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(s): Existing bladder-specific measures lack ability to assess a range of bladder health from poor to optimal health. We report evidence for validity of the self-administered, multidimensional Bladder Health Scales and Function Indices for research in adult women.A cross-sectional population-based validation study with random assignment to paper or electronic administration was conducted using national address-based probability sampling supplemented by purposive sampling of women with lower urinary tract symptoms surrounding 7 clinical research centers. Construct validity of the Bladder Health Scales and Function Indices was guided by Multitrait-Multimethod approach using health and condition-specific questionnaires, bladder diaries, expert ratings of bladder health, and noninvasive bladder function testing. Internal dimensional validity was evaluated using factor analysis; internal reliability was assessed using paired t-tests and 2-way mixed effects Intraclass Correlation Coefficient models. Mode comparisons used chi-square, Fisher Exact or t-tests. Convergent validity was evaluated using Pearson correlations with the external construct measures and known-group validity was established with comparison of women known and unknown to be symptomatic with urinary conditions.The sample included 1,072 participants. Factor analysis identified ten scales with Cronbach's alpha ranging 0.74-0.94. Intraclass correlation coefficients of scales ranged from 0.55-0.94. Convergent validity of ten scales and six indices ranged from 0.52- 0.83. Known-group validity was confirmed for all scales and indices. Item distribution was similar by mode of administration.The paper and electronic forms of the Bladder Health Scales and Function Indices are reliable and valid measures of bladder health for use in women's health research.

When conducting a meta-analysis involving prevalence data for an outcome with several subtypes, each of them is typically analyzed separately using a univariate meta-analysis model. Recently, multivariate meta-analysis models have been shown to correspond to a decrease in bias and variance for multiple correlated outcomes compared to univariate meta-analysis, when some studies only report a subset of the outcomes. In this article, we propose a novel Bayesian multivariate random effects model to account for the natural constraint that the prevalence of any given subtype cannot be larger than that of the overall prevalence. Extensive simulation studies show that this new model can reduce bias and variance when estimating subtype prevalences in the presence of missing data, compared to standard univariate and multivariate random effects models. The data from a rapid review on occupation and lower urinary tract symptoms by the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium are analyzed as a case study to estimate the prevalence of urinary incontinence and several incontinence subtypes among women in suspected high risk work environments.

Antibiotic resistance is a threat to public health, and uncomplicated urinary tract infections (uUTIs) are an example of this concern. This systematic review (International Prospective Register of Systematic Reviews [PROSPERO] ID: CRD42020156674) is the first to determine the prevalence of

An online bladder health survey was administered to national registry volunteers to: (1) determine the feasibility of using ResearchMatch for studying lower urinary tract symptoms (LUTS); (2) pilot the new, comprehensive Lower Urinary Tract Dysfunction Research Network Symptom Index-29 (LURN-SI-29) and determine its ability to detect known associations with LUTS; and (3) explore novel areas of bladder health in community-based women.A cross-sectional web-based survey was administered to a random sample of ResearchMatch adult female, transgender and non-binary volunteers. Participant demographics, health characteristics, the LURN-SI-29, and LUTS-related experiences were collected.A total of 1725 ReseachMatch volunteers with a mean age of 44.0 years completed the study and were eligible for the analysis. Participants were primarily white, cisgendered, highly educated, nulliparous, and premenopausal. The median LURN-SI-29 score was 17 (interquartile range: 11-26). More than half the sample reported urinary urgency (71.0%), nocturia (65.7%), and stress incontinence (52.3%) a "few times" or more in the last 7 days. Approximately half reported sensation of incomplete bladder emptying (49.6%) with one-third reporting urgency incontinence (37.6%); notably, 52.6% of respondents reported being at least "somewhat" bothered by LUTS. LURN-SI-29 scores increased with age, body mass index, decrements in self-reported health, medical comorbidity, parity, menopausal status, and urinary symptom bother, providing evidence of convergent validity. LURN-SI-29 scores varied by race and education, with the lowest scores in Asian and highly educated women.Overall, the prevalence and spectrum of LUTS in an online research registry of women volunteers were high and comparable to other population-based samples. The new LURN-SI-29 demonstrated its ability to detect expected associations with demographic and health characteristics in a nonclinical population.

INTRODUCTION AND OBJECTIVE:Measurement of SUI is often accomplished through use of a single item: Do you leak urine with coughing, sneezing, laughing or physical activity? Response to this item may...

Aim To conduct an evidence synthesis of normative reference values for bladder function parameters in women. Methods We conducted a systematic review and meta-analysis of studies reporting bladder function parameters obtained from noninvasive tests in healthy women. Seven databases were searched for relevant studies from inception through December 2018, with manual searching of reference lists. We included English language articles that provided quantitative data on urination frequency, voided and postvoid residual volumes, and uroflowmetry results in women without lower urinary tract symptoms. Study selection, data extraction, and quality assessment were undertaken by at least two independent reviewers. Random-effects meta-analytic models were used to derive study-level pooled mean estimates and 95% confidence intervals. Results A total of 24 studies (N = 3090 women, age range, 18-91 years) met eligibility criteria. Pooled mean estimates of bladder function parameters were: 6.6 daytime voids (95% confidence interval (95% CI), 6.2, 7.0), 0.4 nighttime voids (95% CI, 0.0, 0.8), 1577 mL for 24-hour voided volume (95% CI 1428,1725); 12 mL for postvoid residual volume (95% CI, 4, 20); and 28 mL/sec for maximum flow rate (95% CI, 27,30). Between-study heterogeneity was high for all outcomes (I2 = 61.1-99.6%), but insufficient data were available to explore reasons for this high heterogeneity (eg, differences by age). Conclusion Although summary mean estimates of bladder function parameters were calculated, the wide heterogeneity across studies precludes generalization of these estimates to all healthy women. Further research is needed to determine normative reference values within specific groups, such as those defined by age.

Author(s): Lowder, Jerry L; Bavendam, Tamara G; Berry, Amanda; Brady, Sonya S; Fitzgerald, Colleen M; Fok, Cynthia S; Goode, Patricia S; Lewis, Cora E; Mueller, Elizabeth R; Newman, Diane K; Palmer, Mary H; Rickey, Leslie; Stapleton, Ann; Lukacz, Emily S | Abstract: AimTo report research terminology and definitions for describing healthy bladder function among women and girls.MethodsThe Prevention of Lower Urinary tract Symptoms (PLUS) Consortium developed research terminology and definitions for elements of healthy bladder function based on existing understanding of storage and emptying functions of the bladder and accepted definitions of lower urinary tract symptoms (LUTS). The novel concept of a bladder "bioregulatory" function was also proposed. Elements of bladder function corresponding to bladder health (BH) and LUTS were developed and refined using an iterative process. A comprehensive reference table structured by bladder function (Storage, Emptying, and Bioregulatory) and elements of each function was created to document proposed research terminology and definitions.ResultsThe BH research definitions for each bladder function are: (1) Storage: the ability to hold urine for a reasonable duration of time and sense bladder fullness without fear of or concern about urgency, discomfort or leakage; (2) Emptying: the ability to empty the bladder completely in a timely, efficient, effortless, comfortable manner; and (3) Bioregulatory: the bladder barrier protects the individual/host from pathogens, chemicals, and malignancy. Research definitions for seven Storage, seven Emptying, and three Bioregulatory elements of function are presented. Novel LUTS research definitions were developed when gaps in existing definitions were identified or nonclinical language was desired.ConclusionsPLUS BH definitions reflect a transdisciplinary approach to standardizing research definitions for elements of bladder function from a perspective of health rather than dysfunction and provide a framework for studying BH in clinical practice, public health promotion, and LUTS prevention.

Summary Background Lower urinary tract symptoms (LUTS) are common in children and adolescents. Non-invasive tests evaluating bladder function are generally preferred over invasive tests, yet few studies have explored the range of normative values for these tests in healthy, asymptomatic children. Objective To define normative reference ranges for non-invasive tests of bladder function in healthy, asymptomatic girls and adolescents. Study design A comprehensive search strategy was performed in seven electronic databases through October 2019. English-language studies reporting data on voiding frequency, voided and postvoid residual volumes (PVR) and uroflowmetry results in healthy, asymptomatic girls (mean age ≥ 5 years) were included. Two independent reviewers performed study review, data extraction, and quality assessment. Overall mean estimates and 95% confidence intervals for each bladder function parameter were calculated using random effects models, and 95% normative reference values were estimated. Results Ten studies met eligibility criteria for the meta-analysis (n = 2143 girls, age range: 3–18). Mean estimates of maximum voided volume and PVR were 233.4 ml (95% CI 204.3–262.6; n = 1 study) and 8.6 ml (95% CI 4.8–12.4; n = 2 studies) respectively. Pooled mean estimates for uroflowmetry parameters were: 21.5 ml/s (95% CI 20.5–2.5) for maximum flow rate (n = 6 studies), 12.5 ml/s (95% CI 11.2–13.8) for mean flow rate (n = 6 studies), 6.8 s (95% CI 4.4–9.3) for time to maximum flow (n = 3 studies), 15.7 s (95% CI 13.0–18.5) for flow time (n = 3 studies), and 198.7 ml (95% CI 154.2–234.2) for voided volume (n = 9 studies). No studies reported estimates of voiding frequency. Between-study heterogeneity was high (89.0–99.6%). Conclusions Although we were able to calculate pooled mean estimates for several parameters, the small number of included studies and the wide age ranges of participants preclude generalization of reference values to all healthy girls. Further research is needed to determine normative reference values within specific age groups.

Antibiotic resistance is a threat to public health, and uncomplicated urinary tract infections (uUTIs) are an example of this concern. This systematic review (International Prospective Register of Systematic Reviews [PROSPERO] ID: CRD42020156674) is the first to determine the prevalence of Escherichia coli resistance to fluoroquinolones in women with community-acquired uUTI. PubMed and Embase searches were conducted; 38 studies fulfilled eligibility criteria and were included in the systematic review. Within Europe, ciprofloxacin resistance in E. coli isolates varied between countries and increased in some from 2006 to 2008 and 2014 to 2016, specifically in the United Kingdom (0.5% to 15.3%), Germany (8.7% to 15.1%), and Spain (22.9% to 30.8%), although methodologies and settings were often not comparable. In Asia, there was a substantial increase in ciprofloxacin resistance during 2008 to 2014 from 25% to more than 40%. In North America, resistance to ciprofloxacin also increased between 2008 and 2017, from 4% to 12%. Data exploring different age groups did not show a consistent relationship with resistance, whereas two studies found that fluoroquinolone resistance was higher in postmenopausal women than premenopausal women. One study indicated a link between fluoroquinolone resistance and uUTI recurrence. These findings may have implications for the empirical treatment of uUTI with fluoroquinolones globally, but more data are needed to fully understand regional situations and impact patient management.

Premise Aerial imagery from small unmanned aerial vehicle systems is a promising approach for high‐throughput phenotyping and precision agriculture. A key requirement for both applications is to create a field‐scale mosaic of the aerial imagery sequence so that the same features are in registration, a very challenging problem for crop imagery. Methods We have developed an improved mosaicking pipeline, Video Mosaicking and summariZation (VMZ), which uses a novel two‐dimensional mosaicking algorithm that minimizes errors in estimating the transformations between successive frames during registration. The VMZ pipeline uses only the imagery, rather than relying on vehicle telemetry, ground control points, or global positioning system data, to estimate the frame‐to‐frame homographies. It exploits the spatiotemporal ordering of the image frames to reduce the computational complexity of finding corresponding features between frames using feature descriptors. We compared the performance of VMZ to a standard two‐dimensional mosaicking algorithm (AutoStitch) by mosaicking imagery of two maize (Zea mays) research nurseries freely flown with a variety of trajectories. Results The VMZ pipeline produces superior mosaics faster. Using the speeded up robust features (SURF) descriptor, VMZ produces the highest‐quality mosaics. Discussion Our results demonstrate the value of VMZ for the future automated extraction of plant phenotypes and dynamic scouting for crop management.

As surface ultraviolet-B (UV-B) radiation levels increase due to the decline in the protective stratospheric ozone layer, ultraviolet radiation sunscreens will become more important for all plant species that grow in sunlight. Epicuticular waxes, which cover the aerial portions of all terrestrial plants, are ideally located to be sunscreens. The sun-screening ability of maize (Zea mays L.) epicuticular waxes was tested using the glossy1 mutant, which is specifically defective in juvenile wax production. A significant difference between the glossy1 mutant and wild type was seen in UV-induced leaf rolling and in some measurements of UV-induced DNA damage levels under enhanced UV. Isolated epicuticular wax layers absorbed significant amounts of UV, and leaves with wax absorbed more UV than leaves with little wax. Thus, by some measures, the epicuticular waxy layer acts as an ultraviolet radiation protectant in maize.

OBJECTIVES: To examine whether the school toilet environment at age 13, including bullying at toilets, is associated with female lower urinary tract symptoms (LUTS) at ages 13 and 19, as little is known about the association among school toilet environment, voiding behaviors, and LUTS in adolescent girls.METHODS: The sample comprised 3962 female participants from the Avon Longitudinal Study of Parents and Children. At age 13, participants reported on 7 school toilet environment characteristics and a range of LUTS items. At age 19, participants completed the Bristol Female Lower Urinary Tract Symptoms questionnaire.RESULTS: All toilet environmental factors were associated with at least 1 LUTS outcome at age 13. Holding behavior was associated with all school toilet environmental factors, with odds ratios ranging from 1.36 (95% confidence interval [CI]: 1.05, 1.76) for dirty toilets to 2.38 (95% CI: 1.60, 3.52) for feeling bullied at toilets. Bullying was associated with all daytime LUTS symptoms and nocturia; odds ratios ranged from 1.60 (95% CI: 1.04, 2.07) for nocturia to 2.90 (95% CI: 1.77, 4.75) for urgency. Associations between age 13 school toilets and age 19 LUTS were in the same direction as age 13 LUTS.CONCLUSION: This is the first examination of associations between school toilets and LUTS. Toileting environments were cross-sectionally associated with LUTS in adolescent girls. While further work is needed to determine whether these associations are causal, school toilet environments are modifiable and thus a promising target for LUTS prevention.

Background Asymptomatic bacteriuria and pyuria in healthy women often trigger inappropriate antimicrobial treatment, but there is a paucity of data on their prevalence and persistence. Methods To evaluate the prevalence and persistence of asymptomatic bacteriuria and pyuria in women at high risk of recurrent urinary tract infection, we conducted an observational cohort study in 104 healthy premenopausal women with a history of recurrent urinary tract infection with daily assessments of bacteriuria, pyuria, and urinary symptoms over a 3-month period. Results The mean age of participants was 22 years, and 74% were white. Asymptomatic bacteriuria events (urine cultures with colony count ≥105 CFU/mL of a uropathogen on days with no symptomatic urinary tract infection diagnosed) occurred in 45 (45%) women on 159 (2.5%) of 6283 days. Asymptomatic bacteriuria events were most commonly caused by Escherichia coli, which was present on 1.4% of days, with a median duration of 1 day (range, 1–10). Pyuria occurred in 70 (78%) of 90 evaluable participants on at least 1 day and 25% of all days on which no symptomatic urinary tract infection was diagnosed. The positive predictive value of pyuria for E. coli asymptomatic bacteriuria was 4%. Conclusions In this population of healthy women at high risk of recurrent urinary tract infection, asymptomatic bacteriuria is uncommon and, when present, rarely lasts more than 2 days. Pyuria, on the other hand, is common but infrequently associated with bacteriuria or symptoms. These data strongly support recommendations not to screen for or treat asymptomatic bacteriuria or pyuria in healthy, nonpregnant women.

In this paper, a new nonparametric methodology is developed for testing whether the changing pattern of a response variable over multiple ordered sub-populations from one treatment group differs with the one from another treatment group. The question is formalized into a nonparametric two-sample comparison problem for the stochastic order among subsamples, through U-statistics with accommodations for zero-inflated distributions. A novel bootstrap procedure is proposed to obtain the critical values with given type I error. Following the procedure, bootstrapped p-values are obtained through simulated samples. It is proven that the distribution of the test statistics is independent from the underlying distributions of the subsamples, when certain sufficient statistics provided. Furthermore, this study also develops a feasible framework for power studies to determine sample sizes, which is necessary in real-world applications. Simulation results suggest that the test is consistent. The methodology is ...

The unfolded protein response (UPR) is a highly conserved response that protects plants from adverse environmental conditions. The UPR is elicited by endoplasmic reticulum (ER) stress, in which unfolded and misfolded proteins accumulate within the ER. Here, we induced the UPR in maize (Zea mays) seedlings to characterize the molecular events that occur over time during persistent ER stress. We found that a multiphasic program of gene expression was interwoven among other cellular events, including the induction of autophagy. One of the earliest phases involved the degradation by regulated IRE1-dependent RNA degradation (RIDD) of RNA transcripts derived from a family of peroxidase genes. RIDD resulted from the activation of the promiscuous ribonuclease activity of ZmIRE1 that attacks the mRNAs of secreted proteins. This was followed by an upsurge in expression of the canonical UPR genes indirectly driven by ZmIRE1 due to its splicing of Zmbzip60 mRNA to make an active transcription factor that directly upregulates many of the UPR genes. At the peak of UPR gene expression, a global wave of RNA processing led to the production of many aberrant UPR gene transcripts, likely tempering the ER stress response. During later stages of ER stress, ZmIRE1’s activity declined, as did the expression of survival modulating genes, Bax inhibitor1 and Bcl-2-associated athanogene7, amid a rising tide of cell death. Thus, in response to persistent ER stress, maize seedlings embark on a course of gene expression and cellular events progressing from adaptive responses to cell death.

Crop improvement must accelerate to feed an increasing human population in the face of environmental changes. Including anticipated climatic changes with genetic architecture in breeding programs could better optimize improvement strategies. Combinations of drought and nitrogen limitation already occur world-wide. We therefore analyzed the genetic architecture underlying the response of Zea mays to combinations of water and nitrogen stresses. Recombinant inbreds were subjected to nine combinations of the two stresses using an optimized response surface design, and their growth was measured. Three-dimensional response surfaces were fit globally and to each polymorphic allele to determine which genetic markers were associated with different response surfaces. Three quantitative trait loci that produced nonlinear surfaces were mapped. To better understand the physiology of the response, we developed a model that reproduced the shapes of the surfaces, their most characteristic feature. The model contains two components that each combine the nitrogen and water inputs. The relative weighting of the two components and the inputs is governed by five parameters, and each QTL affects all five parameters. We estimated the model’s parameter values for the experimental surfaces using a mesh of points that covered the surfaces’ most distinctive regions. Surfaces computed using these values reproduced the experimental surfaces well, as judged by three different criteria at the mesh points. The modeling and shape comparison techniques used here can be extended to other complex, high-dimensional, nonlinear phenotypes. We encourage the application of our findings and methods to experiments that mix crop protection measures, stresses, or both, on elite and landrace germplasm.

Plant growth regulators have documented roles in plant responses to single stresses. In combined-stress environments, plants exhibit novel genetic architecture for growth traits and physiological responses can display synergistic effects. Synergistic responses have been used to optimize agronomic production and recommendations for adaptation to weather and field conditions can be used to improve selective breeding for higher yielding crops. We hypothesized that alterations in hormone balance would alter phenotypic responses to abiotic and crowding stress in a genotype-specific manner. We investigated the role of plant growth regulators in modulating combined-stress growth responses in Zea mays. Maize inbreds were exposed to all single, double and triple combinations of the following stressors in a field environment: drought, nitrogen deprivation, and increased plant density. Growth regulator chemical treatments were applied in a factorial design using a range of inbred genotypes. We found significant differences between the seed weights of plants given different chemical treatments and when single-stress environments were compared to combined stress environments. Different inbred genotypes exhibited contrasting patterns of response to combined stress and plant growth regulator treatment. Plant growth regulators altered combined-stress response pathways in maize inbreds; predictions of growth regulator effects would be improved by better characterization of stress environments and genotype-environment interactions.

This applied paper is intended to serve as a “how to” guide for public health researchers, practitioners, and policy makers who are interested in building conceptual models to convey their ideas to diverse audiences. Conceptual models can provide a visual representation of specific research questions. They also can show key components of programs, practices, and policies designed to promote health. Conceptual models may provide improved guidance for prevention and intervention efforts if they are based on frameworks that integrate social ecological and biological influences on health and incorporate health equity and social justice principles. To enhance understanding and utilization of this guide, we provide examples of conceptual models developed by the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium. PLUS is a transdisciplinary U.S. scientific network established by the National Institutes of Health in 2015 to promote bladder health and prevent lower urinary tract symptoms, an emerging public health and prevention priority. The PLUS Research Consortium is developing conceptual models to guide its prevention research agenda. Research findings may in turn influence future public health practices and policies. This guide can assist others in framing diverse public health and prevention science issues in innovative, potentially transformative ways.

Aims Although lower urinary tract symptoms (LUTS) may occur at different periods during the life course of women, a little research on LUTS has adopted a life course perspective. The purpose of this conceptual paper is to demonstrate how life course theory and life course epidemiology can be applied to study bladder health and LUTS trajectories. We highlight conceptual work from the Prevention of Lower Urinary Tract Symptoms Research Consortium to enhance the understanding of life course concepts. Methods Consortium members worked in transdisciplinary teams to generate examples of how life course concepts may be applied to research on bladder health and LUTS in eight prioritized areas: (a) biopsychosocial ecology of stress and brain health; (b) toileting environment, access, habits, and techniques; (c) pregnancy and childbirth; (d) physical health and medical conditions; (e) musculoskeletal health; (f) lifestyle behaviors; (g) infections and microbiome; and (h) hormonal status across the life span. Results Life course concepts guided consortium members' conceptualization of how potential risk and protective factors may influence women's health. For example, intrapartum interventions across multiple pregnancies may influence trajectories of bladder health and LUTS, illustrating the principle of life span development. Consortium members also identified and summarized methodologic and practical considerations in designing life course research. Conclusions This paper may assist researchers from a variety of disciplines to design and implement research identifying key risk and protective factors for LUTS and bladder health across the life course of women. Results from life course research may inform health promotion programs, policies, and practices.

Today’s biology laboratory courses are primarily instructed by graduate teaching assistants (GTAs) working toward their own graduate degrees in a science field. Even though GTAs are the driving instructional force in biology laboratories, they receive little to no training in pedagogical principles and applications. Here, we present the GTAs’ self-reported unmet training needs with respect to teaching biology laboratory courses. To address these needs, we developed three training cases along with instructions for implementation in online and in-person GTA trainings. We piloted our training materials for GTA training in person at Iowa State University and in a Center for the Integration of Research, Teaching, and Learning three-part online workshop. Upon completion of these training sessions, GTAs reported an increase in both their confidence and knowledge of student-centered instructional approaches. Furthermore, examination of the online workshop participants’ lesson plans demonstrated that GTAs were able to implement effective teaching practices in their own lesson plans. For brief training sessions, these are positive outcomes suggesting these cases are effective tools that could be incorporated into a variety of GTA training programs to improve instruction in biology laboratory courses.

Crop breeding is as ancient as the invention of cultivation. In essence, the objective of crop breeding is to improve plant fitness under human cultivation conditions, making crops more productive while maintaining consistency in life cycle and quality. The applications of predictive breeding has been gaining momentum in agricultural industry and public breeding programs for the last decade, in the aftermath of genomic selection being recognized and widely applied for accelerating genetic gain in breeding programs. The massive amounts of data that has been generated by industry and farmers year after year through several decades has finally been recognized as an asset. A wide range of analytical methods such as machine learning, deep learning and artificial intelligence that were initially developed for diverse quantitative disciplines are now being adopted to crop breeding decision making processes. New technologies are currently being developed that would enable integration of data from various domains such as geospatial variables and a multitude of phenotypic responses as well as genetic information, in order to identify, develop and improve crop faster via partial or full automation of the decisions that pertain to variety development. Here we will discuss and summarize efforts from public and private domains for predictive analytics, and its applications to crop breeding and agricultural product development, and provide suggestions for future research.

Background Urinary tract infections (UTIs) are common in women but most epidemiology studies occurred in specialized settings (university health clinics) or used outdated methods (random digit dialing). Currently, women receive UTI care in systems with electronic health records (EHR), thus documenting care of a wider female demographic in real-world settings. We estimated the prevalence of acute, uncomplicated UTIs in community-dwelling women in a health claims database using various operational definitions of UTI. Methods We conducted a retrospective analysis of claims data from the OptumLabs® Data Warehouse (OLDW), a de-identified claims and clinical information repository for privately insured and Medicare Advantage enrollees in a large, private US health plan. Non-pregnant female patients ≥ 15 years of age with two years of continuous enrollment between 2007-2015 and a visit encounter in an outpatient office, urgent care, or emergency department were included. Women with lower urinary tract disease/abnormalities, neurological disease, urological treatment, procedures or urinary catheter use, cancer or HIV treatment were excluded. Decision rules for identifying UTIs were derived using one or more combinations of: relevant ICD-9 codes, UTI symptom diagnosis codes, positive urine test results, and/or antibiotic prescription recorded in the EHR and claims. Prevalence rates were calculated for each decision rule. Results Of the 7,337,700 females in the claims database, 947,041 (12.97%) had an index UTI diagnosis or symptoms and met eligibility criteria. The table below illustrates prevalence rates according to each decision rule. As shown, applying decision rules based on common UTI definitions resulted in large differences in prevalence rates. Table Conclusion Using common definitions for UTI to analyze claims data from an insurer of large proportions of the US, we obtained significantly different prevalence rates. This study highlights major limitations in using EHR and claims data for UTI quality initiatives such as tracking of practices associated with antimicrobial stewardship and lends credibility to proposals to track these infections as a reportable disease. Disclosures All Authors: No reported disclosures

Plants are increasingly exposed to high temperatures, which can cause accumulation of unfolded protein in the endoplasmic reticulum (ER). This condition, known as ER stress, evokes the unfolded protein response (UPR), a cytoprotective signaling pathway. One important branch of the UPR is regulated by splicing of bZIP60 mRNA by the IRE1 stress sensor. There is increasing evidence that commercial plant growth regulators may protect against abiotic stressors including heat stress and drought, but there is very little mechanistic information about these effects or about the regulatory pathways involved. We evaluated evidence in the B73 Zea mays inbred for differences in the activity of the UPR between permissive and elevated temperature in conjunction with plant growth regulator application. Treatment with elevated temperature and plant growth regulators increased UPR activation, as assessed by an increase in splicing of the mRNA of the IRE1 target bZIP60 following paclobutrazol treatment. We propose that plant growth regulator treatment induces bZIP60 mRNA splicing which ‘primes’ plants for rapid adaptive response to subsequent endoplasmic reticulum-stress inducing conditions.

Increasingly complex statistical models are being used for the analysis of biological data. Recent commentary has focused on the ability to compute the same outcome for a given dataset (reproducibility). We argue that a reproducible statistical analysis is not necessarily valid because of unique patterns of nonindependence in every biological dataset. We advocate that analyses should be evaluated with known-truth simulations that capture biological reality, a process we call “analysis validation.” We review the process of validation and suggest criteria that a validation project should meet. We find that different fields of science have historically failed to meet all criteria, and we suggest ways to implement meaningful validation in training and practice., Just as we do controls for experiments we should all do controls for data analysis – this is easy to say but requires dedication to implement. This Essay explains the need for analysis validation and provides specific suggestions for how to get started.

Recurrent lower urinary tract infections in women are a highly prevalent and burdensome condition for which best practice guidelines for treatment and prevention that minimize harm and optimize well-being are greatly needed. To inform development of practice recommendations, a rapid literature review of original research, systematic reviews, meta-analyses and practice guidelines was conducted.PubMed®, Embase®, Opus, Scopus®, Google Scholar, The Cochrane Library and the U.S. National Guideline Clearinghouse electronic databases were searched from inception to September 22, 2017. Articles and practice guidelines were included if they were in English, were peer reviewed, included women, involved treatment or prevention strategies for recurrent urinary tract infection and reported an outcome related to recurrence rates of urinary tract infection. Critical appraisal of original studies was conducted using the Cochrane risk of bias tool, and of systematic reviews using the AMSTAR 2 tool.Of 1,582 citations identified 74 met our study inclusion criteria. These comprised 49 randomized controlled trials, 23 systematic reviews (16 with meta-analyses) and 2 practice guidelines. No study reported a multi-targeted treatment approach. There was a lack of high quality studies and systematic reviews evaluating prevention strategies for recurrent urinary tract infection.We recommend an algorithmic approach to care that includes education on lifestyle and behavioral modifications, and addresses specific populations of women with antimicrobial based and nonantibiotic alternatives. This approach includes the use of vaginal estrogen with or without lactobacillus containing probiotics in postmenopausal women, low dose post-coital antibiotics for recurrent urinary tract infection associated with sexual activity in premenopausal women, low dose daily antibiotic prophylaxis in premenopausal women with infections unrelated to sexual activity, and methenamine hippurate and/or lactobacillus containing probiotics as nonantibiotic alternatives. Future research should involve consistent use of terminology, validated instruments to assess response to interventions and patient perspectives on care. Our treatment algorithm is based on the best available evidence, and fills a gap in the literature and practice regarding effective strategies to prevent recurrent urinary tract infection in women.

Urinary tract infections (UTIs) are frequently encountered in clinical practice and most commonly caused by Escherichia coli and other Gram-negative uropathogens. We tested RapidBac, a rapid immunoassay for bacteriuria developed by Silver Lake Research Corporation (SLRC), compared with standard bacterial culture using 966 clean-catch urine specimens submitted to a clinical microbiology laboratory in an urban academic medical center. RapidBac was performed in accordance with instructions, providing a positive or negative result in 20 min. RapidBac identified as positive 245/285 (sensitivity 86%) samples with significant bacteriuria, defined as the presence of a Gram-negative uropathogen or Staphylococcus saprophyticus at ≥10 3 CFU/ml. The sensitivities for Gram-negative bacteriuria at ≥10 4 CFU/ml and ≥10 5 CFU/ml were 96% and 99%, respectively. The specificity of the test, detecting the absence of significant bacteriuria, was 94%. The sensitivity and specificity of RapidBac were similar on samples from inpatient and outpatient settings, from male and female patients, and across age groups from 18 to 89 years old, although specificity was higher in men (100%) compared with that in women (92%). The RapidBac test for bacteriuria may be effective as an aid in the point-of-care diagnosis of UTIs especially in emergency and primary care settings.

During Escherichia coli urinary tract infections, cells in the human urinary tract release the antimicrobial protein siderocalin (SCN; also known as lipocalin 2, neutrophil gelatinase-associated lipocalin/NGAL, or 24p3). SCN can interfere with E. coli iron acquisition by sequestering ferric iron complexes with enterobactin, the conserved E. coli siderophore. Here, we find that human urinary constituents can reverse this relationship, instead making enterobactin critical for overcoming SCN-mediated growth restriction. Urinary control of SCN activity exhibits wide ranging individual differences. We used these differences to identify elevated urinary pH and aryl metabolites as key biochemical host factors controlling urinary SCN activity. These aryl metabolites are well known products of intestinal microbial metabolism. Together, these results identify an innate antibacterial immune interaction that is critically dependent upon individualistic chemical features of human urine.

All living things deal with stress. For you, that might be having a cold in addition to not getting enough sleep. For a plant, it is stressful to live through a drought. It turns out that stress is more than a passing annoyance. It can actually change who we are. Sometimes stress can affect our DNA, the instruction manual for building a living thing. Stress does not rewrite the letters in the DNA instruction manual, but it can change which chapters are used, and which ones are skipped over. Researchers are using corn plants to better understand how different kinds of stress can change how tall the plants grow. Understanding how DNA and the environment work together can not only help us grow bigger, better corn but it can also help us understand other organisms too, including ourselves.

Crop improvement must accelerate to feed an increasing human population in the face of environmental changes. Breeding programs can include anticipated climatic changes and genetic architecture to optimize improvement strategies. We analyzed the genetic architecture underlying the response of Zea mays to combinations of water and nitrogen stresses. Recombinant inbreds were subjected to nine combinations of the two stresses using an optimized response surface design, and their growth was measured. Three-dimensional dose response surfaces were fit globally and to each polymorphic allele to determine which genetic markers were associated with different response surfaces. Three quantitative trait loci that produced nonlinear surfaces were mapped. Alleles that performed better in combinations of mid-range stresses were typically not the alleles that performed best under combinations of extreme stresses. To develop physiologically relevant models for future genetic analyses, we modeled the network that explains the response surfaces. The network contains two components, an elliptical paraboloid and a plane, that each combine the nitrogen and water inputs. The relative weighting of the two components and the inputs is governed by five parameters. We estimated parameter values for the smoothed surfaces from the experimental lines using a set of points that covered the most distinctive regions of the three-dimensional surfaces. Surfaces computed using these values reproduced the smoothed experimental surfaces well, especially in the neighborhood of the peaks, as judged by three different criteria. The parameters exaggerated the amplitudes of the simulated surfaces. Experiments using single stresses could misestimate responses to their combinations and disguise loci that respond nonlinearly. The three-dimensional shape evaluation strategy used here more thoroughly compares nonlinear, nonplanar responses. We encourage the application of our findings and methods to experiments that mix crop protection measures, stresses, or both, on elite and landrace germplasm.

Background: The phyllosphere hosts a variety of microorganisms, including bacteria, which can play a positive role in the success of the host plant. Bacterial communities in the phylloplane are influenced by both biotic and abiotic factors, including host plant surface topography and chemistry, which change in concert with microbial communities as the plant leaves develop and age.Methods: We examined how theZea maysL. leaf microbial community structure changed with plant age. Ribosomal spacer length and scanning electron microscopic imaging strategies were used to assess microbial community composition across maize plant ages, using a novel staggered experimental design.Results: Significant changes in community composition were observed for both molecular and imaging analyses, and the two analysis methods provided complementary information about bacterial community structure within each leaf developmental stage.Conclusions: Both taxonomic and cell-size trait patterns provided evidence for niche-based contributions to microbial community development on leaves.

Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in their urovirulence, that is, their ability to infect the bladder in a mouse model of cystitis. We found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the E. coli strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and metabolism, could be used to predict subsequent colonization of the mouse bladder. Together, our findings suggest that UTI risk and outcome may be determined by complex interactions between host susceptibility and the urovirulence potential of diverse bacterial strains.

Clinically, host factors in the pathogenesis of urinary tract infection (UTI) may be considered as modifiable (eg, behaviors associated with increased risk of UTI, anatomic and functional problems of the urinary tract) and thus potentially amenable to a change in patient behavior or treatment approach, or as intrinsic and nonmodifiable host factors that neither the patient nor the clinician can influence (eg, gender and genetic influences associated with UTI). Although considering nonmodifiable host factors may be discouraging to patients and clinicians at present, some genetic associations have the potential for future predictive value and may interface with future treatments.

Background Pyuria has long been considered key to diagnosis of urinary tract infection in women, but there is a paucity of data on its prevalence and association with asymptomatic bacteriuria (ASB) in healthy women, even though pyuria and ASB often trigger inappropriate antimicrobial treatment. Methods We enrolled 104 healthy premenopausal women with a history of recurrent urinary tract infection (UTI) in an observational study and performed daily assessments of bacteriuria, pyuria (leukocyte esterase strips) and UTI symptoms over a 3-month period. These data enabled an evaluation of the prevalence of pyuria and ASB and associations between them. Results The mean age of participants was 22 and 74% were white. Pyuria occurred frequently in this cohort of women, with 72 (77%) of 94 evaluable subjects having pyuria on at least one day with no symptomatic UTI diagnosed. The median percent of days with pyuria reported was 7% (range, 0–100%). Asymptomatic bacteriuria (ASB, urine culture with colony count ≥105 CFU/mL of uropathogen on days with no symptomatic UTI diagnosed) occurred in 45 (45%) women on 159 (2.5%) of 6,283 days. ASB was most commonly caused by E. coli, which was present in 1.4% of days with median duration one day (range, 1–10). The positive predictive value of pyuria in detecting ASB was 4%. Five women had 11 transient episodes of pyuria, significant bacteriuria, and UTI symptoms (“preclinical UTI”) but did not seek medical attention. Conclusion In this population of healthy women at high risk for UTI and ASB, asymptomatic pyuria was a frequent occurrence and ASB rarely lasted more than 2 days. Pyuria, whether associated with bacteriuria or not, was generally not accompanied by urinary symptoms and did not appear to be clinically meaningful. Young women with recurrent UTI are often advised by their providers to test their urine with dipsticks for pyuria or bacteriuria, and be treated if either are positive, regardless of absence of UTI symptoms. Such practices, which contribute to antimicrobial resistance, are not supported by our data. Disclosures All authors: No reported disclosures.

Uropathogenic Escherichia coli (UPEC) fall within a larger group of isolates producing extraintestinal disease. UPEC express type 1 pili as a critical virulence determinant mediating adherence to and invasion into urinary tract tissues. Type 1 pili expression is under regulation by a family of site-specific recombinases, including FimX, which is encoded from a genomic island called PAI-X for pathogenicity island of FimX. Using a new multiplex PCR, fimX and the additional PAI-X genes were found to be highly associated with UPEC (144/173 = 83.2 %), and more prevalent in UPEC of lower urinary tract origin (105/120 = 87.5 %) than upper urinary tract origin (39/53 = 74 %; P

Escherichia coli and other Enterobacteriaceae are among the most common pathogens of the human urinary tract. Among the genetic gains of function associated with urinary E. coli isolates is the Yersinia high pathogenicity island (HPI), which directs the biosynthesis of yersiniabactin (Ybt), a virulence-associated metallophore. Using a metabolomics approach, we found that E. coli and other Enterobacteriaceae expressing the Yersinia HPI also secrete escherichelin, a second metallophore whose chemical structure matches a known synthetic inhibitor of the virulence-associated pyochelin siderophore system in Pseudomonas aeruginosa. We detected escherichelin during clinical E. coli urinary tract infection (UTI) and experimental human colonization with a commensal, potentially probiotic E. coli bacteriuria strain. Escherichelin production by colonizing enterobacteria may help human hosts resist opportunistic infections by Pseudomonas and other pyochelin-expressing bacteria. This siderophore-based mechanism of microbial antagonism may be one of many elements contributing to the protective effects of the human microbiome. Future UTI-preventive probiotic strains may benefit by retaining the escherichelin biosynthetic capacity of the Yersinia HPI while eliminating the Ybt biosynthetic capacity.