A fully autonomous ozone, aerosol and nighttime water vapor lidar: a synergistic approach to profiling the atmosphere in the Canadian oil sands region

Lidar technology has been rapidly advancing over the past several decades. It can be used to measure a variety of atmospheric constituents at very high temporal and spatial resolutions. While the number of lidars continues to increase worldwide, there is generally a dependency on an operator, particularly for high-powered lidar systems. Environment and Climate Change Canada (ECCC) has recently developed a fully autonomous, mobile lidar system called AMOLITE (Autonomous Mobile Ozone Lidar Instrument for Tropospheric Experiments) to simultaneously measure the vertical profile of tropospheric ozone, aerosol and water vapor (nighttime only) from near the ground to altitudes reaching 10 to 15&thinsp;km. This current system uses a dual-laser, dual-lidar design housed in a single climate-controlled trailer. Ozone profiles are measured by the differential absorption lidar (DIAL) technique using a single 1&thinsp;m Raman cell filled with CO2. The DIAL wavelengths of 287 and 299&thinsp;nm are generated as the second and third Stokes lines resulting from stimulated Raman scattering of the cell pumped using the fourth harmonic of a Nd:YAG laser (266&thinsp;nm). The aerosol lidar transmits three wavelengths simultaneously (355, 532 and 1064&thinsp;nm) employing a detector designed to measure the three backscatter channels, two nitrogen Raman channels (387 and 607&thinsp;nm) and one cross-polarization channel at 355&thinsp;nm. In addition, we added a water vapor channel arising from the Raman-shifted 355&thinsp;nm output (407&thinsp;nm) to provide nighttime water vapor profiles. AMOLITE participated in a validation experiment alongside four other ozone DIAL systems before being deployed to the ECCC Oski-ôtin ground site in the Alberta oil sands region in November 2016. Ozone was found to increase throughout the troposphere by as much as a factor of 2 from stratospheric intrusions. The dry stratospheric air within the intrusion was measured to be less than 0.2&thinsp;g&thinsp;kg−1. A biomass burning event that impacted the region over an 8-day period produced lidar ratios of 35 to 65&thinsp;sr at 355&thinsp;nm and 40 to 100&thinsp;sr at 532. Over the same period the Ångström exponent decreased from 1.56±0.2 to 1.35±0.2 in the 2–4&thinsp;km smoke region.</p

Trehalose-6-phosphate-mediated toxicity determines essentiality of OtsB2 in Mycobacterium tuberculosis in vitro and in mice

Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA and T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose and glucose-6-phosphate. In order to assess the drug target potential of T6P phosphatase, we generated a conditional mutant of M. tuberculosis allowing the regulated gene silencing of the T6P phosphatase gene otsB2. We found that otsB2 is essential for growth of M. tuberculosis in vitro as well as for the acute infection phase in mice following aerosol infection. By contrast, otsB2 is not essential for the chronic infection phase in mice, highlighting the substantial remodelling of trehalose metabolism during infection by M. tuberculosis. Blocking OtsB2 resulted in the accumulation of its substrate T6P, which appears to be toxic, leading to the self-poisoning of cells. Accordingly, blocking T6P production in a ΔotsA mutant abrogated otsB2 essentiality. T6P accumulation elicited a global upregulation of more than 800 genes, which might result from an increase in RNA stability implied by the enhanced neutralization of toxins exhibiting ribonuclease activity. Surprisingly, overlap with the stress response caused by the accumulation of another toxic sugar phosphate molecule, maltose-1-phosphate, was minimal. A genome-wide screen for synthetic lethal interactions with otsA identified numerous genes, revealing additional potential drug targets synergistic with OtsB2 suitable for combination therapies that would minimize the emergence of resistance to OtsB2 inhibitors

Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)

Background: The efficacy of infliximab and ciclosporin in treating severe ulcerative colitis (UC) is proven, but there has been no comparative evaluation of effectiveness. Objective: To compare the clinical effectiveness and cost-effectiveness of infliximab and ciclosporin in treating steroid-resistant acute severe UC. Method: Between May 2010 and February 2013 we recruited 270 participants from 52 hospitals in England, Scotland and Wales to an open-label parallel-group, pragmatic randomised trial. Consented patients admitted with severe colitis completed baseline quality-of-life questionnaires before receiving intravenous hydrocortisone. If they failed to respond within about 5 days, and met other inclusion criteria, we invited them to participate and used a web-based adaptive randomisation algorithm to allocate them in equal proportions between 5 mg/kg of intravenous infliximab at 0, 2 and 6 weeks or 2 mg/kg/day of intravenous ciclosporin for 7 days followed by 5.5 mg/kg/day of oral ciclosporin until 12 weeks from randomisation. Further treatment was at the discretion of physicians responsible for clinical management. The primary outcome was quality-adjusted survival (QAS): the area under the curve (AUC) of scores derived from Crohn’s and Ulcerative Colitis Questionnaires completed by participants at 3 and 6 months, and then 6-monthly over 1–3 years, more frequently after surgery. Secondary outcomes collected simultaneously included European Quality of Life-5 Dimensions (EQ-5D) scores and NHS resource use to estimate cost-effectiveness. Blinding was possible only for data analysts. We interviewed 20 trial participants and 23 participating professionals. Funded data collection finished in March 2014. Most participants consented to complete annual questionnaires and for us to analyse their routinely collected health data over 10 years. Results: The 135 participants in each group were well matched at baseline. In 121 participants analysed in each group, we found no significant difference between infliximab and ciclosporin in QAS [mean difference in AUC/day 0.0297 favouring ciclosporin, 95% confidence interval (CI) –0.0088 to 0.0682; p = 0.129]; EQ-5D scores (quality-adjusted life-year mean difference 0.021 favouring ciclosporin, 95% CI –0.032 to 0.096; p = 0.350); Short Form questionnaire-6 Dimensions scores (mean difference 0.0051 favouring ciclosporin, 95% CI –0.0250 to 0.0353; p = 0.737). There was no statistically significant difference in colectomy rates [odds ratio (OR) 1.350 favouring infliximab, 95% CI 0.832 to 2.188; p = 0.223]; numbers of serious adverse reactions (event ratio = 0.938 favouring ciclosporin, 95% CI 0.590 to 1.493; p = 0.788); participants with serious adverse reactions (OR 0.660 favouring ciclosporin, 95% CI 0.282 to 1.546; p = 0.338); numbers of serious adverse events (event ratio 1.075 favouring infliximab, 95% CI 0.603 to 1.917; p = 0.807); participants with serious adverse events (OR 0.999 favouring infliximab, 95% CI 0.473 to 2.114; p = 0.998); deaths (all three who died received infliximab; p = 0.247) or concomitant use of immunosuppressants. The lower cost of ciclosporin led to lower total NHS costs (mean difference –£5632, 95% CI –£8305 to –£2773; p < 0.001). Interviews highlighted the debilitating effect of UC; participants were more positive about infliximab than ciclosporin. Professionals reported advantages and disadvantages with both drugs, but nurses disliked the intravenous ciclosporin. Conclusions: Total cost to the NHS was considerably higher for infliximab than ciclosporin. Nevertheless, there was no significant difference between the two drugs in clinical effectiveness, colectomy rates, incidence of SAEs or reactions, or mortality, when measured 1–3 years post treatment. To assess long-term outcome participants will be followed up for 10 years post randomisation, using questionnaires and routinely collected data. Further studies will be needed to evaluate the efficacy and effectiveness of new anti-tumour necrosis factor drugs and formulations of ciclosporin.322 page(s

Validation of the TOLNet lidars: the Southern California Ozone Observation Project (SCOOP)

The North America-based Tropospheric Ozone Lidar Network (TOLNet) was recently established to provide high spatiotemporal vertical profiles of ozone, to better understand physical processes driving tropospheric ozone variability and to validate the tropospheric ozone measurements of upcoming spaceborne missions such as Tropospheric Emissions: Monitoring Pollution (TEMPO). The network currently comprises six tropospheric ozone lidars, four of which are mobile instruments deploying to the field a few times per year, based on campaign and science needs. In August 2016, all four mobile TOLNet lidars were brought to the fixed TOLNet site of JPL Table Mountain Facility for the 1-week-long Southern California Ozone Observation Project (SCOOP). This intercomparison campaign, which included 400&thinsp;h of lidar measurements and 18 ozonesonde launches, allowed for the unprecedented simultaneous validation of five of the six TOLNet lidars. For measurements between 3 and 10&thinsp;km&thinsp;a.s.l., a mean difference of 0.7&thinsp;ppbv (1.7&thinsp;%), with a root-mean-square deviation of 1.6&thinsp;ppbv or 2.4&thinsp;%, was found between the lidars and ozonesondes, which is well within the combined uncertainties of the two measurement techniques. The few minor differences identified were typically associated with the known limitations of the lidars at the profile altitude extremes (i.e., first 1&thinsp;km above ground and at the instruments' highest retrievable altitude). As part of a large homogenization and quality control effort within the network, many aspects of the TOLNet in-house data processing algorithms were also standardized and validated. This thorough validation of both the measurements and retrievals builds confidence as to the high quality and reliability of the TOLNet ozone lidar profiles for many years to come, making TOLNet a valuable ground-based reference network for tropospheric ozone profiling.</p

Environnement alimentaire de la vente au détail et expériences de magasinage dans les collectivités des Premières nations du nord des provinces

Introduction : Cet article porte sur l'environnement de la vente d’aliments dans les collectivités des Premières nations du nord des provinces, en particulier sur la concurrence éventuelle dans la vente au détail de la North West Company (NWC) ainsi que sur les expériences d'achats alimentaires de la population vivant dans le Nord canadien. Méthodologie : Nous avons utilisé deux méthodologies pour évaluer l’environnement alimentaire de la vente au détail dans le Nord. D’abord, nous avons cartographié les détaillants en alimentation du Nord afin d’examiner le degré de concurrence au détail dans les régions nordiques, en prêtant une attention particulière aux collectivités qui ne sont pas accessibles à l’année par la route. Ensuite, nous avons enquêté auprès des personnes vivant dans les collectivités du Nord canadien à propos de leurs expériences d’achat au détail et de magasinage. Résultats : Cinquante‑quatre pour cent des collectivités du nord des provinces et du Grand Nord n’avaient aucune épicerie en concurrence avec la NWC. Les provinces comptant les plus fortes proportions de collectivités nordiques sans concurrence dans la vente au détail étaient l’Ontario (87 %), la Saskatchewan (83 %) et le Manitoba (72 %). Les participants au sondage (n = 92) ont fait état de leurs préoccupations quant à leurs expériences d'achat dans trois grands secteurs : le coût des aliments, la qualité et la fraîcheur des aliments et la disponibilité de certains aliments. Conclusion : La concurrence dans la vente au détail est limitée dans le nord des provinces. Au Manitoba, en Saskatchewan et en Ontario, la NWC ne fait face à aucune concurrence dans au moins 70 % des collectivités nordiques. Les consommateurs du Nord canadien considèrent que les aliments nutritifs sont peu abordables, et ils souhaitent avoir accès à un plus grand choix d’aliments périssables en bon état

Retail food environments, shopping experiences, First Nations and the provincial Norths

Introduction: This paper looks at the market food environments of First Nations communities located in the provincial Norths by examining the potential retail competition faced by the North West Company (NWC) and by reporting on the grocery shopping experiences of people living in northern Canada. Methods: We employed two methodological approaches to assess northern retail food environments. First, we mapped food retailers in the North to examine the breadth of retail competition in the provincial Norths, focussing specifically on those communities without year-round road access. Second, we surveyed people living in communities in northern Canada about their retail and shopping experiences. Results: Fifty-four percent of communities in the provincial Norths and Far North without year-round road access did not have a grocery store that competed with the NWC. The provinces with the highest percentage of northern communities without retail competition were Ontario (87%), Saskatchewan (83%) and Manitoba (72%). Respondents to the survey (n = 92) expressed concern about their shopping experiences in three main areas: the cost of food, food quality and freshness, and availability of specific foods. Conclusion: There is limited retail competition in the provincial Norths. In Manitoba, Saskatchewan and Ontario, the NWC has no store competition in at least 70% of northern communities. Consumers living in northern Canada find it difficult to afford nutritious foods and would like access to a wider selection of perishable foods in good condition