A four gene signature of chromosome instability (CIN4) predicts for benefit from taxanes in the NCIC-CTG MA21 clinical trial.

Recent evidence demonstrated CIN4 as a predictive marker of anthracycline benefit in early breast cancer. An analysis of the NCIC CTG MA.21 clinical trial was performed to test the role of existing CIN gene expression signatures as prognostic and predictive markers in the context of taxane based chemotherapy.RNA was extracted from patients in cyclophosphamide, epirubicin and flurouracil (CEF) and epirubicin, cyclophosphamide and paclitaxel (EC/T) arms of the NCIC CTG MA.21 trial and analysed using NanoString technology.After multivariate analysis both high CIN25 and CIN70 score was significantly associated with an increased in RFS (HR 1.76, 95%CI 1.07-2.86, p=0.0018 and HR 1.59, 95%CI 1.12-2.25, p=0.0096 respectively). Patients whose tumours had low CIN4 gene expression scores were associated with an increase in RFS (HR: 0.64, 95% CI 0.39-1.03, p=0.06) when treated with EC/T compared to patients treated with CEF.In conclusion we have demonstrated CIN25 and CIN70 as prognostic markers in breast cancer and that CIN4 is a potential predictive maker of benefit from taxane treatment

Time-resolved measurements of black carbon light absorption enhancement in urban and near-urban locations of southern Ontario, Canada

In this study a photoacoustic spectrometer (PA), a laser-induced incandescence instrument system (LII) and an Aerosol Mass Spectrometer were operated in parallel for in-situ measurements of black carbon (BC) light absorption enhancement. Results of a thermodenuder experiment using ambient particles in Toronto are presented first to show that LII measurements of BC are not influenced by the presence of non-refractory material thus providing true atmospheric BC mass concentrations. In contrast, the PA response is enhanced when the non-refractory material is internally mixed with the BC particles. Through concurrent measurements using the LII and PA the specific absorption cross-section (SAC) can be quantified with high time resolution (1 min). Comparisons of ambient PA and LII measurements from four different locations (suburban Toronto; a street canyon with diesel bus traffic in Ottawa; adjacent to a commuter highway in Ottawa and; regional background air in and around Windsor, Ontario), show that different impacts from emission sources and/or atmospheric processes result in different particle light absorption enhancements and hence variations in the SAC. The diversity of measurements obtained, including those with the thermodenuder, demonstrated that it is possible to identify measurements where the presence of externally-mixed non-refractory particles obscures direct observation of the effect of coating material on the SAC, thus allowing this effect to be measured with more confidence. Depending upon the time and location of measurement (urban, rural, close to and within a lake breeze frontal zone), 30 min average SAC varies between 9 ± 2 and 43 ± 4 m<sup>2</sup> g<sup>−1</sup>. Causes of this variation, which were determined through the use of meteorological and gaseous measurements (CO, SO<sub>2</sub>, O<sub>3</sub>), include the particle emission source, airmass source region, the degree of atmospheric processing. Observations from this study also show that the active surface area of the BC aggregate, which is measured by the LII as the PPS, is an important parameter for inferring the degree of particle collapse of a BC particle. In addition, PPS could be a useful measurement for indicating the importance of recently emitted BC (e.g. from gasoline or diesel engines) relative to the total measured BC in the atmosphere

Financial Stability: The Next Frontier for Canadian Monetary Policy

The monetary policy arrangement in Canada has proven very successful. Despite many and varied economic shocks, the Bank of Canada has established the necessary conditions under which the annual rate of inflation, as measured by the rate of change of the Consumer Price Index, has remained very close to its formal 2 percent target for more than 15 years. The recent financial crisis, however, has highlighted the fact that low inflation may not be enough to ensure the stability of the financial system and the economy in general. The goal of achieving and maintaining financial stability has become, in Canada and elsewhere, the next frontier of monetary policy. What is needed is a new Canadian institutional framework to oversee macro-prudential regulation, which would take a systemic approach to safeguarding the financial system as a whole, and clearly define the role of the Bank of Canada within it. It will require the federal government, first, to recognize the importance of the issue and, second, to take the necessary time to assemble the framework with the appropriate parties involved and to assign responsibilities clearly. Doing it right will involve bringing together various policy authorities with different perspectives, specialties, and primary mandates.Monetary Policy, Bank of Canada, inflation targeting, Consumer Price Index (CPI)

Probing the inflaton: Small-scale power spectrum constraints from measurements of the CMB energy spectrum

In the early Universe, energy stored in small-scale density perturbations is quickly dissipated by Silk-damping, a process that inevitably generates mu- and y-type spectral distortions of the cosmic microwave background (CMB). These spectral distortions depend on the shape and amplitude of the primordial power spectrum at wavenumbers k < 10^4 Mpc^{-1}. Here we study constraints on the primordial power spectrum derived from COBE/FIRAS and forecasted for PIXIE. We show that measurements of mu and y impose strong bounds on the integrated small-scale power, and we demonstrate how to compute these constraints using k-space window functions that account for the effects of thermalization and dissipation physics. We show that COBE/FIRAS places a robust upper limit on the amplitude of the small-scale power spectrum. This limit is about three orders of magnitude stronger than the one derived from primordial black holes in the same scale range. Furthermore, this limit could be improved by another three orders of magnitude with PIXIE, potentially opening up a new window to early Universe physics. To illustrate the power of these constraints, we consider several generic models for the small-scale power spectrum predicted by different inflation scenarios, including running-mass inflation models and inflation scenarios with episodes of particle production. PIXIE could place very tight constraints on these scenarios, potentially even ruling out running-mass inflation models if no distortion is detected. We also show that inflation models with sub-Planckian field excursion that generate detectable tensor perturbations should simultaneously produce a large CMB spectral distortion, a link that could potentially be established by PIXIE.Comment: 13 pages, 10 figures, submitted to Ap

Planning for Complete Streets in Toronto: An Exploration of Public Engagement and Policy in Street Design, A Case Study of Queens Quay West

This major paper evaluates the concept of complete streets and the impact this approach to street design has on various users through a case study of the Queens Quay West revitalization process in Toronto. A complete street is defined as treating all street users equally while enhancing the environmental, economic and safety conditions of the street, thus resulting in an enhanced quality of life. Complete streets challenge autocentric street design by enhancing facilities such as cycling lanes to accommodate all modes of transportation. The concept of complete streets is relatively new, resulting in a lack of empirical evidence. This led me to investigate Queens Quay West which is the first complete street in Toronto. I conducted a comprehensive literature review of street design and public engagement strategies to determine if the stakeholder desires in the Queens Quay West revitalization process were reflected in the final outcome of the street. This paper also discusses the legal framework involved in street design and the policies and guidelines that paved the way for the implementation of the Toronto Complete Street Guidelines (2017). This policy review concludes that the guidelines have streamlined complete street implementation and have promoted the ideology. In conclusion, I suggest that the Queens Quay West engagement strategy was extremely successful with a number of efforts being made to fully engage stakeholders. The public's desires were largely reflected in the outcome of the street. My research demonstrates that Queens Quay West sets a precedent for future complete streets in Toronto

“Not Unless Necessary”: Student Responses to War Work at the University of Toronto, 1914-1918

During the First World War, participation in the war effort at the University of Toronto was defined by gender. The university encouraged male students to enlist and female students to work in munitions and agriculture. Though public reaction to the war was overwhelmingly positive in Toronto and at the university, University of Toronto student publications such as The Varsity, student records from the Office of the Registrar, and writings by university students capture more complex student reactions to the war. These sources present voices of discomfort and tiredness with the university’s support of the war effort and complicate gendered expectations of participation during the Great War.Au cours de la Première Guerre mondiale, la participation étudiante à l’effort de guerre à l’Université de Toronto était définie en fonction du sexe. L’université encourageait les hommes à s’enrôler et les femmes à travailler dans les usines de munitions ou en agriculture. Si la réaction publique à la guerre a été très manifestement positive, les publications étudiantes telles que The Varsity, les dossiers étudiants du bureau du registraire et certains écrits d’étudiants permettent de nuancer cette impression. Ces sources révèlent en effet un malaise et une certaine lassitude à l’égard du soutien de l’université à la guerre et complexifient l’histoire des attentes à la fois des étudiants et des étudiantes par rapport à la participation à la Grande Guerre

Recent acquisition of imprinting at the rodent Sfmbt2 locus correlates with insertion of a large block of miRNAs.

BACKGROUND: The proximal region of murine Chr 2 has long been known to harbour one or more imprinted genes from classic genetic studies involving reciprocal translocations. No imprinted gene had been identified from this region until our study demonstrated that the PcG gene Sfmbt2 is expressed from the paternally inherited allele in early embryos and extraembryonic tissues. Imprinted genes generally reside in clusters near elements termed Imprinting Control Regions (ICRs), suggesting that Sfmbt2 might represent an anchor for a new imprinted domain. RESULTS: We analyzed allelic expression of approximately 20 genes within a 3.9 Mb domain and found that Sfmbt2 and an overlapping non-coding antisense transcript are the only imprinted genes in this region. These transcripts represent a very narrow imprinted gene locus. We also demonstrate that rat Sfmbt2 is imprinted in extraembryonic tissues. An interesting feature of both mouse and rat Sfmbt2 genes is the presence of a large block of miRNAs in intron 10. Other mammals, including the bovine, lack this block of miRNAs. Consistent with this association, we show that human and bovine Sfmbt2 are biallelic. Other evidence indicates that pig Sfmbt2 is also not imprinted. Further strengthening the argument for recent evolution of Sfmbt2 is our demonstration that a more distant muroid rodent, Peromyscus also lacks imprinting and the block of miRNAs. CONCLUSIONS: These observations are consistent with the hypothesis that the block of miRNAs are driving imprinting at this locus. Our results are discussed in the context of ncRNAs at other imprinted loci. Accession numbers for Peromyscus cDNA and intron 10 genomic DNA are [Genbank:HQ416417 and Genbank:HQ416418], respectively.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are