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In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
The Institute of Health Economics offers a suite of analyses that provide developers an understanding of the expected commercial viability of an early stage health technology. In combination, these analyses form the Value-Engineered Translation framework. These methods incorporate innovative methods to manage uncertainty in early economic evaluations, in particular, moving beyond current stochastic assessments of headroom to account for inter-market variability in value hurdles, as well as incorporating social value premia considerations. An illustration of these methods is demonstrated using the example of a non-invasive diagnostic test (called DCRSHP) at an early stage of development, compared to current practice of cystoscopy in the diagnosis of bladder cancer.
Competing technologies were identified to inform the headroom assessment based on price and effectiveness. Then, a model-based cost-effectiveness analysis was undertaken incorporating headroom analysis, stochastic one-way sensitivity analysis, and value of information analysis using data from secondary sources.
Currently there are a number of non-invasive tests available, but none have sufficient test accuracy to be suitable for bladder cancer diagnosis alone. From the headroom analysis, DCRSHP can be priced at up to CAD 790 (i.e. USD 588) and still be cost-effective compared to the current practice of cystoscopy. Interestingly this price can be increased for patient groups that have lower levels of bladder cancer prevalence.
The requirements of economic evaluations depend on the stage of technology development, and analysis approaches must reflect this. The results here indicate that DCRSHP clears the value hurdle in terms of being cost-effective, and thus provides the opportunity to make a commercial return on future investment. Future analysis of DCRSHP could consider the cost drivers for development of the technology, including the regulatory pathways, costs associated with the intellectual asset management for the technology, and alternative manufacturing costs. All of which contribute to the research-to-practice continuum.
Both elevated blood pressure and/or depression increase the risk of cardiovascular disease and mortality. This study in treated elderly hypertensive patients explored the incidence of depression, its association (pre-existing and incident) with mortality and predictors of incident depression.
Data from 6,083 hypertensive patients aged ≥65 years enrolled in the Second Australian National Blood Pressure study were used. Participants were followed for a median of 10.8 years (including 4.1 years in-trial) and classified into: “no depression,” “pre-existing” and “incident” depression groups based on either being “diagnosed with depressive disorders” and/or “treated with an anti-depressant drug” at baseline or during in-trial period. Further, we redefined “depression” restricted to presence of both conditions for sensitivity analyses. For the current study, end-points were all-cause and any cardiovascular mortality.
313 (5%) participants had pre-existing depression and a further 916 (15%) participants developed depression during the trial period (incidence 4% per annum). Increased (hazard-ratio, 95% confidence-interval) all-cause mortality was observed among those with either pre-existing (1.23, 1.01–1.50; p = 0.03) or incident (1.26, 1.12–1.41; p < 0.001) depression compared to those without. For cardiovascular mortality, a 24% increased risk (1.24, 1.05–1.47; p = 0.01) was observed among those with incident depression. The sensitivity analyses, using the restricted depression definition showed similar associations. Incident depression was associated with being female, aged ≥75 years, being an active smoker at study entry, and developing new diabetes during the study period.
This elderly cohort had a high incidence of depression irrespective of their randomised antihypertensive regimen. Both pre-existing and incident depression were associated with increased mortality.
Knowledge of the effects of burial depth and burial duration on seed viability and, consequently, seedbank persistence of Palmer amaranth (Amaranthus palmeri S. Watson) and waterhemp [Amaranthus tuberculatus (Moq.) J. D. Sauer] ecotypes can be used for the development of efficient weed management programs. This is of particular interest, given the great fecundity of both species and, consequently, their high seedbank replenishment potential. Seeds of both species collected from five different locations across the United States were investigated in seven states (sites) with different soil and climatic conditions. Seeds were placed at two depths (0 and 15 cm) for 3 yr. Each year, seeds were retrieved, and seed damage (shrunken, malformed, or broken) plus losses (deteriorated and futile germination) and viability were evaluated. Greater seed damage plus loss averaged across seed origin, burial depth, and year was recorded for lots tested at Illinois (51.3% and 51.8%) followed by Tennessee (40.5% and 45.1%) and Missouri (39.2% and 42%) for A. palmeri and A. tuberculatus, respectively. The site differences for seed persistence were probably due to higher volumetric water content at these sites. Rates of seed demise were directly proportional to burial depth (α=0.001), whereas the percentage of viable seeds recovered after 36 mo on the soil surface ranged from 4.1% to 4.3% compared with 5% to 5.3% at the 15-cm depth for A. palmeri and A. tuberculatus, respectively. Seed viability loss was greater in the seeds placed on the soil surface compared with the buried seeds. The greatest influences on seed viability were burial conditions and time and site-specific soil conditions, more so than geographical location. Thus, management of these weed species should focus on reducing seed shattering, enhancing seed removal from the soil surface, or adjusting tillage systems.
Metal–insulator–metal (MIM) resonant absorbers comprise a conducting ground plane, a thin dielectric, and thin separated metal top-surface structures. The dielectric SiO2 strongly absorbs near 9 µm wavelength and has correspondingly strong long-wave-infrared (LWIR) dispersion for the refractive index. This dispersion results in multiple absorption resonances spanning the LWIR, which can enhance broad-band sensitivity for LWIR bolometers. Similar considerations apply to silicon nitride Si3N4. TiO2 and AlN have comparatively low dispersion and give simple single LWIR resonances. These dispersion-dependent features for infrared MIM devices are demonstrated by experiment, electrodynamic simulation, and an analytic model based on standing waves.
We examined risk factors associated with the intestinal acquisition of antimicrobial-resistant extraintestinal pathogenic Escherichia coli (ExPEC) and development of community-acquired urinary tract infection (UTI) in a case-control study of young women across Canada. A total of 399 women were recruited; 164 women had a UTI caused by E. coli resistant to ⩾1 antimicrobial classes and 98 had a UTI caused by E. coli resistant to ⩾3 antimicrobial classes. After adjustment for age, student health service (region of Canada) and either prior antibiotic use or UTI history, consumption of processed or ground chicken, cooked or raw shellfish, street foods and any organic fruit; as well as, contact with chickens, dogs and pet treats; and travel to Asia, were associated with an increased risk of UTI caused by antimicrobial resistant E. coli. A decreased risk of antimicrobial resistant UTI was associated with consumption of apples, nectarines, peppers, fresh herbs, peanuts and cooked beef. Drug-resistant UTI linked to foodborne and environmental exposures may be a significant public health concern and understanding the risk factors for intestinal acquisition of existing or newly emerging lineages of drug-resistant ExPEC is important for epidemiology, antimicrobial stewardship and prevention efforts.
The molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation.
This paper explores the influence of institutions on indigenous entrepreneurship within the muttonbird economy of Ngāi Tahu (a New Zealand Māori tribe). It determines that colonisation removed the traditional Ngāi Tahu institution of executive authority which once regulated muttonbird exchange. Without this regulatory function whānau (family) birders compete against each other at their own expense and to the benefit of traders. As a consequence the birders are constrained in applying their birding knowledge and abilities to realise market opportunity. Furthermore, declining returns and harvesting pressure is in some cases reducing the financial and natural capital of whānau, whilst threats to continuing birding culture potentially undermines the socio-human capital contained within inherited traditions and the maintaining of kinship connections. It is argued that the development of a contemporary executive authority to regulate exchange and market product may reinvigorate entrepreneurial birding activities.
We present multi–epoch VLBI observations of the methanol and water masers in the high–mass star formation region G 339.884−1.259, made using the Australian Long Baseline Array (LBA). Our sub–milliarcsecond precision measurements trace the proper motions of individual maser features in the plane of the sky. When combined with the direct line–of–sight radial velocity (vlsr), these measure the 3 D gas kinematics of the associated high–mass star formation region, allowing us to probe the dynamical processes to within 1000 AU of the core.
Circumstellar SiO masers can be observed in red giant evolved stars throughout the Galaxy. Since stellar masers are not affected by non-gravitational forces, they serve as point-mass probes of the gravitational potential and form an excellent sample for studies of the Galactic structure and dynamics. Compared to optical studies, the non-obscured masers are in particular valuable when observed close to the highly obscured Galactic Bulge and Plane. Their line-of-sight velocities can easily be obtained with high accuracy, proper motions can be measured and distances can be estimated. Furthermore, when different mass and metallicity effects can be accounted for, such a large sample will highlight asymmetries and evolutionary traces in the sample. In our Bulge Asymmetries and Dynamic Evolution (BAaDE) survey we have searched 20,000 infrared selected evolved stars for 43 GHz SiO masers with the VLA in the northern Bulge and Plane and are in the process of observing another 10,000 stars for 86 GHz SiO masers with ALMA in the southern Bulge. Our instantaneous detection rate in the Bulge is close to 70%, both at 43 and 86 GHz, with occasionally up to 7 simultaneous SiO transitions observed in a single star. Here we will outline the BAaDE survey, its first results and some of the peculiar maser features we have observed. Furthermore we will discuss the prospects for obtaining proper motions and parallaxes for individual maser stars to reconstruct individual stellar orbits.
The Bulge Asymmetries and Dynamical Evolution (BAaDE) project aims to map the positions and velocities of up to ~20,000 late-type stars with SiO maser emission along the full Galactic plane, with a large concentration in the Galactic Bulge and inner Galaxy. Both J = 1 → 0 and J = 2 → 1 transitions using the Very Large Array (VLA) and the Atacama Large Millimeter Array (ALMA) are being observed. In the VLA observing setup, in addition to the 28SiO, v = 1 and v = 2J = 1 → 0 maser transitions, the bandwidth was wide enough to include the J = 1 → 0 transitions of the rare isotopologues of the SiO molecule in both the ground and vibrationally excited states: 29SiO, v = 0, 30SiO, v = 0, 29SiO, v = 1, and 29SiO, v = 2. Approximately 10% of the initial ~3500 targets of the project show maser emission from at least one of these lines. Some of these stars (with isotopic maser emission) show high radial velocities which implies that they are indeed in the Galactic Bulge or inner Galaxy (i.e. not foreground objects). We present line profiles, refined detection statistics, and the implications of the detection of the isotopic maser emission on pumping schemes that have been previously presented.
The dwarf galaxies in the Local Group (LG) reveal a surprising amount of spatial structuring. In particular, almost all non-satellite dwarfs belong to one of two planes that show a very pronounced symmetry. In order to determine if these structures in the LG are dynamically stable or, alternatively, if they only represent transient alignments, proper motion measurements of these galaxies are required. A viable method to derive proper motions is offered by VLBI studies of 22-GHz water (and 6.7-GHz methanol) maser lines in star-forming regions.
In 2016, in the framework of the Early Science Program of the Sardinia Radio Telescope (SRT), we have conducted an extensive observational campaign to map the entire optical body of all the LG dwarf galaxies that belong to the two planes, at C and K band, in a search for methanol and water maser emission.
Here, we outline the project and present its first results on 3 targets, NGC 6822, IC 1613, and WLM. While no luminous maser emission has been detected in these galaxies, a number of interesting weaker detections has been obtained, associated with particularly active star forming regions. In addition, we have produced deep radio continuum maps for these galaxies, aimed at investigating their star forming activity and providing an improved assessment of star formation rates in these galaxies.
The first periodic Class II methanol maser was reported on in 2003. Since that time, a number of different monitoring programmes have found periodic masers, as well as other modes of variability. In a few cases, periodicity has been found in other maser species such as formaldehyde and water. Several distinct characteristics of light curves have been noted, possibly pointing to different underlying mechanisms for periodicity if one assumes a linear response to incoming radiation. I will give a brief overview of the known periodic sources, discuss current theories, and present new results obtained from monitoring mainline hydroxyl masers using the seven-element Karoo Array Telescope (KAT-7) during its science verification phase.
Methanol masers observed at high angular resolution are useful tool to investigate the processes of high-mass star formation. Here, we present the results of statistical analysis of the 6.7 GHz methanol maser structures in 60 sources observed with the EVN. The parameters of the maser clouds and exciting stars were derived. There is evidence that the emission structures composed of larger number of maser clouds are formed in the vicinity of more luminous exciting stars.
VLBI observations of SiO masers recover at most 40-50% of the total flux obtained by single dish observations at any spectral channel. Some previous studies seems to indicate that, at least, part of the lost flux is divided up into many weak components rather than in a large resolved emission area. Taking benefit of the high sensitivity and resolution of the HSA, we investigate the problem of the missing flux in VLBI observations of SiO maser emission at 7 mm in the AGB stars and obtain a high dynamic range map of IRC+10011. We conclude that the missing flux is mostly contained in many very weak maser components.
Our 2015-2016 ALMA 1.3 to 0.87 mm observations (resolution ~200 au) of the massive protocluster NGC6334I revealed that an extraordinary outburst had occurred in the dominant millimeter dust core MM1 (luminosity increase of 70×) when compared with earlier SMA data. The outburst was accompanied by the flaring of ten maser transitions of three species. We present new results from our recent JVLA observations of Class II 6.7 GHz methanol masers and 6 GHz excited OH masers in this region. Class II masers had not previously been detected toward MM1 in any interferometric observations recorded over the past 30 years that targeted the bright masers toward other members of the protocluster (MM2 and MM3=NGC6334F). Methanol masers now appear both toward and adjacent to MM1 with the strongest spots located in a dust cavity ~1 arcsec (1300 au) north of the MM1B hypercompact HII region. In addition, new excited OH masers appear on the non-thermal source CM2. These data reveal the dramatic effects of episodic accretion onto a deeply-embedded high mass protostar and demonstrate its ongoing impact on the surrounding protocluster.
High-mass young stellar objects (HMYSO) displaying methanol maser flux variability probably trace a variety of phenomena such as accretion events, magnetospheric activity, stellar flares and stellar wind interactions in binary systems. A long-term monitoring of the 6.7 GHz methanol line in a large sample of HMYSOs has been undertaken to characterize the variability patterns and examine their origins. The majority of the masers show significant variability on time-scales between a week and a few years. High amplitude short flares of individual features occurred in several HMYSOs. The maser features with low luminosity tend to be more variable than those with high luminosity. The variability of the maser features increases when the bolometric luminosity the powering star decreases. Statistical analysis of basic properties of exciting objects and the variability measures supports an idea that burst activity of methanol masers is driven mainly by changes in the infrared pumping rate.
We present subarcsecond resolution pre- and post-outburst JVLA continuum and water maser observations of the massive protostellar outburst source NGC6334I-MM1. The continuum data at 5 and 1.4 cm reveal that the free-free emission powered by MM1B, modeled as a hypercompact HII region from our 2011 JVLA data, has dropped by a factor of 5.4. Additionally, the water maser emission toward MM1, which had previously been strong (500 Jy) has dramatically reduced. In contrast, the water masers in other locations in the protocluster have flared, with the strongest spots associated with CM2, a non-thermal radio source that appears to mark a shock in a jet emanating 2″ (2600 au) northward from MM1. The observed quenching of the HCHII region suggests a reduction in uv photon production due to bloating of the protostar in response to the episodic accretion event.
Observations at low frequencies (<8GHz) are dominated by distinct direction dependent ionospheric propagation errors, which place a very tight limit on the angular separation of a suitable phase referencing calibrator and astrometry. To increase the capability for high precision astrometric measurements an effective calibration strategy of the systematic ionospheric propagation effects that is widely applicable is required. The MultiView technique holds the key to the compensation of atmospheric spatial-structure errors, by using observations of multiple calibrators and two dimensional interpolation. In this paper we present the first demonstration of the power of MultiView using three calibrators, several degrees from the target, along with a comparative study of the astrometric accuracy between MultiView and phase-referencing techniques. MultiView calibration provides an order of magnitude improvement in astrometry with respect to conventional phase referencing, achieving ~100micro-arcseconds astrometry errors in a single epoch of observations, effectively reaching the thermal noise limit.