Effects of plant diversity on productivity strengthen over time due to trait-dependent shifts in species overyielding.

Plant diversity effects on community productivity often increase over time. Whether the strengthening of diversity effects is caused by temporal shifts in species-level overyielding (i.e., higher species-level productivity in diverse communities compared with monocultures) remains unclear. Here, using data from 65 grassland and forest biodiversity experiments, we show that the temporal strength of diversity effects at the community scale is underpinned by temporal changes in the species that yield. These temporal trends of species-level overyielding are shaped by plant ecological strategies, which can be quantitatively delimited by functional traits. In grasslands, the temporal strengthening of biodiversity effects on community productivity was associated with increasing biomass overyielding of resource-conservative species increasing over time, and with overyielding of species characterized by fast resource acquisition either decreasing or increasing. In forests, temporal trends in species overyielding differ when considering above- versus belowground resource acquisition strategies. Overyielding in stem growth decreased for species with high light capture capacity but increased for those with high soil resource acquisition capacity. Our results imply that a diversity of species with different, and potentially complementary, ecological strategies is beneficial for maintaining community productivity over time in both grassland and forest ecosystems.

Cumulative nitrogen enrichment alters the drivers of grassland overyielding.

Effects of plant diversity on grassland productivity, or overyielding, are found to be robust to nutrient enrichment. However, the impact of cumulative nitrogen (N) addition (total N added over time) on overyielding and its drivers are underexplored. Synthesizing data from 15 multi-year grassland biodiversity experiments with N addition, we found that N addition decreases complementarity effects and increases selection effects proportionately, resulting in no overall change in overyielding regardless of N addition rate. However, we observed a convex relationship between overyielding and cumulative N addition, driven by a shift from complementarity to selection effects. This shift suggests diminishing positive interactions and an increasing contribution of a few dominant species with increasing N accumulation. Recognizing the importance of cumulative N addition is vital for understanding its impacts on grassland overyielding, contributing essential insights for biodiversity conservation and ecosystem resilience in the face of increasing N deposition.

Associations between social isolation and diet quality among US adults with disability participating in the National Health and Nutrition Examination Survey, 2013-2018.

Social isolation and disability are established risk factors for poor nutrition. We aimed to assess whether social isolation is associated with diet quality specifically among adults with disabilities. This cross-sectional analysis used data from the National Health and Nutrition Examination Survey, 2013-2018. Adults with a disability, who were not pregnant, breastfeeding, or missing dietary intake data were included (n = 5,167). Disability was defined as a physical functioning limitation based on difficulty with any activities of daily living, instrumental activities of daily living, lower extremity mobility activities, or general physical activities. The Healthy Eating Index (HEI)-2015 measured diet quality; higher scores correspond to higher diet quality. We computed a social isolation index by summing single status, living alone, and two social engagement difficulty measures (one point for each component met; maximum 4 points). Multivariable linear regression, controlling for demographic and health covariates, estimated differences in HEI scores for dietary intake data, by social isolation score. Over half of HEI scores were < 51, corresponding to "poor" diet quality. Higher social isolation score was associated with lower vegetable and seafood/plant proteins intake. Single status and one of two social engagement measures were associated with lower scores on certain adequacy components. Differences were modest. There was little evidence of effect modification by age or gender. Adults with disabilities are not meeting national dietary standards; improving diet quality is a priority. Whether social isolation is associated with specific dietary components in this population requires further investigation. Further research is also needed among younger adults.

Ecosystem consequences of invertebrate decline.

Human activities cause substantial changes in biodiversity.1,2 Despite ongoing concern about the implications of invertebrate decline,3,4,5,6,7 few empirical studies have examined the ecosystem consequences of invertebrate biomass loss. Here, we test the responses of six ecosystem services informed by 30 above- and belowground ecosystem variables to three levels of aboveground (i.e., vegetation associated) invertebrate community biomass (100%, 36%, and 0% of ambient biomass) in experimental grassland mesocosms in a controlled Ecotron facility. In line with recent reports on invertebrate biomass loss over the last decade, our 36% biomass treatment also represented a decrease in invertebrate abundance (-70%) and richness (-44%). Moreover, we simulated the pronounced change in invertebrate biomass and turnover in community composition across the season. We found that the loss of invertebrate biomass decreases ecosystem multifunctionality, including two critical ecosystem services, aboveground pest control and belowground decomposition, while harvested plant biomass increases, likely because less energy was channeled up the food chain. Moreover, communities and ecosystem functions become decoupled with a lower biomass of invertebrates. Our study shows that invertebrate loss threatens the integrity of grasslands by decoupling ecosystem processes and decreasing ecosystem-service supply.

Diagnostic Performance of Prostate-specific Antigen Density for Detecting Clinically Significant Prostate Cancer in the Era of Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

CONTEXT: There has been a dramatic increase in the use of prostate magnetic resonance imaging (MRI) in the diagnostic workup. With prostate volume calculated from MRI, prostate-specific antigen density (PSAD) now is a ready-to-use parameter for prostate cancer (PCa) risk stratification before prostate biopsy, especially among patients with negative MRI or equivocal lesions. OBJECTIVE: In this review, we aimed to evaluate the diagnostic performance of PSAD for clinically significant prostate cancer (CSPCa) among patients who received MRI before prostate biopsy. EVIDENCE ACQUISITION: Two investigators performed a systematic review according of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. Studies (published between January 1, 2012, and December 31, 2021) reporting the diagnostic performance (outcomes) of PSAD (intervention) for CSPCa among men who received prebiopsy prostate MRI and subsequent prostate biopsy (patients), using biopsy pathology as the gold standard (comparison), were eligible for inclusion. EVIDENCE SYNTHESIS: A total of 1536 papers were identified in PubMed, Scopus, and Embase. Of these, 248 studies were reviewed in detail and 39 were qualified. The pooled sensitivity (SENS) and specificity (SPEC) for diagnosing CSPCa among patients with positive MRI were, respectively, 0.87 and 0.35 for PSAD of 0.1 ng/ml/ml, 0.74 and 0.61 for PSAD of 0.15 ng/ml/ml, and 0.51 and 0.81 for PSAD of 0.2 ng/ml/ml. The pooled SENS and SPEC for diagnosing CSPCa among patients with negative MRI were, respectively, 0.85 and 0.36 for PSAD of 0.1 ng/ml/ml, 0.60 and 0.66 for PSAD of 0.15 ng/ml/ml, and 0.33 and 0.84 for PSAD of 0.2 ng/ml/ml. The pooled SENS and SPEC among patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 or Likert 3 lesions were, respectively, 0.87 and 0.39 for PSAD of 0.1 ng/ml/ml, 0.61 and 0.69 for PSAD of 0.15 ng/ml/ml, and 0.42 and 0.82 for PSAD of 0.2 ng/ml/ml. The post-test probability for CSPCa among patients with negative MRI was 6% if PSAD was <0.15 ng/ml/ml and dropped to 4% if PSAD was <0.10 ng/ml/ml. CONCLUSIONS: In this systematic review, we quantitatively evaluated the diagnosis performance of PSAD for CSPCa in combination with prostate MRI. It demonstrated a complementary performance and predictive value, especially among patients with negative MRI and PI-RADS 3 or Likert 3 lesions. Integration of PSAD into decision-making for prostate biopsy may facilitate improved risk-adjusted care. PATIENT SUMMARY: Prostate-specific antigen density is a ready-to-use parameter in the era of increased magnetic resonance imaging (MRI) use in clinically significant prostate cancer (CSPCa) diagnosis. Findings suggest that the chance of having CSPCa was very low (4% or 6% for those with negative prebiopsy MRI or Prostate Imaging Reporting and Data System (Likert) score 3 lesion, respectively, if the PSAD was <0.10 ng/ml/ml), which may lower the need for biopsy in these patients.

Obesity and prostate cancer screening, incidence, and mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: Though obesity, measured by body mass index (BMI), is an established risk factor for several cancer sites, there is conflicting evidence on whether obesity increases prostate cancer risk or mortality and, if it does, whether it increases risk directly or indirectly by affecting prostate cancer screening efficacy. METHODS: We examined associations between BMI and prostate cancer screening outcomes, incidence, and mortality in men randomly assigned to the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (n = 36 756) between 1993 and 2001. Participants received annual screening with the prostate-specific antigen test and digital rectal exam. Associations between baseline BMI and screening outcomes were assessed via multinomial logistic regression, and associations with prostate cancer incidence and mortality were assessed via Cox proportional hazards regression. RESULTS: Individuals with higher BMI were less likely to screen positive via the prostate-specific antigen test and/or digital rectal exam and more likely to have an inadequate screen (all Ptrend < .01). Higher BMI was inversely associated with prostate cancer incidence (per 5 kg/m2 BMI increase: hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.91 to 0.97), including incidence of early stage (HR = 0.94, 95% CI = 0.90 to 0.97) and advanced-stage (HR = 0.91, 95% CI = 0.82 to 1.02) disease, but positively associated with prostate cancer mortality (HR = 1.21, 95% CI = 1.06 to 1.37). The association with mortality was not modified by screening outcome (Pinteraction = .13). CONCLUSIONS: Within this screened population, individuals with higher BMI had lower risk of prostate cancer diagnosis but higher risk of prostate cancer mortality. As higher BMI was not positively associated with advanced-stage prostate cancer risk, the increased mortality is unlikely to be due to delayed prostate cancer detection.

Association of parity with body mass index and cardiometabolic risk in high-parous women.

OBJECTIVE: Postpregnancy weight retention contributes to obesity, but the long-term effect of parity on body mass index (BMI) and other cardiometabolic risk factors is unclear. We aimed to evaluate the relationship between parity and BMI among highly parous Amish women, both before and after menopause, and to evaluate the associations of parity with glucose, blood pressure, and lipids. METHODS: We conducted a cross-sectional study among 3,141 Amish women 18 years or older from Lancaster County, PA, who participated in our community-based Amish Research Program between 2003 and 2020. We evaluated the association between parity and BMI across different age groups, both before and after the menopausal transition. We further assessed associations between parity and cardiometabolic risk factors among the 1,128 postmenopausal women. Finally, we evaluated the association of change in parity with change in BMI in 561 women followed longitudinally. RESULTS: Approximately 62% of women in this sample (mean age, 45.2 y) reported having four or more children, and 36% reported having seven or more. A one-child increase in parity was associated with increased BMI in both premenopausal women (estimate [95% confidence interval], 0.4 kg/m 2 [0.2-0.5]) and to a lesser degree in postmenopausal women (0.2 kg/m 2 [0.02-0.3], Pint = 0.02), suggesting that the impact of parity on BMI decreases over time. Parity was not associated with glucose, blood pressure, total cholesterol, low-density lipoprotein, or triglycerides ( Padj > 0.05). CONCLUSIONS: Higher parity was associated with increased BMI in both premenopausal and postmenopausal women, but more so in younger/premenopausal women. Parity was not associated with other indices of cardiometabolic risk.

The structure of root-associated fungal communities is related to the long-term effects of plant diversity on productivity.

Root-associated fungi could play a role in determining both the positive relationship between plant diversity and productivity in experimental grasslands, and its strengthening over time. This hypothesis assumes that specialized pathogenic and mutualistic fungal communities gradually assemble over time, enhancing plant growth more in species-rich than in species-poor plots. To test this hypothesis, we used high-throughput amplicon sequencing to characterize root-associated fungal communities in experimental grasslands of 1 and 15 years of age with varying levels of plant species richness. Specifically, we tested whether the relationship between fungal communities and plant richness and productivity becomes stronger with the age of the experimental plots. Our results showed that fungal diversity increased with plant diversity, but this relationship weakened rather than strengthened over the two time points. Contrastingly, fungal community composition showed increasing associations with plant diversity over time, suggesting a gradual build-up of specific fungal assemblages. Analyses of different fungal guilds showed that these changes were particularly marked in pathogenic fungi, whose shifts in relative abundance are consistent with the pathogen dilution hypothesis in diverse plant communities. Our results suggest that root-associated fungal pathogens play more specific roles in determining the diversity-productivity relationship than other root-associated plant symbionts.

A prospective nested case-control study of serum concentrations of per- and polyfluoroalkyl substances and aggressive prostate cancer risk.

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested an association between PFAS and prostate cancer, but evidence from population-based studies is limited. We investigated the association between pre-diagnostic serum PFAS concentrations and aggressive prostate cancer risk in a large prospective study. We measured pre-diagnostic serum concentrations of eight PFAS, including perfluorooctanoate (PFOA), for 750 aggressive prostate cancer cases and 750 individually matched controls within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We assessed the reproducibility of PFAS concentrations in serial samples collected up to six years apart among 60 controls using intraclass correlation coefficients (ICCs). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with prostate cancer, adjusting for other PFAS and potential confounders. Concentrations of most PFAS were consistent (ICC>0.7) across the serial samples over time. We observed an inverse association between PFOA and aggressive prostate cancer (ORcontinuous = 0.79, 95% CI = 0.63, 0.99), but the association was limited to cases diagnosed ≤3 years after blood collection and became statistically non-significant for cases diagnosed with later follow-up (>3 years, ORcontinuous = 0.90, 95% CI = 0.79, 1.03). Other PFAS were not associated with aggressive prostate cancer risk. Although we cannot rule out an increased risk at higher levels, our findings from a population with PFAS serum concentrations comparable to the general population do not support an association with increased risk of aggressive prostate cancer.

Universal beta-diversity-functioning relationships are neither observed nor expected.

Widespread evidence shows that local species richness (α-diversity) loss hampers the biomass production and stability of ecosystems. ß-Diversity, namely the variation of species compositions among different ecological communities, represents another important biodiversity component, but studies on how it drives ecosystem functioning show mixed results. We argue that to better understand the importance of ß-diversity we need to consider it across contexts. We focus on three scenarios that cause gradients in ß-diversity: changes in (i) abiotic heterogeneity, (ii) habitat isolation, and (iii) species pool richness. We show that across these scenarios we should not expect universally positive relationships between ß-diversity, production, and ecosystem stability. Nevertheless, predictable relationships between ß-diversity and ecosystem functioning do exist in specific contexts, and can reconcile seemingly contrasting empirical relationships.

Defaunation changes leaf trait composition of recruit communities in tropical forests in French Guiana.

Hunting impacts tropical vertebrate populations, causing declines of species that function as seed dispersers and predators, or that browse seedlings and saplings. Whether and how the resulting reductions in seed dispersal, seed predation, and browsing translate to changes in the tree composition is poorly understood. Here, we assess the effect of defaunation on the functional composition of communities of tree recruits in tropical rainforests in French Guiana. We selected eight sites along a gradient of defaunation, caused by differences in hunting pressure, in otherwise intact old-growth forests in French Guiana. We measured shifts in functional composition by comparing leaf and fruit traits and wood density between tree recruits (up to 5 cm diameter at breast height) and adults, and tested whether and how these compositional shifts related to defaunation. We found a positive relationship with defaunation for shifts in specific leaf area, a negative relationship for shifts of leaf toughness and wood density, and a weak relationship for shifts in fruit traits. Our results suggest that the loss of vertebrates affects ecological processes such as seed dispersal and browsing, of which browsing remains understudied. Even though these changes sometimes seem minor, together they result in major shifts in forest composition. These changes have long-term ramifications that may alter forest dynamics for generations.

Grazing and global change factors differentially affect biodiversity-ecosystem functioning relationships in grassland ecosystems.

Grazing and global change (e.g., warming, nitrogen deposition, and altered precipitation) both contribute to biodiversity loss and alter ecosystem structure and functioning. However, how grazing and global change interactively influence plant diversity and ecosystem productivity, and their relationship remains unclear at the global scale. Here, we synthesized 73 field studies to quantify the individual and/or interactive effects of grazing and global change factors on biodiversity-productivity relationship in grasslands. Our results showed that grazing significantly reduced plant richness by 3.7% and aboveground net primary productivity (ANPP) by 29.1%, but increased belowground net primary productivity (BNPP) by 9.3%. Global change factors, however, decreased richness by 8.0% but increased ANPP and BNPP by 13.4% and 14.9%, respectively. Interestingly, the strength of the change in biodiversity in response to grazing was positively correlated with the strength of the change in BNPP. Yet, global change flipped these relationships from positive to negative even when combined with grazing. These results indicate that the impacts of global change factors are more dominant than grazing on the belowground biodiversity-productivity relationship, which is contrary to the pattern of aboveground one. Therefore, incorporating global change factors with herbivore grazing into Earth system models is necessary to accurately predict climate-grassland carbon cycle feedbacks in the Anthropocene.

Deciphering the role of specialist and generalist plant-microbial interactions as drivers of plant-soil feedback.

Feedback between plants and soil microbial communities can be a powerful driver of vegetation dynamics. Plants elicit changes in the soil microbiome that either promote or suppress conspecifics at the same location, thereby regulating population density-dependence and species co-existence. Such effects are often attributed to the accumulation of host-specific antagonistic or beneficial microbiota in the rhizosphere. However, the identity and host-specificity of the microbial taxa involved are rarely empirically assessed. Here we review the evidence for host-specificity in plant-associated microbes and propose that specific plant-soil feedbacks can also be driven by generalists. We outline the potential mechanisms by which generalist microbial pathogens, mutualists and decomposers can generate differential effects on plant hosts and synthesize existing evidence to predict these effects as a function of plant investments into defence, microbial mutualists and dispersal. Importantly, the capacity of generalist microbiota to drive plant-soil feedbacks depends not only on the traits of individual plants but also on the phylogenetic and functional diversity of plant communities. Identifying factors that promote specialization or generalism in plant-microbial interactions and thereby modulate the impact of microbiota on plant performance will advance our understanding of the mechanisms underlying plant-soil feedback and the ways it contributes to plant co-existence.

Weight Change and Incident Distal Colorectal Adenoma Risk in the PLCO Cancer Screening Trial.

Background: Although obesity is a known risk factor, the impact of weight change on colorectal adenoma risk is less clear and could have important implications in disease prevention. We prospectively evaluated weight change in adulthood and incident colorectal adenoma. Methods: We assessed weight change during early-late (age 20 years to baseline, ie, ages 55-74 years), early-middle (20-50 years), and middle-late (50 years-baseline) adulthood using self-reported weight data in relation to incident distal adenoma in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (cases = 1053; controls = 16 576). For each period, we defined stable weight as greater than -0.5 kg to less than or equal to 1 kg/5 years, weight loss as less than or equal to -0.5 kg/5 years, and weight gain as greater than 1-2, greater than 2-3, or greater than 3 kg/5 years. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression; all tests were 2-sided. Results: Compared with stable weight, weight loss during early-late adulthood was associated with reduced adenoma risk (OR = 0.54, 95% CI = 0.34 to 0.86), particularly among those who were overweight or obese at age 20 years (OR = 0.39, 95% CI = 0.18 to 0.84). Results were similar for early-middle adulthood but less pronounced for middle-late adulthood. Weight gain greater than 3 kg/5 years during early-late adulthood was associated with increased risk (OR = 1.30, 95% CI = 1.07 to 1.58, P trend < .001). Findings appeared stronger among men (OR for >3 kg/5 years = 1.41, 95% CI = 1.11 to 1.80) than women (OR = 1.09, 95% CI = 0.79 to 1.50, P interaction = .21). Conclusions: Weight loss in adulthood was associated with reduced adenoma risk, particularly for those who were overweight or obese, whereas weight gain greater than 3 kg/5 years increased risk. Findings underscore the importance of healthy weight maintenance throughout adulthood in preventing colorectal adenoma.

Species richness stabilizes productivity via asynchrony and drought-tolerance diversity in a large-scale tree biodiversity experiment.

Extreme climatic events threaten forests and their climate mitigation potential globally. Understanding the drivers promoting ecosystem stability is therefore considered crucial for mitigating adverse climate change effects on forests. Here, we use structural equation models to explain how tree species richness, asynchronous species dynamics, species-level population stability, and drought-tolerance traits relate to the stability of forest productivity along an experimentally manipulated species richness gradient ranging from 1 to 24 tree species. Tree species richness improved community stability by increasing asynchrony. That is, at higher species richness, interannual variation in productivity among tree species buffered the community against stress-related productivity declines. This effect was positively related to variation in stomatal control and resistance-acquisition strategies among species, but not to the community-weighted means of these trait syndromes. The identified mechanisms by which tree species richness stabilizes forest productivity emphasize the importance of diverse, mixed-species forests to adapt to climate change.

Are we missing the forest for the trees? Conspecific negative density dependence in a temperate deciduous forest.

One of the central goals of ecology is to determine the mechanisms that enable coexistence among species. Evidence is accruing that conspecific negative density dependence (CNDD), the process by which plant seedlings are unable to survive in the area surrounding adults of their same species, is a major contributor to tree species coexistence. However, for CNDD to maintain community-level diversity, three conditions must be met. First, CNDD must maintain diversity for the majority of the woody plant community (rather than merely specific groups). Second, the pattern of repelled recruitment must increase in with plant size. Third, CNDD should extend to the majority of plant life history strategies. These three conditions are rarely tested simultaneously. In this study, we simultaneously test all three conditions in a woody plant community in a North American temperate forest. We examined whether understory and canopy woody species across height categories and dispersal syndromes were overdispersed-a spatial pattern indicative of CNDD-using spatial point pattern analysis across life history stages and strategies. We found that there was a strong signal of overdispersal at the community level. Across the whole community, larger individuals were more overdispersed than smaller individuals. The overdispersion of large individuals, however, was driven by canopy trees. By contrast, understory woody species were not overdispersed as adults. This finding indicates that the focus on trees for the vast majority of CNDD studies may have biased the perception of the prevalence of CNDD as a dominant mechanism that maintains community-level diversity when, according to our data, CNDD may be restricted largely to trees.

The function-dominance correlation drives the direction and strength of biodiversity-ecosystem functioning relationships.

Community composition is a primary determinant of how biodiversity change influences ecosystem functioning and, therefore, the relationship between biodiversity and ecosystem functioning (BEF). We examine the consequences of community composition across six structurally realistic plant community models. We find that a positive correlation between species' functioning in monoculture versus their dominance in mixture with regard to a specific function (the "function-dominance correlation") generates a positive relationship between realised diversity and ecosystem functioning across species richness treatments. However, because realised diversity declines when few species dominate, a positive function-dominance correlation generates a negative relationship between realised diversity and ecosystem functioning within species richness treatments. Removing seed inflow strengthens the link between the function-dominance correlation and BEF relationships across species richness treatments but weakens it within them. These results suggest that changes in species' identities in a local species pool may more strongly affect ecosystem functioning than changes in species richness.

Aspirin, ibuprofen, and reduced risk of advanced colorectal adenoma incidence and recurrence and colorectal cancer in the PLCO Cancer Screening Trial.

BACKGROUND: Studying the differential impact of aspirin and other nonsteroidal anti-inflammatory drugs across the stages of colorectal neoplasia from early adenoma to cancer is critical for understanding the benefits of these widely used drugs. METHODS: With 13 years of follow-up, the authors prospectively evaluated the association between aspirin and ibuprofen use and incident distal adenoma (1221 cases), recurrent adenoma (862 cases), and incident colorectal cancer (CRC; 2826 cases) among men and women in the population-based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. With multivariable-adjusted models, odds ratio (ORs) and 95% confidence intervals (CIs) for adenoma incidence and recurrence and hazard ratios (HRs) and 95% CIs for incident CRC were determined. RESULTS: The authors observed a significantly reduced risk of incident adenoma with ibuprofen use (≥30 vs <4 pills per month: OR, 0.76 [95% CI, 0.60-0.95]; Ptrend = .04), particularly advanced adenoma (OR, 0.48 [95% CI, 0.28-0.83]; Ptrend = .005). Among those with a previous adenoma detected through screening, aspirin use was associated with a decreased risk of advanced recurrent adenoma (≥30 vs <4 pills per month: OR, 0.56 [95% CI, 0.36-0.87]; Ptrend = 0.006). Both aspirin (HR, 0.88 [95% CI, 0.81-0.96]; Ptrend <.0001) and ibuprofen use (HR, 0.81 [95% CI, 0.70-0.93); Ptrend = 0.003) ≥30 versus <4 pills per month were significantly associated with reduced CRC risk. CONCLUSIONS: In this large prospective study with long-term follow-up, a beneficial role for not only aspirin, but also ibuprofen, in preventing advanced adenoma and curbing progression to recurrence and cancer among older adults was observed.

Recommended Definitions of Aggressive Prostate Cancer for Etiologic Epidemiologic Research.

BACKGROUND: In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. METHODS: Among prostate cancer cases diagnosed in 2007 in the National Cancer Institute's Surveillance, Epidemiology, and End Results-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). RESULTS: In our case population (n = 55 900), 3073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM staging and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of category T4 or N1 or M1 or Gleason score of 8 or greater prostate cancer, because this definition had one of the higher PPVs (0.23, 95% confidence interval = 0.22 to 0.24) and reasonable sensitivity (0.66, 95% confidence interval = 0.64 to 0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. CONCLUSIONS: We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced category (T4 or N1 or M1), high-grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.