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Abstract Background While the effects of daily fine particulate exposure (PM) have been well reviewed, the epidemiological and physiological evidence of cardiovascular effects associated to sub-daily exposures has not. We performed a theoretical model-driven systematic non-meta-analytical literature review to document the association between PM sub-daily exposures (≤6 hours) and arrhythmia, ischemia and myocardial infarction (MI) as well as the likely mechanisms by which sub-daily PM exposures might induce these acute cardiovascular effects. This review was motivated by the assessment of the risk of exposure to elevated sub-daily levels of PM during fireworks displays. Methods Medline and Elsevier's EMBase were consulted for the years 1996-2008. Search keywords covered potential cardiovascular effects, the pollutant of interest and the short duration of the exposure. Only epidemiological and experimental studies of adult humans (age > 18 yrs) published in English were reviewed. Information on design, population and PM exposure characteristics, and presence of an association with selected cardiovascular effects or physiological assessments was extracted from retrieved articles. Results Of 231 articles identified, 49 were reviewed. Of these, 17 addressed the relationship between sub-daily exposures to PM and cardiovascular effects: five assessed ST-segment depression indicating ischemia, eight assessed arrhythmia or fibrillation and five considered MI. Epidemiologic studies suggest that exposure to sub-daily levels of PM is associated with MI and ischemic events in the elderly. Epidemiological studies of sub-daily exposures suggest a plausible biological mechanism involving the autonomic nervous system while experimental studies suggest that vasomotor dysfunction may also relate to the occurrence of MI and ischemic events. Conclusions Future studies should clarify associations between cardiovascular effects of sub-daily PM exposure with PM size fraction and concurrent gaseous pollutant exposures. Experimental studies appear more promising for elucidating the physiological mechanisms, time courses and causes than epidemiological studies which employ central pollution monitors for measuring effects and for assessing their time course. Although further studies are needed to strengthen the evidence, given that exposure to sub-daily high levels of PM (for a few hours) is frequent and given the suggestive evidence that sub-daily PM exposures are associated with the occurrence of cardiovascular effects, we recommend that persons with cardiovascular diseases avoid such situations.

Although the relaxation time constants of free water are relatively long, the relaxation of water in concrete and other sedimentary materials is significantly shorter. Dissolved ions and porous environments can cause increased magnetic susceptibility effects, leading to the apparent transverse relaxation time T 2 ⁎ of this water to decrease drastically, from seconds to less than a millisecond. The longer T 2 ⁎ of the low field regime (less than 0.5 T) should allow for 2D and even 3D imaging of water content in these types of materials; developing a suitable technique for imaging of short-T 2 ⁎ samples would permit imaging of porous rocks and concrete. A 12 mL wet bentonite clay sample was placed within a syringe and allowed to absorb increasing volumes of standing water. This progressing absorption was imaged on a 73.5 mT magnetic resonance imaging (MRI) system using the X-Centric pulse sequence. This pulse sequence is a modified version of the common gradient echo (GE) pulse sequence, in which each half of k-space is acquired separately, from the centre outwards in the readout direction, ensuring minimal T 2 ⁎ -weighting of the resulting image and allowing for 2D imaging within the short time frame of the shorter T 2 ⁎ of water in the clay. Bulk relaxation measurements of T 2 ⁎ and the longitudinal relaxation time T 1 were performed for increasing water content, with a mean T 1 of 12.0 ± 1.1 ms and mean T 2 ⁎ of 4.5 ± 0.7 ms; 2D imaging of the clay sample was performed with both GE and X-Centric. In addition, a 2D T 2 ⁎ map was generated from eight X-Centric images taken at different echo times. The X-Centric pulse sequence was demonstrated to be an effective imaging method for short signal-lifetime samples, such as water trapped in bentonite clay. The ease of implementation, minimal diffusion-weighting and T 2 ⁎ weighting of the k-space centre, and considerable gains in signal-to-noise ratio and imaging efficiency position this pulse sequence as a viable alternative or complement to conventional GE acquisitions. Additionally, the short echo-time of the X-Centric pulse sequence allows it to be used effectively with non-proton MRI, including 23 Na and fluorinated gases (e.g., 19 F) where the T 2 ⁎ -decay is a potentially significant source of signal decay., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexei Ouriadov reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. James J. Noel reports financial support was provided by Ontario research fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Platelets display unexpected roles in immune and coagulation responses. Emerging evidence suggests that STING is implicated in hypercoagulation. STING is an adaptor protein downstream of the DNA sensor cyclic GMP-AMP synthase (cGAS) that is activated by cytosolic microbial and self-DNA during infections, and in the context of loss of cellular integrity, to instigate the production of type-I IFN and pro-inflammatory cytokines. To date, whether the cGAS-STING pathway is present in platelets and contributes to platelet functions is not defined. Using a combination of pharmacological and genetic approaches, we demonstrate here that megakaryocytes and platelets possess a functional cGAS-STING pathway. Our results suggest that in megakaryocytes, STING stimulation activates a type-I IFN response, and during thrombopoiesis, cGAS and STING are transferred to proplatelets. Finally, we show that both murine and human platelets contain cGAS and STING proteins, and the cGAS-STING pathway contributes to potentiation of platelet activation and aggregation. Taken together, these observations establish for the first time a novel role of the cGAS-STING DNA sensing axis in the megakaryocyte and platelet lineage., (© 2023 El-Mortada et al.)

Background: We investigated whether hypertension may be a mediator in the pathway linking environmental noise exposure to incident MI and stroke., Methods: Separately for MI and stroke, we built two population-based cohorts from linked health administrative data. Participants were residents of Montreal (Canada) between 2000 and 2014, aged 45 years and older who were free of hypertension and MI or stroke at time of entry. MI, stroke and hypertension were ascertained from validated case definitions. Residential long-term environmental noise exposure, expressed as the annual mean level acoustic equivalent 24 h (L Aeq24h ), was estimated from a land use regression model. We performed mediation analysis based on the potential outcomes framework. We used a Cox proportional hazards model for the exposure-outcome model and a logistic regression for the exposure-mediator model. In sensitivity analysis we applied a marginal structural approach to estimate the natural direct and indirect effects., Results: Each cohort included approximately 900 000 individuals, with 26 647 incident cases of MI and 16 656 incident cases of stroke. 36% of incident MI and 40% of incident stokes had previously developed hypertension. The estimated total effect per interquartile range increase (from 55.0 to 60.5 dB A) in the annual mean L Aeq24h was 1.073 (95% confidence interval (CI): 1.070-1.077) for both MI for stroke. We found no evidence of exposure-mediator interaction for both outcomes. The relationships between environmental noise and MI and stroke was not mediated by hypertension., Conclusions: This population-based cohort study suggests that the main route by which environmental noise exposure may cause MI or stroke is not through hypertension., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Multi-b diffusion-weighted hyperpolarized gas MRI measures pulmonary airspace enlargement using apparent diffusion coefficients (ADC) and mean linear intercepts ( L m Xe MRI using k-space undersampling. We evaluated multi-b (0, 12, 20, 30 s/cm 129 Xe MRI using k-space undersampling. We evaluated multi-b (0, 12, 20, 30 s/cm 2 ) diffusion-weighted 129 Xe ADC/morphometry estimates using a fully sampled and retrospectively undersampled k-space with two acceleration-factors (AF = 2 and 3) in never-smokers and ex-smokers with chronic obstructive pulmonary disease (COPD) or alpha-one anti-trypsin deficiency (AATD). For the three sampling cases, mean ADC/ L m values were not significantly different (all p s L m values were significantly different for the COPD subgroup (0.08 cm 2 s -1 /580 µm, AF = 3; all p < 0.001) as compared to never-smokers (0.05 cm 2 s -1 /300 µm, AF = 3). For never-smokers, mean differences of 7%/7% and 10%/7% were observed between fully sampled and retrospectively undersampled (AF = 2/AF = 3) ADC and L m values, respectively. For the COPD subgroup, mean differences of 3%/4% and 11%/10% were observed between fully sampled and retrospectively undersampled (AF = 2/AF = 3) ADC and L m , respectively. There was no relationship between acceleration factor with ADC or L m ( p = 0.9); voxel-wise ADC/ L m measured using AF = 2 and AF = 3 were significantly and strongly related to fully-sampled values (all p < 0.0001). Multi-b diffusion-weighted 129 Xe MRI is feasible using two different acceleration methods to measure pulmonary airspace enlargement using L m and ADC in COPD participants and never-smokers.

Magnetic Resonance Imaging (MRI) is dictated by the magnetization of the sample, and is thus a low-sensitivity imaging method. Inhalation of hyperpolarized (HP) noble gases, such as helium-3 and xenon-129, is a non-invasive, radiation-risk free imaging technique permitting high resolution imaging of the lungs and pulmonary functions, such as the lung microstructure, diffusion, perfusion, gas exchange, and dynamic ventilation. Instead of increasing the magnetic field strength, the higher spin polarization achievable from this method results in significantly higher net MR signal independent of tissue/water concentration. Moreover, the significantly longer apparent transverse relaxation time T 2 * of these HP gases at low magnetic field strengths results in fewer necessary radiofrequency (RF) pulses, permitting larger flip angles; this allows for high-sensitivity imaging of in vivo animal and human lungs at conventionally low (<0.5 T) field strengths and suggests that the low field regime is optimal for pulmonary MRI using hyperpolarized gases. In this review, theory on the common spin-exchange optical-pumping method of hyperpolarization and the field dependence of the MR signal of HP gases are presented, in the context of human lung imaging. The current state-of-the-art is explored, with emphasis on both MRI hardware (low field scanners, RF coils, and polarizers) and image acquisition techniques (pulse sequences) advancements. Common challenges surrounding imaging of HP gases and possible solutions are discussed, and the future of low field hyperpolarized gas MRI is posed as being a clinically-accessible and versatile imaging method, circumventing the siting restrictions of conventional high field scanners and bringing point-of-care pulmonary imaging to global facilities., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Alexei Ouriadov reports financial support was provided by Natural Sciences and Engineering Research Council of Canada.]., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Research often borrows on common yet somewhat unsubstantiated beliefs that unions influence inequality attitudes among unionized and nonunionized workers. This paper draws on inequality attitude data from the General Social Survey and state-level union data from the Current Population Survey and County Business Patterns between 1973 and 2016 to test this hypothesis. Linear probability, fixed-effects, and marginal structural models estimate that a large increase in state union density moderately increases workers' support for reducing income inequality by three to 12 percentage points. Findings lend some empirical support for the capacity of unions to influence redistributive policy and market attitudes., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Southern Sociological Society 2022.)

Background: Noise has been related to several cardiovascular diseases (CVDs) such as coronary heart disease and to their risk factors such as hypertension, but associations with stroke remain under-researched, even if CVD likely share similar pathophysiologic mechanisms., Aim: The objective of the study was to examine the association between long-term residential exposure to total environmental noise and stroke incidence in Montreal, Canada., Materials and Methods: We created an open cohort of adults aged ≥45years, free of stroke before entering the cohort for the years 2000 to 2014 with health administrative data. Residential total environmental noise levels were estimated with land use regression (LUR) models. Incident stroke was based on hospital admissions. Cox hazard models with age as the time axis and time-varying exposures were used to estimate associations, which were adjusted for material deprivation, year, nitrogen dioxide, stratified for sex, and indirectly adjusted for smoking., Results: There were 9,072,492 person-years of follow-up with 47% men; 26,741 developed stroke (21,402 ischemic; 4947 hemorrhagic; 392 had both). LUR total noise level acoustic equivalent for 24 hours (LAeq24h) ranged 44 to 79 dBA. The adjusted hazard ratio (HR) for stroke (all types), for a 10-dBA increase in LAeq24h, was 1.06 [95% confidence interval (CI): 1.03-1.09]. The LAeq24h was associated with ischemic (HR per 10 dBA: 1.08; 95% CI: 1.04-1.12) but not hemorrhagic stroke (HR per 10 dBA: 0.97; 95% CI: 0.90-1.04)., Conclusion: The results suggest that total environmental noise is associated with incident stroke, which is consistent with studies on transportation noise and other CVD., Competing Interests: None

Inhaled hyperpolarized 129 Xe MRI is a non-invasive and radiation risk free lung imaging method, which can directly measure the business unit of the lung where gas exchange occurs: the alveoli and acinar ducts (lung function). Currently, three imaging approaches have been demonstrated to be useful for hyperpolarized 129 Xe MR in lungs: Fast Gradient Recalled Echo (FGRE), Radial Projection Reconstruction (PR), and spiral/cones. Typically, non-Cartesian acquisitions such as PR and spiral/cones require specific data post-processing, such as interpolating, regridding, and density-weighting procedures for image reconstruction, which often leads to smoothing effects and resolution degradation. On the other hand, Cartesian methods such as FGRE are not short-echo time (TE) methods; they suffer from imaging gradient-induced diffusion-weighting of the k-space center, and employ a significant number of radio-frequency (RF) pulses. Due to the non-renewable magnetization of the hyperpolarized media, the use of a large number of RF pulses (FGRE/PR) required for full k-space coverage is a significant limitation, especially for low field (<0.5 T) hyperpolarized gas MRI. We demonstrate an ultra-fast, purely frequency-encoded, Cartesian pulse sequence called Frequency-Encoding Sectoral (FES), which takes advantage of the long T 2 * of hyperpolarized 129 Xe gas at low field strength (0.074 T). In contrast to PR/FGRE, it uses a much smaller number of RF pulses, and consequently maximizes image Signal-to-Noise Ratio (SNR) while shortening acquisition time. Additionally, FES does not suffer from non-uniform T 2 * decay leading to image blurring; a common issue with interleaved spirals/cones. The Cartesian k-space coverage of the proposed FES method does not require specific k-space data post-processing, unlike PR/FGRE and spiral/cones methods. Proton scans were used to compare the FES sequence to both FGRE and Phase Encoding Sectoral, in terms of their SNR values and imaging efficiency estimates. Using FES, proton and hyperpolarized 129 Xe images were acquired from a custom hollow acrylic phantom (0.04L) and two normal rats ( 129 Xe only), utilizing both single-breath and multiple-breath schemes. For the 129 Xe phantom images, the apparent diffusion coefficient, T 1 , and T 2 * relaxation maps were acquired and generated. Blurring due to the T 2 * decay and B 0 field variation were simulated to estimate dependence of the image resolution on the duration of the data acquisition windows (i.e. sector length), and temperature-induced resonance frequency shift from the low field magnet hardware., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the accuracy of INTERGROWTH-21 (IG-21) versus Hadlock1 formulae for birth weight prediction on third-trimester ultrasound in a North American population., Methods: This single-centre retrospective cohort study included all pregnant patients who had a third-trimester ultrasound between 34 0 and 36 6 weeks gestation and delivered a term singleton at our maternal-fetal medicine reference centre between April 1 and July 30, 2019. Estimated ultrasound fetal weight was calculated with both Hadlock1 and IG-21 formulae for each fetus, then reported on a centile curve to adjust for gestational age at delivery, and compared with the actual birth weight., Results: The cohort included 600 women. The IG-21 formula had a comparable accuracy to Hadlock1 with mean absolute percentage errors (MAPEs) of 8.64 and 8.86, respectively (P = 0.191). Success rate, defined by a <10% discrepancy range of the actual birth weight, was significantly higher for IG-21 than for Hadlock1 (67.5% vs. 64.3%; P = 0.044)., Conclusion: Our results do not support the superiority of IG-21 to Hadlock1. There is a need for continued research to improve birth weight prediction with the ultimate objective of increasing the detection of small for gestation age and macrosomic fetuses., (Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular effects of environmental noise are a growing concern. However, the evidence remains largely limited to the association between road traffic noise and hypertension and coronary heart diseases., Objectives: To investigate the association between long-term residential exposure to environmental/transportation noise and the incidence of myocardial infarction (MI) in the adult population living in Montreal., Methods: An open cohort of adults aged 45 years old and over, living on the island of Montreal and free of MI before entering the cohort was created for the years 2000-2014 with the Quebec Integrated Chronic Disease Surveillance System; a systematic surveillance system from the Canadian province of Quebec starting in 1996. Residential noise exposure was calculated in three ways: 1) total ambient noise levels estimated by Land use regression (LUR) models; 2) road traffic noise estimated by a noise propagation model CadnaA and 3) distances to transportation sources (roads, airport, railways). Incident MI was based on diagnostic codes in hospital admission records. Cox models with time-varying exposures (age as the time axis) were used to estimate the associations with various adjustments (material deprivation indicator, calendar year, nitrogen dioxide, stratification for sex). Indirect adjustment based on ancillary data for smoking was performed., Results: 1,065,414 individuals were followed (total of 9,000,443 person-years) and 40,718 (3.8%) developed MI. We found positive associations between total environmental noise, estimated by LUR models and the incidence of MI. Total noise LUR levels ranged from ~44 to ~79 dBA and varied slightly with the metric used. The adjusted hazard ratios (HRs) (also adjusted for smoking) were 1.12 (95% Confidence Intervals [CI]: 1.08-1.15), 1.11 (95%CI: 1.07-1.14) and 1.10 (95%CI: 1.06-1.14) per 10 dBA noise levels increase respectively in Level Accoustic equivalent 24 h (LAeq24 h), Level day-evening-night (Lden) and night level (Lnight). We found a borderline negative association between road noise levels estimated with CadnaA and MI (HR: 0.99 per 10 dBA; 95%CI: 0.98-1.00). Distances to major roads and highways were not associated with MI while the proximity to railways was positively associated with MI (HR for ≤100 vs > 1000 m: 1.07; 95%CI: 1.01-1.14). A negative association was found with the proximity to the airport noise exposure forecast (NEF25); HR (<1 vs >1000 m) = 0.88 (95%CI: 0.81-0.96)., Conclusions: These associations suggest that exposure to total environmental noise at current urban levels may be related to the incidence of MI. Additional studies with more accurate road noise estimates are needed to explain the counterintuitive associations with road noise and specific transportation sources., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Objectives: Since 2004, the Montreal heat response plan (MHRP) has been developed and implemented on the Island of Montreal to reduce heat-related health effects in the general population. In this paper, we aimed to assess the barriers and facilitators to implementation of the MHRP and evaluate the awareness of key elements of the plan by healthcare professionals and individuals from vulnerable populations., Methods: Data were gathered from monitoring reports and a questionnaire administered to managers of healthcare institutions and healthcare workers in Montreal-area health and social services institutions. Individual interviews and focus groups with healthcare workers and with individuals with schizophrenia or suffering from drug or alcohol dependencies were performed. Data were categorized according to predefined subthemes. Coding matrices were then used to determine the most frequently occurring elements in the subthemes., Results: Our results indicate that actions are progressively implemented each year in the healthcare network. Intensification of surveillance for signs of heat-related illness is the most frequently reported measure. Identification and prioritization of clientele and homecare patients are identified as a challenge, as is ensuring the availability of sufficient personnel during a heat wave. Analysis of practice and awareness in healthcare professionals reveals that preventive measures are known and applied by the personnel. Individuals from vulnerable population groups were not uniformly aware of preventive measures, and consequently, variability was observed in their application., Conclusion: The framework proposed in this study revealed valuable information that can be useful to improve plans aimed at reducing heat-related health effects in the population.

Background: Heart disease is a leading cause of morbidity and mortality in women. To date, the majority of knowledge regarding heart disease is based on research conducted in men. As a result, a male-oriented model of heart disease constitutes the basis for diagnostic and therapeutic strategies for both sexes. This article reports findings from the first survey of Canadian physicians to examine their knowledge, beliefs, and practices regarding heart disease in women., Materials and Methods: This cross-sectional survey, adapted from an instrument used in the United States, was undertaken in the spring of 2015. A sample of 504 physicians from a randomly selected sample of online responses was produced., Results: Overall, physician responses demonstrate a general lack of awareness regarding the prevalence and approaches to the identification of, and treatments for, heart disease in women. In addition, physicians did not provide high ratings of their own effectiveness in supporting female patients to prevent or manage heart disease. The barriers that physicians face and the strategies to support them in improving women's heart health were explored., Conclusions: There is a clear need to educate physicians about heart disease in women and its prevention and management. More female-specific research, prevention, and clinical programs will enhance our ability to significantly improve cardiovascular health in Canadian women.

Diesel exhaust (DE) emissions from a parking garage located in the basement of a school were characterized during spring and winter using direct reading devices and integrated sampling methods. Concentrations of CO and NO 2 were evaluated using electrochemical sensors and passive colorimetric tubes, respectively. Elemental and total carbon concentrations were measured using the NIOSH 5040 method. Particle number concentrations (PNCs), respirable particulate matter (PM resp ) mass concentrations, and size distributions were evaluated using direct reading devices. Indoor concentrations of elemental carbon, PNC, CO, and NO 2 showed significant seasonal variation; concentrations were much higher during winter (p < 0.01). Concentrations of the PM resp and total carbon did not show significant seasonal variation. Pearson correlation coefficients were 0.9 (p < 0.01) and 0.94 (p < 0.01) between the parking garage and ground floor average daily PNCs, and between the parking garage and first floor average daily PNCs, respectively. Since DE is the main identified source of fine and ultrafine particles in the school, these results suggest that DE emissions migrate from the parking garage into the school. Our results highlight the relevance of direct reading instruments in identifying migration of contaminants and suggest that monitoring PNC is a more specific way of assessing exposure to DE than monitoring the common PM resp fraction.

The availability of noise maps to assess exposure to noise is often limited, especially in North American cities. We developed land use regression (LUR) models for LA eq24h , L night , and L den to assess the long-term spatial variability of environmental noise levels in Montreal, Canada, considering various transportation noise sources (road, rail, and air). To explore the effects of sampling duration, we compared our LA eq24h levels that were computed over at least five complete contiguous days of measurements to shorter sampling periods (20 min and 24 h). LUR models were built with General Additive Models using continuous 2-min noise measurements from 204 sites. Model performance (adjusted R 2 ) was 0.68, 0.59, and 0.69 for LA eq24h , L night , and L den , respectively. Main predictors of measured noise levels were road-traffic and vegetation variables. Twenty-minute non-rush hour measurements corresponded well with LA eq24h levels computed over 5 days at road-traffic sites (bias: -0.7 dB(A)), but not at rail (-2.1 dB(A)) nor at air (-2.2 dB(A)) sites. Our study provides important insights into the spatial variation of environmental noise levels in a Canadian city. To assess long-term noise levels, sampling strategies should be stratified by noise sources and preferably should include 1 week of measurements at locations exposed to rail and aircraft noise.

The objective of our study was to measure the impact of transportation-related noise and total environmental noise on sleep disturbance for the residents of Montreal, Canada. A telephone-based survey on noise-related sleep disturbance among 4336 persons aged 18 years and over was conducted. LNight for each study participant was estimated using a land use regression (LUR) model. Distance of the respondent's residence to the nearest transportation noise source was also used as an indicator of noise exposure. The proportion of the population whose sleep was disturbed by outdoor environmental noise in the past 4 weeks was 12.4%. The proportion of those affected by road traffic, airplane and railway noise was 4.2%, 1.5% and 1.1%, respectively. We observed an increased prevalence in sleep disturbance for those exposed to both rail and road noise when compared for those exposed to road only. We did not observe an increased prevalence in sleep disturbance for those that were both exposed to road and planes when compared to those exposed to road or planes only. We developed regression models to assess the marginal proportion of sleep disturbance as a function of estimated LNight and distance to transportation noise sources. In our models, sleep disturbance increased with proximity to transportation noise sources (railway, airplane and road traffic) and with increasing LNight values. Our study provides a quantitative estimate of the association between total environmental noise levels estimated using an LUR model and sleep disturbance from transportation noise.

There is a lack of studies assessing the exposure-response relationship between transportation noise and annoyance in North America. Our aims were to investigate the prevalence of noise annoyance induced by road traffic, trains and airplanes in relation to distance to transportation noise sources, and to total environmental noise levels in Montreal, Canada; annoyance was assessed as noise-induced disturbance. A telephone-based survey among 4336 persons aged >18 years was conducted. Exposure to total environmental noise (A-weighted outdoor noise levels-LAeq24h and day-evening-night equivalent noise levels-Lden) for each study participant was determined using a statistical noise model (land use regression-LUR) that is based on actual outdoor noise measurements. The proportion of the population annoyed by road traffic, airplane and train noise was 20.1%, 13.0% and 6.1%, respectively. As the distance to major roads, railways and the Montreal International Airport increased, the percentage of people disturbed and highly disturbed due to the corresponding traffic noise significantly decreased. When applying the statistical noise model we found a relationship between noise levels and disturbance from road traffic and total environmental noise, with Prevalence Proportion Ratios (PPR) for highly disturbed people of 1.10 (95% CI: 1.07-1.13) and 1.04 (1.02-1.06) per 1 dB(A) Lden, respectively. Our study provides the first comprehensive information on the relationship between transportation noise levels and disturbance in a Canadian city. LUR models are still in development and further studies on transportation noise induced annoyance are consequently needed, especially for sources other than road traffic.

Background: This study's objective was to determine whether socioeconomically deprived populations are exposed to greater levels of environmental noise., Methods: Indicators of socioeconomic status were correlated with LAeq24h noise levels estimated with a land-use regression model at a small geographic scale., Results: We found that noise exposure was associated with all socioeconomic indicators, with the strongest correlations found for median household income, proportion of people who spend over 30% of their income on housing, proportion of people below the low income boundary and with a social deprivation index combining several socio-economic variables., Conclusion: Our results were inconsistent with a number of studies performed elsewhere, indicating that locally conducted studies are imperative to assessing whether this double burden of noise exposure and low socioeconomic status exists in other contexts. The primary implication of our study is that noise exposure represents an environmental injustice in Montreal, which is an issue that merits both investigation and concern.

The Aurora family of serine/threonine kinases is essential for mitosis. Their crucial role in cell cycle regulation and aberrant expression in a broad range of malignancies have been demonstrated and have prompted intensive search for small molecule Aurora inhibitors. Indeed, over 10 of them have reached the clinic as potential anticancer therapies. We report herein the discovery and optimization of a novel series of tricyclic molecules that has led to SAR156497, an exquisitely selective Aurora A, B, and C inhibitor with in vitro and in vivo efficacy. We also provide insights into its mode of binding to its target proteins, which could explain its selectivity.

Background: Heart disease is a leading cause of morbidity and mortality in men and women. Our understanding of heart disease stems chiefly from clinical trials on men, but key features of the disease differ in women. This article reports findings from the first Canadian national survey of women that focuses on knowledge, perceptions, and lifestyle related to heart health., Methods: A cross-country survey using an adaptation of an instrument used in the United States was undertaken in spring of 2013. Based on online (208) and telephone (1446) responses from a randomly selected sample of women aged 25 or older, a total sample of 1654 weighted percentage estimates were produced. The overall response rate was 12.5%., Results: Just under half of women were able to name smoking as a risk factor of heart disease, and less than one quarter named hypertension or high cholesterol. Fewer than half of women knew the major symptoms of heart disease. Most women prefer to receive information on heart health from their doctor, but only slightly more than half report that their doctor includes discussion of prevention and lifestyle during clinical consultations., Conclusions: Most women lack knowledge of heart disease symptoms and risk factors, and significant proportions are unaware of their own risk status. The findings underscore the opportunity for patient education and intervention regarding risk and prevention of heart disease., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Compelling molecular biology publications have reported the implication of phosphoinositide kinase PI3Kβ in PTEN-deficient cell line growth and proliferation. These findings supported a scientific rationale for the development of PI3Kβ-specific inhibitors for the treatment of PTEN-deficient cancers. This paper describes the discovery of 2-[2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (7) and the optimization of this new series of active and selective pyrimidone indoline amide PI3Kβ inhibitors. 2-[2-(2-Methyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (28), identified following a carefully designed methyl scan, displayed improved physicochemical and in vitro pharmacokinetic properties. Structural biology efforts enabled the acquisition of the first X-ray cocrystal structure of p110β with the selective inhibitor compound 28 bound to the ATP site. The nonplanar binding mode described herein is consistent with observed structure-activity relationship for the series. Compound 28 demonstrated significant in vivo activity in a UACC-62 xenograft model in mice, warranting further preclinical investigation. Following successful development, compound 28 entered phase I/Ib clinical trial in patients with advanced cancer.

Objectives: This review assessed the confounding effect of one traffic-related exposure (noise or air pollutants) on the association between the other exposure and cardiovascular outcomes., Methods: A systematic review was conducted with the databases Medline and Embase. The confounding effects in studies were assessed by using change in the estimate with a 10 % cutoff point. The influence on the change in the estimate of the quality of the studies, the exposure assessment methods and the correlation between road noise and air pollutions were also assessed., Results: Nine publications were identified. For most studies, the specified confounders produced changes in estimates <10 %. The correlation between noise and pollutants, the quality of the study and of the exposure assessment do not seem to influence the confounding effects., Conclusions: Results from this review suggest that confounding of cardiovascular effects by noise or air pollutants is low, though with further improvements in exposure assessment, the situation may change. More studies using pollution indicators specific to road traffic are needed to properly assess if noise and air pollution are subjected to confounding.

Objectives: We investigated whether the installation of a suicide prevention barrier on Jacques-Cartier Bridge led to displacement of suicides to other jumping sites on Montréal Island and Montérégie, Québec, the 2 regions it connects., Methods: Suicides on Montréal Island and Montérégie were extracted from chief coroners' records. We used Poisson regression to assess changes in annual suicide rates by jumping from Jacques-Cartier Bridge and from other bridges and other sites and by other methods before (1990-June 2004) and after (2005-2009) installation of the barrier., Results: Suicide rates by jumping from Jacques-Cartier Bridge decreased after installation of the barrier (incidence rate ratio [IRR] = 0.24; 95% confidence interval [CI] = 0.13, 0.43), which persisted when all bridges (IRR = 0.39; 95% CI = 0.27, 0.55) and all jumping sites (IRR = 0.66; 95% CI = 0.54, 0.80) in the regions were considered., Conclusions: Little or no displacement to other jumping sites may occur after installation of a barrier at an iconic site such as Jacques-Cartier Bridge. A barrier's design is important to its effectiveness and should be considered for new bridges with the potential to become symbolic suicide sites.

Patient: Male, 62., Final Diagnosis: Bipolar disorder., Symptoms: Bordeline personality disorder., Medication: -, Clinical Procedure: Bed bug infestation., Specialty: Psychiatry., Objective: Unusual clinical course., Background: In the past decade, bed bug infestations have been increasingly common in high income countries. Psychological consequences of these infestations are rarely examined in the scientific literature., Case Report: We present a case, based on a coroner's investigation report, of a woman with previous psychiatric morbidity who jumped to her death following repeated bed bug infestations in her apartment. Our case report shows that the bed bug infestations were the likely trigger for the onset a negative psychological state that ultimately led to suicide., Conclusions: Given the recent surge in infestations, rapid action needs to be taken not only in an attempt to control and eradicate the bed bugs but also to adequately care for those infested by bed bugs.

Objectives: The objective of this paper is to describe Montreal's heat response plan and its application during the July 2010 heat wave., Participants and Setting: The Montreal heat response plan is designed to ensure the surveillance of weather and health indicators during the summer season and to coordinate actions to be undertaken during this period to reduce morbidity and mortality due to heat, particularly when weather thresholds are reached or an increase in health indicators is observed. It was developed to coordinate and apply intervention measures on the Island of Montreal and has been in effect since 2004., Intervention: In the beginning of July 2010, Montreal experienced a heat wave that lasted 5 days. During this period, health indicators such as total mortality, prehospital emergency transports, calls to the health information line and hospital admissions were monitored by the Montreal public health surveillance system. The decision to implement emergency interventions and actions performed by regional and local public health and municipal partners (intervention level) was made following attainment of a predetermined weather threshold and increases in health indicators. The significant increase in daily observed mortality from all causes and in particular people dying at home or in the community prompted the Director of public health to conduct a chart review of all people deceased from July 5 to July 11, 2010 to determine cause of death and underlying health conditions., Outcome: During the heat wave, there were 304 reported deaths from all causes in Montreal residents, of which 106 were probably or possibly heat-related. Major underlying health conditions in heat-related deaths included cardiovascular problems and mental health illness. Furthermore, in the case of people with mental illness who died during the heat wave, the chart review revealed that many were contacted 24 hours prior to their death by health care professionals, family members, neighbours or friends., Conclusion: Following the 2010 heat wave, the Montreal heat response plan and heat surveillance system were updated to include initiatives to better communicate preventive measures to the vulnerable populations and to intervene earlier during a heat wave.

Objective: To share four Canadian cities' experiences with bed bug infestations and to explore public health roles in managing them., Methods: We summarize presentations from a workshop at the 2010 Canadian Public Health Association Conference which examined the re-emergence of bed bugs in Canada and compared management approaches of municipal and public health authorities in four large Canadian cities. We include updates on their activities since the workshop., Results: Cities across Canada have observed an increase in complaints of bed bug infestations over recent years. Toronto Public Health considers bed bugs to be a threat to health and has been heavily involved in the front-line response to bed bug complaints. In Winnipeg, Montreal and Vancouver, city inspectors are responsible for investigating complaints, and public health plays a supporting or secondary role. We identified factors that may contribute to successful management of bed bugs: sufficient funding, partnerships among many stakeholders, training and education, and surveillance and evaluation., Conclusion: Various public health agencies in Canadian cities have played key roles in the fight against bed bugs through new initiatives, education, and encouragement and support for others. By working with the public, owners, tenants, the health sector and other stakeholders, public health practitioners can begin to curb the resurgence of bed bugs and the social strains associated with them.

From a HTS campaign, a new series of pyrimidone anilides exemplified by compound 1 has been identified with good inhibitory activity for the PI3Kβ isoform. The structure of compound 1 in PI3Kγ was solved revealing a binding mode in agreement with the SAR observed on PI3Kβ. These compounds displayed inhibition in the nanomolar range in the biochemical assay and were also potent p-Akt inhibitors in a PTEN-deficient PC3 prostate cancer cell line. Optimization of in vitro pharmocokinetic properties led to compound 25 exhibiting 52% bioavailability in mice and target engagement in an acute PK/PD study., (Copyright © 2012 Elsevier Ltd. All rights reserved.)