Hydrotalcite Colloidal Stability and Interactions with Uranium(VI) at Neutral to Alkaline pH.

In the United Kingdom, decommissioning of legacy spent fuel storage facilities involves the retrieval of radioactive sludges that have formed as a result of corrosion of Magnox nuclear fuel. Retrieval of sludges may re-suspend a colloidal fraction of the sludge, thereby potentially enhancing the mobility of radionuclides including uranium. The colloidal properties of the layered double hydroxide (LDH) phase hydrotalcite, a key product of Magnox fuel corrosion, and its interactions with U(VI) are of interest. This is because colloidal hydrotalcite is a potential transport vector for U(VI) under the neutral-to-alkaline conditions characteristic of the legacy storage facilities and other nuclear decommissioning scenarios. Here, a multi-technique approach was used to investigate the colloidal stability of hydrotalcite and the U(VI) sorption mechanism(s) across pH 7-11.5 and with variable U(VI) surface loadings (0.01-1 wt %). Overall, hydrotalcite was found to form stable colloidal suspensions between pH 7 and 11.5, with some evidence for Mg2+ leaching from hydrotalcite colloids at pH ≤ 9. For systems with U present, >98% of U(VI) was removed from the solution in the presence of hydrotalcite, regardless of pH and U loading, although the sorption mode was affected by both pH and U concentrations. Under alkaline conditions, U(VI) surface precipitates formed on the colloidal hydrotalcite nanoparticle surface. Under more circumneutral conditions, Mg2+ leaching from hydrotalcite and more facile exchange of interlayer carbonate with the surrounding solution led to the formation of uranyl carbonate species (e.g., Mg(UO2(CO3)3)2-(aq)). Both X-ray absorption spectroscopy (XAS) and luminescence analysis confirmed that these negatively charged species sorbed as both outer- and inner-sphere tertiary complexes on the hydrotalcite surface. These results demonstrate that hydrotalcite can form pseudo-colloids with U(VI) under a wide range of pH conditions and have clear implications for understanding the uranium behavior in environments where hydrotalcite and other LDHs may be present.

Using EEG to decode semantics during an artificial language learning task.

BACKGROUND: As we learn a new nonnative language (L2), we begin to build a new map of concepts onto orthographic representations. Eventually, L2 can conjure as rich a semantic representation as our native language (L1). However, the neural processes for mapping a new orthographic representation to a familiar meaning are not well understood or characterized. METHODS: Using electroencephalography and an artificial language that maps symbols to English words, we show that it is possible to use machine learning models to detect a newly formed semantic mapping as it is acquired. RESULTS: Through a trial-by-trial analysis, we show that we can detect when a new semantic mapping is formed. Our results show that, like word meaning representations evoked by a L1, the localization of the newly formed neural representations is highly distributed, but the representation may emerge more slowly after the onset of the symbol. Furthermore, our mapping of word meanings to symbols removes the confound of the semantics to the visual characteristics of the stimulus, a confound that has been difficult to disentangle previously. CONCLUSION: We have shown that the L1 semantic representation conjured by a newly acquired L2 word can be detected using decoding techniques, and we give the first characterization of the emergence of that mapping. Our work opens up new possibilities for the study of semantic representations during L2 learning.

Words as a window: Using word embeddings to explore the learned representations of Convolutional Neural Networks.

As deep neural net architectures minimize loss, they accumulate information in a hierarchy of learned representations that ultimately serve the network's final goal. Different architectures tackle this problem in slightly different ways, but all create intermediate representational spaces built to inform their final prediction. Here we show that very different neural networks trained on two very different tasks build knowledge representations that display similar underlying patterns. Namely, we show that the representational spaces of several distributional semantic models bear a remarkable resemblance to several Convolutional Neural Network (CNN) architectures (trained for image classification). We use this information to explore the network behavior of CNNs (1) in pretrained models, (2) during training, and (3) during adversarial attacks. We use these findings to motivate several applications aimed at improving future research on CNNs. Our work illustrates the power of using one model to explore another, gives new insights into the function of CNN models, and provides a framework for others to perform similar analyses when developing new architectures. We show that one neural network model can provide a window into understanding another.

Greater BOLD Variability is Associated With Poorer Cognitive Function in an Adult Lifespan Sample.

Moment-to-moment fluctuations in brain signal assessed by functional magnetic resonance imaging blood oxygenation level dependent (BOLD) variability is increasingly thought to represent important "signal" rather than measurement-related "noise." Efforts to characterize BOLD variability in healthy aging have yielded mixed outcomes, demonstrating both age-related increases and decreases in BOLD variability and both detrimental and beneficial associations. Utilizing BOLD mean-squared-successive-differences (MSSD) during a digit n-back working memory (WM) task in a sample of healthy adults (aged 20-94 years; n = 171), we examined effects of aging on whole-brain 1) BOLD variability during task (mean condition MSSD across 0-2-3-4 back conditions), 2) BOLD variability modulation to incrementally increasing WM difficulty (linear slope from 0-2-3-4 back), and 3) the association of age-related differences in variability with in- and out-of-scanner WM performance. Widespread cortical and subcortical regions evidenced increased mean variability with increasing age, with no regions evidencing age-related decrease in variability. Additionally, posterior cingulate/precuneus exhibited increased variability to WM difficulty. Notably, both age-related increases in BOLD variability were associated with significantly poorer WM performance in all but the oldest adults. These findings lend support to the growing corpus suggesting that brain-signal variability is altered in healthy aging; specifically, in this adult lifespan sample, BOLD-variability increased with age and was detrimental to cognitive performance.

Functional Connectivity Within and Between n-Back Modulated Regions: An Adult Lifespan Psychophysiological Interaction Investigation.

Introduction: Working memory (WM) and its blood-oxygen-level-dependent-related parametric modulation under load decrease with age. Functional connectivity (FC) generally increases with WM load; however, how aging impacts connectivity and whether this is load-dependent, region-dependent, or associated with cognitive performance is unclear. Methods: This study examines these questions in 170 healthy adults (meanage = 52.99 ± 19.18) who completed functional magnetic resonance imaging scanning during an n-back task (0-, 2-, 3-, and 4-back). The FC was estimated by utilizing a modified generalized psychophysiological interaction approach with seeds from fronto-parietal (FP) and default mode (DM) regions that modulated to n-back difficulty. The FC analyses focused on both connectivity during WM engagement (task vs. control) and connectivity in response to increased WM load (linear slope across conditions). Each analysis utilized within- and between-region FC, predicted by age (linear or quadratic), and its associations with in- and out-of-scanner task performance. Results: Engaging in WM either generally (task vs. control) or as a function of difficulty strengthened integration within- and between-FP and DM regions. Notably, these task-sensitive functional connections were robust to the effects of age. Stronger negative FC between FP and DM regions was also associated with better WM performance in an age-dependent manner, occurring selectively in middle-aged and older adults. Discussion: These results suggest that FC is critical for engaging in cognitively demanding tasks, and its lack of sensitivity to healthy aging may provide a means to maintain cognition across the adult lifespan. Thus, this study highlights the contribution of maintenance in brain function to support working memory processing with aging.

Pediatric Patient With Concurrent Eosinophilic Esophagitis, Erosive Reflux Esophagitis, and Barrett's Esophagus.

Eosinophilic esophagitis and Barrett's esophagus are believed to be separate disease processes, with erosive esophagitis leading to Barrett's esophagus. We report a rare case of concurrent diagnoses in a pediatric patient and examine the relevant genetic profiles in the esophagus.

Contribution of iron and Aß to age differences in entorhinal and hippocampal subfield volume.

OBJECTIVE: To test the hypothesis that the combination of elevated global ß-AMYLOID (Aß) burden and greater striatal iron content would be associated with smaller entorhinal cortex (ERC) volume, but not hippocampal subfield volumes, we measured volume and iron content using high-resolution MRI and Aß using PET imaging in a cross-sectional sample of 70 cognitively normal older adults. METHODS: Participants were scanned with florbetapir 18F PET to obtain Aß standardized uptake value ratios. Susceptibility-weighted MRI was collected and processed to yield R2* images, and striatal regions of interest (ROIs) were manually placed to obtain a measure of striatal iron burden. Ultra-high resolution T2/PD-weighted MRIs were segmented to measure medial temporal lobe (MTL) volumes. Analyses were conducted using mixed-effects models with MTL ROI as a within-participant factor; age, iron content, and Aß as between-participant factors; and MTL volumes (ERC and 3 hippocampal subfield regions) as the dependent variable. RESULTS: The model indicated a significant 4-way interaction among age, iron, Aß, and MTL region. Post hoc analyses indicated that the 3-way interaction among age, Aß, and iron content was selective to the ERC (ß = -3.34, standard error = 1.33, 95% confidence interval -5.95 to -0.72), whereas a significant negative association between age and ERC volume was present only in individuals with both elevated iron content and Aß. CONCLUSIONS: These findings highlight the importance of studying Aß in the context of other, potentially synergistic age-related brain factors such as iron accumulation and the potential role for iron as an important contributor to the earliest, preclinical stages of pathologic aging.

Beta-amyloid burden predicts poorer mnemonic discrimination in cognitively normal older adults.

One of the earliest indicators of Alzheimer's disease pathology is the presence of beta-amyloid (Αß) protein deposition. Significant amyloid deposition is evident even in older adults who exhibit little or no overt cognitive or memory impairment. Hippocampal-based processes that help distinguish between highly similar memory representations may be the most susceptible to early disease pathology. Amyloid associations with memory have been difficult to establish, possibly because typical memory assessments do not tax hippocampal operations sufficiently. Thus, the present study utilized a spatial mnemonic discrimination task designed to tax hippocampal pattern separation/completion processes in a sample of cognitively normal middle-aged and older adults (53-98 years old) who underwent PET 18F-Florbetapir Αß scanning. The degree of interference between studied and new information varied, allowing for an examination of mnemonic discrimination as a function of mnemonic similarity. Results indicated that greater beta-amyloid burden was associated with poorer discrimination across decreasing levels of interference, suggesting that even subtle elevation of beta-amyloid in cognitively normal adults is associated with impoverished performance on a hippocampally demanding memory task. The present study demonstrates that degree of amyloid burden negatively impacts the ability of aging adults to accurately distinguish old from increasingly distinct new information, providing novel insight into the cognitive expression of beta-amyloid neuropathology.

Winter Wheat Yield Response to Plant Density as a Function of Yield Environment and Tillering Potential: A Review and Field Studies.

Wheat (Triticum aestivum L.) grain yield response to plant density is inconsistent, and the mechanisms driving this response are unclear. A better understanding of the factors governing this relationship could improve plant density recommendations according to specific environmental and genetics characteristics. Therefore, the aims of this paper were to: i) execute a synthesis-analysis of existing literature related to yield-plant density relationship to provide an indication of the need for different agronomic optimum plant density (AOPD) in different yield environments (YEs), and ii) explore a data set of field research studies conducted in Kansas (USA) on yield response to plant density to determine the AOPD at different YEs, evaluate the effect of tillering potential (TP) on the AOPD, and explain changes in AOPD via variations in wheat yield components. Major findings of this study are: i) the synthesis-analysis portrayed new insights of differences in AOPD at varying YEs, reducing the AOPD as the attainable yield increases (with AOPD moving from 397 pl m-2 for the low YE to 191 pl m-2 for the high YE); ii) the field dataset confirmed the trend observed in the synthesis-analysis but expanded on the physiological mechanisms underpinning the yield response to plant density for wheat, mainly highlighting the following points: a) high TP reduces the AOPD mainly in high and low YEs, b) at canopy-scale, both final number of heads and kernels per square meter were the main factors improving yield response to plant density under high TP, c) under varying YEs, at per-plant-scale, a compensation between heads per plant and kernels per head was the main factor contributing to yield with different TP.

Domain general processes moderate age-related performance differences on the mnemonic similarity task.

Several prominent domain general theories (e.g., processing speed and inhibitory function) have been developed to explain cognitive changes associated with aging. A bias to "pattern complete" in aging has also been suggested to account for some of the age-related changes in episodic memory. The current experiments test whether domain-general processes of cognitive aging moderate age-related performance decrements on the mnemonic similarity task, a task thought to rely on hippocampal pattern separation and completion. The study phase of the mnemonic similarity task, a memory task with old, new, and similar trials at recognition, was manipulated to assess the contribution of processing speed (Experiment 1 - different encoding times) and inhibitory function (Experiment 2 - item-level directed forgetting) to age-related performance differences in a sample of 100 healthy younger and older adults. Both experiments exhibited significant interactions between age group and encoding manipulation, replicating a decrement in performance in older adults, and indicating that processing speed and inhibitory function moderate this effect. Results suggest that age-related differences in performance on the mnemonic similarity task can at least partially be accounted for by experimental manipulations of domain general processes that also decline with age.

Striatal iron content is linked to reduced fronto-striatal brain function under working memory load.

Non-heme iron accumulation contributes to age-related decline in brain structure and cognition via a cascade of oxidative stress and inflammation, although its effect on brain function is largely unexplored. Thus, we examine the impact of striatal iron on dynamic range of BOLD modulation to working memory load. N â€‹= â€‹166 healthy adults (age 20-94) underwent cognitive testing and an imaging session including n-back (0-, 2-, 3-, and 4-back fMRI), R2*-weighted imaging, and pcASL to measure cerebral blood flow. A statistical model was constructed to predict voxelwise BOLD modulation by age, striatal iron content and an age â€‹× â€‹iron interaction, controlling for cerebral blood flow, sex, and task response time. A significant interaction between age and striatal iron content on BOLD modulation was found selectively in the putamen, caudate, and inferior frontal gyrus. Greater iron was associated with reduced modulation to difficulty, particularly in middle-aged and younger adults with greater iron content. Further, iron-related decreases in modulation were associated with poorer executive function in an age-dependent manner. These results suggest that iron may contribute to differences in functional brain activation prior to older adulthood, highlighting the potential role of iron as an early factor contributing to trajectories of functional brain aging.

Contributions of White Matter Connectivity and BOLD Modulation to Cognitive Aging: A Lifespan Structure-Function Association Study.

The ability to flexibly modulate brain activation to increasing cognitive challenge decreases with aging. This age-related decrease in dynamic range of function of regional gray matter may be, in part, due to age-related degradation of regional white matter tracts. Here, a lifespan sample of 171 healthy adults (aged 20-94) underwent magnetic resonance imaging (MRI) scanning including diffusion-weighted imaging (for tractography) and functional imaging (a digit n-back task). We utilized structural equation modeling to test the hypothesis that age-related decrements in white matter microstructure are associated with altered blood-oxygen-level-dependent (BOLD) modulation, and both in turn, are associated with scanner-task accuracy and executive function performance. Specified structural equation model evidenced good fit, demonstrating that increased age negatively affects n-back task accuracy and executive function performance in part due to both degraded white matter tract microstructure and reduced task-difficulty-related BOLD modulation. We further demonstrated that poorer white matter microstructure integrity was associated with weakened BOLD modulation, particularly in regions showing positive modulation effects, as opposed to negative modulation effects. This structure-function association study provides further evidence that structural connectivity influences functional activation, and the two mechanisms in tandem are predictive of cognitive performance, both during the task, and for cognition measured outside the scanner environment.

The role of hippocampal subfield volume and fornix microstructure in episodic memory across the lifespan.

Advancing age is associated with both declines in episodic memory and degradation of medial temporal lobe (MTL) structure. The contribution of MTL to episodic memory is complex and depends upon the interplay among hippocampal subfields and surrounding structures that participate in anatomical connectivity to the cortex through inputs (parahippocampal and entorhinal cortices) and outputs (fornix). However, the differential contributions of MTL system components in mediating age effects on memory remain unclear. In a sample of 177 healthy individuals aged 20-94 we collected high-resolution T1-weighted, ultrahigh-resolution T2/PD, and diffusion tensor imaging (DTI) MRI sequences on a 3T Phillips Achieva scanner. Hippocampal subfield and entorhinal cortex (ERC) volumes were measured from T2/PD scans using a combination of manual tracings and training of a semiautomated pipeline. Parahippocampal gyrus volume was estimated using Freesurfer and DTI scans were used to obtain diffusion metrics from tractography of the fornix. Item and associative episodic memory constructs were formed from multiple tests. Competing structural equation models estimating differential association among these structural variables were specified and tested to investigate whether and how fornix diffusion and volume of parahippocampal gyrus, ERC, and hippocampal subfields mediate age effects on associative and/or item memory. The most parsimonious, best-fitting model included an anatomically based path through the MTL as well as a single hippocampal construct which combined all subfields. Results indicated that fornix microstructure independently mediated the effect of age on associative memory, but not item memory. Additionally, all regions and estimated paths (including fornix) combined to significantly mediate the age-associative memory relationship. These findings suggest that preservation of fornix connectivity and MTL structure with aging is important for maintenance of associative memory performance across the lifespan.

Increasing beta-amyloid deposition in cognitively healthy aging predicts nonlinear change in BOLD modulation to difficulty.

Recent evidence indicates that the relationship between increased beta-amyloid (Aß) deposition and functional task-activation can be characterized by a non-linear trajectory of change in functional activation (Foster et al., 2017), explaining mixed results in prior literature showing both increases and decreases in activation as a function of beta-amyloid burden in cognitively normal adults. Here we sought to replicate this nonlinear effect in the same sample using a different functional paradigm to test the generalizability of this phenomenon. Participants (N = 68 healthy adults aged 49-94) underwent fMRI (0-, 2-, 3-, 4-back working memory task; WM) and 18F-Florbetapir PET scanning. A parametric WM load contrast was used as the dependent variable in a model with age, mean cortical Aß, and Aß2 as predictors. Results revealed that nonlinear amyloid (Aß2) was a significant negative predictor of modulation of activation to WM load in two large inferior clusters: bilateral subcortical nuclei and bilateral lateral cerebellum. Individuals with slightly elevated Aß burden evidenced greater modulation as compared to individuals with little or no Aß burden, whereas individuals with the greatest Aß burden evidenced lesser modulation as compared to individuals with slightly elevated Aß. Increased modulation to WM load predicted better task accuracy and executive function measured outside the scanner. The current study provides further evidence for a dose-response, nonlinear relationship between increasing Aß burden and alteration in brain activation in cognitively healthy adults, extending the existing evidence to dynamic range of activation to task difficulty, and reconciling seemingly discrepant effects of amyloid on brain function.

Both hyper- and hypo-activation to cognitive challenge are associated with increased beta-amyloid deposition in healthy aging: A nonlinear effect.

Beta-amyloid (Aß) positive individuals hyper-activate brain regions compared to those not at-risk; however, hyperactivation is then thought to diminish as Alzheimer's disease symptomatology begins, evidencing eventual hypoactivation. It remains unclear when in the disease staging this transition occurs. We hypothesized that differential levels of amyloid burden would be associated with both increased and decreased activation (i.e., a quadratic trajectory) in cognitively-normal adults. Participants (N = 62; aged 51-94) underwent an fMRI spatial distance-judgment task and Amyvid-PET scanning. Voxelwise regression modeled age, linear-Aß, and quadratic-Aß as predictors of BOLD activation to difficult spatial distance-judgments. A significant quadratic-Aß effect on BOLD response explained differential activation in bilateral angular/temporal and medial prefrontal cortices, such that individuals with slightly elevated Aß burden exhibited hyperactivation whereas even higher Aß burden was then associated with hypoactivation. Importantly, in high-Aß individuals, Aß load moderated the effect of BOLD activation on behavioral task performance, where in lower-elevation, greater deactivation was associated with better accuracy, but in higher-elevation, greater deactivation was associated with poorer accuracy during the task. This study reveals a dose-response, quadratic relationship between increasing Aß burden and alterations in BOLD activation to cognitive challenge in cognitively-normal individuals that suggests 1) the shift from hyper-to hypo-activation may begin early in disease staging, 2) depends, in part, on degree of Aß burden, and 3) tracks cognitive performance.

Dynamic range in BOLD modulation: lifespan aging trajectories and association with performance.

Alteration of dynamic range of modulation to cognitive difficulty has been proposed as a salient predictor of cognitive aging. Here, we examine in 171 adults (aged 20-94 years) the effects of age on dynamic modulation of blood oxygenation-level dependent activation to difficulty in parametrically increasing working memory (WM) load (0-, 2-, 3-, and 4-back conditions). First, we examined parametric increases and decreases in activation to increasing WM load (positive modulation effect and negative modulation effect). Second, we examined the effect of age on modulation to difficulty (WM load) to identify regions that differed with age as difficulty increased (age-related positive and negative modulation effects). Weakened modulation to difficulty with age was found in both the positive modulation (middle frontal, superior/inferior parietal) and negative modulation effect (deactivated) regions (insula, cingulate, medial superior frontal, fusiform, and parahippocampal gyri, hippocampus, and lateral occipital cortex). Age-related alterations to positive modulation emerged later in the lifespan than negative modulation. Furthermore, these effects were significantly coupled in that greater upmodulation was associated with lesser downmodulation. Importantly, greater fronto-parietal upmodulation to difficulty and greater downmodulation of deactivated regions were associated with better task accuracy and upmodulation with better WM span measured outside the scanner. These findings suggest that greater dynamic range of modulation of activation to cognitive challenge is in service of current task performance, as well as generalizing to cognitive ability beyond the scanner task, lending support to its utility as a marker of successful cognitive aging.

Differential Aging Trajectories of Modulation of Activation to Cognitive Challenge in APOE ε4 Groups: Reduced Modulation Predicts Poorer Cognitive Performance.

The present study was designed to investigate the effect of a genetic risk factor for Alzheimer's disease (AD), ApolipoproteinE ε4 (APOEε4), on the ability of the brain to modulate activation in response to cognitive challenge in a lifespan sample of healthy human adults. A community-based sample of 181 cognitively intact, healthy adults were recruited from the Dallas-Fort Worth metroplex. Thirty-one APOEε4+ individuals (48% women), derived from the parent sample, were matched based on sex, age, and years of education to 31 individuals who were APOEε4-negative (APOEε4-). Ages ranged from 20 to 86 years of age. Blood oxygen level-dependent functional magnetic resonance imaging was collected during the performance of a visuospatial distance judgment task with three parametric levels of difficulty. Multiple regression was used in a whole-brain analysis with age, APOE group, and their interaction predicting functional brain modulation in response to difficulty. Results revealed an interaction between age and APOE in a large cluster localized primarily to the bilateral precuneus. APOEε4- individuals exhibited age-invariant modulation in response to task difficulty, whereas APOEε4+ individuals showed age-related reduction of modulation in response to increasing task difficulty compared with ε4- individuals. Decreased modulation in response to cognitive challenge was associated with reduced task accuracy as well as poorer name-face associative memory performance. Findings suggest that APOEε4 is associated with a reduction in the ability of the brain to dynamically modulate in response to cognitive challenge. Coupled with a significant genetic risk factor for AD, changes in modulation may provide additional information toward identifying individuals potentially at risk for cognitive decline associated with preclinical AD.SIGNIFICANCE STATEMENT Understanding how risk factors for Alzheimer's disease (AD) affect brain function and cognition in healthy adult samples may help to identify the biomarkers needed to detect nonsymptomatic, preclinical phases of the disease. Findings from the current study show that ApolipoproteinE ε4-positive (APOEε4+) individuals exhibit an altered lifespan trajectory in the ability of the brain to dynamically modulate function to cognitive challenge compared with APOEε4- individuals. This effect manifests in otherwise healthy individuals who are at increased risk for AD in the precuneus, a salient region for early AD changes. Notably, these functional alterations are detrimental to performance, and thus, the combination of a genetic risk factor and altered modulation may provide important information for identifying individuals who are at increased risk for AD.

Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. OBJECTIVE: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. RESULTS AND LIMITATIONS: A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. CONCLUSIONS: The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. PATIENT SUMMARY: The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.