Convergence in Nitrogen Deposition and Cryptic Isotopic Variation Across Urban and Agricultural Valleys in Northern Utah

The extent to which atmospheric nitrogen (N) deposition reflects land use differences and biogenic versus fossil fuel reactive N sources remains unclear yet represents a critical uncertainty in ecosystem N budgets. We compared N concentrations and isotopes in precipitation-event bulk (wet + dry) deposition across nearby valleys in northern Utah with contrasting land use (highly urban versus intensive agriculture/low-density urban). We predicted greater nitrate (NO3−) versus ammonium (NH4+) and higher δ15N of NO3− and NH4+ in urban valley sites. Contrary to expectations, annual N deposition (3.5–5.1 kg N ha−1 yr−1) and inorganic N concentrations were similar within and between valleys. Significant summertime decreases in δ15N of NO3− possibly reflected increasing biogenic emissions in the agricultural valley. Organic N was a relatively minor component of deposition (~13%). Nearby paired wildland sites had similar bulk deposition N concentrations as the urban and agricultural sites. Weighted bulk deposition δ15N was similar to natural ecosystems (−0.6 ± 0.7‰). Fine atmospheric particulate matter (PM2.5) had consistently high values of bulk δ15N (15.6 ± 1.4‰), δ15N in NH4+ (22.5 ± 1.6‰), and NO3− (8.8 ± 0.7‰), consistent with equilibrium fractionation with gaseous species. The δ15N in bulk deposition NH4+ varied by more than 40‰, and spatial variation in δ15N within storms exceeded 10‰. Sporadically high values of δ15N were thus consistent with increased particulate N contributions as well as potential N source variation. Despite large differences in reactive N sources, urban and agricultural landscapes are not always strongly reflected in the composition and fluxes of local N deposition—an important consideration for regional-scale ecosystem models

A web-based normative calculator for the uniform data set (UDS) neuropsychological test battery

Introduction: With the recent publication of new criteria for the diagnosis of preclinical Alzheimer's disease (AD), there is a need for neuropsychological tools that take premorbid functioning into account in order to detect subtle cognitive decline. Using demographic adjustments is one method for increasing the sensitivity of commonly used measures. We sought to provide a useful online z-score calculator that yields estimates of percentile ranges and adjusts individual performance based on sex, age and/or education for each of the neuropsychological tests of the National Alzheimer's Coordinating Center Uniform Data Set (NACC, UDS). In addition, we aimed to provide an easily accessible method of creating norms for other clinical researchers for their own, unique data sets. Methods: Data from 3,268 clinically cognitively-normal older UDS subjects from a cohort reported by Weintraub and colleagues (2009) were included. For all neuropsychological tests, z-scores were estimated by subtracting the raw score from the predicted mean and then dividing this difference score by the root mean squared error term (RMSE) for a given linear regression model. Results: For each neuropsychological test, an estimated z-score was calculated for any raw score based on five different models that adjust for the demographic predictors of SEX, AGE and EDUCATION, either concurrently, individually or without covariates. The interactive online calculator allows the entry of a raw score and provides five corresponding estimated z-scores based on predictions from each corresponding linear regression model. The calculator produces percentile ranks and graphical output. Conclusions: An interactive, regression-based, normative score online calculator was created to serve as an additional resource for UDS clinical researchers, especially in guiding interpretation of individual performances that appear to fall in borderline realms and may be of particular utility for operationalizing subtle cognitive impairment present according to the newly proposed criteria for Stage 3 preclinical Alzheimer's disease

Double jeopardy: the influence of excessive daytime sleepiness and impaired cognition on health‐related quality of life in adults with heart failure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106066/1/ejhfhfs054.pd

Predictors of Objectively Measured Medication Nonadherence in Adults With Heart Failure

Background—Medication nonadherence rates are high. The factors predicting nonadherence in heart failure remain unclear. Methods and Results—A sample of 202 adults with heart failure was enrolled from the northeastern United States and followed for 6 months. Specific aims were to describe the types of objectively measured medication adherence (eg, taking, timing, dosing, drug holidays) and to identify contributors to nonadherence 6 months after enrollment. Latent growth mixture modeling was used to identify distinct trajectories of adherence. Indicators of the 5 World Health Organization dimensions of adherence (socioeconomic, condition, therapy, patient, and healthcare system) were tested to identify contributors to nonadherence. Two distinct trajectories were identified and labeled persistent adherence (77.8%) and steep decline (22.3%). Three contributors to the steep decline in adherence were identified. Participants with lapses in attention (adjusted OR, 2.65; P=0.023), those with excessive daytime sleepiness (OR, 2.51; P=0.037), and those with ≥2 medication dosings per day (OR, 2.59; P=0.016) were more likely to have a steep decline in adherence over time than to have persistent adherence. Conclusions—Two distinct patterns of adherence were identified. Three potentially modifiable contributors to nonadherence have been identified

Bcl-xL Deamidation Is a Critical Switch in the Regulation of the Response to DNA Damage

AbstractThe therapeutic value of DNA-damaging antineoplastic agents is dependent upon their ability to induce tumor cell apoptosis while sparing most normal tissues. Here, we show that a component of the apoptotic response to these agents in several different types of tumor cells is the deamidation of two asparagines in the unstructured loop of Bcl-xL, and we demonstrate that deamidation of these asparagines imports susceptibility to apoptosis by disrupting the ability of Bcl-xL to block the proapoptotic activity of BH3 domain-only proteins. Conversely, Bcl-xL deamidation is actively suppressed in fibroblasts, and suppression of deamidation is an essential component of their resistance to DNA damage-induced apoptosis. Our results suggest that the regulation of Bcl-xL deamidation has a critical role in the tumor-specific activity of DNA-damaging antineoplastic agents

Exploratory Case‐Control Analysis of Psychosocial Factors and Adult Periodontitis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141163/1/jper1060.pd

In vivo cholinergic basal forebrain atrophy predicts cognitive decline in de novo Parkinson’s disease

Cognitive impairments are a prevalent and disabling non-motor complication of Parkinson’s disease, but with variable expression and progression. The onset of serious cognitive decline occurs alongside substantial cholinergic denervation, but imprecision of previously available techniques for in vivo measurement of cholinergic degeneration limit their use as predictive cognitive biomarkers. However, recent developments in stereotactic mapping of the cholinergic basal forebrain have been found useful for predicting cognitive decline in prodromal stages of Alzheimer’s disease. These methods have not yet been applied to longitudinal Parkinson’s disease data. In a large sample of people with de novo Parkinson’s disease (n = 168), retrieved from the Parkinson’s Progressive Markers Initiative database, we measured cholinergic basal forebrain volumes, using morphometric analysis of T1-weighted images in combination with a detailed stereotactic atlas of the cholinergic basal forebrain nuclei. Using a binary classification procedure, we defined patients with reduced basal forebrain volumes (relative to age) at baseline, based on volumes measured in a normative sample (n = 76). Additionally, relationships between the basal forebrain volumes at baseline, risk of later cognitive decline, and scores on up to 5 years of annual cognitive assessments were assessed with regression, survival analysis and linear mixed modelling. In patients, smaller volumes in a region corresponding to the nucleus basalis of Meynert were associated with greater change in global cognitive, but not motor scores after 2 years. Using the binary classification procedure, patients classified as having smaller than expected volumes of the nucleus basalis of Meynert had ∼3.5-fold greater risk of being categorized as mildly cognitively impaired over a period of up to 5 years of follow-up (hazard ratio = 3.51). Finally, linear mixed modelling analysis of domain-specific cognitive scores revealed that patients classified as having smaller than expected nucleus basalis volumes showed more severe and rapid decline over up to 5 years on tests of memory and semantic fluency, but not on tests of executive function. Thus, we provide the first evidence that volumetric measurement of the nucleus basalis of Meynert can predict early cognitive decline. Our methods therefore provide the opportunity for multiple-modality biomarker models to include a cholinergic biomarker, which is currently lacking for the prediction of cognitive deterioration in Parkinson’s disease. Additionally, finding dissociated relationships between nucleus basalis status and domain-specific cognitive decline has implications for understanding the neural basis of heterogeneity of Parkinson’s disease-related cognitive decline