Peer support in small towns: A decentralized mobile Hepatitis C virus clinic for people who inject drugs.

BACKGROUND & AIMS: New models of HCV care are needed to reach people who inject drugs (PWID). The primary aim was to evaluate HCV treatment uptake among HCV RNA positive individuals identified by point-of-care (POC) testing and liver disease assessment in a peer-driven decentralized mobile clinic. METHODS: This prospective study included consecutive patients assessed in a mobile clinic visiting 32 small towns in Southern Norway from November 2019 to November 2020. The clinic was staffed by a bus driver and a social educator offering POC HCV RNA testing (GeneXpert®), liver disease staging (FibroScan® 402) and peer support. Viremic individuals were offered prompt pan-genotypic treatment prescribed by local hospital-employed specialists following a brief telephone assessment. RESULTS: Among 296 tested individuals, 102 (34%) were HCV RNA positive (median age 51 years, 77% male, 24% advanced liver fibrosis/cirrhosis). All participants had a history of injecting drug use, 71% reported past 3 months injecting, and 37% received opioid agonist treatment. Treatment uptake within 6 months following enrolment was achieved in 88%. Treatment uptake was negatively associated with recent injecting (aHR 0.60; 95% CI 0.36-0.98), harmful alcohol consumption (aHR 0.44; 95% CI 0.20-0.99), and advanced liver fibrosis/cirrhosis (aHR 0.44; 95% CI 0.25-0.80). HCV RNA prevalence increased with age (OR 1.81 per 10-year increase; 95% 1.41-2.32), ranging from 3% among those <30 years to 55% among those ≥60 years. CONCLUSIONS: A peer-driven mobile HCV clinic is an effective and feasible model of care that should be considered for broader implementation to reach PWID outside the urban centres.

Spatiotemporally variable snow properties drive habitat use of an Arctic mesopredator.

Climate change is rapidly altering the composition and availability of snow, with implications for snow-affected ecological processes, including reproduction, predation, habitat selection, and migration. How snowpack changes influence these ecological processes is mediated by physical snowpack properties, such as depth, density, hardness, and strength, each of which is in turn affected by climate change. Despite this, it remains difficult to obtain meaningful snow information relevant to the ecological processes of interest, precluding a mechanistic understanding of these effects. This problem is acute for species that rely on particular attributes of the subnivean space, for example depth, thermal resistance, and structural stability, for key life-history processes like reproduction, thermoregulation, and predation avoidance. We used a spatially explicit snow evolution model to investigate how habitat selection of a species that uses the subnivean space, the wolverine, is related to snow depth, snow density, and snow melt on Arctic tundra. We modeled these snow properties at a 10 m spatial and a daily temporal resolution for 3 years, and used integrated step selection analyses of GPS collar data from 21 wolverines to determine how these snow properties influenced habitat selection and movement. We found that wolverines selected deeper, denser snow, but only when it was not undergoing melt, bolstering the evidence that these snow properties are important to species that use the Arctic snowpack for subnivean resting sites and dens. We discuss the implications of these findings in the context of climate change impacts on subnivean species.

Enhanced shrub growth in the Arctic increases habitat connectivity for browsing herbivores.

Habitat connectivity is a key factor influencing species range dynamics. Rapid warming in the Arctic is leading to widespread heterogeneous shrub expansion, but impacts of these habitat changes on range dynamics for large herbivores are not well understood. We use the climate-shrub-moose system of northern Alaska as a case study to examine how shrub habitat will respond to predicted future warming, and how these changes may impact habitat connectivity and the distribution of moose (Alces alces). We used a 19 year moose location dataset, a 568 km transect of field shrub sampling, and forecasted warming scenarios with regional downscaling to map current and projected shrub habitat for moose on the North Slope of Alaska. The tall-shrub habitat for moose exhibited a dendritic spatial configuration correlated with river corridor networks and mean July temperature. Warming scenarios predict that moose habitat will more than double by 2099. Forecasted warming is predicted to increase the spatial cohesion of the habitat network that diminishes effects of fragmentation, which improves overall habitat quality and likely expands the range of moose. These findings demonstrate how climate change may increase habitat connectivity and alter the distributions of shrub herbivores in the Arctic, including creation of novel communities and ecosystems.

The Consensus Hepatitis C Cascade of Care: Standardized Reporting to Monitor Progress Toward Elimination.

Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate, in simple terms, the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of individuals with HCV to diagnosis, treatment, and cure. The value of reporting would be enhanced if a standardized approach were used for generating CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway, and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and for ensuring accurate monitoring of progress toward WHO's 2030 hepatitis C elimination targets.

Fire severity effects on soil carbon and nutrients and microbial processes in a Siberian larch forest.

Fire frequency and severity are increasing in tundra and boreal regions as climate warms, which can directly affect climate feedbacks by increasing carbon (C) emissions from combustion of the large soil C pool and indirectly via changes in vegetation, permafrost thaw, hydrology, and nutrient availability. To better understand the direct and indirect effects of changing fire regimes in northern ecosystems, we examined how differences in soil burn severity (i.e., extent of soil organic matter combustion) affect soil C, nitrogen (N), and phosphorus (P) availability and microbial processes over time. We created experimental burns of three fire severities (low, moderate, and high) in a larch forest in the northeastern Siberian Arctic and analyzed soils at 1, 8 days, and 1 year postfire. Labile dissolved C and N increased with increasing soil burn severity immediately (1 day) postfire by up to an order of magnitude, but declined significantly 1 week later; both variables were comparable or lower than unburned soils by 1 year postfire. Soil burn severity had no effect on P in the organic layer, but P increased with increasing severity in mineral soil horizons. Most extracellular enzyme activities decreased by up to 70% with increasing soil burn severity. Increasing soil burn severity reduced soil respiration 1 year postfire by 50%. However, increasing soil burn severity increased net N mineralization rates 1 year postfire, which were 10-fold higher in the highest burn severity. While fires of high severity consumed approximately five times more soil C than those of low severity, soil C pools will also be driven by indirect effects of fire on soil processes. Our data suggest that despite an initial increase in labile C and nutrients with soil burn severity, soil respiration and extracellular activities related to the turnover of organic matter were greatly reduced, which may mitigate future C losses following fire.

Leaf herbivory by insects during summer reduces overwinter browsing by moose.

BACKGROUND: Damage to plants by herbivores potentially affects the quality and quantity of the plant tissue available to other herbivore taxa that utilize the same host plants at a later time. This study addresses the indirect effects of insect herbivores on mammalian browsers, a particularly poorly-understood class of interactions. Working in the Alaskan boreal forest, we investigated the indirect effects of insect damage to Salix interior leaves during the growing season on the consumption of browse by moose during winter, and on quantity and quality of browse production. RESULTS: Treatment with insecticide reduced leaf mining damage by the willow leaf blotch miner, Micrurapteryx salicifoliella, and increased both the biomass and proportion of the total production of woody tissue browsed by moose. Salix interior plants with experimentally-reduced insect damage produced significantly more stem biomass than controls, but did not differ in stem quality as indicated by nitrogen concentration or protein precipitation capacity, an assay of the protein-binding activity of tannins. CONCLUSIONS: Insect herbivory on Salix, including the outbreak herbivore M. salicifoliella, affected the feeding behavior of moose. The results demonstrate that even moderate levels of leaf damage by insects can have surprisingly strong impacts on stem production and influence the foraging behavior of distantly related taxa browsing on woody tissue months after leaves have dropped.

Can snowshoe hares control treeline expansions?

Treelines in Alaska are advancing in elevation and latitude because of climate warming, which is expanding the habitat available for boreal wildlife species, including snowshoe hares (Lepus americanus). Snowshoe hares are already present in tall shrub communities beyond treeline and are the main browser of white spruce (Picea glauca), the dominant tree species at treeline in Alaska. We investigated the processes involved in a "snowshoe hare filter" to white spruce establishment near treeline in Denali National Park, Alaska, USA. We modeled the pattern of spruce establishment from 1970 to 2009 and found that fewer spruce established during periods of high hare abundance. Multiple factors interact to influence browsing of spruce, including the hare cycle, snow depth and the characteristics of surrounding vegetation. Hares are abundant at treeline and may exclude spruce from otherwise optimal establishment sites, particularly floodplain locations with closed shrub canopies. The expansion of white spruce treeline in response to warming climate will be strongly modified by the spatial and temporal dynamics of the snowshoe hare filter.

Liver fibrosis progression at autopsy in injecting drug users infected by hepatitis C: a longitudinal long-term cohort study.

BACKGROUND & AIMS: There is a paucity of unbiased data on the natural history of hepatitis C virus (HCV) infection in injecting drug users (IDUs). The purpose of this study was to assess the risk of developing advanced fibrosis associated with chronic hepatitis C (CHC) infection among injecting drug users (IDUs) who underwent an autopsy. METHODS: A longitudinal cohort design was applied, in which the stage of liver fibrosis in anti-HCV positive IDUs with or without chronic HCV infection was assessed in liver tissue from autopsies performed up to 35 years after HCV exposure. The cohort originated from 864 IDUs consecutively admitted for drug abuse treatment 1970-1984. Stored sera, mostly drawn at the time of admission for drug treatment, were available in 635 subjects. 220 out of 523 anti-HCV positive subjects had died before 2009. Liver tissue from autopsies was available from 102/220 subjects, of which 61 were HCV RNA positive. Liver sections were classified according to METAVIR scores for fibrosis. Two pathologists, both blinded for serologic results, scored sections of liver tissue. RESULTS: Among HCV RNA positive subjects 16.4% (10/61) had septal fibrosis (F3) or cirrhosis (F4) compared to 2.4% (1/41) among anti HCV positive/HCV RNA negative subjects (p=0.026). Of 18 HCV RNA positive subjects autopsied <15 years after HCV exposure none had F3 or F4. Among subjects autopsied >25 years after exposure 35% (6/17) had F3-F4. CONCLUSIONS: Among IDUs chronically infected by HCV, 1/3 developed septal fibrosis or cirrhosis 25 years or more after exposure.

HCV treatment uptake in people who have injected drugs - observations in a large cohort that received addiction treatment 1970-1984.

OBJECTIVES: The aim of this study was to document antiviral treatment uptake among former or current people who inject drugs (PWID) with chronic hepatitis C and to explore a possible association between treatment and mortality. MATERIAL AND METHODS: This is a longitudinal cohort study of PWID admitted for drug abuse treatment 1970-1984. The 245 hepatitis C virus (HCV) RNA-positive patients alive by the end of 1996 were followed 1997-2012 through linkage to several health registers. Treatment uptake was mainly documented by information on prescription of antiviral medication registered in the Norwegian Prescription Database from 2004. Cox regression, with a time-dependent covariate measuring end-of-treatment, was employed to evaluate mortality after treatment. RESULTS: At the end of the follow-up, median time since HCV exposure was 36 years, and 19.2% (47/245) had been prescribed antiviral treatment for chronic HCV infection. No gender difference was observed. Among those alive at the end of the study period, 27.8% (44/158) had been treated. Relative hazard of death was 0.21 (95% confidence interval [CI] 0.07-0.68), comparing periods for patients after versus before or without treatment. Mortality rate after treatment was 0.8 per 100 person years (95% CI 0.3-2.4) compared to 2.8 (95% CI 2.2-3.5) in untreated patients and before treatment. The most important causes of death among the untreated were drug-related. CONCLUSIONS: Among PWID infected with HCV, approximately one-fourth of those still alive at a median of 36 years after exposure had received HCV treatment. Treatment was associated with increased survival, probably mainly due to selection bias.

All-cause and liver-related mortality in hepatitis C infected drug users followed for 33 years: a controlled study.

BACKGROUND & AIMS: The course of chronic hepatitis C virus (HCV) in injecting drug users (IDUs) has not been well described. The aim of this study was to compare long-term all-cause and liver-related mortality among anti-HCV positive IDUs with and without persisting HCV infection. METHODS: A retrospective-prospective controlled cohort design was applied. All IDUs admitted to resident drug treatment (1970-1984) and with available stored sera were screened for anti-HCV antibody. Anti-HCV positive individuals were further tested for the presence of HCV RNA. All-cause and liver-related mortality was compared between HCV RNA positive (n=328) and HCV RNA negative individuals (n=195). The observation was accomplished through register linkage to national registers. Mean observation time was 33 years. RESULTS: All-cause mortality rate was 1.85 (95% CI 1.62-2.11) per 100 person-years, male 2.11 (95% CI 1.84-2.46), female 1.39 (95% CI 1.07-1.79). Mortality rates were not influenced by persisting HCV infection. Main causes of death were intoxications (45.0%), suicide (9.1%), and accidents (8.2%). Liver disease was the cause of death in 7.5% of deaths among HCV RNA positive subjects. Five of 13 deaths among male IDUs with persisting HCV infection occurring after the age of 50 years were caused by liver disease. CONCLUSIONS: The all-cause mortality in IDUs is high and with no difference between HCV RNA positive and HCV RNA negative individuals, the first three decades after HCV transmission. However, among IDUs with chronic HCV infection who have survived until 50years of age, HCV infection emerges as the main cause of death.

Prior choice and data requirements of Bayesian multivariate hierarchical models fit to tag-recovery data: The need for power analyses.

Recent empirical studies have quantified correlation between survival and recovery by estimating these parameters as correlated random effects with hierarchical Bayesian multivariate models fit to tag-recovery data. In these applications, increasingly negative correlation between survival and recovery has been interpreted as evidence for increasingly additive harvest mortality. The power of these hierarchal models to detect nonzero correlations has rarely been evaluated, and these few studies have not focused on tag-recovery data, which is a common data type. We assessed the power of multivariate hierarchical models to detect negative correlation between annual survival and recovery. Using three priors for multivariate normal distributions, we fit hierarchical effects models to a mallard (Anas platyrhychos) tag-recovery data set and to simulated data with sample sizes corresponding to different levels of monitoring intensity. We also demonstrate more robust summary statistics for tag-recovery data sets than total individuals tagged. Different priors led to substantially different estimates of correlation from the mallard data. Our power analysis of simulated data indicated most prior distribution and sample size combinations could not estimate strongly negative correlation with useful precision or accuracy. Many correlation estimates spanned the available parameter space (-1,1) and underestimated the magnitude of negative correlation. Only one prior combined with our most intensive monitoring scenario provided reliable results. Underestimating the magnitude of correlation coincided with overestimating the variability of annual survival, but not annual recovery. The inadequacy of prior distributions and sample size combinations previously assumed adequate for obtaining robust inference from tag-recovery data represents a concern in the application of Bayesian hierarchical models to tag-recovery data. Our analysis approach provides a means for examining prior influence and sample size on hierarchical models fit to capture-recapture data while emphasizing transferability of results between empirical and simulation studies.

Hepatitis C treatment uptake among people who inject drugs in Oslo, Norway: A registry-based study.

BACKGROUND: Improving HCV treatment uptake among people who inject drugs (PWID) is crucial to achieving the WHO elimination targets. The aims were to evaluate HCV treatment uptake and HCV RNA prevalence in a large cohort of PWID in Norway. METHODS: Registry-based observational study where all users of the City of Oslo's low-threshold social and health services for PWID between 2010-2016 (n = 5330) were linked to HCV notifications (1990-2019) and dispensions of HCV treatment, opioid agonist treatment (OAT) and benzodiazepines (2004-2019). Cases were weighted to account for spontaneous HCV clearance. Treatment rates were calculated using person-time of observation, and factors associated with treatment uptake were analysed using logistic regression. HCV RNA prevalence was estimated among individuals alive by the end of 2019. RESULTS: Among 2436 participants with chronic HCV infection (mean age 46.8 years, 30.7% female, 73.3% OAT), 1118 (45.9%) had received HCV treatment between 2010-2019 (88.7% DAA-based). Treatment rates increased from 1.4/100 PY (95% CI 1.1-1.8) in the pre-DAA period (2010-2013) to 3.5/100 PY (95% CI 3.0-4.0) in the early DAA period (2014-2016; fibrosis restrictions) and 18.4/100 PY (95% CI 17.2-19.7) in the late DAA period (2017-2019; no restrictions). Treatment rates for 2018 and 2019 exceeded a previously modelled elimination threshold of 50/1000 PWID. Treatment uptake was less likely among women (aOR 0.74; 95% CI 0.62-0.89) and those aged 40-49 years (aOR 0.74; 95% CI 0.56-0.97), and more likely among participants with current OAT (aOR 1.21; 95% CI 1.01-1.45). The estimated HCV RNA prevalence by the end of 2019 was 23.6% (95% CI 22.3-24.9). CONCLUSION: Although HCV treatment uptake among PWID increased, strategies to improve treatment among women and individuals not engaged in OAT should be addressed.

Wolverines (Gulo gulo) in the Arctic: Revisiting distribution and identifying research and conservation priorities amid rapid environmental change.

Wolverines (Gulo gulo) occupy most of the globe's Arctic tundra. Given the rapidly warming climate and expanding human activity in this biome, understanding wolverine ecology, and therefore the species' vulnerability to such changes, is increasingly important for developing research priorities and effective management strategies. Here, we review and synthesize knowledge of wolverines in the Arctic using both Western science sources and available Indigenous Knowledge (IK) to improve our understanding of wolverine ecology in the Arctic and better predict the species' susceptibility to change. To accomplish this, we update the pan-Arctic distribution map of wolverines to account for recent observations and then discuss resulting inference and uncertainties. We use these patterns to contextualize and discuss potential underlying drivers of distribution and population dynamics, drawing upon knowledge of food habits, habitat associations, and harvest, as well as studies of wolverine ecology elsewhere. We then identify four broad areas to prioritize conservation and research efforts: (1) Monitoring trends in population abundance, demographics, and distribution and the drivers thereof, (2) Evaluating and predicting wolverines' responses to ongoing climate change, particularly the consequences of reduced snow and sea ice, and shifts in prey availability, (3) Understanding wolverines' response to human development, including the possible impact of wintertime over-snow travel and seismic testing to reproductive denning, as well as vulnerability to hunting and trapping associated with increased human access, and (4) Ensuring that current and future harvest are sustainable. Supplementary Information: The online version contains supplementary material available at 10.1007/s00300-022-03079-4.

Inhibition of snowshoe hare succinate dehydrogenase activity as a mechanism of deterrence for papyriferic acid in birch.

The plant secondary metabolite papyriferic acid (PA) deters browsing by snowshoe hares (Lepus americanus) on the juvenile developmental stage of the Alaska paper birch (Betula neoalaskana). However, the physiological mechanism that reduces browsing remains unknown. We used pharmacological assays and molecular modeling to test the hypothesis that inhibition of succinate dehydrogenase (SDH) is a mode of action (MOA) of toxicity of PA in snowshoe hares. We tested this hypothesis by measuring the effect of PA on the activity of SDH in liver mitochondria isolated from wild hares. In addition, we used molecular modeling to determine the specific binding site of PA on SDH. We found that PA inhibits SDH from hares by an uncompetitive mechanism in a dose-dependent manner. Molecular modeling suggests that inhibition of SDH is a result of binding of PA at the ubiquinone binding sites in complex II. Our results provide a MOA for toxicity that may be responsible for the concentration-dependent anti-feedant effects of PA. We propose that snowshoe hares reduce the dose-dependent toxic consequences of PA by relying on efflux transporters and metabolizing enzymes that lower systemic exposure to dietary PA.

Mechanistic movement models identify continuously updated autumn migration cues in Arctic caribou.

BACKGROUND: Migrations in temperate systems typically have two migratory phases, spring and autumn, and many migratory ungulates track the pulse of spring vegetation growth during a synchronized spring migration. In contrast, autumn migrations are generally less synchronous and the cues driving them remain understudied. Our goal was to identify the cues that migrants use in deciding when to initiate migration and how this is updated while en route. METHODS: We analyzed autumn migrations of Arctic barren-ground caribou (Rangifer tarandus) as a series of persistent and directional movements and assessed the influence of a suite of environmental factors. We fitted a dynamic-parameter movement model at the individual-level and estimated annual population-level parameters for weather covariates on 389 individual-seasons across 9 years. RESULTS: Our results revealed strong, consistent effects of decreasing temperature and increasing snow depth on migratory movements, indicating that caribou continuously update their migratory decision based on dynamic environmental conditions. This suggests that individuals pace migration along gradients of these environmental variables. Whereas temperature and snow appeared to be the most consistent cues for migration, we also found interannual variability in the effect of wind, NDVI, and barometric pressure. The dispersed distribution of individuals in autumn resulted in diverse environmental conditions experienced by individual caribou and thus pronounced variability in migratory patterns. CONCLUSIONS: By analyzing autumn migration as a continuous process across the entire migration period, we found that caribou migration was largely related to temperature and snow conditions experienced throughout the journey. This mechanism of pacing autumn migration based on indicators of the approaching winter is analogous to the more widely researched mechanism of spring migration, when many migrants pace migration with a resource wave. Such a similarity in mechanisms highlights the different environmental stimuli to which migrants have adapted their movements throughout their annual cycle. These insights have implications for how long-distance migratory patterns may change as the Arctic climate continues to warm.

Uptake of organic nitrogen by plants.

Languishing for many years in the shadow of plant inorganic nitrogen (N) nutrition research, studies of organic N uptake have attracted increased attention during the last decade. The capacity of plants to acquire organic N, demonstrated in laboratory and field settings, has thereby been well established. Even so, the ecological significance of organic N uptake for plant N nutrition is still a matter of discussion. Several lines of evidence suggest that plants growing in various ecosystems may access organic N species. Many soils display amino acid concentrations similar to, or higher than, those of inorganic N, mainly as a result of rapid hydrolysis of soil proteins. Transporters mediating amino acid uptake have been identified both in mycorrhizal fungi and in plant roots. Studies of endogenous metabolism of absorbed amino acids suggest that L- but not D-enantiomers are efficiently utilized. Dual labelled amino acids supplied to soil have provided strong evidence for plant uptake of organic N in the field but have failed to provide information on the quantitative importance of this process. Thus, direct evidence that organic N contributes significantly to plant N nutrition is still lacking. Recent progress in our understanding of the mechanisms underlying plant organic N uptake may open new avenues for the exploration of this subject.

Black spruce assimilates nitrate in boreal winter.

Winter has long been considered a dormant season in boreal forests regarding plant physiological activity such as nutrient acquisition. However, biogeochemical data clearly show that soil can remain unfrozen with substantial rates of nutrient transformation for several weeks following autumn snowfall. Here we examined nitrate (NO3--N) assimilation by black spruce (Picea mariana (Mill.) Britton, Sterns and Poggenb.) during summer and winter in Interior Alaska to test our hypothesis that this boreal species is able to assimilate NO3--N, even at the very low temperatures typical of early winter. Nitrate reductase activity (NRA) was measured in current year needles and fine roots of black spruce as an indicator of NO3--N assimilation in the summer and winter at two boreal forest sites. Nitrate concentration in the needles and roots were also measured to determine whether NO3--N was available in plant tissue for the enzyme. Nitrate reductase activity and NO3--N were detected in needles and roots in the winter as well as the summer. The results of a generalized linear mixed model showed that season had minimal effects on NRA and NO3--N concentration in this species. Additionally, the effect of incubation temperature for the NRA assays was tested at 30 °C and -3 °C for samples collected in the winter. Substantial enzyme activity was detected in winter-collected samples, even in incubations conducted at -3 °C. These results indicate that this dominant tree species in the boreal forests of Interior Alaska, black spruce, has the capacity to assimilate NO3--N below freezing temperatures, suggesting that the physiological activity required for nitrogen (N) resource acquisition may extend beyond the typical growing season. Our findings coupled to biogeochemical evidence for high microbial activity under the snow also indicate that winter N acquisition should be taken into account when estimating the annual N budgets of boreal forest ecosystems.