Risk factors associated with the prevalence of Shiga-toxin-producing Escherichia coli in manured soils on certified organic farms in four regions of the USA

IntroductionBiological soil amendments of animal origin (BSAAO), including untreated amendments are often used to improve soil fertility and are particularly important in organic agriculture. However, application of untreated manure on cropland can potentially introduce foodborne pathogens into the soil and onto produce. Certified organic farms follow the USDA National Organic Program (NOP) standards that stipulate a 90- or 120-day interval between application of untreated manure and crop harvest, depending on whether the edible portion of the crop directly contacts the soil. This time-interval metric is based on environmental factors and does not consider a multitude of factors that might affect the survival of the main pathogens of concern. The objective of this study was to assess predictors for the prevalence of Shiga-toxin-producing Escherichia coli (non-O157 STEC) in soils amended with untreated manure on USDA-NOP certified farms.MethodsA longitudinal, multi-regional study was conducted on 19 farms in four USA regions for two growing seasons (2017–2018). Untreated manure (cattle, horse, and poultry), soil, and irrigation water samples were collected and enrichment cultured for non-O157 STEC. Mixed effects logistic regression models were used to analyze the predictors of non-O157 STEC in the soil up to 180 days post-manure application.Results and discussionResults show that farm management practices (previous use with livestock, presence of animal feces on the field, season of manure application) and soil characteristics (presence of generic E. coli in the soil, soil moisture, sodium) increased the odds of STEC-positive soil samples. Manure application method and snowfall decreased the odds of detecting STEC in the soil. Time-variant predictors (year and sampling day) affected the presence of STEC. This study shows that a single metric, such as the time interval between application of untreated manure and crop harvest, may not be sufficient to reduce the food safety risks from untreated manure, and additional environmental and farm-management practices should also be considered. These findings are of particular importance because they provide multi-regional baseline data relating to current NOP wait-time standards. They can therefore contribute to the development of strategies to reduce pathogen persistence that may contribute to contamination of fresh produce typically eaten raw from NOP-certified farms using untreated manure

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Defining the Impact of Family History on Detection of High-grade Prostate Cancer in a Large Multi-institutional Cohort

BACKGROUND The risk of high-grade prostate cancer, given a family history of cancer, has been described in the general population, but not among men selected for prostate biopsy in an international cohort. OBJECTIVE To estimate the risk of high-grade prostate cancer on biopsy based on a family history of cancer. DESIGN, SETTING, AND PARTICIPANTS This is a multicenter study of men undergoing prostate biopsy from 2006 to 2019, including 12 sites in North America and Europe. All sites recorded first-degree prostate cancer family histories; four included more detailed data on the number of affected relatives, second-degree relatives with prostate cancer, and breast cancer family history. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable logistic regressions evaluated odds of high-grade (Gleason grade group ≥2) prostate cancer. Separate models were fit for family history definitions, including first- and second-degree prostate cancer and breast cancer family histories. RESULTS AND LIMITATIONS A first-degree prostate cancer family history was available for 15 799 men, with a more detailed family history for 4617 (median age 65 yr, both cohorts). Adjusted odds of high-grade prostate cancer were 1.77 times greater (95% confidence interval [CI] 1.57-2.00, p < 0.001, risk ratio [RR] = 1.40) with first-degree prostate cancer, 1.38 (95% CI 1.07-1.77, p = 0.011, RR = 1.22) for second-degree prostate cancer, and 1.30 (95% CI 1.01-1.67, p = 0.040, RR = 1.18) for first-degree breast cancer family histories. Interaction terms revealed that the effect of a family history did not differ based on prostate-specific antigen but differed based on age. This study is limited by missing data on race and prior negative biopsy. CONCLUSIONS Men with indications for biopsy and a family history of prostate or breast cancer can be counseled that they have a moderately increased risk of high-grade prostate cancer, independent of other risk factors. PATIENT SUMMARY In a large international series of men selected for prostate biopsy, finding a high-grade prostate cancer was more likely in men with a family history of prostate or breast cancer

Risk factors associated with the prevalence of Shiga-toxin-producing Escherichia coli in manured soils on certified organic farms in four regions of the USA

Introduction: Biological soil amendments of animal origin (BSAAO), including untreated amendments are often used to improve soil fertility and are particularly important in organic agriculture. However, application of untreated manure on cropland can potentially introduce foodborne pathogens into the soil and onto produce. Certified organic farms follow the USDA National Organic Program (NOP) standards that stipulate a 90- or 120-day interval between application of untreated manure and crop harvest, depending on whether the edible portion of the crop directly contacts the soil. This time-interval metric is based on environmental factors and does not consider a multitude of factors that might affect the survival of the main pathogens of concern. The objective of this study was to assess predictors for the prevalence of Shiga-toxin-producing Escherichia coli (non-O157 STEC) in soils amended with untreated manure on USDA-NOP certified farms. Methods: A longitudinal, multi-regional study was conducted on 19 farms in four USA regions for two growing seasons (2017–2018). Untreated manure (cattle, horse, and poultry), soil, and irrigation water samples were collected and enrichment cultured for non-O157 STEC. Mixed effects logistic regression models were used to analyze the predictors of non-O157 STEC in the soil up to 180 days post-manure application. Results and discussion: Results show that farm management practices (previous use with livestock, presence of animal feces on the field, season of manure application) and soil characteristics (presence of generic E. coli in the soil, soil moisture, sodium) increased the odds of STEC-positive soil samples. Manure application method and snowfall decreased the odds of detecting STEC in the soil. Time-variant predictors (year and sampling day) affected the presence of STEC. This study shows that a single metric, such as the time interval between application of untreated manure and crop harvest, may not be sufficient to reduce the food safety risks from untreated manure, and additional environmental and farm-management practices should also be considered. These findings are of particular importance because they provide multi-regional baseline data relating to current NOP wait-time standards. They can therefore contribute to the development of strategies to reduce pathogen persistence that may contribute to contamination of fresh produce typically eaten raw from NOP-certified farms using untreated manure

Survival and Persistence of Foodborne Pathogens in Manure-Amended Soils and Prevalence on Fresh Produce in Certified Organic Farms: A Multi-Regional Baseline Analysis

Biological soil amendments of animal origin (BSAAOs), including untreated (e.g., raw or aged manure, or incompletely composted manure) and treated animal products (e.g., compost), are used for crop production and as part of soil health management. Application of BSAAO's must be done cautiously, as raw manure commonly contains enteric foodborne pathogens that can potentially contaminate edible produce that may be consumed without cooking. USDA National Organic Program (NOP) certified production systems follow the 90-or 120-day interval standards between applications of untreated BSAAOs and crop harvest, depending on whether the edible portions of the crops are in indirect or direct contact with the soil, respectively. This study was conducted to evaluate the survival of four foodborne pathogens in soils amended with BSAAOs and to examine the potential for bacterial transfer to fresh produce harvested from USDA NOP certified organic farms (19) from four states. Only 0.4% (2/527) of produce samples were positive for L. monocytogenes. Among the untreated manure and compost samples, 18.0% (42/233) were positive for at least one of the tested and culturable bacterial foodborne pathogens. The prevalence of non-O157 STEC and Salmonella in untreated manure was substantially &gt; that of E. coli O157:H7 and L. monocytogenes. Of the 2,461 soil samples analyzed in this study, 12.9% (318) were positive for at least one pathogen. In soil amended with untreated manure, the prevalence of non-O157 STEC [7.7% (190) and L. monocytogenes (5.0% (122), was &gt; that of Salmonella (1.1% (26)] or E. coli O157 [0.04% (1)]. Foodborne pathogen prevalence in the soil peaked after manure application and decreased significantly 30 days post-application (dpa). However, non-O157 STEC and L. monocytogenes were recovered from soil samples after 90 and 120 dpa. Results indicate that produce contamination by tested foodborne pathogens was infrequent, but these data should not be generalized outside of the specific wait-time regulations for organic crop production and the farms studied. Moreover, other sources of contamination, e.g., irrigation, wildlife, environmental conditions, cropping and management practices, should be considered. This study also provides multi-regional baseline data relating to current NOP application intervals and development of potential risk mitigation strategies to reduce pathogen persistence in soils amended with BSAAOs. These findings contribute to filling critical data gaps concerning occurrence of fecal pathogens in NOP-certified farming systems used for production of fresh produce in different US regions

Data_Sheet_2_Risk factors associated with the prevalence of Listeria monocytogenes in manured soils on certified organic farms in four regions of the United States.docx

IntroductionBiological soil amendments, including raw or untreated manure, are currently used to improve soil fertility, especially in organic operations that prohibit use of synthetic fertilizers. However, addition of untreated manure may pose a risk of contamination of fresh produce by pathogens of public health significance, including Listeria monocytogenes. Organic growers follow United States Department of Agriculture (USDA) National Organic Program regulations for raw manure use, which stipulate that harvest should commence no earlier than 90- or 120-days post-application, depending on direct contact between the edible portion of the produce and the soil. To inform the protection that such time-intervals provide, this study explored the farm-level risk factors associated with L. monocytogenes prevalence in USDA-certified organic farm soils amended with untreated manures.MethodsA longitudinal, multi-regional study was conducted on 19 farms in four states (California, Minnesota, Maine, and Maryland) over two growing seasons (2017 and 2018). Untreated manure, soil, irrigation water, and produce samples were collected and cultured for L. monocytogenes. Mixed effect logistic regression was used to investigate risk factors associated with L. monocytogenes prevalence in soil.Results and DiscussionResults showed that multiple factors influenced the odds of a soil-positive sample, including temporal [year (OR = 0.19), sampling day (OR = 0.09–0.48)] and weather-related [temperature range (OR = 0.48)] variables, manure characteristics [season of application (OR = 0.04, summer), presence of L. monocytogenes (OR = 2.89) and other pathogens in manure (OR = 5.24)], farm management factors [water source (OR = 2.73, mixed), number of year-round staff (OR = 0.02)], and soil characteristics [concentration of generic Escherichia coli (OR = 1.45), moisture (OR = 0.46), organic matter (OR = 7.30), nitrate (OR = 3.07), potassium (OR = 0.09) and calcium (OR = 2.48)]. This study highlights the complexity of L. monocytogenes prevalence in soil and contributes science-based metrics that may be used when determining risk-mitigation strategies for pathogen contamination.</p

Data_Sheet_1_Risk factors associated with the prevalence of Listeria monocytogenes in manured soils on certified organic farms in four regions of the United States.PDF

IntroductionBiological soil amendments, including raw or untreated manure, are currently used to improve soil fertility, especially in organic operations that prohibit use of synthetic fertilizers. However, addition of untreated manure may pose a risk of contamination of fresh produce by pathogens of public health significance, including Listeria monocytogenes. Organic growers follow United States Department of Agriculture (USDA) National Organic Program regulations for raw manure use, which stipulate that harvest should commence no earlier than 90- or 120-days post-application, depending on direct contact between the edible portion of the produce and the soil. To inform the protection that such time-intervals provide, this study explored the farm-level risk factors associated with L. monocytogenes prevalence in USDA-certified organic farm soils amended with untreated manures.MethodsA longitudinal, multi-regional study was conducted on 19 farms in four states (California, Minnesota, Maine, and Maryland) over two growing seasons (2017 and 2018). Untreated manure, soil, irrigation water, and produce samples were collected and cultured for L. monocytogenes. Mixed effect logistic regression was used to investigate risk factors associated with L. monocytogenes prevalence in soil.Results and DiscussionResults showed that multiple factors influenced the odds of a soil-positive sample, including temporal [year (OR = 0.19), sampling day (OR = 0.09–0.48)] and weather-related [temperature range (OR = 0.48)] variables, manure characteristics [season of application (OR = 0.04, summer), presence of L. monocytogenes (OR = 2.89) and other pathogens in manure (OR = 5.24)], farm management factors [water source (OR = 2.73, mixed), number of year-round staff (OR = 0.02)], and soil characteristics [concentration of generic Escherichia coli (OR = 1.45), moisture (OR = 0.46), organic matter (OR = 7.30), nitrate (OR = 3.07), potassium (OR = 0.09) and calcium (OR = 2.48)]. This study highlights the complexity of L. monocytogenes prevalence in soil and contributes science-based metrics that may be used when determining risk-mitigation strategies for pathogen contamination.</p

A genetics-first approach to dissecting the heterogeneity of autism: phenotypic comparison of autism risk copy number variants

Objective: Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships. Methods: This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing. Results: The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits. Conclusions: Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant