A monoacylglycerol lipase inhibitor showing therapeutic efficacy in mice without central side effects or dependence.

Monoacylglycerol lipase (MAGL) regulates endocannabinoid 2-arachidonoylglycerol (2-AG) and eicosanoid signalling. MAGL inhibition provides therapeutic opportunities but clinical potential is limited by central nervous system (CNS)-mediated side effects. Here, we report the discovery of LEI-515, a peripherally restricted, reversible MAGL inhibitor, using high throughput screening and a medicinal chemistry programme. LEI-515 increased 2-AG levels in peripheral organs, but not mouse brain. LEI-515 attenuated liver necrosis, oxidative stress and inflammation in a CCl4-induced acute liver injury model. LEI-515 suppressed chemotherapy-induced neuropathic nociception in mice without inducing cardinal signs of CB1 activation. Antinociceptive efficacy of LEI-515 was blocked by CB2, but not CB1, antagonists. The CB1 antagonist rimonabant precipitated signs of physical dependence in mice treated chronically with a global MAGL inhibitor (JZL184), and an orthosteric cannabinoid agonist (WIN55,212-2), but not with LEI-515. Our data support targeting peripheral MAGL as a promising therapeutic strategy for developing safe and effective anti-inflammatory and analgesic agents.

The ingestion of large plastics by recreationally caught southern bluefin tuna Thunnus maccoyii off southern Australia.

The occurrence of plastic ingestion by fish is increasing around the world, however there are currently very few studies focusing on the ingestion of macro (>20 mm) and mega (>100 mm) plastics in pelagic predatory fish, particularly in Australian waters. Further to this, information on plastic ingestion in recreationally caught fish is deficient. We report on two cases of macroplastic ingestion and another case of megaplastic ingestion by southern bluefin tuna Thunnus maccoyii (Castelnau, 1872), caught recreationally in Tasmania and Victoria. The plastics ingested ranged from 62 to 283 mm. Despite the large obstructive shapes of the pieces of plastic, all three specimens possessed a healthy body mass, with one actively feeding at the time of capture. These preliminary records contribute to the limited information on the effects of plastic pollution on high value recreationally and commercially important pelagic fish in Australia.

The Impact of Mindfulness Training on Police Officer Stress, Mental Health, and Salivary Cortisol Levels.

Unaddressed occupational stress and trauma contribute to elevated rates of mental illness and suicide in policing, and to violent and aggressive behavior that disproportionately impacts communities of color. Emerging evidence suggests mindfulness training with police may reduce stress and aggression and improve mental health, but there is limited evidence for changes in biological outcomes or the lasting benefits of mindfulness training. We conducted a randomized controlled trial (RCT) of 114 police officers from three Midwestern U.S. law enforcement agencies. We assessed stress-related physical and mental health symptoms, blood-based inflammatory markers, and hair and salivary cortisol. Participants were then randomized to an 8-week mindfulness intervention or waitlist control (WLC), and the same assessments were repeated post-intervention and at 3-month follow-up. Relative to waitlist control, the mindfulness group had greater improvements in psychological distress, mental health symptoms, and sleep quality post-training, gains that were maintained at 3-month follow-up. Intervention participants also had a significantly lower cortisol awakening response (CAR) at 3-month follow-up relative to waitlist control. Contrary to hypotheses, there were no intervention effects on hair cortisol, diurnal cortisol slope, or inflammatory markers. In summary, an 8-week mindfulness intervention for police officers led to self-reported improvements in distress, mental health, and sleep, and a lower CAR. These benefits persisted (or emerged) at 3-month follow-up, suggesting that this training may buffer against the long-term consequences of chronic stress. Future research should assess the persistence of these benefits over a longer period while expanding the scope of outcomes to consider the broader community of mindfulness training for police. Clinical Trial Registration: ClinicalTrials.gov#NCT03488875.

Newly diagnosed cases of HIV in those aged 50 years and older and those less than 50: 2008-2017.

BACKGROUND: Canada's population is aging, with nearly forty percent of Canadians aged 50 years or more. As the population ages, unique challenges related to health are becoming evident, including increasing rates of sexually transmitted and bloodborne infections. Understanding the epidemiology of HIV in older adults is important to guide prevention and control programs. OBJECTIVE: To assess trends in newly diagnosed cases of HIV in Canada among those aged 50 years and older (≥50 years) and those aged less than 50 (<50 years), and to compare their basic demographic characteristics and exposure categories for the period of 2008 to 2017. METHODS: National surveillance of HIV is conducted by the Public Health Agency of Canada through voluntary submission of data by provincial/territorial public health authorities. Descriptive analyses were conducted on reported cases of HIV between January 1, 2008, to December 31, 2017 to compare the demographic profiles and exposure category for the two age groups. RESULTS: Between 2008 and 2017, the proportion of newly diagnosed HIV cases among those ≥50 years increased from 15.1% to 22.8%. The HIV diagnosis rates for both older males and older females increased over time, with a relatively higher increase for females. A higher proportion of newly diagnosed HIV cases were male in the older group (81.2%) compared to the younger group (74.6%). Among both older and younger males, the most common exposure category for HIV was being gay, bisexual and other men who have sex with men (gbMSM), followed by heterosexual contact and injection drug use; however, the relative proportions varied by age with the gbMSM category being higher in the <50 group. CONCLUSION: In Canada, over 20% of all newly diagnosed cases of HIV are now in people 50 years of age and older. HIV testing and prevention initiatives, historically aimed at younger populations, may not have the same impact for older populations. These data can be used to inform future public health actions designed to address HIV in older populations.

Estimating the intensity of use by interacting predators and prey using camera traps.

Understanding how organisms distribute themselves in response to interacting species, ecosystems, climate, human development and time is fundamental to ecological study and practice. A measure to quantify the relationship among organisms and their environments is intensity of use: the rate of use of a specific resource in a defined unit of time. Estimating the intensity of use differs from estimating probabilities of occupancy or selection, which can remain constant even when the intensity of use varies. We describe a method to evaluate the intensity of use across conditions that vary in both space and time. We demonstrate its application on a large mammal community where linear developments and human activity are conjectured to influence the interactions between white-tailed deer (Odocoileus virginianus) and wolves (Canis lupus) with possible consequences on threatened woodland caribou (Rangifer tarandus caribou). We collect and quantify intensity of use data for multiple, interacting species with the goal of assessing management efficacy, including a habitat restoration strategy for linear developments. We test whether blocking linear developments by spreading logs across a 200-m interval can be applied as an immediate mitigation to reduce the intensities of use by humans, predator and prey species in a boreal caribou range. We deployed camera traps on linear developments with and without restoration treatments in a landscape exposed to both timber and oil development. We collected a three-year dataset and employed spatial recurrent event models to analyse intensity of use by an interacting human and large mammal community across a range of environmental and climatic conditions. Spatial recurrent event models revealed that intensity of use by humans influenced the intensity of use by all five large mammal species evaluated, and the intensities of use by wolves and deer were inextricably linked in space and time. Conditions that resist travel on linear developments had a strong negative effect on the intensity of human and large mammal use. Mitigation strategies that resist, or redirect, animal travel on linear developments can reduce the effects of resource development on interacting human and predator-prey interactions. Our approach is easily applied to other continuous time point-based survey methodologies and shows that measuring the intensity of use within animal communities can help scientists monitor, mitigate and understand ecological states and processes.

Relative Selection Strength: Quantifying effect size in habitat- and step-selection inference.

Habitat-selection analysis lacks an appropriate measure of the ecological significance of the statistical estimates-a practical interpretation of the magnitude of the selection coefficients. There is a need for a standard approach that allows relating the strength of selection to a change in habitat conditions across space, a quantification of the estimated effect size that can be compared both within and across studies. We offer a solution, based on the epidemiological risk ratio, which we term the relative selection strength (RSS). For a "used-available" design with an exponential selection function, the RSS provides an appropriate interpretation of the magnitude of the estimated selection coefficients, conditional on all other covariates being fixed. This is similar to the interpretation of the regression coefficients in any multivariable regression analysis. Although technically correct, the conditional interpretation may be inappropriate when attempting to predict habitat use across a given landscape. Hence, we also provide a simple graphical tool that communicates both the conditional and average effect of the change in one covariate. The average-effect plot answers the question: What is the average change in the space use probability as we change the covariate of interest, while averaging over possible values of other covariates? We illustrate an application of the average-effect plot for the average effect of distance to road on space use for elk (Cervus elaphus) during the hunting season. We provide a list of potentially useful RSS expressions and discuss the utility of the RSS in the context of common ecological applications.

Estimating plant abundance using inflated beta distributions: Applied learnings from a lichen-caribou ecosystem.

Quantifying abundance and distribution of plant species can be difficult because data are often inflated with zero values due to rarity or absence from many ecosystems. Terrestrial fruticose lichens (Cladonia and Cetraria spp.) occupy a narrow ecological niche and have been linked to the diets of declining caribou and reindeer populations (Rangifer tarandus) across their global distribution, and conditions related to their abundance and distribution are not well understood. We attempted to measure effects related to the occupancy and abundance of terrestrial fruticose lichens by sampling and simultaneously modeling two discrete conditions: absence and abundance. We sampled the proportion cover of terrestrial lichens at 438 vegetation plots, including 98 plots having zero lichens. A zero-inflated beta regression model was employed to simultaneously estimate both the absence and the proportion cover of terrestrial fruticose lichens using fine resolution satellite imagery and light detection and ranging (LiDAR) derived covariates. The probability of lichen absence significantly increased with shallower groundwater, taller vegetation, and increased Sphagnum moss cover. Vegetation productivity, Sphagnum moss cover, and seasonal changes in photosynthetic capacity were negatively related to the abundances of terrestrial lichens. Inflated beta regression reliably estimated the abundance of terrestrial lichens (R2 = .74) which was interpolated on a map at fine resolution across a caribou range to support ecological conservation and reclamation. Results demonstrate that sampling for and simultaneously estimating both occupancy and abundance offer a powerful approach to improve statistical estimation and expand ecological inference in an applied setting. Learnings are broadly applicable to studying species that are rare, occupy narrow niches, or where the response variable is a proportion value containing zero or one, which is typical of vegetation cover data.

HIV in Canada-Surveillance Report, 2016.

BACKGROUND: Human immunodeficiency virus (HIV) continues to be a global public health concern, with 2.1 million people newly infected in 2015. Although many high-income countries have noted decreasing rates of HIV, between 2013 and 2015 Canada's rates had stabilized at 5.8 per 100,000 population. OBJECTIVE: To provide a descriptive overview of reported cases of HIV in Canada up until 2016 by geographic location, sex, age group, exposure category and race/ethnicity, with a focus on the most recent data. METHODS: The Public Health Agency of Canada (PHAC) monitors HIV through the national HIV/AIDS Surveillance System (HASS), Immigration, Refugees and Citizenship Canada (IRCC), and the Canadian Perinatal HIV Surveillance Program (CPHSP). HASS is a passive, case-based system that collates non-nominal data voluntarily submitted by all Canadian provinces and territories. Data were also received from the IRCC and the CPHSP. Data were collated, tables and figures were prepared, then descriptive statistics were applied by PHAC and validated by each province and territory. RESULTS: A total of 2,344 new diagnoses of HIV were reported in 2016 in Canada, with a cumulative total of 84,409 cases since 1985. The national diagnosis rate increased from 5.8 per 100,000 population in 2015 to 6.4 per 100,000 population in 2016. Saskatchewan reported the highest provincial diagnosis rate in 2016 (15.1 per 100,000 population). In 2016, 76.6% of reported HIV cases were among males. Adults aged 30-39 years old accounted for 28.7% of all reported cases. There was a similar age distribution of HIV cases between sexes with notable increases in the proportion of the 50 years and over age group over the past five years. The "men who have sex with men" exposure category continued to represent the largest number and proportion of all reported HIV cases in adults (44.1%). White (40.4%), Black (21.9%) and Indigenous (21.2%) race/ethnicity categories represented the largest proportions of cases. CONCLUSION: In 2016, Canada saw a slight increase in the number and rate of reported HIV cases compared with previous years. Although the diagnostic rate was lower than in all years prior to 2012, it is the highest of the past five years. While a number of possibilities exist to explain this increase, further investigation and additional data are needed in order to determine the cause and significance.

AIDS in Canada-Surveillance Report, 2016.

BACKGROUND: Although there continues to be a global epidemic of people living with human immunodeficiency virus (HIV) there has been a decrease in the number of people dying of acquired immunodeficiency syndrome (AIDS), largely due to successful treatment with antiretroviral therapy. OBJECTIVE: To provide a descriptive overview of the reported cases of AIDS in Canada by identifying trends by geographic location, sex, age group and mortality. While the descriptive analysis focuses on the year 2016, results are presented for reported cases from the beginning of national AIDS surveillance in 1979. METHODS: The Public Health Agency of Canada (PHAC) monitors AIDS in Canada through the national HIV/AIDS Surveillance System (HASS) and Statistics Canada. HASS is a passive, case-based surveillance system that maintains non-nominal data on cases of HIV and AIDS provided voluntarily by the Canadian provinces and territories. Of note, AIDS is no longer a reportable disease in Newfoundland and Labrador (as of 2009) and in Prince Edward Island (as of 2012). Data were also retrieved on annual deaths attributed to HIV/AIDS from Statistics Canada. Data were collated, tables and figures were prepared, then descriptive statistics were applied by PHAC and validated by each province and territory. RESULTS: A total of 114 AIDS cases were reported in 2016, with a cumulative total of 24,179 since 1979. These numbers represent a steady decline in the number of reported AIDS cases per year of diagnosis in Canada since 1993. Of reporting provinces, the greatest numbers of cases in 2016 were reported by Ontario, Saskatchewan and Alberta. Males accounted for 72.8% of reported AIDS cases and adults aged 50 years and older accounted for the greatest proportion by age group (36.0%). For all reporting years combined, the age distribution of AIDS cases is similar by sex, though a larger proportion of female cases were under the age of 30 years old. Limited data were reported for ethnicity and risk factors. The numbers of annual deaths attributed to AIDS infection have been declining since 1995. There were a record low of 241 AIDS-related deaths reported in 2013-the most recent year for which data were available. The number of AIDS-related deaths in Canada has declined 86.2% since 1995. CONCLUSION: The number of AIDS cases reported by participating provinces and territories and the number of AIDS-related deaths reported by Statistics Canada has declined. While this represents a promising trend, the data should be interpreted with caution given the limitations of the dataset which could lead to an underestimate of the magnitude of the disease.

Non-fluoroscopic navigation systems for radiofrequency catheter ablation for supraventricular tachycardia reduce ionising radiation exposure.

INTRODUCTION: The use of non-fluoroscopic systems (NFS) to guide radiofrequency catheter ablation (RFCA) for the treatment of supraventricular tachycardia (SVT) is associated with lower radiation exposure. This study aimed to determine if NFS reduces fluoroscopy time, radiation dose and procedure time. METHODS: We prospectively enrolled patients undergoing RFCA for SVT. NFS included EnSiteTM NavXTM or CARTO® mapping. We compared procedure and fluoroscopy times, and radiation exposure between NFS and conventional fluoroscopy (CF) cohorts. Procedural success, complications and one-year success rates were reported. RESULTS: A total of 200 patients over 27 months were included and RFCA was guided by NFS for 79 patients; those with atrioventricular nodal reentrant tachycardia (AVNRT), left-sided atrioventricular reentrant tachycardia (AVRT) and right-sided AVRT were included (n = 101, 63 and 36, respectively). Fluoroscopy times were significantly lower with NFS than with CF (10.8 ± 11.1 minutes vs. 32.0 ± 27.5 minutes; p < 0.001). The mean fluoroscopic dose area product was also significantly reduced with NFS (NSF: 5,382 ± 5,768 mGy*cm2 vs. CF: 21,070 ± 23,311 mGy*cm2; p < 0.001); for all SVT subtypes. There was no significant reduction in procedure time, except for left-sided AVRT ablation (NFS: 79.2 minutes vs. CF: 116.4 minutes; p = 0.001). Procedural success rates were comparable (NFS: 97.5% vs. CF: 98.3%) and at one-year follow-up, there was no significant difference in the recurrence rates (NFS: 5.2% vs. CF: 4.2%). No clinically significant complications were observed in both groups. CONCLUSION: The use of NFS for RFCA for SVT is safe, with significantly reduced radiation dose and fluoroscopy time.

Factors affecting gas migration and contaminant redistribution in heterogeneous porous media subject to electrical resistance heating.

A series of intermediate-scale laboratory experiments were completed in a two-dimensional flow cell to investigate gas production and migration during the application of electrical resistance heating (ERH) for the removal of dense non-aqueous phase liquids (DNAPLs). Experiments consisted of heating water in homogeneous silica sand and heating 270 mL of trichloroethene (TCE) and chloroform (CF) DNAPL pools in heterogeneous silica sands, both under flowing groundwater conditions. Spatial and temporal distributions of temperature were measured using thermocouples and observations of gas production and migration were collected using front-face image capture throughout the experiments. Post-treatment soil samples were collected and analyzed to assess DNAPL removal. Results of experiments performed in homogeneous sand subject to different groundwater flow rates showed that high groundwater velocities can limit subsurface heating rates. In the DNAPL pool experiments, temperatures increased to achieve DNAPL-water co-boiling, creating estimated gas volumes of 131 and 114 L that originated from the TCE and CF pools, respectively. Produced gas migrated vertically, entered a coarse sand lens and subsequently migrated laterally beneath an overlying capillary barrier to outside the heated treatment zone where 31-56% of the original DNAPL condensed back into a DNAPL phase. These findings demonstrate that layered heterogeneity can potentially facilitate the transport of contaminants outside the treatment zone by mobilization and condensation of gas phases during ERH applications. This underscores the need for vapor phase recovery and/or control mechanisms below the water table during application of ERH in heterogeneous porous media during the co-boiling stage, which occurs prior to reaching the boiling point of water.

Non-fluoroscopic navigation systems for radiofrequency catheter ablation for supraventricular tachycardia reduce ionising radiation exposure

<p><b>INTRODUCTION</b>The use of non-fluoroscopic systems (NFS) to guide radiofrequency catheter ablation (RFCA) for the treatment of supraventricular tachycardia (SVT) is associated with lower radiation exposure. This study aimed to determine if NFS reduces fluoroscopy time, radiation dose and procedure time.</p><p><b>METHODS</b>We prospectively enrolled patients undergoing RFCA for SVT. NFS included EnSiteTM NavXTM or CARTO® mapping. We compared procedure and fluoroscopy times, and radiation exposure between NFS and conventional fluoroscopy (CF) cohorts. Procedural success, complications and one-year success rates were reported.</p><p><b>RESULTS</b>A total of 200 patients over 27 months were included and RFCA was guided by NFS for 79 patients; those with atrioventricular nodal reentrant tachycardia (AVNRT), left-sided atrioventricular reentrant tachycardia (AVRT) and right-sided AVRT were included (n = 101, 63 and 36, respectively). Fluoroscopy times were significantly lower with NFS than with CF (10.8 ± 11.1 minutes vs. 32.0 ± 27.5 minutes; p < 0.001). The mean fluoroscopic dose area product was also significantly reduced with NFS (NSF: 5,382 ± 5,768 mGy*cm2 vs. CF: 21,070 ± 23,311 mGy*cm2; p < 0.001); for all SVT subtypes. There was no significant reduction in procedure time, except for left-sided AVRT ablation (NFS: 79.2 minutes vs. CF: 116.4 minutes; p = 0.001). Procedural success rates were comparable (NFS: 97.5% vs. CF: 98.3%) and at one-year follow-up, there was no significant difference in the recurrence rates (NFS: 5.2% vs. CF: 4.2%). No clinically significant complications were observed in both groups.</p><p><b>CONCLUSION</b>The use of NFS for RFCA for SVT is safe, with significantly reduced radiation dose and fluoroscopy time.</p>

Quantifying past and present connectivity illuminates a rapidly changing landscape for the African elephant.

There is widespread concern about impacts of land-use change on connectivity among animal and plant populations, but those impacts are difficult to quantify. Moreover, lack of knowledge regarding ecosystems before fragmentation may obscure appropriate conservation targets. We use occurrence and population genetic data to contrast connectivity for a long-lived mega-herbivore over historical and contemporary time frames. We test whether (i) historical gene flow is predicted by persistent landscape features rather than human settlement, (ii) contemporary connectivity is most affected by human settlement and (iii) recent gene flow estimates show the effects of both factors. We used 16 microsatellite loci to estimate historical and recent gene flow among African elephant (Loxodonta africana) populations in seven protected areas in Tanzania, East Africa. We used historical gene flow (FST and G'ST ) to test and optimize models of historical landscape resistance to movement. We inferred contemporary landscape resistance from elephant resource selection, assessed via walking surveys across ~15 400 km(2) of protected and unprotected lands. We used assignment-based recent gene flow estimates to optimize and test the contemporary resistance model, and to test a combined historical and contemporary model. We detected striking changes in connectivity. Historical connectivity among elephant populations was strongly influenced by slope but not human settlement, whereas contemporary connectivity was influenced most by human settlement. Recent gene flow was strongly influenced by slope but was also correlated with contemporary resistance. Inferences across multiple timescales can better inform conservation efforts on large and complex landscapes, while mitigating the fundamental problem of shifting baselines in conservation.

Resource selection and its implications for wide-ranging mammals of the brazilian cerrado.

Conserving animals beyond protected areas is critical because even the largest reserves may be too small to maintain viable populations for many wide-ranging species. Identification of landscape features that will promote persistence of a diverse array of species is a high priority, particularly, for protected areas that reside in regions of otherwise extensive habitat loss. This is the case for Emas National Park, a small but important protected area located in the Brazilian Cerrado, the world's most biologically diverse savanna. Emas Park is a large-mammal global conservation priority area but is too small to protect wide-ranging mammals for the long-term and conserving these populations will depend on the landscape surrounding the park. We employed novel, noninvasive methods to determine the relative importance of resources found within the park, as well as identify landscape features that promote persistence of wide-ranging mammals outside reserve borders. We used scat detection dogs to survey for five large mammals of conservation concern: giant armadillo (Priodontes maximus), giant anteater (Myrmecophaga tridactyla), maned wolf (Chrysocyon brachyurus), jaguar (Panthera onca), and puma (Puma concolor). We estimated resource selection probability functions for each species from 1,572 scat locations and 434 giant armadillo burrow locations. Results indicate that giant armadillos and jaguars are highly selective of natural habitats, which makes both species sensitive to landscape change from agricultural development. Due to the high amount of such development outside of the Emas Park boundary, the park provides rare resource conditions that are particularly important for these two species. We also reveal that both woodland and forest vegetation remnants enable use of the agricultural landscape as a whole for maned wolves, pumas, and giant anteaters. We identify those features and their landscape compositions that should be prioritized for conservation, arguing that a multi-faceted approach is required to protect these species.

Predators choose prey over prey habitats: evidence from a lynx-hare system.

Resource selection is grounded in the understanding that animals select resources based on fitness requirements. Despite uncertainty in how mechanisms relate to the landscape, resource selection studies often assume, but rarely demonstrate, a relationship between modeled variables and fitness mechanisms. Using Canada lynx (Lynx canadensis) and snowshoe hare (Lepus americanus) as a model system, we assess whether prey habitat is a viable surrogate for encounters between predators and prey. We simultaneously collected winter track data for lynx and hare in two study areas. We used information criteria to determine whether selection by lynx is best characterized by a hare resource selection probability function (RSPF) or by the amount of hare resource use. Results show that lynx selection is better explained by the amount of hare use (SIC = -21.9; Schwarz's Information Criterion) than by hare RSPF (SIC = -16.71), and that hare RSPF cannot be assumed to reveal the amount of resource use, a primary mechanism of predator selection. Our study reveals an obvious but important distinction between selection and use that is applicable to all resource selection studies. We recommend that resource selection studies be coupled with mechanistic data (e.g., metrics of diet, forage, fitness, or abundance) when investigating mechanisms of resource selection.

Weighted distributions and estimation of resource selection probability functions.

Understanding how organisms selectively use resources is essential for designing wildlife management strategies. The probability that an individual uses a given resource, as characterized by environmental factors, can be quantified in terms of the resource selection probability function (RSPF). The present literature on the topic has claimed that, except when both used and unused sites are known, the RSPF is non-estimable and that only a function proportional to RSPF, namely, the resource selection function (RSF) can be estimated. This paper describes a close connection between the estimation of the RSPF and the estimation of the weight function in the theory of weighted distributions. This connection can be used to obtain fully efficient, maximum likelihood estimators of the resource selection probability function under commonly used survey designs in wildlife management. The method is illustrated using GPS collar data for mountain goats (Oreamnos americanus de Blainville 1816) in northwest British Columbia, Canada.