Implementation of a medication delivery service for ambulatory oncology infusion patients.

OBJECTIVE: Patients receiving infusions for the treatment of cancer are commonly prescribed supportive care medications which are filled through retail pharmacies. The initial phase of the COVID-19 pandemic created hurdles for patients to receive supportive care medications due to concerns related to exposure risk. Meds-to-Chemo Chairs (M2CC) was created allowing an onsite retail pharmacy to dispense and hand-deliver supportive care prescriptions to patients in the infusion suite. The purpose of this study was to assess the value of this program. DATA SOURCES: The volume of prescriptions dispensed through the M2CC service, as well as the financial impact, was tracked through the prescription software system used by the onsite retail pharmacy dispensing and delivering the medications. DATA SUMMARY: Through the first 2.5 years of the program, M2CC has delivered over 13,000 prescriptions with an estimated gross revenue of $3.5 million. CONCLUSIONS: The M2CC medication delivery program has proved to be highly successful and feasible.

Combining population genomics with demographic analyses highlights habitat patchiness and larval dispersal as determinants of connectivity in coastal fish species.

Gene flow shapes spatial genetic structure and the potential for local adaptation. Among marine animals with nonmigratory adults, the presence or absence of a pelagic larval stage is thought to be a key determinant in shaping gene flow and the genetic structure of populations. In addition, the spatial distribution of suitable habitats is expected to influence the distribution of biological populations and their connectivity patterns. We used whole genome sequencing to study demographic history and reduced representation (double-digest restriction associated DNA) sequencing data to analyse spatial genetic structure in broadnosed pipefish (Syngnathus typhle). Its main habitat is eelgrass beds, which are patchily distributed along the study area in southern Norway. Demographic connectivity among populations was inferred from long-term (~30-year) population counts that uncovered a rapid decline in spatial correlations in abundance with distance as short as ~2 km. These findings were contrasted with data for two other fish species that have a pelagic larval stage (corkwing wrasse, Symphodus melops; black goby, Gobius niger). For these latter species, we found wider spatial scales of connectivity and weaker genetic isolation-by-distance patterns, except where both species experienced a strong barrier to gene flow, seemingly due to lack of suitable habitat. Our findings verify expectations that a fragmented habitat and absence of a pelagic larval stage promote genetic structure, while presence of a pelagic larvae stage increases demographic connectivity and gene flow, except perhaps over extensive habitat gaps.

Responses of ichthyoplankton assemblages to the recent marine heatwave and previous climate fluctuations in several Northeast Pacific marine ecosystems.

The effects of climate warming on ecosystem dynamics are widespread throughout the world's oceans. In the Northeast Pacific, large-scale climate patterns such as the El Niño/Southern Oscillation and Pacific Decadal Oscillation, and recently unprecedented warm ocean conditions from 2014 to 2016, referred to as a marine heatwave (MHW), resulted in large-scale ecosystem changes. Larval fishes quickly respond to environmental variability and are sensitive indicators of ecosystem change. Categorizing ichthyoplankton dynamics across marine ecosystem in the Northeast Pacific can help elucidate the magnitude of assemblage shifts, and whether responses are synchronous or alternatively governed by local responses to regional oceanographic conditions. We analyzed time-series data of ichthyoplankton abundances from four ecoregions in the Northeast Pacific ranging from subarctic to subtropical: the Gulf of Alaska (1981-2017), British Columbia (2001-2017), Oregon (1998-2017), and the southern California Current (1981-2017). We assessed the impact of the recent (2014-2016) MHW and how ichthyoplankton assemblages responded to past major climate perturbations since 1981 in these ecosystems. Our results indicate that the MHW caused widespread changes in the ichthyoplankton fauna along the coast of the Northeast Pacific Ocean, but impacts differed between marine ecosystems. For example, abundances for most dominant taxa were at all-time lows since the beginning of sampling in the Gulf of Alaska and British Columbia, while in Oregon and the southern California Current species richness increased as did abundances of species associated with warmer waters. Lastly, species associated with cold waters also increased in abundances close to shore in southern California during the MHW, a pattern that was distinctly different from previous El Niño events. We also found several large-scale, synchronized ichthyoplankton assemblage composition shifts during past major climate events. Current climate projections suggest that MHWs will become more intense and thus our findings can help project future changes in larval dynamics, allowing for improved ecosystem management decisions.

Inferring genetic connectivity in real populations, exemplified by coastal and oceanic Atlantic cod.

Genetic data are commonly used to estimate connectivity between putative populations, but translating them to demographic dispersal rates is complicated. Theoretical equations that infer a migration rate based on the genetic estimator FST , such as Wright's equation, FST ≈ 1/(4Nem + 1), make assumptions that do not apply to most real populations. How complexities inherent to real populations affect migration was exemplified by Atlantic cod in the North Sea and Skagerrak and was examined within an age-structured model that incorporated genetic markers. Migration was determined under various scenarios by varying the number of simulated migrants until the mean simulated level of genetic differentiation matched a fixed level of genetic differentiation equal to empirical estimates. Parameters that decreased the Ne /Nt ratio (where Ne is the effective and Nt is the total population size), such as high fishing mortality and high fishing gear selectivity, increased the number of migrants required to achieve empirical levels of genetic differentiation. Higher maturity-at-age and lower selectivity increased Ne /Nt and decreased migration when genetic differentiation was fixed. Changes in natural mortality, fishing gear selectivity, and maturity-at-age within expected limits had a moderate effect on migration when genetic differentiation was held constant. Changes in population size had the greatest effect on the number of migrants to achieve fixed levels of FST , particularly when genetic differentiation was low, FST ≈ 10-3 Highly variable migration patterns, compared with constant migration, resulted in higher variance in genetic differentiation and higher extreme values. Results are compared with and provide insight into the use of theoretical equations to estimate migration among real populations.

Effects of climate and demography on reproductive phenology of a harvested marine fish population.

Shifts in phenology are a well-documented ecological response to changes in climate, which may or may not be adaptive for a species depending on the climate sensitivity of other ecosystem processes. Furthermore, phenology may be affected by factors in addition to climate, which may accentuate or dampen climate-driven phenological responses. In this study, we investigate how climate and population demographic structure jointly affect spawning phenology of a fish species of major commercial importance: walleye pollock (Gadus chalcogrammus). We use 32 years of data from ichthyoplankton surveys to reconstruct timing of pollock reproduction in the Gulf of Alaska and find that the mean date of spawning has varied by over 3 weeks throughout the last >3 decades. Climate clearly drives variation in spawn timing, with warmer temperatures leading to an earlier and more protracted spawning period, consistent with expectations of advanced spring phenology under warming. However, the effects of temperature were nonlinear, such that additional warming above a threshold value had no additional effect on phenology. Population demographics were equally as important as temperature: An older and more age-diverse spawning stock tended to spawn earlier and over a longer duration than a younger stock. Our models suggest that demographic shifts associated with sustainable harvest rates could shift the mean spawning date 7 days later and shorten the spawning season by 9 days relative to an unfished population, independent of thermal conditions. Projections under climate change suggest that spawn timing will become more stable for walleye pollock in the future, but it is unknown what the consequences of this stabilization will be for the synchrony of first-feeding larvae with production of zooplankton prey in spring. With ongoing warming in the world's oceans, knowledge of the mechanisms underlying reproductive phenology can improve our ability to monitor and manage species under changing climate conditions.

Fine-scale population dynamics in a marine fish species inferred from dynamic state-space models.

Identifying the spatial scale of population structuring is critical for the conservation of natural populations and for drawing accurate ecological inferences. However, population studies often use spatially aggregated data to draw inferences about population trends and drivers, potentially masking ecologically relevant population sub-structure and dynamics. The goals of this study were to investigate how population dynamics models with and without spatial structure affect inferences on population trends and the identification of intrinsic drivers of population dynamics (e.g. density dependence). Specifically, we developed dynamic, age-structured, state-space models to test different hypotheses regarding the spatial structure of a population complex of coastal Atlantic cod (Gadus morhua). Data were from a 93-year survey of juvenile (age 0 and 1) cod sampled along >200 km of the Norwegian Skagerrak coast. We compared two models: one which assumes all sampled cod belong to one larger population, and a second which assumes that each fjord contains a unique population with locally determined dynamics. Using the best supported model, we then reconstructed the historical spatial and temporal dynamics of Skagerrak coastal cod. Cross-validation showed that the spatially structured model with local dynamics had better predictive ability. Furthermore, posterior predictive checks showed that a model which assumes one homogeneous population failed to capture the spatial correlation pattern present in the survey data. The spatially structured model indicated that population trends differed markedly among fjords, as did estimates of population parameters including density-dependent survival. Recent biomass was estimated to be at a near-record low all along the coast, but the finer scale model indicated that the decline occurred at different times in different regions. Warm temperatures were associated with poor recruitment, but local changes in habitat and fishing pressure may have played a role in driving local dynamics. More generally, we demonstrated how state-space models can be used to test evidence for population spatial structure based on survey time-series data. Our study shows the importance of considering spatially structured dynamics, as the inferences from such an approach can lead to a different ecological understanding of the drivers of population declines, and fundamentally different management actions to restore populations.

Population diversity and the portfolio effect in an exploited species.

One of the most pervasive themes in ecology is that biological diversity stabilizes ecosystem processes and the services they provide to society, a concept that has become a common argument for biodiversity conservation. Species-rich communities are thought to produce more temporally stable ecosystem services because of the complementary or independent dynamics among species that perform similar ecosystem functions. Such variance dampening within communities is referred to as a portfolio effect and is analogous to the effects of asset diversity on the stability of financial portfolios. In ecology, these arguments have focused on the effects of species diversity on ecosystem stability but have not considered the importance of biologically relevant diversity within individual species. Current rates of population extirpation are probably at least three orders of magnitude higher than species extinction rates, so there is a pressing need to clarify how population and life history diversity affect the performance of individual species in providing important ecosystem services. Here we use five decades of data from Oncorhynchus nerka (sockeye salmon) in Bristol Bay, Alaska, to provide the first quantification of portfolio effects that derive from population and life history diversity in an important and heavily exploited species. Variability in annual Bristol Bay salmon returns is 2.2 times lower than it would be if the system consisted of a single homogenous population rather than the several hundred discrete populations it currently consists of. Furthermore, if it were a single homogeneous population, such increased variability would lead to ten times more frequent fisheries closures. Portfolio effects are also evident in watershed food webs, where they stabilize and extend predator access to salmon resources. Our results demonstrate the critical importance of maintaining population diversity for stabilizing ecosystem services and securing the economies and livelihoods that depend on them. The reliability of ecosystem services will erode faster than indicated by species loss alone.

Centennial-scale fluctuations and regional complexity characterize Pacific salmon population dynamics over the past five centuries.

Observational data from the past century have highlighted the importance of interdecadal modes of variability in fish population dynamics, but how these patterns of variation fit into a broader temporal and spatial context remains largely unknown. We analyzed time series of stable nitrogen isotopes from the sediments of 20 sockeye salmon nursery lakes across western Alaska to characterize temporal and spatial patterns in salmon abundance over the past ∼500 y. Although some stocks varied on interdecadal time scales (30- to 80-y cycles), centennial-scale variation, undetectable in modern-day catch records and survey data, has dominated salmon population dynamics over the past 500 y. Before 1900, variation in abundance was clearly not synchronous among stocks, and the only temporal signal common to lake sediment records from this region was the onset of commercial fishing in the late 1800s. Thus, historical changes in climate did not synchronize stock dynamics over centennial time scales, emphasizing that ecosystem complexity can produce a diversity of ecological responses to regional climate forcing. Our results show that marine fish populations may alternate between naturally driven periods of high and low abundance over time scales of decades to centuries and suggest that management models that assume time-invariant productivity or carrying capacity parameters may be poor representations of the biological reality in these systems.

Climate and population density drive changes in cod body size throughout a century on the Norwegian coast.

Understanding how populations respond to changes in climate requires long-term, high-quality datasets, which are rare for marine systems. We estimated the effects of climate warming on cod lengths and length variability using a unique 91-y time series of more than 100,000 individual juvenile cod lengths from surveys that began in 1919 along the Norwegian Skagerrak coast. Using linear mixed-effects models, we accounted for spatial population structure and the nested structure of the survey data to reveal opposite effects of spring and summer warming on juvenile cod lengths. Warm summer temperatures in the coastal Skagerrak have limited juvenile growth. In contrast, warmer springs have resulted in larger juvenile cod, with less variation in lengths within a cohort, possibly because of a temperature-driven contraction in the spring spawning period. A density-dependent reduction in length was evident only at the highest population densities in the time series, which have rarely been observed in the last decade. If temperatures rise because of global warming, nonlinearities in the opposing temperature effects suggest that negative effects of warmer summers will increasingly outweigh positive effects of warmer springs, and the coastal Skagerrak will become ill-suited for Atlantic cod.

Outcomes and predictors of response to fractionated radiotherapy as primary treatment for intracranial meningiomas.

Background: Surgery is the primary treatment for most meningiomas. However, primary fractionated radiotherapy (fRT) remains an option for patients with larger meningiomas in challenging anatomic locations or patients at prohibitively high surgical risk. Outcome prediction for these patients is uncertain and cannot be guided by histopathology without available tumor tissue from surgery. Therefore, we aimed to assess the clinical factors that contribute to treatment failure in a large cohort of meningiomas consecutively treated with fRT as primary therapy, with the goal of identifying predictors of response. Methods: Patients treated with primary fRT for intracranial meningiomas from 1998 to 2017 were reviewed. Those who received primary surgical resection, radiosurgery, previous fRT, or had <6 months of clinical follow-up were excluded. We applied logistic regression and Cox regression modeling to ascertain key predictors of treatment failure, progression-free survival (PFS), and adverse events (AE) following fRT. Results: Our cohort included 137 meningiomas, 21 of which progressed after fRT (median PFS 3.45 years). Progressive meningiomas had a larger median gross tumor volume (GTV) compared to those that remained stable (19.1 cm3 vs 9.6 cm3, p = 2.86 × 10-2). GTV > 11.27 cm3 was independently predictive of progression and larger GTV was associated with higher risk of significant (grades 3/4) AE following fRT. Cavernous sinus and optic nerve sheath meningiomas had overall excellent outcomes post-fRT. Conclusions: We present a large cohort of meningiomas treated with primary fRT and find GTV and anatomic location to be key predictors of outcome, adding to the complex treatment considerations for this heterogeneous disease.

Fractionated radiotherapy for surgically resected intracranial meningiomas: A multicentre retrospective cohort study.

BACKGROUND: Aside from surgical resection, the only standard of care treatment modality for meningiomas is radiotherapy (RT). Despite this, few studies have focused on identifying clinical covariates associated with failure of fractionated RT following surgical resection (fRT), and the timing of fRT following surgery still remains controversial (adjuvant versus salvage fRT). We assessed the outcomes of the largest, multi-institutional cohort of surgically resected meningiomas treated with subsequent adjuvant and salvage fRT to identify factors associated with local freedom from recurrence (LFFR) over 3-10 years post-fRT and to determine the optimal timing of fRT. METHODS: Patients with intracranial meningiomas who underwent surgery and fRT between 1997 and 2018 were included. Primary endpoints were radiographic recurrence/progression and time to progression from the completion of fRT. RESULTS: 404 meningiomas were included for analysis. Of these, 167 (41.3%) recurred post-fRT. Clinical covariates independently associated with worse PFS post-fRT included receipt of previous RT to the meningioma, having a WHO grade 3 meningioma or recurrent meningioma, the meningioma having a higher MIB1-index or brain invasion on pathology, and older patient age at diagnosis. Subgroup analysis identified higher MIB1-index as a histological factor associated with poorer LFFR in WHO grade 2 meningiomas. 179 patients underwent adjuvant RT shortly after surgery whereas 225 patients had delayed, salvage fRT after recurrence/progression. Following propensity score matching, patients that underwent adjuvant fRT had improved LFFR post-fRT compared to those that received salvage fRT. CONCLUSION: There is a paucity of clinical factors that can predict a meningioma's response to fRT following surgery. Adjuvant fRT may be associated with improved PFS post-fRT compared to salvage fRT. Molecular biomarkers of RT-responsiveness are needed to better inform fRT treatment decisions.

Methods to evaluate the impact of SARS-CoV-2 nucleocapsid mutations on antigen detection by rapid diagnostic tests.

Mutations in the nucleocapsid of SARS-CoV-2 may interfere with antigen detection by diagnostic tests. We used several methods to evaluate the effect of various SARS-CoV-2 nucleocapsid mutations on the performance of the Panbio™ and BinaxNOW™ lateral flow rapid antigen tests and a prototype high-throughput immunoassay that utilizes Panbio antibodies. Variant detection was also evaluated by immunoblot and BIAcore™ assay. A panel of 23 recombinant nucleocapsid antigens (rAgs) were produced that included mutations found in circulating SARS-CoV-2 variants, including variants of concern. All mutant rAgs were detected by all assays, at a sensitivity equivalent to wild-type control (Wuhan strain). Thus, using a rAg approach, we found that the SARS-CoV-2 nucleocapsid mutations examined do not directly impact antigen detection or antigen assay performance.

Using a climate attribution statistic to inform judgments about changing fisheries sustainability.

Sustainability-maintaining catches within the historical range of socially and ecologically acceptable values-is key to fisheries success. Climate change may rapidly threaten sustainability, and recognizing these instances is important for effective climate adaptation. Here, we present one approach for evaluating changing sustainability under a changing climate. We use Bayesian regression models to compare fish population processes under historical climate norms and emerging anthropogenic extremes. To define anthropogenic extremes we use the Fraction of Attributable Risk (FAR), which estimates the proportion of risk for extreme ocean temperatures that can be attributed to human influence. We illustrate our approach with estimates of recruitment (production of young fish, a key determinant of sustainability) for two exploited fishes (Pacific cod Gadus macrocephalus and walleye pollock G. chalcogrammus) in a rapidly warming ecosystem, the Gulf of Alaska. We show that recruitment distributions for both species have shifted towards zero during anthropogenic climate extremes. Predictions based on the projected incidence of anthropogenic temperature extremes indicate that expected recruitment, and therefore fisheries sustainability, is markedly lower in the current climate than during recent decades. Using FAR to analyze changing population processes may help fisheries managers and stakeholders to recognize situations when historical sustainability expectations should be reevaluated.

Impact of Peer-Assisted Learning on Ultrasound.

PURPOSE: The aim of this study was to understand how peer-assisted learning (PAL) could be utilized by physician assistant (PA) students in an ultrasound student interest group (USIG) as a means of developing cognitive confidence and practical competence with the imaging modality. METHODS: An observational study that included 3 USIG workshops was designed. Pre- and postworkshop surveys were administered. All first-year PA students, regardless of participation in the USIG workshops, were asked to complete the voluntary and anonymous surveys. RESULTS: A statistically significant difference between those who attended at least one workshop and those who did not attend any workshops on their postworkshop scores (p = 0.02) was seen. There was a statistically significant association between the number of workshops attended and the postworkshop difference (p = 0.03). CONCLUSION: Results show that, in the context of social cognitive theory, PAL is an efficacious learning modality that enhances learner and tutor performance in ultrasound.

Ecosystem response persists after a prolonged marine heatwave.

Some of the longest and most comprehensive marine ecosystem monitoring programs were established in the Gulf of Alaska following the environmental disaster of the Exxon Valdez oil spill over 30 years ago. These monitoring programs have been successful in assessing recovery from oil spill impacts, and their continuation decades later has now provided an unparalleled assessment of ecosystem responses to another newly emerging global threat, marine heatwaves. The 2014-2016 northeast Pacific marine heatwave (PMH) in the Gulf of Alaska was the longest lasting heatwave globally over the past decade, with some cooling, but also continued warm conditions through 2019. Our analysis of 187 time series from primary production to commercial fisheries and nearshore intertidal to offshore oceanic domains demonstrate abrupt changes across trophic levels, with many responses persisting up to at least 5 years after the onset of the heatwave. Furthermore, our suite of metrics showed novel community-level groupings relative to at least a decade prior to the heatwave. Given anticipated increases in marine heatwaves under current climate projections, it remains uncertain when or if the Gulf of Alaska ecosystem will return to a pre-PMH state.

Improving nutritional discharge planning and follow up in older medical inpatients: Hospital to Home Outreach for Malnourished Elders.

AIM: Nutritional decline during and after acute hospitalisation is common amongst older people. This quality improvement initiative aimed to introduce a dietitian-led discharge planning and follow-up program (Hospital to Home Outreach for Malnourished Elders, HHOME) at two hospitals within usual resources to improve nutritional and functional recovery. METHODS: Prospective pre-post evaluation design was used. Medical patients aged 65+ years at-risk of malnutrition and discharged to independent living were eligible. Participants receiving nutrition discharge planning and dietetic telephone follow up for four weeks post-discharge ('HHOME') were compared to usual care ('pre-HHOME'). Nutritional (weight and mini nutritional assessment (MNA)), functional (gait speed, handgrip strength and modified Barthel index) and assessment of quality of life-6D (AQoL-6D) outcomes were measured on discharge and six weeks later. RESULTS: At six weeks, no significant difference in nutritional status was observed between pre-HHOME (n = 39) and HHOME cohorts, although the HHOME cohort on average maintained weight while pre-HHOME cohort lost weight (0.4 ± 2.9 kg vs -1.0 ± 3.7 kg, P = 0.060). Greater improvement in gait speed was seen in HHOME group (+0.24 ± 0.27 vs +0.11 ± 0.22, P = 0.046) with no other significant outcome improvements. Across both cohorts, half were readmitted to hospital and 10% died within 12 weeks post-discharge. CONCLUSIONS: The nutritional discharge planning and dietetic follow up provided to older community-living malnourished patients made a small impact on nutritional and functional parameters but clinical outcomes remained poor.

Stochasticity and determinism: how density-independent and density-dependent processes affect population variability.

A persistent debate in population ecology concerns the relative importance of environmental stochasticity and density dependence in determining variability in adult year-class strength, which contributes to future reproduction as well as potential yield in exploited populations. Apart from the strength of the processes, the timing of density regulation may affect how stochastic variation, for instance through climate, translates into changes in adult abundance. In this study, we develop a life-cycle model for the population dynamics of a large marine fish population, Northeast Arctic cod, to disentangle the effects of density-independent and density-dependent processes on early life-stages, and to quantify the strength of compensatory density dependence in the population. The model incorporates information from scientific surveys and commercial harvest, and dynamically links multiple effects of intrinsic and extrinsic factors on all life-stages, from eggs to spawners. Using a state-space approach we account for observation error and stochasticity in the population dynamics. Our findings highlight the importance of density-dependent survival in juveniles, indicating that this period of the life cycle largely determines the compensatory capacity of the population. Density regulation at the juvenile life-stage dampens the impact of stochastic processes operating earlier in life such as environmental impacts on the production of eggs and climate-dependent survival of larvae. The timing of stochastic versus regulatory processes thus plays a crucial role in determining variability in adult abundance. Quantifying the contribution of environmental stochasticity and compensatory mechanisms in determining population abundance is essential for assessing population responses to climate change and exploitation by humans.

Rationally designed peptoids modulate aggregation of amyloid-beta 40.

Alzheimer's disease (AD) is the most common form of dementia and the sixth leading cause of death in the United States. Plaques composed of aggregated amyloid-beta protein (Aß) accumulate between the neural cells in the brain and are associated with dementia and cellular death. Many strategies have been investigated to prevent Aß self-assembly into disease-associated ß-sheet amyloid aggregates; however, a promising therapeutic has not yet been identified. In this study, a peptoid-based mimic of the peptide KLVFF (residues 16-20 of Aß) was tested for its ability to modulate Aß aggregation. Peptoid JPT1 includes chiral, aromatic side chains to induce formation of a stable helical secondary structure that allows for greater interaction between the aromatic side chains and the cross ß-sheet of Aß. JPT1 was found to modulate Aß40 aggregation, specifically decreasing lag time to ß-sheet aggregate formation as well as the total number of fibrillar, ß-sheet structured aggregates formed. These results suggest that peptoids may be able to limit the formation of Aß aggregates that are associated with AD.

Impact of comorbidities and drug therapy on development of renal impairment in a predominantly African American and Hispanic HIV clinic population.

PURPOSE: Renal impairment in human immunodeficiency virus (HIV)-infected patients could potentially be caused by many factors. HIV-related renal impairment risks have been little studied in African Americans and Hispanics. We investigated the impact of HIV itself, highly active antiretroviral therapy (HAART), comorbidities, and non-HIV-related drug treatment on glomerular filtration rate in a predominantly African American/Hispanic HIV-infected population who had received HAART for at least one year. This study was a retrospective electronic medical record database evaluation of renal impairment risks in a largely African American/Hispanic HIV population obtaining medical care at an HIV clinic in Dallas, Texas. METHODS: Proportional hazards models were used to investigate an association between an estimated glomerular filtration rate decrease >25% from baseline (ie, renal impairment) and demographics, antiretroviral/nonantiretroviral medications, comorbidities (hypertension, diabetes mellitus, hepatitis C virus [HCV] infection, hepatitis B virus [HBV] infection), CD4+ counts, viral load, and duration patients were monitored at the clinic (time on study). RESULTS: In total, 323 patients were evaluated: 82% males; 61% African American/12% Hispanic/19% Caucasian; mean age 37.9 years (standard deviation [SD] 8.5); 6% HBV-positive; 34% HCV-positive; 29% hypertensive; 3% diabetic; 52% tenofovir-treated; mean weight 75.4 kg (SD, 15.4); mean estimated glomerular filtration 114.5 mL/min/1.73 m(2) (SD, 36.7) using the Modification of Diet in Renal Disease (MDRD) calculation method; mean creatinine clearance (from which estimated glomerular filtration was extrapolated) by the Cockcroft-Gault calculation method 120.6 mL/min/1.73 m(2) (SD, 41.2); mean time on study 2.7 years (SD, 1.0 year). An estimated glomerular filtration rate decrease of >25% from baseline was significantly associated with time on study (P = 0.0017; hazards ratio [HR] = 0.999) and hypertension (HR = 1.706; P = 0.0158) by the MDRD method, and with age (HR = 1.039; P = 0.0077), weight (HR = 0.987; P = 0.0023), and time on study (HR = 0.999; P = 0.0043) by extrapolation of Cockcroft-Gault creatinine clearance calculation. No specific HAART agent was associated with significant renal impairment risk by the definition used in this study. CONCLUSION: This retrospective database study showed time on study, hypertension, weight, and age to be the only significant predictors of an estimated glomerular filtration rate decrease >25% from baseline.

A coherent signature of anthropogenic nitrogen deposition to remote watersheds of the Northern Hemisphere.

Humans have more than doubled the amount of reactive nitrogen (Nr) added to the biosphere, yet most of what is known about its accumulation and ecological effects is derived from studies of heavily populated regions. Nitrogen (N) stable isotope ratios ((15)N:(14)N) in dated sediments from 25 remote Northern Hemisphere lakes show a coherent signal of an isotopically distinct source of N to ecosystems beginning in 1895 ± 10 years (±1 standard deviation). Initial shifts in N isotope composition recorded in lake sediments coincide with anthropogenic CO(2) emissions but accelerate with widespread industrial Nr production during the past half century. Although current atmospheric Nr deposition rates in remote regions are relatively low, anthropogenic N has probably influenced watershed N budgets across the Northern Hemisphere for over a century.