Despite high hepatitis C virus (HCV) prevalence, opioid use disorder (OUD) patients on methadone rarely engage in HCV treatment. We investigated the effectiveness of HCV management via telemedicine ...in an opioid substitution therapy (OST) program.
OUD patients on methadone underwent biweekly telemedicine sessions between a hepatologist and physician assistant during the entire HCV treatment course. All pretreatment labs (HCV RNA, genotype, and noninvasive fibrosis assessments) were obtained onsite and direct-acting antivirals were coadministered with methadone using modified directly observed therapy. We used multiple correspondence analysis, least absolute shrinkage and selection operator, and logistic regression to identify variables associated with pursuit of HCV care.
Sixty-two HCV RNA-positive patients (24% human immunodeficiency virus HIV infected, 61% male, 61% African American, 25.8% Hispanic) were evaluated. All patients were stabilized on methadone and all except 4 were HCV genotype 1 infected. Advanced fibrosis/cirrhosis was present in 34.5% of patients. Of the 45 treated patients, 42 (93.3%) achieved viral eradication. Of 17 evaluated patients who were not treated, 5 were discontinued from the drug treatment program or did not follow up after the evaluation, 2 had HIV adherence issues, and 10 had insurance authorization issues. Marriage and a mental health diagnosis other than depression were the strongest positive predictors of treatment pursuit, whereas being divorced, separated, or widowed was the strongest negative predictor.
HCV management via telemedicine integrated into an OST program is a feasible model with excellent virologic effectiveness. Psychosocial and demographic variables can assist in identification of subgroups with a propensity or aversion to pursue HCV treatment.
We utilize energy budget diagnostics from the Coupled Model Intercomparison Project phase 5 (CMIP5) to evaluate the models' climate forcing since preindustrial times employing an established ...regression technique. The climate forcing evaluated this way, termed the adjusted forcing (AF), includes a rapid adjustment term associated with cloud changes and other tropospheric and land‐surface changes. We estimate a 2010 total anthropogenic and natural AF from CMIP5 models of 1.9 ± 0.9 W m−2 (5–95% range). The projected AF of the Representative Concentration Pathway simulations are lower than their expected radiative forcing (RF) in 2095 but agree well with efficacy weighted forcings from integrated assessment models. The smaller AF, compared to RF, is likely due to cloud adjustment. Multimodel time series of temperature change and AF from 1850 to 2100 have large intermodel spreads throughout the period. The intermodel spread of temperature change is principally driven by forcing differences in the present day and climate feedback differences in 2095, although forcing differences are still important for model spread at 2095. We find no significant relationship between the equilibrium climate sensitivity (ECS) of a model and its 2003 AF, in contrast to that found in older models where higher ECS models generally had less forcing. Given the large present‐day model spread, there is no indication of any tendency by modelling groups to adjust their aerosol forcing in order to produce observed trends. Instead, some CMIP5 models have a relatively large positive forcing and overestimate the observed temperature change.
Key PointsRadiative forcing of RCP scenarios in 2095 is underestimatedCMIP5 models have a large spread in temperature changes and radiative forcingClimate sensitivity was not adjusted to reproduce observed temperature trends
The recent range expansion of Barred Owls (
Strix varia
) into the Pacific Northwest, where the species now co-occurs with the endemic Northern Spotted Owl (
Strix occidentalis
caurina
), resulted in ...a unique opportunity to investigate potential competition between two congeneric, previously allopatric species. The primary criticism of early competition research was the use of current species' distribution patterns to infer past processes; however, the recent expansion of the Barred Owl and the ability to model the processes that result in site occupancy (i.e., colonization and extinction) allowed us to address the competitive process directly rather than inferring past processes through current patterns. The purpose of our study was to determine whether Barred Owls had any negative effects on occupancy dynamics of nesting territories by Northern Spotted Owls and how these effects were influenced by habitat characteristics of Spotted Owl territories. We used single-species, multi-season occupancy models and covariates quantifying Barred Owl detections and habitat characteristics to model extinction and colonization rates of Spotted Owl pairs in southern Oregon, USA. We observed a strong, negative association between Barred Owl detections and colonization rates and a strong positive effect of Barred Owl detections on extinction rates of Spotted Owls. We observed increased extinction rates in response to decreased amounts of old forest at the territory core and higher colonization rates when old-forest habitat was less fragmented. Annual site occupancy for pairs reflected the strong effects of Barred Owls on occupancy dynamics with much lower occupancy rates predicted for territories where Barred Owls were detected. The strong Barred Owl and habitat effects on occupancy dynamics of Spotted Owls provided evidence of interference competition between the species. These effects increase the importance of conserving large amounts of contiguous, old-forest habitat to maintain Northern Spotted Owls in the landscape.
Slow ecological processes challenge conservation. Short-term variability can obscure the importance of slower processes that may ultimately determine the state of a system. Furthermore, management ...actions with slow responses can be hard to justify. One response to slow processes is to explicitly concentrate analysis on state dynamics. Here, we focus on identifying drivers of Northern Spotted Owl (Strix occidentalis caurina) territorial occupancy dynamics across 11 study areas spanning their geographic range and forecasting response to potential management actions. Competition with Barred Owls (Strix varia) has increased Spotted Owl territory extinction probabilities across all study areas and driven recent declines in Spotted Owl populations. Without management intervention, the Northern Spotted Owl subspecies will be extirpated from parts of its current range within decades. In the short term, Barred Owl removal can be effective. Over longer time spans, however, maintaining or improving habitat conditions can help promote the persistence of northern spotted owl populations. In most study areas, habitat effects on expected Northern Spotted Owl territorial occupancy are actually greater than the effects of competition from Barred Owls. This study suggests how intensive management actions (removal of a competitor) with rapid results can complement a slower management action (i.e., promoting forest succession).
The northern spotted owl (Strix occidentalis caurina) is one of the most intensively studied raptors in the world; however, little is known about the impacts of wildfire on the subspecies and how ...they use recently burned areas. Three large-scale wildfires in southwest Oregon provided an opportunity to investigate the short-term impacts of wildfire and salvage logging on site occupancy of spotted owls. We used Program MARK to develop single-species, multiple-season models of site occupancy using data collected during demographic surveys of spotted owl territories. In our first analysis, we compared occupancy dynamics of spotted owl nesting territories before (1992—2002). and after the Timbered Rock burn (2003—2006) to a reference area in the south Cascade Mountains that was not affected recently by wildfire. We found that the South Cascades had greater colonization probabilities than Timbered Rock before and after wildfire (β̂ = 1.31, 95% CI = 0.60−2.03), and colonization probabilities declined over time at both areas (β̂ = −0.06, 95% CI = −0.12 to 0.00). Extinction probabilities were greater at South Cascades than at Timbered Rock prior to the burn (β̂ = 0.69, 95% CI = 0.23−2.62); however, Timbered Rock had greater extinction probabilities following wildfire (β̂ = 1.46, 95% CI = 0.29−2.62). The Timbered Rock and South Cascades study areas had similar patterns in site occupancy prior to the Timbered Rock burn (1992—2001). Furthermore, Timbered Rock had a 64% reduction in site occupancy following wildfire (2003—2006) in contrast to a 25% reduction in site occupancy at South Cascades during the same time period. This suggested that the combined effects of habitat disturbances due to wildfire and subsequent salvage logging on private lands negatively affected site occupancy by spotted owls. In our second analysis, we investigated the relationship between wildfire, salvage logging, and occupancy of spotted owl territories at the Biscuit, Quartz, and Timbered Rock burns from 2003 to 2006. Extinction probabilities increased as the combined area of early seral forests, high severity burn, and salvage logging increased within the core nesting areas (β̂ = 1.88, 95% CI = 0.10−3.66). We were unable to identify any relationships between initial occupancy or colonization probabilities and the habitat covariates that we considered in our analysis where the β coefficient did not overlap zero. We concluded that site occupancy of spotted owl nesting territories declined in the short-term following wildfire, and habitat modification and loss due to past timber harvest, high severity fire, and salvage logging jointly contributed to declines in site occupancy.
Estimates of species' vital rates and an understanding of the factors affecting those parameters over time and space can provide crucial information for management and conservation. We used ...mark–recapture, reproductive output, and territory occupancy data collected during 1985–2013 to evaluate population processes of Northern Spotted Owls (Strix occidentalis caurina) in 11 study areas in Washington, Oregon, and northern California, USA. We estimated apparent survival, fecundity, recruitment, rate of population change, and local extinction and colonization rates, and investigated relationships between these parameters and the amount of suitable habitat, local and regional variation in meteorological conditions, and competition with Barred Owls (Strix varia). Data were analyzed for each area separately and in a meta-analysis of all areas combined, following a strict protocol for data collection, preparation, and analysis. We used mixed effects linear models for analyses of fecundity, Cormack-Jolly-Seber open population models for analyses of apparent annual survival (φ), and a reparameterization of the Jolly-Seber capture–recapture model (i.e. reverse Jolly-Seber; RJS) to estimate annual rates of population change (λRJS) and recruitment. We also modeled territory occupancy dynamics of Northern Spotted Owls and Barred Owls in each study area using 2-species occupancy models. Estimated mean annual rates of population change (λ) suggested that Spotted Owl populations declined from 1.2% to 8.4% per year depending on the study area. The weighted mean estimate of λ for all study areas was 0.962 (± 0.019 SE; 95% CI: 0.925–0.999), indicating an estimated range-wide decline of 3.8% per year from 1985 to 2013. Variation in recruitment rates across the range of the Spotted Owl was best explained by an interaction between total winter precipitation and mean minimum winter temperature. Thus, recruitment rates were highest when both total precipitation (29 cm) and minimum winter temperature (−9.5°C) were lowest. Barred Owl presence was associated with increased local extinction rates of Spotted Owl pairs for all 11 study areas. Habitat covariates were related to extinction rates for Spotted Owl pairs in 8 of 11 study areas, and a greater amount of suitable owl habitat was generally associated with decreased extinction rates. We observed negative effects of Barred Owl presence on colonization rates of Spotted Owl pairs in 5 of 11 study areas. The total amount of suitable Spotted Owl habitat was positively associated with colonization rates in 5 areas, and more habitat disturbance was associated with lower colonization rates in 2 areas. We observed strong declines in derived estimates of occupancy in all study areas. Mean fecundity of females was highest for adults (0.309 ± 0.027 SE), intermediate for 2-yr-olds (0.179 ± 0.040 SE), and lowest for 1-yr-olds (0.065 ± 0.022 SE). The presence of Barred Owls and habitat covariates explained little of the temporal variation in fecundity in most study areas. Climate covariates occurred in competitive fecundity models in 8 of 11 study areas, but support for these relationships was generally weak. The fecundity meta-analysis resulted in 6 competitive models, all of which included the additive effects of geographic region and annual time variation. The 2 top-ranked models also weakly supported the additive negative effects of the amount of suitable core area habitat, Barred Owl presence, and the amount of edge habitat on fecundity. We found strong support for a negative effect of Barred Owl presence on apparent survival of Spotted Owls in 10 of 11 study areas, but found few strong effects of habitat on survival at the study area scale. Climate covariates occurred in top or competitive survival models for 10 of 11 study areas, and in most cases the relationships were as predicted; however, there was little consistency among areas regarding the relative importance of specific climate covariates. In contrast, meta-analysis results suggested that Spotted Owl survival was higher across all study areas when the Pacific Decadal Oscillation (PDO) was in a warming phase and the Southern Oscillation Index (SOI) was negative, with a strongly negative SOI indicative of El Niño events. The best model that included the Barred Owl covariate (BO) was ranked 4th and also included the PDO covariate, but the BO effect was strongly negative. Our results indicated that Northern Spotted Owl populations were declining throughout the range of the subspecies and that annual rates of decline were accelerating in many areas. We observed strong evidence that Barred Owls negatively affected Spotted Owl populations, primarily by decreasing apparent survival and increasing local territory extinction rates. However, the amount of suitable owl habitat, local weather, and regional climatic patterns also were related to survival, occupancy (via colonization rate), recruitment, and, to a lesser extent, fecundity, although there was inconsistency in regard to which covariates were important for particular demographic parameters or across study areas. In the study areas where habitat was an important source of variation for Spotted Owl demographics, vital rates were generally positively associated with a greater amount of suitable owl habitat. However, Barred Owl densities may now be high enough across the range of the Northern Spotted Owl that, despite the continued management and conservation of suitable owl habitat on federal lands, the long-term prognosis for the persistence of Northern Spotted Owls may be in question without additional management intervention. Based on our study, the removal of Barred Owls from the Green Diamond Resources (GDR) study area had rapid, positive effects on Northern Spotted Owl survival and the rate of population change, supporting the hypothesis that, along with habitat conservation and management, Barred Owl removal may be able to slow or reverse Northern Spotted Owl population declines on at least a localized scale.
Alzheimer's disease is defined by abnormal levels of amyloid and tau biomarkers. Even cognitively normal older adults with clinically relevant amyloid and tau levels perform worse on memory tests. ...However, it is unclear if the relationship between biomarker level and memory extends below clinical thresholds. We hypothesized that even subclinical biomarker levels are associated with memory when measured with neuropsychological tests designed to detect dysfunction in preclinical disease states. In a group of cognitively normal, “biomarker-negative” older men and women, we investigated the relationship between cerebrospinal fluid biomarker levels and memory measured with the ModRey, a list-learning task designed to assess memory in preclinical and cognitively normal adults. Cerebrospinal amyloid levels were associated with ModRey memory retention, the proportion of information retained after a delay period. When older adults with mild impairment were included, cerebrospinal fluid tau levels were also associated with ModRey retention. The association of amyloid and tau levels with memory was independent of each other. These results suggest cognitive changes associated with Alzheimer's disease pathology might occur earlier than currently thought.
•CSF amyloid correlates with memory retention even in biomarker-negative older adults.•CSF amyloid and tau significantly predict memory retention independent of each other.•AD-related cognitive changes may be occurring earlier than currently believed.
The small GTPase Rac controls cell morphology, gene expression, and reactive oxygen species formation. Manipulations of Rac activity levels in the cerebellum result in motor coordination defects, but ...activators of Rac in the cerebellum are unknown. P-Rex family guanine-nucleotide exchange factors activate Rac. We show here that, whereas P-Rex1 expression within the brain is widespread, P-Rex2 is specifically expressed in the Purkinje neurons of the cerebellum. We have generated P-Rex2⁻/⁻ and P-Rex1⁻/⁻/P-Rex2⁻/⁻ mice, analyzed their Purkinje cell morphology, and assessed their motor functions in behavior tests. The main dendrite is thinned in Purkinje cells of P-Rex2⁻/⁻ pups and dendrite structure appears disordered in Purkinje cells of adult P-Rex2⁻/⁻ and P-Rex1⁻/⁻/P-Rex2⁻/⁻ mice. P-Rex2⁻/⁻ mice show a mild motor coordination defect that progressively worsens with age and is more pronounced in females than in males. P-Rex1⁻/⁻/P-Rex2⁻/⁻ mice are ataxic, with reduced basic motor activity and abnormal posture and gait, as well as impaired motor coordination even at a young age. We conclude that P-Rex1 and P-Rex2 are important regulators of Purkinje cell morphology and cerebellar function.
GH and GH receptors are expressed throughout life, and GH elicits a diverse range of responses, including growth and altered metabolism. It is therefore important to understand the full spectrum of ...GH signaling pathways and cellular responses. We applied mass spectrometry-based phosphoproteomics combined with stable isotope labeling with amino acids in cell culture to identify proteins rapidly phosphorylated in response to GH in 3T3-F442A preadipocytes. We identified 132 phosphosites in 95 proteins that exhibited rapid (5 or 15 min) GH-dependent statistically significant increases in phosphorylation by more than or equal to 50% and 96 phosphosites in 46 proteins that were down-regulated by GH by more than or equal to 30%. Several of the GH-stimulated phosphorylation sites were known (e.g. regulatory Thr/Tyr in Erks 1 and 2, Tyr in signal transducers and activators of transcription (Stat) 5a and 5b, Ser939 in tuberous sclerosis protein (TSC) 2 or tuberin). The remaining 126 GH-stimulated sites were not previously associated with GH. Kyoto Encyclopedia of Genes and Genomes pathway analysis of GH-stimulated sites indicated enrichment in proteins associated with the insulin and mammalian target of rapamycin (mTOR) pathways, regulation of the actin cytoskeleton, and focal adhesions. Akt/protein kinase A consensus sites (RXRXXS/T) were the most commonly phosphorylated consensus sites. Immunoblotting confirmed GH-stimulated phosphorylation of all seven novel GH-dependent sites tested regulatory sites in proline-rich Akt substrate, 40 kDA (PRAS40), regulatory associated protein of mTOR, ATP-citrate lyase, Na(+)/H(+) exchanger-1, N-myc downstream regulated gene 1, and Shc). The immunoblot results suggest that many, if not most, of the GH-stimulated phosphosites identified in this large-scale quantitative phosphoproteomics analysis, including sites in multiple proteins in the Akt/ mTOR complex 1 pathway, are phosphorylated in response to GH. Their identification significantly broadens our thinking of GH-regulated cell functions.
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