Person-specific dynamics between negative emotions and suicidal thoughts.

INTRODUCTION: Recent technology has enabled researchers to collect ecological momentary assessments (EMA) to examine within-person correlates of suicidal thoughts. Prior studies examined generalized temporal dynamics of emotions and suicidal thinking over brief periods, but it is not yet known how variable these processes are across people. METHOD: We use data EMA data delivered over two weeks with youth/young adults (N = 60) who reported past year self-injurious thoughts/behaviors. We used group iterative multiple model estimation (GIMME) to model group- and person-specific associations of negative emotions (i.e., fear, sadness, shame, guilt, and anger) and suicidal thoughts. RESULTS: 29 participants (48.33%) reported at least one instance of a suicidal thought and were included in GIMME models. In group level models, we consistently observed autoregressive effects for suicidal thoughts (e.g., earlier thoughts predicting later thoughts), although the magnitude and direction of this link varied from person-to-person. Among emotions, sadness was most frequently associated with contemporaneous suicidal thoughts, but this was evident for less than half of the sample, while other emotional correlates of suicidal thoughts broadly differed across people. No emotion variable was linked to future suicidal thoughts in >14% of the sample, CONCLUSIONS: Emotion-based correlates of suicidal thoughts are heterogeneous across people. Better understanding of the individual-level pathways maintaining suicidal thoughts/behaviors may lead to more effective, personalized interventions.

MinION Sequencing of Fungi in Sub-Saharan African Air and a Novel LAMP Assay for Rapid Detection of the Tropical Phytopathogenic Genus Lasiodiplodia.

To date, there have been no DNA-based metabarcoding studies into airborne fungi in tropical Sub-Saharan Africa. In this initial study, 10 air samples were collected onto Vaseline-coated acrylic rods mounted on drones flown at heights of 15-50 meters above ground for 10-15 min at three sites in Ghana. Purified DNA was extracted from air samples, the internal transcribed spacer (ITS) region was amplified using fungal-specific primers, and MinION third-generation amplicon sequencing was undertaken with downstream bioinformatics analyses utilizing GAIA cloud-based software (at genus taxonomic level). Principal coordinate analyses based on Bray-Curtis beta diversity dissimilarity values found no clear evidence for the structuring of fungal air communities, nor were there significant differences in alpha diversity, based on geographic location (east vs. central Ghana), underlying vegetation type (cocoa vs. non-cocoa), or height above ground level (15-23 m vs. 25-50 m), and despite the short flight times (10-15 min), ~90 operational taxonomic units (OTUs) were identified in each sample. In Ghanaian air, fungal assemblages were skewed at the phylum taxonomic level towards the ascomycetes (53.7%) as opposed to basidiomycetes (24.6%); at the class level, the Dothideomycetes were predominant (29.8%) followed by the Agaricomycetes (21.8%). The most common fungal genus in Ghanaian air was cosmopolitan and globally ubiquitous Cladosporium (9.9% of reads). Interestingly, many fungal genera containing economically important phytopathogens of tropical crops were also identified in Ghanaian air, including Corynespora, Fusarium, and Lasiodiplodia. Consequently, a novel loop-mediated isothermal amplification (LAMP) assay, based on translation elongation factor-1α sequences, was developed and tested for rapid, sensitive, and specific detection of the fungal phytopathogenic genus Lasiodiplodia. Potential applications for improved tropical disease management are considered.

New phosphorus losses via tile drainage depend on fertilizer form, placement, and timing.

Agricultural phosphorus (P) losses are harmful to water quality, but knowledge gaps about the importance of fertilizer management practices on new (recently applied) sources of P may limit P loss mitigation efforts. Weighted regression models applied to subsurface tile drainage water quality data enabled estimating the new P losses associated with 155 P applications in Ohio and Indiana, USA. Daily discharge and dissolved reactive P (DRP) and total P (TP) loads were used to detect increases in P loss following each application which was considered new P. The magnitude of new P losses was small relative to fertilizer application rates, averaging 79.3 g DRP ha-1 and 96.1 g TP ha-1 , or <3% of P applied. The eight largest new P losses surpassed 330 g DRP ha-1 or 575 g TP ha-1 . New P loss mitigation strategies should focus on broadcast liquid manure applications; on average, manure applications caused greater new P losses than inorganic fertilizers, and surface broadcast applications were associated with greater new P losses than injected or incorporated applications. Late fall applications risked having large new P losses applications. On an annual basis, new P contributed an average of 14% of DRP and 5% of TP losses from tile drains, which is much less than previous studies that included surface runoff, suggesting that tile drainage is relatively buffered with regard to new P losses. Therefore old (preexisting soil P) P sources dominated tile drain P losses, and P loss reduction efforts will need to address this source.

An experimental investigation into the effect of negative affect on the behavioral economic demand for alcohol.

OBJECTIVE: It is hypothesized that alcohol use is reinforcing when used as a strategy to cope with negative affect. Although the evidence for this hypothesis in observational data is weak, some experimental evidence suggests that the behavioral economic demand for alcohol increases immediately following a negative emotional event. We hypothesized that people show a higher demand for alcohol following negative (vs. neutral) mood inductions and that this effect is stronger in people who report heavier drinking compared to people who report lighter drinking as well as stronger on days characterized by higher coping motives and negative urgency. METHOD: 309 college students who reported recent alcohol consumption (MAUDIT = 6.86) completed the alcohol purchase task after being subjected to 12 mood inductions (six negative, six neutral, order randomized) on 12 separate days. RESULTS: In our preregistered analyses, we found no evidence that the behavioral economic demand for alcohol was elevated following negative mood inductions. The mood inductions in our study were not as strong as has been reported in previous research, weakening the preregistered inferences. In exploratory analyses performed on a subset of the data in which the mood inductions worked as intended, demand was higher following negative mood inductions. CONCLUSIONS: The results of this study are not conclusive. In light of previous research, we consider these data to slightly increase our confidence that demand for alcohol is increased immediately following a negative emotional event. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Inter-Organizational Alignment and Implementation Outcomes in Integrated Mental Healthcare for Children and Adolescents: A Cross-Sectional Observational Study.

Background: Integrated care involves care provided by a team of professionals, often in non-traditional settings. A common example worldwide is integrated school-based mental health (SBMH), which involves externally employed clinicians providing care at schools. Integrated mental healthcare can improve the accessibility and efficiency of evidence-based practices (EBPs) for vulnerable populations suffering from fragmented traditional care. However, integration can complicate EBP implementation due to overlapping organizational contexts, diminishing the public health impact. Emerging literature suggests that EBP implementation may benefit from the similarities in the implementation context factors between the different organizations in integrated care, which we termed inter-organizational alignment (IOA). This study quantitatively explored whether and how IOAs in general and implementation context factors are associated with implementation outcomes in integrated SBMH. Methods: SBMH clinicians from community-based organizations (CBOs; nclinician=27) and their proximal student-support school staff (nschool=99) rated their schools and CBOs (clinician only) regarding general (organizational culture and molar climate) and implementation context factors (Implementation Climate and Leadership), and nine common implementation outcomes (e.g., treatment integrity, service access, acceptability). The levels of IOA were estimated by intra-class correlations (ICCs). We fitted multilevel models to estimate the standalone effects of context factors from CBOs and schools on implementation outcomes. We also estimated the 2-way interaction effects between CBO and school context factors (i.e., between-setting interdependence) on implementation outcomes. Results: The IOA in general context factors exceeded those of implementation context factors. The standalone effects of implementation context factors on most implementation outcomes were larger than those of general context factors. Similarly, implementation context factors between CBOs and schools showed larger 2-way interaction effects on implementation outcomes than general context factors. Conclusions: This study preliminarily supported the importance of IOA in context factors for integrated SBMH. The findings shed light on how IOA in implementation and general context factors may be differentially associated with implementation outcomes across a broad array of integrated mental healthcare settings.

Efficient qPCR estimation and discrimination of airborne inoculum of Leptosphaeria maculans and L. biglobosa, the causal organisms of phoma leaf spotting and stem canker of oilseed rape.

BACKGROUND: Detection of the inoculum of phytopathogens greatly assists in the management of diseases, but is difficult for pathogens with airborne fungal propagules. Here, we present experiments to determine the abundance and distribution frequencies of the ascospores of Leptosphaeria (Plenodomus) species that were collected on the tapes of volumetric Hirst-type traps near oilseed rape fields in Poznan, Poland and Harpenden, UK. Fungal detection and species discrimination were achieved using a SYBR-Green quantitative polymerase chain reaction (qPCR) with two different pairs of primers previously reported to differentiate Leptosphaeria maculans (Plenodomus lingam) or L. biglobosa (P. biglobosus). RESULTS: Detection was successful even at fewer than five spores per m3 of air. The primer pairs differed in the correlation coefficients obtained between DNA yields and the daily abundance of ascospores that were quantified by microscopy on duplicate halves of the spore trap tapes. Important differences in the specificity and sensitivity of the published SYBR-Green assays were also found, indicating that the Liu primers did not detect L. biglobosa subclade 'canadensis', whereas the Mahuku primers detected L. biglobosa subclade 'canadensis' and also the closely related Plenodomus dezfulensis. CONCLUSIONS: Comparisons confirmed that application of qPCR assays to spore trap samples can be used for the early detection, discrimination and quantification of aerially dispersed L. maculans and L. biglobosa propagules before leaf spot symptoms are visible in winter oilseed rape fields. The specificity of the primers must be taken into consideration because the final result will greatly depend on the local population of the pathogen. © 2023 Society of Chemical Industry.

Multiparametric Magnetic Resonance Imaging- Guided Dose-Escalated Radiation Therapy for Localized Prostate Cancer: A Prospective Phase 2 Trial.

PURPOSE: This trial's purpose was to determine the late toxicity associated with dose escalation to Prostate Imaging Reporting and Data System (PI-RADS) III-V lesions on multiparametric magnetic resonance imaging (MRI) with an image guided combined IMRT-stereotactic body radiation therapy (SBRT) approach in men with localized prostate cancer. METHODS AND MATERIALS: In this phase 2 trial patients with localized prostate cancer with clinical tumor stage T1-T3bN0 and at least one PIRADS III-V lesion were recruited to receive 45 Gy in 25 fractions to the prostate and seminal vesicles followed by a boost of 18 Gy in 3 fractions to the prostate with a simultaneous integrated boost 21 Gy in 3 fractions to the PI-RADS lesion(s). The primary endpoint was the cumulative incidence of late grade ≥3 genitourinary and gastrointestinal toxicity by 18 months (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). RESULTS: Overall, 50 patients were enrolled in this study, and 43 patients completed at least 18 months of follow-up. The cumulative incidence of grade 1, 2, and 3 late genitourinary toxicity at 18 months was 18%, 53%, and 2%. One patient was noted to have grade 3 hematuria and needed cystoscopy-guided cauterization. No acute grade 3 gastrointestinal or genitourinary toxicities were observed. The cumulative incidence of grade 1, 2, and 3 late gastrointestinal toxicity at 18 months was 31%, 4%, and 0%, respectively. At a median follow-up of 43.5 months, 3 patients developed biochemical recurrence, each with distant bone metastases without local or nodal recurrence. At 3 years, freedom from biochemical failure rate was 95.3% (95% CI, 89.2%-100%). CONCLUSIONS: Multiparametric MRI-guided dose escalation to PI-RADS III-V lesions using a combined image guided IMRT-SBRT approach is associated with an acceptable risk of late gastrointestinal and genitourinary toxicity. The results should be interpreted with caution considering their single institutional nature, small sample size, and short follow-up and should be validated in a larger study.

Mechanistic insights on age-related changes in heart-aorta-brain hemodynamic coupling using a pulse wave model of the entire circulatory system.

Age-related changes in aortic biomechanics can impact the brain by reducing blood flow and increasing pulsatile energy transmission. Clinical studies have shown that impaired cardiac function in patients with heart failure is associated with cognitive impairment. Although previous studies have attempted to elucidate the complex relationship between age-associated aortic stiffening and pulsatility transmission to the cerebral network, they have not adequately addressed the effect of interactions between aortic stiffness and left ventricle (LV) contractility (neither on energy transmission nor on brain perfusion). In this study, we use a well-established and validated one-dimensional blood flow and pulse wave computational model of the circulatory system to address how age-related changes in cardiac function and vasculature affect the underlying mechanisms involved in the LV-aorta-brain hemodynamic coupling. Our results reveal how LV contractility affects pulsatile energy transmission to the brain, even with preserved cardiac output. Our model demonstrates the existence of an optimal heart rate (near the normal human heart rate) that minimizes pulsatile energy transmission to the brain at different contractility levels. Our findings further suggest that the reduction in cerebral blood flow at low levels of LV contractility is more prominent in the setting of age-related aortic stiffening. Maintaining optimal blood flow to the brain requires either an increase in contractility or an increase in heart rate. The former consistently leads to higher pulsatile power transmission, and the latter can either increase or decrease subsequent pulsatile power transmission to the brain.NEW & NOTEWORTHY We investigated the impact of major aging mechanisms of the arterial system and cardiac function on brain hemodynamics. Our findings suggest that aging has a significant impact on heart-aorta-brain coupling through changes in both arterial stiffening and left ventricle (LV) contractility. Understanding the underlying physical mechanisms involved here can potentially be a key step for developing more effective therapeutic strategies that can mitigate the contributions of abnormal LV-arterial coupling toward neurodegenerative diseases and dementia.

White matter hyperintensity volume modifies the association between CSF vascular inflammatory biomarkers and regional FDG-PET along the Alzheimer's disease continuum.

In older adults with abnormal levels of Alzheimer's disease neuropathology, lower cerebrospinal fluid (CSF) vascular endothelial growth factor (VEGF) levels are associated with lower [¹8F]-fluorodeoxyglucose positron emission tomography (FDG-PET) signal, but whether this association is (1) specific to VEGF or broadly driven by vascular inflammation, or (2) modified by vascular risk (e.g., white matter hyperintensities [WMHs]) remains unknown. To address this and build upon our past work, we evaluated whether 5 CSF vascular inflammation biomarkers (vascular cell adhesion molecule 1, VEGF, C-reactive protein, fibrinogen, and von Willebrand factor)-previously associated with CSF amyloid levels-were related to FDG-PET signal and whether WMH volume modified these associations in 158 Alzheimer's Disease Neuroimaging Initiative participants (55-90 years old, 39 cognitively normal, 80 mild cognitive impairment, 39 Alzheimer's disease). We defined regions both by cortical boundary and by the 3 major vascular territories: anterior, middle, and posterior cerebral arteries. We found that WMH volume had interactive effects with CSF biomarkers (VEGF and C-reactive protein) on FDG-PET throughout the cortex in both vascular territories and conventionally defined regions of interest.

Decoding neural activity to assess individual latent state in ecologically valid contexts.

Objective.Currently, there exists very few ways to isolate cognitive processes, historically defined via highly controlled laboratory studies, in more ecologically valid contexts. Specifically, it remains unclear as to what extent patterns of neural activity observed under such constraints actually manifest outside the laboratory in a manner that can be used to make accurate inferences about latent states, associated cognitive processes, or proximal behavior. Improving our understanding of when and how specific patterns of neural activity manifest in ecologically valid scenarios would provide validation for laboratory-based approaches that study similar neural phenomena in isolation and meaningful insight into the latent states that occur during complex tasks.Approach.Domain generalization methods, borrowed from the work of the brain-computer interface community, have the potential to capture high-dimensional patterns of neural activity in a way that can be reliably applied across experimental datasets in order to address this specific challenge. We previously used such an approach to decode phasic neural responses associated with visual target discrimination. Here, we extend that work to more tonic phenomena such as internal latent states. We use data from two highly controlled laboratory paradigms to train two separate domain-generalized models. We apply the trained models to an ecologically valid paradigm in which participants performed multiple, concurrent driving-related tasks while perched atop a six-degrees-of-freedom ride-motion simulator.Main Results.Using the pretrained models, we estimate latent state and the associated patterns of neural activity. As the patterns of neural activity become more similar to those patterns observed in the training data, we find changes in behavior and task performance that are consistent with the observations from the original, laboratory-based paradigms.Significance.These results lend ecological validity to the original, highly controlled, experimental designs and provide a methodology for understanding the relationship between neural activity and behavior during complex tasks.

Daily level examination indicates that positive affect, but not negative affect, is associated with alcohol and marijuana use among adolescents and young adults.

OBJECTIVE: Although there is growing evidence that alcohol use at the daily level is associated with positive but not negative affect, results are mixed when examining marijuana use and simultaneous alcohol and marijuana (SAM) use (i.e., use with overlapping effects). In addition, less is known about these daily level associations among diverse samples of adolescents and young adults. The present study will address these gaps. METHOD: Participants (N = 1,006; 57.3% female, 43.1% White, Non-Hispanic, ages 15-25; Mage = 20.0) were part of a study on substance use that consisted of a 3-week ecological momentary assessment (EMA) burst design (eight surveys per week, up to 2×/day) that was repeated quarterly over a 12-month period. RESULTS: Within-person results indicated that on days with elevated positive affect, participants reported consuming more drinks, whereas positive affect was not significant for hours high from marijuana. In addition, on days with elevated negative affect, participants reported fewer hours high from marijuana. No association was found between negative affect and number of drinks. Finally, within-person results indicated that on alcohol or marijuana days with elevated positive affect, individuals were more likely to report SAM use. There was no association found between negative affect and SAM use. CONCLUSIONS: Results have implications such that in-the-moment interventions for alcohol and SAM use may be more salient when individuals have higher positive affect than average, whereas such interventions may be more relevant for marijuana use when negative affect is lower compared to average levels. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Single cell transcriptomics of bone marrow derived macrophages reveals Ccl5 as a biomarker of direct IFNAR-independent responses to DNA sensing.

Introduction: The type I interferon (IFN) response is an innate immune program that mediates anti-viral, anti-cancer, auto-immune, auto-inflammatory, and sterile injury responses. Bone marrow derived macrophages (BMDMs) are commonly used to model macrophage type I IFN responses, but the use of bulk measurement techniques obscures underlying cellular heterogeneity. This is particularly important for the IFN response to immune stimulatory double-stranded DNA (dsDNA) because it elicits overlapping direct and indirect responses, the latter of which depend on type I IFN cytokines signaling via the IFN alpha receptor (IFNAR) to upregulate expression of interferon stimulated genes (ISGs). Single cell transcriptomics has emerged as a powerful tool for revealing functional variability within cell populations. Methods: Here, we use single cell RNA-Seq to examine BMDM heterogeneity at steady state and after immune-stimulatory DNA stimulation, with or without IFNAR-dependent amplification. Results: We find that many macrophages express ISGs after DNA stimulation. We also find that a subset of macrophages express ISGs even if IFNAR is inhibited, suggesting that they are direct responders. Analysis of this subset reveals Ccl5 to be an IFNAR-independent marker gene of direct DNA sensing cells. Discussion: Our studies provide a method for studying direct responders to IFN-inducing stimuli and demonstrate the importance of characterizing BMDM models of innate immune responses with single cell resolution.

Uncertainty in phosphorus fluxes and budgets across the US long-term agroecosystem research network.

Phosphorus (P) budgets can be useful tools for understanding nutrient cycling and quantifying the effectiveness of nutrient management planning and policies; however, uncertainties in agricultural nutrient budgets are not often quantitatively assessed. The objective of this study was to evaluate uncertainty in P fluxes (fertilizer/manure application, atmospheric deposition, irrigation, crop removal, surface runoff, and leachate) and the propagation of these uncertainties to annual P budgets. Data from 56 cropping systems in the P-FLUX database, which spans diverse rotations and landscapes across the United States and Canada, were evaluated. Results showed that across cropping systems, average annual P budget was 22.4 kg P ha-1 (range = -32.7 to 340.6 kg P ha-1 ), with an average uncertainty of 13.1 kg P ha-1 (range = 1.0-87.1 kg P ha-1 ). Fertilizer/manure application and crop removal were the largest P fluxes across cropping systems and, as a result, accounted for the largest fraction of uncertainty in annual budgets (61% and 37%, respectively). Remaining fluxes individually accounted for <2% of the budget uncertainty. Uncertainties were large enough that determining whether P was increasing, decreasing, or not changing was inconclusive in 39% of the budgets evaluated. Findings indicate that more careful and/or direct measurements of inputs, outputs, and stocks are needed. Recommendations for minimizing uncertainty in P budgets based on the results of the study were developed. Quantifying, communicating, and constraining uncertainty in budgets among production systems and multiple geographies is critical for engaging stakeholders, developing local and national strategies for P reduction, and informing policy.

Modeling the value-based decision to consume alcohol in response to emotional experiences.

Evidence for negative reinforcement of alcohol use is mixed; one possible explanation for this is that people make value-based decisions whether to regulate their emotions via alcohol or an alternative, and only drink-to-cope when alcohol's reinforcing value is larger than that of available alternatives. If this is the case, immediately following a negative emotional event, the value for alcohol should increase primarily in heavy drinkers, whereas in light drinkers, alternative ways of coping should be valued. We conducted a preregistered online experiment (N = 200) with a mixed design (between: heavy vs. light drinker; within: negative/neutral/positive mood induction). In each of three experimental sessions, participants first provided value ratings for a set of alcohol and food stimuli. Second, they were subjected to a mood induction. Third, they made forced choices between either two alcohol or food stimuli. We then applied a drift-diffusion model to these data and tested whether alcohol- and food-related decision-making parameters are differentially affected following the mood inductions in heavy and light drinkers. In preregistered analyses, we found that heavy drinkers did not value alcohol more but valued food less after the negative mood induction. Exploratory analyses uncovered that both heavy- and light-drinking participants valued alcohol more following the negative mood induction if they reported high alcohol craving at the start of the session. Collectively, these results provide some evidence for the idea that drinking-to-cope might be a value-based decision-making process. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Exploring associations between affect and marijuana use in everyday life via specification curve analysis.

Although frequently hypothesized, the evidence for associations between affect and marijuana use in everyday life remains ambiguous. Inconsistent findings across existing work may be due, in part, to differences in study design and analytic decisions, such as study inclusion criteria, the operationalization of affect, or the timing of affect assessment. We used specification curves to assess the robustness of the evidence for affect predicting same-day marijuana use and marijuana use predicting next-day affect across several hundred models that varied in terms of decisions that reflect those typical in this literature (e.g., whether to average affect prior to marijuana use or select the affect report closest in time to marijuana use). We fitted these curves to data from two ecological momentary assessment studies of regular marijuana and/or alcohol using college students (N = 287). Results provided robust evidence that marijuana use was slightly less likely following experiences of negative affect and slightly more likely following positive affect. Specification curves suggested that differences in previous findings are most likely a function of the specific emotion items used to represent affect rather than differences in inclusion criteria, the temporal assessment and modeling of affect, or the covariates added to the model. There was little evidence for an association between marijuana use and next-day affect. Overall, our findings provide evidence against the predictions made by affect reinforcement models in college students and suggest that future research should model the associations of marijuana use with discrete emotional states rather than general negative and positive affect. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effect of Prior Local Therapy on Response to First-line Androgen Receptor Axis Targeted Therapy in Metastatic Castrate-resistant Prostate Cancer: A Secondary Analysis of the COU-AA-302 Trial.

BACKGROUND: Men with localized prostate cancer are often treated with local therapy (LT). However, a proportion of these patients will eventually develop recurrence and progression requiring systemic therapy. Whether primary LT affects the response to this subsequent systemic treatment is unclear. OBJECTIVE: We investigated whether the receipt of prior prostate-directed LT influenced the response to first-line systemic therapy and survival in docetaxel-naïve metastatic castrate-resistant prostate cancer (mCRPC) patients. DESIGN, SETTING, AND PARTICIPANTS: This is an exploratory analysis of the COU-AA-302 trial, a multicentric double-blinded phase 3 randomized controlled trial in which mCRPC patients with no to mild symptoms were randomized to receive abiraterone plus prednisone or placebo plus prednisone. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared the time-varying effects of first-line abiraterone in patients with and without prior LT using a Cox proportional hazard model. The cut points were chosen using grid search, and were 6 and 36 mo for radiographic progression-free survival (rPFS) and overall survival (OS), respectively. We also investigated whether there was any difference in treatment effect on score change (relative to baseline) in various patient-reported outcomes (measured by Functional Assessment of Cancer Therapy-Prostate [FACT-P]) over time depending on the receipt of prior LT. The adjusted association of prior LT with survival was determined using weighted Cox regression models. RESULTS AND LIMITATIONS: Among 1053 eligible patients, 64% (n = 669) received prior LT. We did not find any statistically significant heterogeneity of time-dependent treatment effect from abiraterone on rPFS in patients with (hazard ratio [HR]: 0.36 [95% confidence interval: 0.27-0.49] at ≤6 mo; 0.64 [0.49-0.83] at >6 mo) or without (HR: 0.37 [0.26-0.55] at ≤6 mo; 0.72 [0.50-1.03] at >6 mo) prior LT. Similarly, there was no significant heterogeneity in time-dependent treatment effect on OS with (HR: 0.88 [0.71-1.10] at ≤36 mo; 0.76 [0.52-1.11] at >36 mo) or without (0.78 [0.60-1.01] at ≤36 mo; 0.55 [0.30-0.99] at >36 mo) prior LT. We did not find sufficient evidence of a difference in treatment effect from abiraterone on score change over time in prostate cancer subscale (interaction p = 0.4), trial outcome index (interaction p = 0.8), and FACT-P total score (interaction p = 0.6) depending on the receipt of prior LT. Receipt of prior LT was associated with a significant improvement in OS (average HR: 0.72 [0.59-0.89]). CONCLUSIONS: This study demonstrates that the efficacy of first-line abiraterone and prednisone in docetaxel-naïve mCRPC do not vary significantly based on the receipt of prior prostate-directed LT. Further studies are needed to explore the plausible mechanisms of the association of prior LT with superior OS. PATIENT SUMMARY: This secondary analysis of the COU-AA-302 trial suggests that survival benefits and temporal changes in quality of life with first-line abiraterone in docetaxel-naïve mCRPC do not differ significantly among patients who received versus those who did not receive prior prostate-directed local therapy.

Subsurface phosphorus and nitrogen loss following liquid dairy manure and commercial fertilizer application on a clay soil in northwest Ohio.

Nutrient source has been the focus of much debate regarding the re-eutrophication of Lake Erie, despite that only 20% of nutrients applied to crops in the Western Lake Erie Basin (WLEB) originate from organic sources. However, limited data and assessments exist on the subsurface tile drainage water quality comparison between organic (liquid dairy manure) and commercial (mono-ammonium phosphate [MAP]) sources in crop production systems. Subsurface tile drainage, dissolved reactive phosphorus (DRP) and total phosphorus (TP) losses in tile drainage discharge following equal phosphorus (P) based applications of liquid dairy manure and MAP were assessed using a before-after control-impact design and 4 years of data from a paired field system located in northwest Ohio. Nitrate-nitrogen (NO3 - -N ) and total nitrogen (TN) losses were also examined to supplement the P findings; however, due to dissimilar nitrogen application rates, losses were assessed in a different context. No significant differences (p > 0.05) were detected in drainage discharge volumes or TP loads between the control and impact sites. However, statistically significant increases (p < 0.05) were measured for mean daily DRP, NO3 - -N, and TN loads from the dairy manure site. While significant, mean daily DRP differences between commercial (MAP) and liquid dairy manure treatments were only on the order of 0.01 g DRP ha-1 . Assuming current manure application extent and rates, when accumulated annually across the WLEB watershed, these losses are equivalent to less than 1% of target loads. These findings also help to inform nutrient management stewardship as it relates to nutrient source. Furthermore, additional research across a range of soil characteristics and cropping managements should be explored as well as the impacts of other livestock manure nutrients.