in rural and remote areas. This observation may have implications for achieving the goals of equitable access, and optimal patient care and resource utilization in a single universal insurer health care system

HypertenGene: extracting key hypertension genes from biomedical literature with position and automatically-generated template features

<p>Abstract</p> <p>Background</p> <p>The genetic factors leading to hypertension have been extensively studied, and large numbers of research papers have been published on the subject. One of hypertension researchers' primary research tasks is to locate key hypertension-related genes in abstracts. However, gathering such information with existing tools is not easy: (1) Searching for articles often returns far too many hits to browse through. (2) The search results do not highlight the hypertension-related genes discovered in the abstract. (3) Even though some text mining services mark up gene names in the abstract, the key genes investigated in a paper are still not distinguished from other genes. To facilitate the information gathering process for hypertension researchers, one solution would be to extract the key hypertension-related genes in each abstract. Three major tasks are involved in the construction of this system: (1) gene and hypertension named entity recognition, (2) section categorization, and (3) gene-hypertension relation extraction.</p> <p>Results</p> <p>We first compare the retrieval performance achieved by individually adding template features and position features to the baseline system. Then, the combination of both is examined. We found that using position features can almost double the original AUC score (0.8140vs.0.4936) of the baseline system. However, adding template features only results in marginal improvement (0.0197). Including both improves AUC to 0.8184, indicating that these two sets of features are complementary, and do not have overlapping effects. We then examine the performance in a different domain--diabetes, and the result shows a satisfactory AUC of 0.83.</p> <p>Conclusion</p> <p>Our approach successfully exploits template features to recognize true hypertension-related gene mentions and position features to distinguish key genes from other related genes. Templates are automatically generated and checked by biologists to minimize labor costs. Our approach integrates the advantages of machine learning models and pattern matching. To the best of our knowledge, this the first systematic study of extracting hypertension-related genes and the first attempt to create a hypertension-gene relation corpus based on the GAD database. Furthermore, our paper proposes and tests novel features for extracting key hypertension genes, such as relative position, section, and template features, which could also be applied to key-gene extraction for other diseases.</p