A New Metropolitan Cultural Ligament: Toronto Eglinton Crosstown LRT Prototypical Design Proposal

This thesis strives to establish a set of design guidelines for the upcoming Eglinton Crosstown Light Rail Transit development in Toronto. The primary design goals are to promote an enjoyable travel experience to commuters, offer positive public spaces in vicinity, and contribute to the greater social and cultural matrices of the city. Under a realistic project setting, the study will meditate upon spatial anthropological theories to identify essential public space qualities and to formulate underground lighting strategies. The main objective is to complete the development of both underground station and surface stop prototypes that can be flexibly implemented along the entire transit line. The vision is for these stations to not only provide convenient public transit amenities but also function as locale identifiers, showcasing Toronto’s culture virtually as unique rooms in a gallery. Three sites are chosen: Mount Pleasant, Dufferin, and Keele stations. These stations will provide interesting conditions to demonstrate the way in which a set of design guidelines can facilitate the positive development of subway stations into the powerful loci envisioned

Occurrence of Highly Conjugative IncX3 Epidemic Plasmid Carrying blaNDM in Enterobacteriaceae Isolates in Geographically Widespread Areas

The emergence of New Delhi metallo-β-lactamase (NDM) in common enterobacterial species is a major concern for healthcare. Early reports have revealed that the spread of NDM involved diverse and heterogeneous plasmids. Recently, the involvement of a rare, IncX3 subtype plasmid has been increasingly recognized. Here, we studied the prevalence of IncX plasmid subtypes in 198 carbapenem-resistant Enterobacteriaceae, originating from a territory-wide active surveillance in Hong Kong in 2016. The complete sequences and biological features of the blaNDM-carrying plasmids were investigated. A total of 62 NDM-type, 21 OXA-48 type, 14 IMP-type, 8 KPC-type, 4 IMI-type producers, and 89 non-carbapenemase-producers were tested for presence of IncX subtypes. IncX3 (n = 60) was the most common subtype, followed by IncX4 (n = 6) and IncX1 (n = 2). The prevalence of IncX3 subtype in isolates producing NDM, other carbapenemase types and non-carbapenemase producers were 75.8, 21.3, and 3.4%, respectively (P < 0.001). An IncX3 plasmid (size ∼50 kb) was confirmed to carry blaNDM in 47 isolates of different enterobacterial species. Thirteen IncX3 plasmids originating from six healthcare regions in Hong Kong were completely sequenced. The results showed that the IncX3 plasmids carrying blaNDM share a high degree of sequence identity with a previously reported plasmid, pNDM-HN380 (GenBank accession JX104760), over the backbone and genetic load regions. A blast search further revealed the occurrence of identical or nearly identical IncX3 plasmids carrying blaNDM in other part of China, Korea, Myanmar, India, Oman, Kuwait, Italy, and Canada. Two IncX3 carrying blaNDM were investigated further. Conjugation experiments demonstrated that the IncX3 plasmids could be efficiently transferred to multiple enterobacterial species at frequencies that are comparable or higher than the epidemic IncFII plasmid carrying blaCTX-M (pHK01). In addition, efficient transfer of the NDM plasmids occurred over a range of temperatures. In conclusion, this study demonstrated the important role played by IncX3 in the dissemination of NDM and the occurrence of pNDM-HN380-like plasmids in geographically widespread areas. The high mobility of IncX3 plasmid across different enterobacterial species highlights the ability of this plasmid replicon to be an important vehicle in worldwide dissemination of NDM

Retrospective cohort study to investigate the 10-year trajectories of disease patterns in patients with hypertension and/or diabetes mellitus on subsequent cardiovascular outcomes and health service utilisation: a study protocol.

INTRODUCTION: Hypertension (HT) and diabetes mellitus (DM) and are major disease burdens in all healthcare systems. Given their high impact on morbidity, premature death and direct medical costs, we need to optimise effectiveness and cost-effectiveness of primary care for patients with HT/DM. This study aims to find out the association of trajectories in disease patterns and treatment of patients with HT/DM including multimorbidity and continuity of care with disease outcomes and service utilisation over 10 years in order to identify better approaches to delivering primary care services. METHODS AND ANALYSIS: A 10-year retrospective cohort study on a population-based primary care cohort of Chinese patients with documented doctor-diagnosed HT and/or DM, managed in the Hong Kong Hospital Authority (HA) public primary care clinics from 1 January 2006 to 31 December 2019. Data will be extracted from the HA Clinical Management System to identify trajectory patterns of patients with HT/DM. Complications defined by ICPC-2/International Classification of Diseases-Ninth Revision, Clinical Modification diagnosis codes, all-cause mortality rates and public service utilisation rates are included as independent variables. Changes in clinical parameters will be investigated using a growth mixture modelling analysis with standard quadratic trajectories. Dependent variables including effects of multimorbidity, measured by (1) disease count and (2) Charlson's Comorbidity Index, and continuity of care, measured by the Usual Provide Continuity Index, on patient outcomes and health service utilisation will be investigated. Multivariable Cox proportional hazards regression will be conducted to estimate the effect of multimorbidity and continuity of care after stratification of patients into groups according to respective definitions. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of the University of Hong Kong-the HA Hong Kong West Cluster, reference no: UW 19-329. The study findings will be disseminated through peer-reviewed publications and international conferences. TRIAL REGISTRATION NUMBER: NCT04302974

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6% +/- 8.7%, respectively (p < 0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% +/- 2% vs. 57.4% +/- 1.8% (p < 0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5% +/- 1.5% in lithium treated cells vs. 56.6 +/- 3% (p < 0.01)) accompanied by increased number of.H2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% +/- 8% for lithium treated cells vs. 27% +/- 3% for untreated controls (p = 0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.B.R.A.I.N Child Canada; Cancer Research UK; Brain Tumour Charity; Hungarian Brain Research Program [KTIA_13_NAP-A-V/3]; Janos Bolyai Scholarship of the Hungarian Academy of Sciences [TAMOP-4.2.2. A-11/1/KONV-2012-0025]; German Cancer Aid/Dr. Mildred Scheel Foundation for Cancer Research; Cure Childhood Cancer Foundation; St. Baldrick's Foundation; Southeastern Brain Tumor Foundation; Action Medical Research; [CZ.1.05/2.1.00/03.0101]; [CZ.1.07/2.3.00/20.0183

Distinct monocyte gene-expression profiles in autoimmune diabetes

OBJECTIVE-There is evidence that monocytes of patients with type 1 diabetes show proinflammatory activation and disturbed migration/adhesion, but the evidence is inconsistent. Our hypothesis is that monocytes are distinctly activated/disturbed in different subforms of autoimmune diabetes. RESEARCH DESIGN AND METHODS-We studied patterns of inflammatory gene expression in monocytes of patients with type 1 diabetes (juvenile onset, n = 30; adult onset, n = 30) and latent autoimmune diabetes of the adult (LADA) (n = 30) (controls subjects, n = 49; type 2 diabetic patients, n = 30) using quantitative PCR. We tested 25 selected genes: 12 genes detected in a prestudy via whole-genome analyses plus an additional 13 genes identified as part of a monocyte inflammatory signature previously reported. RESULTS-We identified two distinct monocyte gene expression clusters in autoimmune diabetes. One cluster (comprising 12 proinflammatory cytokine/compound genes with a putative key gene PDE4B) was detected in 60% of LADA and 28% of adult-onset type 1 diabetic patients but in only 10% of juvenile - onset type 1 diabetic patients. A second cluster (comprising 10 chemotaxis, adhesion, motility, and metabolism genes) was detected in 43% of juvenile-onset type 1 diabetic and 33% of LADA patients but in only 9% of adult-onset type 1 diabetic patients. CONCLUSIONS-Subgroups of type 1 diabetic patients show an abnormal monocyte gene expression with two profiles, supporting a concept of heterogeneity in the pathogenesis of autoimmune diabetes only partly overlapping with the presently known diagnostic categories

기업의 고객만족도가 배당수익에 미치는 영향

학위논문 (석사)-- 서울대학교 대학원 : 경영학과(마케팅 전공), 2011.8. 송인성.Maste

Environmental attitudes and travel behavior of youth

Environmental problems relating to transportation have increased in severity in many cities within Canada. Reduction in emissions generated from the transport sector will require far reaching technological advances as well as behavioral shifts by the population. This study is carried out with a focus on influencing youths to increase the use of sustainable transportation. Studying the attitudes of young people towards the environment is important given they will be the ones affected by environmental issues arising from our current actions and consequently will be the individuals who will ultimately have to come up with resolutions. In preparation to address future transportation issues, it is critical to conduct researches with a focus on children and young people as attitudes toward the environment begin to develop in childhood. This study surveyed over 1000 students from 11 secondary schools in Richmond, Canada and Vancouver, Canada. The purpose of the survey is to examine the relationship between environmental knowledge, environmental attitudes and travel behavior. Structural equation models (SEMs) were used to quantify environmental attitudes as latent variables, as well as to examine the relationship between environmental knowledge, attitudes and travel behavior while controlling demographic and socioeconomic variables. The results indicate that 1) Students who have better knowledge on environmental issues hold higher levels of proenvironmental attitudes; 2) Students who use active transportation, public transit and school buses to/from school have stronger pro-environmental attitudes than students who travel to/from school by car; 3) Environmental attitude is found to be a mediating variable between environmental knowledge and travel behavior; and 4) Environmental knowledge has a significant impact on the relationship between environmental attitudes and travel behavior. Based on these findings, it is evident that continual improvement of the environmental education curriculum is needed. It is recommended that the curriculum should not be limited to knowledge-based education on transportation. Rather, it should include activities that will help induce a positive environmental attitude. It was also found that social media and school courses are major sources of environmental information for the students. Therefore, educational institutes, government, environmental NGOs should continue to leverage these channels to effectively disburse information.Applied Science, Faculty ofCivil Engineering, Department ofGraduat

High-throughput determination of ultra-low concentrations of LAG078, a lipid modulator, in human plasma.

A high throughput method with ultra-low level quantification limit (10 pg/ml) was developed and validated for the quantitative determination of LAG078, a lipid modulator, in human plasma to support clinical studies employing low doses of the compound. The method consisted of reverse phase chromatographic separation of the analyte from plasma extract followed by electrospray ionization (ESI) in the negative ion mode and tandem mass spectrometry in the multiple reaction monitoring mode (MRM). Extraction was performed using a combination of protein precipitation and liquid-liquid extraction in the 96-well plate format to increase the throughput of the method. Optimised chromatographic separation in a short and high-resolution column (50 mm x 2.0 mm i.d., 3 microm particle size) coupled with MRM mode of detection yielded clean chromatograms with minimal signal suppression. The standard curve was linear (r=0.996) within the concentration range of 0.01 (lower limit of quantification) to 50 ng/ml using 0.5 ml of human plasma. The accuracy of the method varied from 95-101% with a precision (CV) of 5.29-13.2% over the concentration range. The method was simple and rapid

DPP4i, thiazolidinediones, or insulin and risks of cancer in patients with type 2 diabetes mellitus on metformin–sulfonylurea dual therapy with inadequate control

Introduction This study aims to compare the risks of cancer among patients with type 2 diabetes mellitus (T2DM) on metformin–sulfonylurea dual therapy intensified with dipeptidyl peptidase 4 inhibitors (DPP4i), thiazolidinediones, or insulin.Research design and methods We assembled a retrospective cohort data of 20 577 patients who were free of cancer and on metformin–sulfonylurea dual therapy, and whose drug treatments were intensified with DPP4i (n=9957), insulin (n=7760), or thiazolidinediones (n=2860) from January 2006 to December 2017. Propensity-score weighting was used to balance out baseline covariates across the three groups. HRs for any types of cancer, cancer mortality, and all-cause mortality were assessed using Cox proportional-hazards models.Results Over a mean follow-up period of 34 months with 58 539 person-years, cumulative incidences of cancer, cancer mortality, and all-cause mortality were 0.028, 0.009, and 0.072, respectively. Patients intensified with insulin had the highest incidence of all-cause mortality (incidence rate=3.22/100 person-years) and the insulin itself posed the greatest risk (HR 2.46, 95% CI 2.25 to 2.70, p&lt;0.001; 2.44, 95% CI 2.23 to 2.67) compared with thiazolidinediones and DPP4i, respectively. Comparing between thiazolidinediones and DPP4i, thiazolidinediones was associated with higher risk of cancer (HR 1.43, 95% CI 1.25 to 1.63) but not cancer mortality (HR 1.21, 95% CI 0.92 to 1.58) and all-cause mortality (HR 0.99, 95% CI 0.88 to 1.11). Insulin was associated with the greatest risk of cancer mortality (HR 1.36, 95% CI 1.09 to 1.71; 1.65, 95% CI 1.31 to 2.07) compared with thiazolidinediones and DPP4i, respectively.Conclusions For patients with T2DM on metformin–sulfonylurea dual therapy, the addition of DPP4i was the third-line medication least likely to be associated with cancer mortality and cancer effect among three options, and posed no increased risk for all-cause mortality when compared with thiazolidinediones