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Introduction: Supplemental Instruction (SI) is an internationally-recognised academic support programme serving students in historically challenging courses across higher education via peer-assisted learning. Methods: A survey was deployed to gather perceptions of SI among student pharmacists, near-peer leaders, faculty, and staff of a traditional, four-year doctor of pharmacy programme hosted by a private institution in the United States. Results: Ninety-eight participants shared perceptions and viewpoints of the SI programme. Overall, positive perceptions were expressed and were independent of proximity to either attending sessions (students) or teaching activities (faculty). Student respondents identified audience-response polling or “gamification” as the most effective modality while the traditional use of student small groups was deemed less useful. Curiously, the student results also support SI improving student-faculty interactions. Conclusion: Given the current landscape of pharmacy education, it is critical to provide the best resources possible to ensure student success, and SI is an easily adaptable model to support student pharmacists.

Objective:To describe national antibiotic prescribing for acute gastroenteritis (AGE).Setting:Ambulatory care.Methods:We included visits with diagnoses for bacterial and viral gastrointestinal infections from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (NAMCS/NHAMCS; 2006–2015) and the IBM Watson 2014 MarketScan Commercial Claims and Encounters Database. For NAMCS/NHAMCS, we calculated annual percentage estimates and 99% confidence intervals (CIs) of visits with antibiotics prescribed; sample sizes were too small to calculate estimates by pathogen. For MarketScan, we used Poisson regression to calculate the percentage of visits with antibiotics prescribed and 95% CIs, including by pathogen.Results:We included 10,210 NAMCS/NHAMCS AGE visits; an estimated 13.3% (99% CI, 11.2%–15.4%) resulted in antibiotic prescriptions, most frequently fluoroquinolones (28.7%; 99% CI, 21.1%–36.3%), nitroimidazoles (20.2%; 99% CI, 14.0%–26.4%), and penicillins (18.9%; 99% CI, 11.6%–26.2%). In NAMCS/NHAMCS, antibiotic prescribing was least frequent in emergency departments (10.8%; 99% CI, 9.5%–12.1%). Among 1,868,465 MarketScan AGE visits, antibiotics were prescribed for 13.8% (95% CI, 13.7%−13.8%), most commonly for Yersinia (46.7%; 95% CI, 21.4%–71.9%), Campylobacter (44.8%; 95% CI, 41.5%–48.1%), Shigella (39.7%; 95% CI, 35.9%–43.6%), typhoid or paratyphoid fever (32.7%; (95% CI, 27.2%–38.3%), and nontyphoidal Salmonella (31.7%; 95% CI, 29.5%–33.9%). Antibiotics were prescribed for 12.3% (95% CI, 11.7%–13.0%) of visits for viral gastroenteritis.Conclusions:Overall, ∼13% of AGE visits resulted in antibiotic prescriptions. Antibiotics were unnecessarily prescribed for viral gastroenteritis and some bacterial infections for which antibiotics are not recommended. Antibiotic stewardship assessments and interventions for AGE are needed in ambulatory settings.

Foodborne illness is common in the United States with most, but not all, foodborne pathogens causing symptoms of acute gastroenteritis (AGI). Outpatient care is the most frequent type of medical care sought; however, more accurate estimates of outpatient costs are needed to inform food safety policy decision. Using the U.S. MarketScan Commercial Claims and Encounters database, we quantified the per-visit cost of outpatient visits with any AGI-related diagnosis (including pathogen-specific and nonspecific or symptom-based diagnoses) and for those with a pathogen-specific diagnosis for 1 of 29 pathogens commonly transmitted through food (including pathogens that cause AGI and some that do not). Our estimates included the per-case cost of office visits and associated laboratory tests and procedures as well as the conservative estimates of prescription cost. Most AGI outpatient visits were coded using nonspecific codes (e.g., infectious gastroenteritis), rather than pathogen-specific codes (e.g.

Potentially mineralizable nitrogen (PMN) is a widely used indicator of a soil’s organic nitrogen (N) availability, and is often measured by incubation. While it is known that the handling of soil p...

Provision of safe drinking water in the United States is a great public health achievement. However, new waterborne disease challenges have emerged (e.g., aging infrastructure, chlorine-tolerant and biofilm-related pathogens, increased recreational water use). Comprehensive estimates of the health burden for all water exposure routes (ingestion, contact, inhalation) and sources (drinking, recreational, environmental) are needed. We estimated total illnesses, emergency department (ED) visits, hospitalizations, deaths, and direct healthcare costs for 17 waterborne infectious diseases. About 7.15 million waterborne illnesses occur annually (95% credible interval [CrI] 3.88 million-12.0 million), results in 601,000 ED visits (95% CrI 364,000-866,000), 118,000 hospitalizations (95% CrI 86,800-150,000), and 6,630 deaths (95% CrI 4,520-8,870) and incurring US $3.33 billion (95% CrI 1.37 billion-8.77 billion) in direct healthcare costs. Otitis externa and norovirus infection were the most common illnesses. Most hospitalizations and deaths were caused by biofilm-associated pathogens (nontuberculous mycobacteria, Pseudomonas, Legionella), costing US $2.39 billion annually.

Naegleria fowleri is a free-living ameba that causes primary amebic meningoencephalitis (PAM), a rare but usually fatal disease. We analyzed trends in recreational water exposures associated with PAM cases reported during 1978–2018 in the United States. Although PAM incidence remained stable, the geographic range of exposure locations expanded northward.

Objectives. To investigate a shigellosis outbreak in Genesee County, Michigan (including the City of Flint), and Saginaw County, Michigan, in 2016 and address community concerns about the role of the Flint water system. Methods. We met frequently with community members to understand concerns and develop the investigation. We surveyed households affected by the outbreak, analyzed Shigella isolate data, examined the geospatial distribution of cases, and reviewed available water quality data. Results. We surveyed 83 households containing 158 cases; median age was 10 years. Index case-patients from 55 of 83 households (66%) reported contact with a person outside their household who wore diapers or who had diarrhea in the week before becoming ill; results were similar regardless of household drinking water source. Genomic diversity was not consistent with a point source. In Flint, no space-time clustering was identified, and average free chlorine residual values remained above recommended levels throughout the outbreak period. Conclusions. The outbreak was most likely caused by person-to-person contact and not by the Flint water system. Consistent community engagement was essential to the design and implementation of the investigation.

Contaminated powdered infant formula from opened containers is the most commonly identified transmission vehicle., Invasive Cronobacter infections among infants are associated with severe neurologic disabilities and death. Early Cronobacter reports typically featured hospitalized and preterm infants and recognized contaminated powdered infant formula (PIF) as a transmission vehicle. To clarify recent epidemiology, we reviewed all cases of bloodstream infection or meningitis among infants that were reported to the Centers for Disease Control and Prevention and in the literature (1961–2018; n = 183). Most infants were neonates (100/150 [67%]); 38% (42/112) died, and 79% (81/102) had reported recent PIF consumption. In the final quarter of the study period (2004–2018), case counts were significantly higher (global average 8.7 cases/year); among US cases, significantly higher proportions occurred among full-term (56% [27/48]) and nonhospitalized (78% [42/54]) infants. PIF contamination, most commonly from opened containers, was identified in 30% (21/71) of investigations. Our findings reaffirm the need to promote safer alternatives for infant feeding, particularly among neonates.

Background The coronavirus disease 2019 (COVID-19) pandemic profoundly affected food systems including food security. Understanding how the COVID-19 pandemic impacted food security is important to provide support and identify long-term impacts and needs. Objective The National Food Access and COVID research Team (NFACT) was formed to assess food security over different US study sites throughout the pandemic, using common instruments and measurements. This study presents results from 18 study sites across 15 states and nationally over the first year of the COVID-19 pandemic. Methods A validated survey instrument was developed and implemented in whole or part through an online survey of adults across the sites throughout the first year of the pandemic, representing 22 separate surveys. Sampling methods for each study site were convenience, representative, or high-risk targeted. Food security was measured using the USDA 6-item module. Food security prevalence was analyzed using ANOVA by sampling method to assess statistically significant differences. Results Respondents (n = 27,168) indicate higher prevalence of food insecurity (low or very low food security) since the COVID-19 pandemic, compared with before the pandemic. In nearly all study sites, there is a higher prevalence of food insecurity among Black, Indigenous, and People of Color (BIPOC), households with children, and those with job disruptions. The findings demonstrate lingering food insecurity, with high prevalence over time in sites with repeat cross-sectional surveys. There are no statistically significant differences between convenience and representative surveys, but a statistically higher prevalence of food insecurity among high-risk compared with convenience surveys. Conclusions This comprehensive study demonstrates a higher prevalence of food insecurity in the first year of the COVID-19 pandemic. These impacts were prevalent for certain demographic groups, and most pronounced for surveys targeting high-risk populations. Results especially document the continued high levels of food insecurity, as well as the variability in estimates due to the survey implementation method., Multi-site assessment demonstrates widespread food insecurity during COVID-19, especially for households with children, job loss, and Black, Indigenous, People of Color across multiple survey methods.

Through the use of published estimates of medical costs and new calculations of productivity losses, we estimate the lifetime economic burden of 2014 Legionnaires’ disease cases in the United States at ≈$835 million. This total includes $21 million in productivity losses caused by absenteeism and $412 million in productivity losses caused by premature deaths.

An estimated 45 million U.S. residents enjoy the benefits of contact lens wear, but many of them might be at increased risk for complications stemming from improper wear and care behaviors (1). One of the most serious complications of contact lens wear is a corneal infection known as microbial keratitis, which can sometimes result in reduced vision or blindness (2). In 2014, 50% of contact lens wearers reported ever sleeping in contact lenses, and 55% reported topping off* their contact lens solutions (3), which put them at greater risk for a contact lens-related eye infection (2,4). Data on communication between eye care providers and contact lens wearers on contact lens wear and care recommendations are limited. Two surveys were conducted to better understand and assess contact lens education about nine recommendations: the first assessed contact lens wearer experiences regarding recommendations received from eye care providers during their most recent appointment; the second evaluated provider-reported practices for communicating contact lens wear and care recommendations to their patients. One third (32.9%) of contact lens wearers aged ≥18 years recalled never hearing any lens wear and care recommendations. Fewer than half (47.9%) recalled hearing their provider recommend not sleeping in lenses at their last visit, and 19.8% recalled being told to avoid topping off their contact lens solution. A majority of providers reported sharing recommendations always or most of the time at initial visits, regular checkups, and complication-related visits. Providers reported sharing nearly all recommendations more frequently at initial and complication-related visits than at regular checkups. Of the nine recommendations for safe contact lens wear and care, eye care providers at regular checkups most often recommend complying with the recommended lens replacement schedules (85% of regular visits), not sleeping in lenses (79.0% of regular visits), and not topping off solutions (64.4% of regular visits). Eye care providers play an important role in the health of their contact lens-wearing patients and can share health communication messages with their patients to help educate them about healthy wear and care habits. These findings can assist in the creation of health communication messages to help encourage eye care providers to communicate more effectively with their patients.

BackgroundSince December 2020, public health agencies have implemented a variety of vaccination strategies to curb the spread of SARS-CoV-2, along with pre-existing Nonpharmaceutical Interventions (NPIs). Initial strategy focused on vaccinating the elderly to prevent hospitalizations and deaths. With vaccines becoming available to the broader population, we aimed to determine the optimal strategy to enable the safe lifting of NPIs while avoiding virus resurgence.MethodsWe developed a compartmental deterministic SEIR model to simulate the lifting of NPIs under different vaccination rollout scenarios. Using case and vaccination data from Toronto, Canada between December 28, 2020 and May 19, 2021, we estimated transmission throughout past stages of NPI escalation/relaxation to compare the impact of lifting NPIs on different dates on cases, hospitalizations, and deaths, given varying degrees of vaccine coverages by 20-year age groups, accounting for waning immunity.ResultsWe found that, once coverage among the elderly is high enough (80% with at least one dose), the main age groups to target are 20-39 and 40-59 years, whereby first-dose coverage of at least 70% by mid-June 2021 is needed to minimize the possibility of resurgence if NPIs are to be lifted in the summer. While a resurgence was observed for every scenario of NPI lifting, we also found that under an optimistic vaccination coverage (70% by mid-June, postponing reopening from August 2021 to September 2021can reduce case counts and severe outcomes by roughly 80% by December 31, 2021.ConclusionsOur results suggest that focusing the vaccination strategy on the working-age population can curb the spread of SARS-CoV-2. However, even with high vaccination coverage in adults, lifting NPIs to pre-pandemic levels is not advisable since a resurgence is expected to occur, especially with earlier reopening.

BackgroundThe COVID-19 pandemic profoundly affected food systems including food security. Understanding how the COVID-19 pandemic impacted food security is important to provide support, and identify long-term impacts and needs.ObjectiveOur team- the National Food Access and COVID research Team (NFACT) was formed to assess food security over different U.S. study sites throughout the pandemic, using common instruments and measurements. Here we present results from 18 study sites across 15 states and nationally over the first year of the COVID-19 pandemic.MethodsA validated survey instrument was developed and implemented in whole or part across the sites throughout the first year of the pandemic, representing 22 separate surveys. Sampling methods for each study site were convenience, representative, or high-risk targeted. Food security was measured using the USDA six-item module. Food security prevalence was analyzed using analysis of variance by sampling method to statistically significant differences.ResultsIn total, more than 27,000 people responded to the surveys. We find higher prevalence of food insecurity (low or very low food security) since the COVID-19 pandemic, as compared to before the pandemic. In nearly all study sites, we find higher prevalence of food insecurity among Black, Indigenous, and People of Color (BIPOC), households with children, and those with job disruptions. We also demonstrate lingering food insecurity, with high or increased prevalence over time in sites with repeat surveys. We find no statistically significant differences between convenience and representative surveys, but statistically higher prevalence of food insecurity among high-risk compared to convenience surveys.ConclusionsThis comprehensive multi-study site effort demonstrates higher prevalence of food insecurity since the beginning of the COVID-19 pandemic, which in multiple survey sites continues throughout the first year of the pandemic. These impacts were prevalent for certain demographic groups, and most pronounced for surveys targeting high-risk populations.

Background Giardiasis is the most common intestinal parasitic disease of humans identified in the United States (US) and an important waterborne disease. In the United States, giardiasis has been variably reportable since 1992 and was made a nationally notifiable disease in 2002. Our objective was to describe the epidemiology of US giardiasis cases from 1995 through 2016 using National Notifiable Diseases Surveillance System data. Methods Negative binomial regression models were used to compare incidence rates by age group (0–4, 5–9, 10–19, 20–29, 30–39, 40–49, 50–64, and ≥ 65 years) during 3 time periods (1995–2001, 2002–2010, and 2011–2016). Results During 1995–2016, the average number of reported cases was 19 781 per year (range, 14 623–27 778 cases). The annual incidence of reported giardiasis in the United States decreased across all age groups. This decrease differs by age group and sex and may reflect either changes in surveillance methods (eg, changes to case definitions or reporting practices) or changes in exposure. Incidence rates in males and older age groups did not decrease to the same extent as rates in females and children. Conclusions Trends suggest that differences in exposures by sex and age group are important to the epidemiology of giardiasis. Further investigation into the risk factors of populations with higher rates of giardiasis will support prevention and control efforts.

Significance Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies. Purpose The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting. Methods Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives. Results The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed. Conclusions The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain.

Efforts to mitigate the COVID-19 pandemic have relied heavily on non-pharmaceutical interventions (NPIs), including physical distancing, hand hygiene, and mask-wearing. However, an effective vaccine is essential to containing the spread of the virus. The first doses were distributed at the end of 2020, but the efficacy, period of immunity it will provide, and percentage of coverage still remain unclear. We developed a compartment model to examine different vaccine strategies for controlling the spread of COVID-19. Our framework accounts for testing rates, test-turnaround times, and vaccination waning immunity. Using reported case data from the city of Toronto, Canada between Mar-Dec, 2020 we defined epidemic phases of infection using contact rates, which depend on individuals’ duration of time spent within the household, workplace/school, or community settings, as well as the probability of transmission upon contact. We investigated the impact of vaccine distribution by comparing different permutations of waning immunity, vaccine coverage and efficacy throughout various stages of NPI’s relaxation in terms of cases, deaths, and household transmission, as measured using the basic reproduction number (R0). We observed that widespread vaccine coverage substantially reduced the number of cases and deaths. In order for NPIs to be relaxed 8 months after vaccine distribution, infection spread can be kept under control with either 60% vaccine coverage, no waning immunity, and 70% efficacy, or with 60% coverage with a 12-month waning immunity and 90% vaccine efficacy. Widespread virus resurgence can result when the immunity wanes under 3 months and/or when NPI’s are relaxed in concomitance with vaccine distribution. In addition to vaccination, our analysis of R0 showed that the basic reproduction number is reduced by decreasing the tests turnaround time and transmission in the household. While we found that household transmission can decrease following the introduction of a vaccine, public health efforts to reduce test turnaround times remain important for virus containment. Our findings suggest that vaccinating two-thirds of the population with a vaccine that is at least 70% effective may be sufficient for controlling COVID-19 spread, as long as NPI’s are not immediately relaxed.

Background The closure of communities, including schools, has been adopted to control the coronavirus disease 2019 (COVID-19) epidemic in most countries. Operating schools safely during the pandemic requires a balance between health risks and the need for in-person learning. We use compartmental models to explore school reopening scenarios. Methods Using demographic and epidemiological data between July 31 and November 23, 2020 from the city of Toronto, we developed a Susceptible-Exposed-Asymptomatic-Infectious-Recovered-Hospitalized-Isolated model. Our model with age, household, and community transmission allow us to study the impact of schools open in September 2020. The model mimics the transmission in households, the community, and schools, accounting for differences in infectiousness between adults and children and youth and adults’ working status. We assessed the extent to which school opening may have contributed to COVID-19 resurgence in the fall and simulated scenarios for the safe reopening of schools up to May 31, 2021. We further considered the impact of the introduction of the new variant of concern. Findings Though a slight increase in infections among adults (2.8%) and children (5.4%) is anticipated by the end of the year, safe school opening is possible with stringent nonpharmaceutical interventions (NPIs) decreasing the risk of transmission in the community and the household. We found that while school reopening was not the key driver in virus resurgence, but rather it was community spread that determined the outbreak trajectory, brief school closures did reduce infections when transmission risk within the home was low. When considered possible cross-infection amongst households, communities, and schools, we found that home transmission was crucial for mitigating the epidemic and safely operating schools. Simulating the introduction of a new strain with higher infectiousness, we observed substantial increases in infections, even when both schools and communities are closed. Interpretation Schools can open safely under strict maintenance of strict public health measures in the community. The gradual opening of schools and communities can only be achieved by maintaining NPIs and mitigating household transmission risk to avoid the broader escape of infections acquired in schools into the community via households. If the new COVID-19 strain is more infectious for children, public spaces, including schools, should be closed, and additional NPIs, including the use of masks, should be extended to toddlers. Funding This research was supported by Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada, and York University Research Chair program. Research in context Evidence before this study The design of a gradual school reopening strategy remains at the heart of decision-making on reopening after shut-downs to control the epidemic. Although available studies have assessed the risk of school reopening by modelling the transmission across schools and communities, it remains unclear whether the risk is due to increased transmission in adults or children and youth.We used GoogleScholar and PubMed searches to identify previous published works. We used te following terms: “school closure”, “covid 19 school closure”, “reopening schools”, “reopening screening school”, “school household second wave model”. The search of the studies ended in January 2021. Papers in other languages than English and letters were excluded from the search. Two modelling studies examined the effects of screening and delayed school reopening, two other agent-based modelling studies explored the epidemic spread across different age groups. Added-value of this study We find that the resurgence of COVID-19 in Toronto in fall 2020 mainly resulted from the increase of contact rate among adults in the community, and that the degree of in-person attendance had the most significant impact on transmission in schools. To our knowledge, our work is the first to investigate the resurgence in infections following school reopening and the impact of risk mitigation measures in schools operation during the pandemic. Our novel and comprehensive model considers the age and household structure, but also considers three different settings, school, household and community. We further examined the effects of self-screening procedures, class size, and schooling days on transmission, which enabled us to compare scenarios of school reopening separately for both adults and children and youth, and model the cross-infection between them to avoid potential underestimation. We found that after schools opened, reducing household transmission was crucial for mitigating the epidemic since it can reduce cross-infection amongst households, communities and schools. Lastly, given the recent report of SARS-CoV-2 variant (VOC202012/01), we investigated the impact of the new variant that may be more infectious in children and youth. Implications of all the available evidence Our analysis can inform policymakers of planning the safe reopening of schools during COVID-19. We suggest that integrating strict NPIs and school control measures are crucial for safe reopening. When schools are open, reducing transmission risk at home and community is paramount in curbing the spread of COVID-19. Lastly, if children are more susceptible to the new COVID-19 VOC, both schools and community must be closed, the time children spend in essential services locations minimized, and NPI’s for those aged less than three years enforced.

Background Shigella infections are an important cause of diarrhea in young children and can result in severe complications. Disparities in Shigella infections are well documented among US adults. Our objective was to characterize disparities in incidence and severity of Shigella infections among US children. Methods We analyzed laboratory-diagnosed Shigella infections reported to FoodNet, an active, population-based surveillance system in 10 US sites, among children during 2009-2018. We calculated the incidence rate stratified by sex, age, race/ethnicity, Shigella species, and disease severity. Criteria for severe classification were hospitalization, bacteremia, or death. The odds of severe infection were calculated using logistic regression. Results During 2009-2018, 10 537 Shigella infections were reported in children and 1472 (14.0%) were severe. The incidence rate was 9.5 infections per 100 000 child-years and the incidence rate of severe infections was 1.3 per 100 000 child-years. Incidence was highest among children aged 1-4 years (19.5) and lowest among children aged 13-17 years (2.3); however, children aged 13-17 years had the greatest proportion of severe infections (21.2%). Incidence was highest among Black (16.2 total; 2.3 severe), Hispanic (13.1 total; 2.3 severe), and American Indian/Alaska Native (15.2 total; 2.5 severe) children. Infections caused by non-sonnei species had higher odds of severity than infections caused by Shigella sonnei (adjusted odds ratio 2.58; 95% confidence interval 2.12-3.14). Conclusions The incidence and severity of Shigella infections among US children vary by age, race/ethnicity, and Shigella species, warranting investigation of unique risk factors among pediatric subpopulations.

The microbiome is the collection of commensal microorganisms along with their genomes inhabiting the human body. Despite the many known beneficial effects of these microbes on human health, the 2016 ACPE Standards for Doctor of Pharmacy curricula describe Medical Microbiology in Appendix 1 with a pathogen-centered focus. Over the last twenty years, evolving biotechnology has enabled a deeper understanding of the microbiome in the context of both wellness and disease. Retail stores are allocating increasing shelf space to commercial probiotic products, while the approach to PharmD training on the selection and use of these natural care products remains static, creating a disproportionate footprint between PharmD curricula and consumer markets. Looking to the future of patient care, we brief pharmacy educators on the current evidence and invite discussion around a proposed revision to the 2025 ACPE Standards that would add language recognizing the beneficial role of the commensal microbiota and expanding therapeutic applications of microbiome supplementation. We suggest a variety of opportunities within Doctor of Pharmacy curricula as leverage points for including relevant aspects of the microbiome in the training of future pharmacists.

Process-based models are increasingly used to study agroecosystem interactions and N2 O emissions from agricultural fields. The widespread use of these models to conduct research and inform policy benefits from periodic model comparisons that assess the state of agroecosystem modeling and indicate areas for model improvement. This work provides an evaluation of simulated N2 O flux from three process-based models: DayCent, DNDC, and EPIC. The models were calibrated and validated using data collected from two research sites over five years that represent cropping systems and nitrogen fertilizer management strategies common to dairy cropping systems. We also evaluated the use of a multi-model ensemble strategy, which inconsistently outperformed individual model estimations. Regression analysis indicated a cross-model bias to underestimate high magnitude daily and cumulative N2 O flux. Model estimations of observed soil temperature and water content did not sufficiently explain model underestimations, and we found significant variation in model estimates of heterotrophic respiration, denitrification, soil NH4+ , and soil NO3- , which may indicate that additional types of observed data are required to evaluate model performance and possible biases. Our results suggest a bias in the model estimation of N2 O flux from agroecosystems that limits the extension of models beyond calibration and as instruments of policy development. This highlights a growing need for the modeling and measurement communities to collaborate in the collection and analysis of the data necessary to improve models and coordinate future development.

Aim: Sympathetic activation suppresses insulin secretion via pancreatic ADRA2A. Because sympathetic activity and insulin demand increase during pregnancy, we tested the hypothesis that ADRA2A variants are associated with gestational diabetes (GDM). Patients & methods: Among Caucasian pregnant women without pre-existing diabetes, we genotyped 458 who had GDM and 1537 without GDM for seven ADRA2A variants. Results: rs1800038 (OR: 2.34; p = 0.020) and rs3750625 (OR: 1.56; p = 0.010) increased the risk of GDM, and rs11195418 decreased it (OR: 0.62; p = 0.025). The associations remained significant after adjustment for maternal age, maternal BMI, parity and a genetic risk score that included variants previously associated with Type 2 diabetes mellitus and GDM. Conclusion: ADRA2A genetic variation contributes independently to the risk of GDM in Caucasian women.

Purpose: To understand soft contact lens (SCL) and gas-permeable (GP) lens wearers' behaviors and knowledge regarding exposure of lenses to water. Methods: The Contact Lens Risk Survey (CLRS) and health behavior questions were completed online by a convenience sample of 1056 SCL and 85 GP lens wearers aged 20 to 76 years. Participants were asked about exposing their lenses to water and their understanding of risks associated with these behaviors. Chi-square analyses examined relationships between patient behaviors and perceptions. Results: GP lens wearers were more likely than SCL wearers to ever rinse or store lenses in water (rinsing: 91% GP, 31% SCL, P < 0.001; storing: 33% GP, 15% SCL P < 0.001). Among SCL wearers, men were more likely to store (24% vs. 13%, P = 0.003) or rinse (41% vs. 29%, P = 0.012) their lenses in water. Showering while wearing lenses was more common in SCL wearers (86%) than GP lens wearers (67%) (P < 0.0001). Swimming while wearing lenses was reported by 62% of SCL wearers and 48% of GP lens wearers (P = 0.027). Wearers who rinsed (SCL; P < 0.0001, GP; P = 0.11) or stored lenses in water (SCL; P < 0.0001, GP P = 0.007) reported that this behavior had little or no effect on their infection risk, compared with those who did not. Both SCL (P < 0.0001) and GP lens wearers (P < 0.0001) perceived that distilled water was safer than tap water for storing or rinsing lenses. Conclusions: Despite previously published evidence of Acanthamoeba keratitis' association with water exposure, most SCL, and nearly all GP lens wearers, regularly expose their lenses to water, with many unaware of the risk.

Uncertainty exists regarding the depth and extent to which agricultural practices affect soil properties, in particular soil organic C (SOC). In this study we examined the impact of 53 yr of continuous corn (Zea mays L.) receiving varying rates of inorganic N fertilizer with complete stover return on soil properties including SOC, total N, and bulk density (BD) to a depth of 1 m. In the treatment receiving virtually no applied N there was a significant reduction in soil N content at 0 to 30 cm over the study period, while the treatment receiving N in excess of recommended application levels was similar to the treatment receiving recommended rates of N fertilizer. Trends in SOC content were similar to those for total N, but a significant treatment effect was detectable throughout the entire 1-m soil profile sampled. Over the course of the study, all experimental fields appeared to have lost approximately 6 cm of topsoil through erosion, with the lowest N rate plots subsiding a further 2 cm due to compaction. Despite using disruptive management practices (moldboard plowing and application of anhydrous ammonia), declines in soil C and N content were not apparent for this soil type under conditions of low slope and the linear gains in productivity realized under the two higher N rate treatments. Thus N fertilizer was a benefit to this cropping system, rather than a detriment, and was sufficient to allow maintenance—but not building—of SOC.

Background: In many parts of the world, restrictive non-pharmaceutical interventions (NPI) that aim to reduce contact rates, including stay-at-home orders, limitations on gatherings, and closure of public places, are being lifted, with the possibility that the epidemic resurges if alternative measures are not strong enough. Here we aim to capture the combination of use of NPI’s and reopening measures which will prevent an infection rebound. Methods: We employ an SEAIR model with household structure able to capture the stay-at-home policy (SAHP). To reflect the changes in the SAHP over the course of the epidemic, we vary the SAHP compliance rate, assuming that the time to compliance of all the people requested to stay-at-home follows a Gamma distribution. Using confirmed case data for the City of Toronto, we evaluate basic and instantaneous reproduction numbers and simulate how the average household size, the stay-at-home rate, the efficiency and duration of SAHP implementation, affect the outbreak trajectory. Findings: The estimated basic reproduction number R_0 was 2.36 (95% CI: 2.28, 2.45) in Toronto. After the implementation of the SAHP, the contact rate outside the household fell by 39%. When people properly respect the SAHP, the outbreak can be quickly controlled, but extending its duration beyond two months (65 days) had little effect. Our findings also suggest that to avoid a large rebound of the epidemic, the average number of contacts per person per day should be kept below nine. This study suggests that fully reopening schools, offices, and other activities, is possible if the use of other NPIs is strictly adhered to. Interpretation: Our model confirmed that the SAHP implemented in Toronto had a great impact in controlling the spread of COVID-19. Given the lifting of restrictive NPIs, we estimated the thresholds values of maximum number of contacts, probability of transmission and testing needed to ensure that the reopening will be safe, i.e. maintaining an Rt

The importance of building/maintaining soil carbon, for soil health and CO2 mitigation, is of increasing interest to a wide audience, including policymakers, NGOs and land managers. Integral to any approaches to promote carbon sequestering practices in managed soils are reliable, accurate and cost-effective means to quantify soil C stock changes and forecast soil C responses to different management, climate and edaphic conditions. While technology to accurately measure soil C concentrations and stocks has been in use for decades, many challenges to routine, cost-effective soil C quantification remain, including large spatial variability, low signal-to-noise and often high cost and standardization issues for direct measurement with destructive sampling. Models, empirical and process-based, may provide a cost-effective and practical means for soil C quantification to support C sequestration policies. Examples are described of how soil science and soil C quantification methods are being used to support domestic climate change policies to promote soil C sequestration on agricultural lands (cropland and grazing land) at national and provincial levels in Australia and Canada. Finally, a quantification system is outlined – consisting of well-integrated data-model frameworks, supported by expanded measurement and monitoring networks, remote sensing and crowd-sourcing of management activity data – that could comprise the core of a new global soil information system.

BACKGROUND: Circulating biomarkers can facilitate diagnosis and risk stratification for complex conditions such as heart failure (HF). Newer molecular platforms can accelerate biomarker discovery, but they require significant resources for data and sample acquisition. OBJECTIVES: To test a pragmatic biomarker discovery strategy integrating automated clinical biobanking with proteomics. METHODS: Using the EHR, we identified patients with and without HF, retrieved their discarded plasma samples, and screened these specimens using a DNA aptamer-based proteomic platform (1,129 proteins). Candidate biomarkers were validated in three different prospective cohorts. RESULTS: In an automated manner, plasma samples from 1,315 patients (31% with HF) were collected. Proteomic analysis of a 96-patient subset identified nine candidate biomarkers (p

Understanding endemic infectious disease risk factors through traditional epidemiological tools is challenging. Population-based case–control studies are costly and time-consuming. A case–case analyses using surveillance data addresses these limitations by using resources more efficiently. We conducted a case–case analyses using routine surveillance data reported by 16 U.S. states (2005–2015), wherein reported cases of salmonellosis were used as a comparison group to identify exposure associations with reported cases of cryptosporidiosis and giardiasis. Odds ratios adjusted for age and reporting state (aOR) and 95% confidence intervals (95% CI) were calculated. A total of 10 704 cryptosporidiosis cases, 17 544 giardiasis cases, and 106 351 salmonellosis cases were included in this analyses. When compared with cases of salmonellosis, exposure to treated recreational water (aOR 4.7, 95% CI 4.3–5.0) and livestock (aOR: 3.2; 95% CI: 2.9–3.5) were significantly associated with cryptosporidiosis and exposure to untreated drinking (aOR 4.1, 95% CI 3.6–4.7) and recreational water (aOR 4.1, 95% CI 3.7–4.5) were associated with giardiasis. Our analyses shows that routine surveillance data with standardised exposure information can be used to identify associations of interest for cryptosporidiosis and giardiasis.

Background Giardia intestinalis is the most commonly reported human intestinal parasite in the United States. Increased incidence of chronic gastrointestinal complaints has been reported after some giardiasis outbreaks. We examined the relationship between giardiasis diagnosis and irritable bowel syndrome (IBS) diagnosis. Methods We used the 2006-2010 MarketScan commercial insurance database. Persons with at least 1 giardiasis diagnosis were individually matched on age group, sex, and enrollment length in months to 5 persons without a giardiasis diagnosis. Persons diagnosed with IBS before the date of study entry were excluded. We calculated crude incidence rates (IRs) and developed Cox proportional hazards models. Results The matched cohort included 3935 persons with giardiasis and 19663 persons without giardiasis. One-year incidence of IBS was higher in persons with giardiasis (IR = 37.7/1000 person-years vs 4.4/1000 person-years). The unadjusted hazard ratio was 4.8 (95% confidence interval [CI] = 3.6-6.4), attenuated slightly to 3.9 (95% CI = 2.9-5.4) after adjusting for anxiety, depression, and healthcare utilization. Conclusions In a large insurance database, individuals diagnosed with giardiasis were more likely to have a subsequent IBS diagnosis, despite accounting for confounders. Future research on risk factors for IBS among giardiasis patients and the pathophysiology of postinfectious IBS is needed.

Keratitis (inflammation of the cornea) can result from contact lens wear or other causes. Keratitis from all causes, including contact lens wear, results in approximately 1 million clinic and emergency department visits annually, with an estimated cost of $175 million in direct health care expenditures in 2010 (1). Approximately 41 million U.S. residents wear contact lenses, and in 2014, >99% of contact lens wearers surveyed reported at least one behavior that puts them at risk for a contact lens-related eye infection (2). The Center for Devices and Radiological Health at the Food and Drug Administration (FDA) regulates contact lenses as medical devices, and certain adverse events related to contact lenses are reported to FDA's Medical Device Report (MDR) database. To describe contact lens-related corneal infections reported to the FDA, 1,075 contact lens-related MDRs containing the terms "ulcer" or "keratitis" reported to FDA during 2005-2015 were analyzed. Among these 1,075 reports, 925 (86.0%) were reported by a contact lens manufacturer and 150 (14.0%) by an eye care provider or patient. Overall, 213 (19.8%) reports described a patient who had a central corneal scar, had a decrease in visual acuity, or required a corneal transplant following the event. Among the reports, 270 (25.1%) described modifiable factors known to be associated with an increased risk for contact lens-related corneal infections, including sleeping in contact lenses or poor contact lens hygiene; the remainder did not provide details that permitted determination of associated factors. Continued efforts to educate contact lens wearers about prevention of contact lens-related eye infections are needed.

Purpose To describe the clinical presentation and outcomes of Acanthamoeba keratitis (AK) in rigid gas permeable (RGP) contact lens wearers and to identify modifiable risk factors. Design Case-control investigation. Participants Patients were RGP contact lens–wearing United States residents with a diagnosis of AK from 2005 through 2011. Controls were RGP contact lens wearers with no history of AK who were at least 12 years of age. Methods Patients were identified during 2 multistate AK outbreak investigations. Controls from the first investigation in 2007 were identified using a reverse address directory. In the second investigation, controls were recruited from participating ophthalmology and optometry practices. Patients and controls were interviewed by phone using a standardized questionnaire. Odds ratios (ORs) and Fisher exact P values were calculated to assess risk factors associated with infection. Main Outcome Measures Acanthamoeba keratitis, a rare eye disease primarily affecting contact lens wearers, is caused by free-living amebae, Acanthamoeba species. Results We identified 37 patients in the 2 investigations, 10 (27%) from the 2007 investigation and 27 (73%) from 2011. There were 17 healthy controls, 9 (53%) from 2007 and 8 (47%) from 2011. Among patients, 9 (24%) wore RGP lenses for orthokeratology or therapeutic indication; no controls wore RGP lenses for these indications. Significant risk factors for AK were wearing lenses for orthokeratology (OR, undefined; P = 0.02), sleeping while wearing lenses (OR, 8.00; P = 0.04), storing lenses in tap water (OR, 16.00; P = 0.001), and topping off contact lens solution in the case (OR, 4.80; P = 0.01). After stratifying by use of RGP lenses for orthokeratology, storing lenses in tap water and topping off remained significant exposures. Conclusions Nearly one quarter of patients were orthokeratology wearers. Using tap water to store RGP lenses and topping off solution in the lens case were modifiable risk behaviors identified in RGP wearers who wore lenses for both orthokeratology and nonorthokeratology indications. Rigid gas permeable wearers should avoid exposing their lenses to tap water and should empty their cases and use fresh lens solution each time they take out their lenses.

PROBLEM/CONDITION Aquatic facility-associated illness and injury in the United States include disease outbreaks of infectious or chemical etiology, drowning, and pool chemical-associated health events (e.g., respiratory distress or burns). These conditions affect persons of all ages, particularly young children, and can lead to disability or even death. A total of 650 aquatic facility-associated outbreaks have been reported to CDC for 1978-2012. During 1999-2010, drownings resulted in approximately 4,000 deaths each year in the United States. Drowning is the leading cause of injury deaths in children aged 1-4 years, and approximately half of fatal drownings in this age group occur in swimming pools. During 2003-2012, pool chemical-associated health events resulted in an estimated 3,000-5,000 visits to U.S. emergency departments each year, and approximately half of the patients were aged

One of the most widespread approaches for measurement of greenhouse gas emissions from soils involves the use of static chambers. This method is relatively inexpensive, is easily replicated, and is ideally suited to plot-based experimental systems. Among its limitations is the loss of detection sensitivity with increasing chamber height, which creates challenges for deployment in systems including tall vegetation. It is not always possible to avoid inclusion of plants within chambers or to extend chamber height to fully accommodate plant growth. Thus, in many systems, such as perennial forages and biomass crops, plants growing within static chambers must either be trimmed or folded during lid closure. Currently, data on how different types of biomass manipulation affect measured results is limited. Here, we compare the effects of cutting vs. folding of biomass on nitrous oxide measurements in switchgrass ( L.) and alfalfa ( L.) systems. We report only limited evidence of treatment effects during discrete sampling events and little basis for concern that effects may intensify over time as biomass manipulation is repeatedly imposed. However, nonsignificant treatment effects that were consistently present amounted to significant overall trends in three out of the four systems studied. Such minor disparities in flux could amount to considerable quantities over time, suggesting that caution should be exercised when comparing cumulative emission values from studies using different biomass manipulation strategies.

Giardia duodenalis is the most common intestinal parasite of humans in the USA, but the risk factors for sporadic (non-outbreak) giardiasis are not well described. The Centers for Disease Control and Prevention and the Colorado and Minnesota public health departments conducted a case-control study to assess risk factors for sporadic giardiasis in the USA. Cases (N = 199) were patients with non-outbreak-associated laboratory-confirmed Giardia infection in Colorado and Minnesota, and controls (N = 381) were matched by age and site. Identified risk factors included international travel (aOR = 13.9; 95% CI 4.9–39.8), drinking water from a river, lake, stream, or spring (aOR = 6.5; 95% CI 2.0–20.6), swimming in a natural body of water (aOR = 3.3; 95% CI 1.5–7.0), male–male sexual behaviour (aOR = 45.7; 95% CI 5.8–362.0), having contact with children in diapers (aOR = 1.6; 95% CI 1.01–2.6), taking antibiotics (aOR = 2.5; 95% CI 1.2–5.0) and having a chronic gastrointestinal condition (aOR = 1.8; 95% CI 1.1–3.0). Eating raw produce was inversely associated with infection (aOR = 0.2; 95% CI 0.1–0.7). Our results highlight the diversity of risk factors for sporadic giardiasis and the importance of non-international-travel-associated risk factors, particularly those involving person-to-person transmission. Prevention measures should focus on reducing risks associated with diaper handling, sexual contact, swimming in untreated water, and drinking untreated water.

Background Treatment of drinking water is one of the greatest US public health achievements of the twentieth century and provides a safe, reliable water supply. However, waterborne disease and outbreaks continue to occur, and are associated with a variety of water sources and exposure routes. New estimates of the burden of waterborne disease in the United States will direct prevention activities and set public health goals. Methods We chose 17 waterborne diseases for which domestic waterborne transmission was plausible, substantial burden of illness or death was likely, and data were available. Diseases included were campylobacteriosis, cryptosporidiosis, giardiasis, Legionnaires’ disease, norovirus infection, nontuberculous mycobacteria [NTM] infection, otitis externa, Pseudomonas pneumonia and septicemia, salmonellosis, Shiga toxin-producing E. coli infection, shigellosis, and vibriosis. Adapting previously used methods, disease-specific multipliers were used to adjust the reported/documented number of cases of each disease for under-reporting, under-diagnosis, proportion domestically acquired, and proportion transmitted via water, to generate point estimates with 95% credible intervals (CrI). Data sources included surveillance data, population studies, and expert judgment if no other data were available. We estimated the number of illnesses, ED visits, hospitalizations, and deaths, and costs of ED visits and hospitalizations due to waterborne disease in the United States in 2014. Results 7.2 million waterborne illnesses (CrI 3.9–12.0 million) from the selected diseases occur annually, including 600,000 (CrI 365,000–865,000) ED visits, 120,000 (CrI 85,000–150,000) hospitalizations, and 6,500 deaths (CrI 4,300–8,900) deaths, incurring US$3.2 billion (2014 dollars) in direct healthcare costs. Hospitalizations and deaths were predominantly caused by environmental pathogens commonly associated with biofilm in plumbing systems (NTM, Pseudomonas, Legionella) costing US$2 billion annually. Conclusion Millions of domestically acquired waterborne illnesses from these 17 infections occur in the United States each year, and incur billions of dollars in healthcare costs. Disclosures All Authors: No reported Disclosures.

Contact lenses provide safe and effective vision correction for many Americans. However, contact lens wearers risk infection if they fail to wear, clean, disinfect, and store their contact lenses as directed. Over the past decade, CDC has investigated several multistate outbreaks of serious eye infections among contact lens wearers, including Acanthamoeba keratitis. Each investigation identified frequent contact lens hygiene-related risk behaviors among patients. To guide prevention efforts, a population-based survey was used to estimate the number of contact lens wearers aged ≥18 years in the United States. A separate online survey of contact lens wearers assessed the prevalence of contact lens hygiene-related risk behaviors. Approximately 99% of wearers reported at least one contact lens hygiene risk behavior. Nearly one third of contact lens wearers reported having experienced a previous contact lens-related red or painful eye requiring a doctor's visit. An estimated 40.9 million U.S. adults wear contact lenses, and many could be at risk for serious eye infections because of poor contact lens wear and care behaviors. These findings have informed the creation of targeted prevention messages aimed at contact lens wearers such as keeping all water away from contact lenses, discarding used disinfecting solution from the case and cleaning with fresh solution each day, and replacing their contact lens case every 3 months.

National emergency department (ED) visit prevalence and costs for selected diseases that can be transmitted by water were estimated using large healthcare databases (acute otitis externa, campylobacteriosis, cryptosporidiosis, Escherichia coli infection, free-living ameba infection, giardiasis, hepatitis A virus (HAV) infection, Legionnaires’ disease, nontuberculous mycobacterial (NTM) infection, Pseudomonas-related pneumonia or septicemia, salmonellosis, shigellosis, and vibriosis or cholera). An estimated 477,000 annual ED visits (95% CI: 459,000–494,000) were documented, with 21% (n = 101,000, 95% CI: 97,000–105,000) resulting in immediate hospital admission. The remaining 376,000 annual treat-and-release ED visits (95% CI: 361,000–390,000) resulted in $194 million in annual direct costs. Most treat-and-release ED visits (97%) and costs ($178 million/year) were associated with acute otitis externa. HAV ($5.5 million), NTM ($2.3 million), and salmonellosis ($2.2 million) were associated with next highest total costs. Cryptosporidiosis ($2,035), campylobacteriosis ($1,783), and NTM ($1,709) had the highest mean costs per treat-and-release ED visit. Overall, the annual hospitalization and treat-and-release ED visit costs associated with the selected diseases totaled $3.8 billion. As most of these diseases are not solely transmitted by water, an attribution process is needed as a next step to determine the proportion of these visits and costs attributable to waterborne transmission.

Contact lens-related eye infections, which can lead to serious outcomes, including blindness, are associated with several risk factors, including sleeping in lenses, exposing lenses to water, not adhering to replacement schedules, and reusing disinfecting solution (1). In some studies, adolescent and young adult contact lens wearers have been reported to be more likely than older adult contact lens wearers to develop eye infections (2,3) and more likely to have poor contact lens hygiene practices (2). In 2015, CDC reported the number and demographics of adult contact lens wearers in the United States to define the population at risk for contact lens-related eye infections (4); however, this estimate did not include adolescents. To better understand this group of younger contact lens wearers and guide prevention efforts, a population-based survey was used to assess contact lens wear, care behaviors, risk factors, and demographics among persons aged 12-17 years (referred to as adolescents in this report), young adults aged 18-24 years, and older adults aged ≥25 years in the United States. In 2016, an estimated 3.6 million adolescents (14.5%) wore contact lenses. Of the adolescents who wore contact lenses, 85% reported at least one behavior that put them at risk for a contact lens-related eye infection, compared with 81% of young adults, and 88% of older adults. These findings can inform the creation of age-specific targeted prevention messages aimed at contact lens wearers and establish a baseline for evaluating trends in contact lens wear, care habits, and contact lens-related risk behaviors.

Background Giardiasis, the most common enteric parasitic infection in the United States, causes an estimated 1.2 million episodes of illness annually. Published clinical recommendations include readily available Giardia-specific diagnostic testing and antiparasitic drugs. We investigated sequences of giardiasis diagnostic and treatment events using MarketScan, a large health insurance claims database. Methods We created a longitudinal cohort of 2995 persons diagnosed with giardiasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 007.1) from 2006 to 2010, and analyzed claims occurring 90 days before to 90 days after initial diagnosis. We evaluated differences in number and sequence of visits, diagnostic tests, and prescriptions by age group (children 1-17 years, adults 18-64 years) using χ2 tests and data visualization software. Results Among 2995 patients (212433 claims), 18% had a Giardia-specific test followed by or concurrent with an effective antiparasitic drug, without ineffective antibiotics. Almost two-thirds of patients had an antiparasitic and 27% had an antibiotic during the study window. Compared with children, adults more often had ≥3 visits before diagnosis (19% vs 15%; P = .02). Adults were also less likely to have a Giardia-specific diagnostic test (48% vs 58%; P < .001) and more likely to have an antibiotic prescription (28% vs 25%; P = .04). When Giardia-specific tests and antiparasitic and antibiotic prescriptions were examined, pediatric clinical event sequences most frequently began with a Giardia-specific test, whereas adult sequences most frequently began with an antiparasitic prescription. Conclusions Giardiasis care infrequently follows all aspects of clinical recommendations. Multiple differences between pediatric and adult care, despite age-agnostic recommendations, suggest opportunities for provider education or tailored guidance.

The potato (Solanum tuberosum) disease resistance protein Rx has a modular arrangement that contains coiled-coil (CC), nucleotide-binding (NB), and leucine-rich repeat (LRR) domains and mediates resistance to potato virus X. The Rx N-terminal CC domain undergoes an intramolecular interaction with the Rx NB-LRR region and an intermolecular interaction with the Rx cofactor RanGAP2 (Ran GTPase-activating protein 2). Here, we report the crystal structure of the Rx CC domain in complex with the Trp-Pro-Pro (WPP) domain of RanGAP2. The structure reveals that the Rx CC domain forms a heterodimer with RanGAP2, in striking contrast to the homodimeric structure of the CC domain of the barley disease resistance protein MLA10. Structure-based mutagenesis identified residues from both the Rx CC domain and the RanGAP2 WPP domain that are crucial for their interaction and function in vitro and in vivo. Our results reveal the molecular mechanism underlying the interaction of Rx with RanGAP2 and identify the distinct surfaces of the Rx CC domain that are involved in intramolecular and intermolecular interactions.

To identify modifiable risk factors contributing to Acanthamoeba keratitis (AK) infection.A case-control investigation was conducted. Case patients were soft contact lens wearers with laboratory-confirmed AK. Control were soft contact lens wearers ≥12 years of age, with no history of AK. Case patients were recruited from 14 ophthalmology referral centers and a clinical laboratory. Control were matched on state of residence and type of primary eye care provider (ophthalmologist or optometrist). Participants were interviewed using a standardized questionnaire. Univariable and multivariable conditional logistic regression analyses were conducted. Matched odds ratios (mORs) were calculated.Participants included 88 case patients and 151 matched control. Case patients were more likely to be aged25 years (unadjusted mOR 2.7, 95% confidence interval 1.3-5.5) or aged53 years (mOR 2.5, 1.1-5.7), and more likely to be men (mOR 2.6, 1.4-4.8). Unadjusted analyses identified multiple risk factors: rinsing (mOR 6.3, 1.3-29.9) and storing lenses in tap water (mOR 3.9, 1.2-12.3), topping off solution in the lens case (mOR 4.0, 2.0-8.0), having worn lenses ≤5 years (mOR 2.4, 1.3-4.4), rinsing the case with tap water before storing lenses (mOR 2.1, 1.1-4.1), and using hydrogen peroxide (mOR 3.6, 1.1-11.7) versus multipurpose solution. Significant risk factors in multivariable modeling included age53 years, male sex, topping off, and using saline solution.Numerous modifiable risk factors for AK were identified, mostly involving hygiene practices. To reduce the risk of AK, lens wearers should observe recommended lens care practices.

Cryptosporidium is a common cause of sporadic diarrheal disease and outbreaks in the United States. Increasingly, immunochromatography-based rapid cartridge assays (RCAs) are providing community laboratories with a quick cryptosporidiosis diagnostic method. In the current study, the Centers for Disease Control and Prevention (CDC), the Association of Public Health Laboratories (APHL), and four state health departments evaluated RCA-positive samples obtained during routine Cryptosporidium testing. All samples underwent "head to head" re-testing using both RCA and direct fluorescence assay (DFA). Community level results from three sites indicated that 54.4% (166/305) of Meridian ImmunoCard STAT! positives and 87.0% (67/77) of Remel Xpect positives were confirmed by DFA. When samples were retested by RCA at state laboratories and compared with DFA, 83.3% (155/186) of Meridian ImmunoCard STAT! positives and 95.2% (60/63) of Remel Xpect positives were confirmed. The percentage of confirmed community results varied by site: Minnesota, 39.0%; New York, 63.9%; and Wisconsin, 72.1%. The percentage of confirmed community results decreased with patient age; 12.5% of community positive tests could be confirmed by DFA for patients 60 years of age or older. The percentage of confirmed results did not differ significantly by sex, storage temperature, time between sample collection and testing, or season. Findings from this study demonstrate a lower confirmation rate of community RCA positives when compared to RCA positives identified at state laboratories. Elucidating the causes of decreased test performance in order to improve overall community laboratory performance of these tests is critical for understanding the epidemiology of cryptosporidiosis in the United States (US).

Giardiasis is the most commonly reported intestinal parasitic infection in the United States. Outbreak investigations have implicated poorly maintained private wells, and hypothesized a role for wastewater systems in giardiasis transmission. Surveillance data consistently show geographic variability in reported giardiasis incidence. We explored county-level associations between giardiasis cases, household water and sanitation (1990 census), and US Census division. Using 368,847 reported giardiasis cases (1993–2010), we mapped county-level giardiasis incidence rates, private well reliance, and septic system reliance, and assessed spatiotemporal clustering of giardiasis. We used negative binomial regression to evaluate county-level associations between giardiasis rates, region, and well and septic reliance, adjusted for demographics. Adjusted giardiasis incidence rate ratios (aIRRs) were highest (aIRR 1.3; 95% confidence interval 1.2–1.5) in counties with higher private well reliance. There was no significant association between giardiasis and septic system reliance in adjusted models. Consistent with visual geographic distributions, the aIRR of giardiasis was highest in New England (aIRR 3.3; 95% CI 2.9–3.9; reference West South Central region). Our results suggest that, in the USA, private wells are relevant to giardiasis transmission; giardiasis risk factors might vary regionally; and up-to-date, location-specific national data on water sources and sanitation methods are needed.