University of Minnesota Health Maple Grove Clinics

Duplication or deficiency of the X-linked MECP2 gene reliably produces profound neurodevelopmental impairment. MECP2 mutations are almost universally responsible for Rett syndrome (RTT), and particular mutations and cellular mosaicism of MECP2 may underlie the spectrum of RTT symptomatic severity. No clinically approved treatments for RTT are currently available, but human pluripotent stem cell technology offers a platform to identify neuropathology and test candidate therapeutics. Using a strategic series of increasingly complex human stem cell-derived technologies, including human neurons, MECP2-mosaic neurospheres to model RTT female brain mosaicism, and cortical organoids, we identified synaptic dysregulation downstream from knockout of MECP2 and screened select pharmacological compounds for their ability to treat this dysfunction. Two lead compounds, Nefiracetam and PHA 543613, specifically reversed MECP2-knockout cytologic neuropathology. The capacity of these compounds to reverse neuropathologic phenotypes and networks in human models supports clinical studies for neurodevelopmental disorders in which MeCP2 deficiency is the predominant etiology.

OBJECTIVES: To determine the epidemiology of recurrent acute rhinosinusitis (RARS) and to understand direct health care costs attributable to RARS as a potentially underdiagnosed form of chronic rhinosinusitis. STUDY DESIGN: Retrospective longitudinal analysis of a medical claims database. SETTING: Academic medical center. METHODS: Medical claims data (2003-2008) from a large payer database were analyzed. Adult patients with RARS (defined as at least 4 acute rhinosinusitis claims each with a filled oral antibiotic prescription in a 12-month period) were extracted. Sinonasal diagnostic procedures, provider visits, and medical costs were determined. RESULTS: A total of 4588 patients were identified (mean age, 43.5 years; 72.1% female) among 13.1 million patients, for a point prevalence of 0.035%, which remained consistent across years. After 1, 2, and 4 years, 2.4%, 5.4%, and 9.2% of patients subsequently received nasal endoscopy and 11.4%, 23.5%, and 39.9% received paranasal sinus computed tomography, respectively. RARS patients averaged 3.8 antibiotic prescriptions, 5.6 other sinus-related prescriptions, and 5.6 provider visits per year. Total direct health care costs related to RARS averaged $1091/patient-year, with oral antibiotic and nasal prescription costs averaging $210 and $452 per year, respectively. CONCLUSIONS: RARS may affect approximately 1 in 3000 adults per year. Despite significant direct health care costs of more than $1000/year per individual patient with RARS, nasal endoscopy and computed tomography are not commonly obtained early after potential diagnosis. RARS is likely an underdiagnosed condition warranting further study.

BACKGROUND: Imidocarb or a combination of atovaquone and azithromycin (A&A) has been suggested for treatment of cats with cytauxzoonosis, but neither has been prospectively evaluated for efficacy. HYPOTHESIS/OBJECTIVES: That survival to hospital discharge is improved by treatment with A&A as compared with imidocarb. ANIMALS: Eighty acutely ill cats with Cytauxzoon felis infection treated at one of 18 veterinary clinics in 5 states. METHODS: An open-label, randomized prospective study compared survival in cats treated with atovaquone (15 mg/kg p.o. q8h) and azithromycin (10 mg/kg p.o. q24h) or imidocarb (3.5 mg/kg i.m.). All received heparin, fluids, and supportive care. Clinical and clinicopathologic data from initial presentation were collated. Parasitemia was quantified (n = 79) and pathogens genotyped (n = 60). Logistic regression was used to determine the impact of treatment group on the primary endpoint, survival to hospital discharge or death. Covariants were analyzed by rank-sum testing. RESULTS: Of 53 cats treated with A&A, 32 (60%) survived to discharge while only 7 of 27 cats (26%) treated with imidocarb survived (P = .0036; odds ratio 7.2, 95% CI 2.2, 24). Cats with a lower parasitemia were more likely to survive, as were cats with higher white blood cell counts and lower total bilirubin. Unique pathogen genotypes were identified from 15 cats, while genotype isolated from 21 cats had been described previously. There were multiple pathogen genotypes identified in 24 cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Survival to discharge was more likely in cats treated with A&A as compared with imidocarb, although case fatality rate remained high.

The International Committee on Allergic Diseases of Animals (ICADA) considers recent literature to coordinate reviews of important advances in atopic and allergic diseases over time. These review articles and translations can be found on the website www.icada.org and include the following: feline atopic syndrome—pathogenesis,1 diagnosis2 and treatment3; canine atopic dermatitis—pathogenesis,4-8 diagnosis,9, 10 research guidelines11, 12 and treatments.13, 14 The purpose of the following papers is to include new information since the last ICADA review papers pathogenesis of canine atopic dermatitis were published in 2015. These updated reviews were prepared by searching for articles and meeting abstracts from 2015 to 2022, and the manuscripts were submitted to the ICADA membership for review before submission to this journal. This new definition is useful in that it includes our current broader understanding of the pathogenesis of this condition beyond allergy. This new definition highlights the multiple factors involved in this disease, which supports the recommendation that the management of canine atopic dermatitis must be multimodal (as seen in the former14 and soon-to-be updated Canine Atopic Dermatitis Practice Guidelines). The first paper includes multiple studies showing the importance of environmental factors in the development of atopy, including lifestyle, diet and parasite exposure. Although atopy is unquestionably a hereditary condition and large atopy prevalence studies continue to show strong breed predispositions, unfortunately no consistent genetic markers have yet been found. The next paper reviews skin barrier measurement (which continues to be difficult and controversial), as well as updates on ceramides, filaggrins and other skin proteins, and interesting studies on the cutaneous microbiome and dysbiosis, and cutaneous host defence peptides. Most new knowledge on the pathogenesis of cAD is in the last paper, which examines the role of cytokines and chemokines. However, many studies are conflicting. Several consistently show upregulation of many T-helper (Th) cell cytokines that is not restricted to certain groups (such as only Th2 cytokines, for example). There also is a consistently strong central role for interleukin (IL)-31 in pruritus, in line with successful therapies targeting this cytokine for relief of clinical signs of AD. Certain topics were not included in the updated pathogenesis papers (e.g. the role of eosinophils, basophils, IgE and dendritic cells) because there is a lack of new information in these areas in dogs. In conclusion, these articles summarise the most important studies on cAD since 2015. Our knowledge of the pathogenesis and the definition of cAD will continue to evolve over the years. Hopefully these review papers will be useful to help direct future research endeavours to better understand the multifactorial complexity of cAD. Melissa Eisenschenk on behalf of the group of authors. Self-funded. The International Committee of Allergic Diseases of Animals (ICADA) should be acknowledged as they reviewed all of these review articles including this introduction and coming to a consensus on the new definition of atopic dermatitis. ICADA was also listed as an author, but the system would not accept it, perhaps acknowledgement would be more appropriate. No conflicts of interest have been declared.

BACKGROUND: The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and Cutaneous Assessment Tool-Binary Method (CAT-BM) have been shown to be reliable and valid outcome measures to assess cutaneous disease in adult dermatomyositis (DM) and juvenile DM (JDM), respectively. OBJECTIVES: This study compared the CDASI and CAT-BM for use by paediatric dermatologists, paediatric rheumatologists and paediatric neurologists in patients with JDM. METHODS: Five paediatric dermatologists, five paediatric rheumatologists and five paediatric neurologists each evaluated 14 patients with JDM using the CDASI, CAT-BM, and skin Physician Global Assessment (PGA) scales. Inter-rater reliability, intra-rater reliability, construct validity and completion time were compared. RESULTS: Inter-rater reliability for CDASI activity and damage scores was good to moderate for paediatric dermatologists and rheumatologists, but poor for paediatric neurologists. The inter-rater reliability for CAT-BM activity scores was moderate for paediatric dermatologists and rheumatologists, but poor for paediatric neurologists and poor across all specialties for damage scores. Intra-rater reliability for the CDASI and CAT-BM activity and damage scores was moderate to excellent for paediatric dermatologists, rheumatologists and neurologists. Strong associations were found between skin PGA activity and damage scores and CDASI or CAT-BM activity and damage scores, respectively (P < 0·002). The CDASI had a mean completion time of 5·4 min compared with that for the CAT-BM of 3·1 min. CONCLUSIONS: Our data confirm the reliability of the CDASI activity and damage scores and the CAT-BM activity scores when used by paediatric dermatologists and rheumatologists in assessing JDM. Significant variation existed in the paediatric neurologists' scores.

Ruxolitinib for steroid-refractory acute graft-versus-host disease (SR-aGVHD) results in resistance or intolerance in 1/5 of patients. Outcomes of such patients are undefined. We identified these patients in a multicentre review and reported outcomes. Ruxolitinib-resistant aGVHD was identified in 48/307 patients. Among patients receiving additional therapy, the overall response rate to next therapy was 36%. Median survival was 21 days. Ruxolitinib intolerance led to treatment discontinuation in 16/307 patients. Ten intolerant patients received additional therapy with 50% experiencing continued improvement of aGVHD. Median survival was 50 days in these patients. These data serve as a baseline for future SR-aGVHD studies.

BACKGROUND: Canine atopic dermatitis (AD) is a complex inflammatory skin disease associated with cutaneous microbiome, immunological and skin barrier alterations. This review summarises the current evidence on skin barrier defects and on cutaneous microbiome dysfunction in canine AD. OBJECTIVE: To this aim, online citation databases, abstracts and proceedings from international meetings on skin barrier and cutaneous microbiome published between 2015 and 2023 were reviewed. RESULTS: Since the last update on the pathogenesis of canine AD, published by the International Committee on Allergic Diseases of Animals in 2015, 49 articles have been published on skin barrier function, cutaneous/aural innate immunity and the cutaneous/aural microbiome in atopic dogs. Skin barrier dysfunction and cutaneous microbial dysbiosis are essential players in the pathogenesis of canine AD. It is still unclear if such alterations are primary or secondary to cutaneous inflammation, although some evidence supports their primary involvement in the pathogenesis of canine AD. CONCLUSION AND CLINICAL RELEVANCE: Although many studies have been published since 2015, the understanding of the cutaneous host-microbe interaction is still unclear, as is the role that cutaneous dysbiosis plays in the development and/or worsening of canine AD. More studies are needed aiming to design new therapeutic approaches to restore the skin barrier, to increase and optimise the cutaneous natural defences, and to rebalance the cutaneous microbiome.

BACKGROUND: Cytokines and chemokines play central roles in the pathogenesis of canine atopic dermatitis (cAD). Numerous studies have been published and provide new insights into their roles in cAD. OBJECTIVES: To summarise the research updates on the role of cytokines and chemokines in the pathogenesis of cAD since the last review by the International Committee on Allergic Diseases of Animals in 2015. MATERIAL AND METHODS: Online citation databases, abstracts and proceedings from international meetings on cytokines and chemokines relevant to cAD that had been published between 2015 and 2022 were reviewed. RESULTS: Advances in technologies have allowed the simultaneous analysis of a broader range of cytokines and chemokines, which revealed an upregulation of a multipolar immunological axis (Th1, Th2, Th17 and Th22) in cAD. Most studies focused on specific cytokines, which were proposed as potential novel biomarkers and/or therapeutic targets for cAD, such as interleukin-31. Most other cytokines and chemokines had inconsistent results, perhaps as a consequence of their varied involvement in the pathogenesis of different endotypes of cAD. CONCLUSIONS AND CLINICAL RELEVANCE: Inconsistent results for many cytokines and chemokines illustrate the difficulty of studying the complex cytokine and chemokine networks in cAD, and highlight the need for more comprehensive and structured studies in the future.

BACKGROUND: Canine atopic dermatitis (cAD) is a common, complex and multifactorial disease involving, among others, genetic predisposition, environmental factors and allergic sensitisation. OBJECTIVE: This review summarises the current evidence on the role of genetic and environmental factors and allergic sensitisation in the pathogenesis of cAD since the last review by ICADA in 2015. MATERIALS AND METHODS: Online citation databases and proceedings from international meetings on genetic factors, environmental factors and allergens relevant to cAD that had been published between 2015 and 2022 were reviewed. RESULTS: Despite intensive research efforts, the detailed genetic background predisposing to cAD and the effect of a wide range of environmental factors still need more clarification. Genome-wide association studies and investigations on genetic biomarkers, such as microRNAs, have provided some new information. Environmental factors appear to play a major role. Lifestyle, especially during puppyhood, appears to have an important impact on the developing immune system. Factors such as growing up in a rural environment, large size of family, contact with other animals, and a nonprocessed meat-based diet may reduce the risk for subsequent development of cAD. It appears that Toxocara canis infection may have a protective effect against Dermatophagoides farinae-induced cAD. House dust mites (D. farinae and D. pteronyssinus) remain the most common allergen group to which atopic dogs react. Currently, the major allergens related to D. farinae in dogs include Der f 2, Der f 15, Der f 18 and Zen 1. CONCLUSIONS AND CLINICAL RELEVANCE: Canine atopic dermatitis remains a complex, genetically heterogeneous disease that is influenced by multiple environmental factors. Further, well-designed studies are necessary to shed more light on the role of genetics, environmental factors and major allergens in the pathogenesis of cAD.

Reperfusion with intravenous tissue plasminogen activator (tPA) has been the goal of therapy for acute ischemic stroke; however, tPA is contraindicated in many patients, has low recanalization rates in major occlusions, and carries a substantial risk of symptomatic intracerebral hemorrhage. In the present study, we hypothesized that partial intra-aortic occlusion of the abdominal aorta would increase salvage of ischemic penumbra and reduce infarct volume after focal embolic stroke in rats. We examined the effects of aortic occlusion on infarct volume, expression and activation of matrix metalloprotease-9, and hemorrhagic transformation with or without treatment with tPA. We then examined the effects of aortic occlusion on perfusion deficits following embolic occlusion. Results showed that partial aortic occlusion significantly reduces brain infarction volume with or without treatment with tPA after focal ischemia, but does not increase risk for hemorrhagic transformation or matrix metalloprotease-9 expression and activation. Partial intra-aortic occlusion also reduces perfusion deficits after focal cerebral ischemia as compared to control. The present study shows that partial intra-aortic occlusion significantly decreases infarction volume and perfusion deficits following ischemic injury in an embolic model of cerebral ischemia. Moreover, combination treatment with tPA and partial intra-aortic occlusion further reduces infarction volume without any increase in hemorrhagic transformation.

Abstract In 2009, the Sustainable Remediation Forum released a white paper entitled “Integrating sustainable principles, practices, and metrics into remediation projects” (Ellis &amp; Hadley, 2009, Remediation , 19, pp. 5–114). Sustainable remediation was a relatively new concept, and the white paper explored a range of approaches on how sustainability could be integrated into traditional remediation projects. This paper revisits the 2009 white paper, providing an overview of the early days of the evolving sustainable remediation practice and an assessment of the progress of sustainable remediation over the last 10 years with a primary focus on the United States. The current state of the sustainable remediation practice includes published literature, current practices and resources, applications, room for improvement, international progress, the virtuous cycle that applying sustainable remediation creates, and the status of the objectives cited in the 2009 white paper. Over the last decade, several sustainable remediation frontiers have emerged that will likely be a focus in advancing the practice. These frontiers include climate change and resiliency, weighting and valuation to help better consolidate different sustainable remediation metrics, programmatic implementation, and better integration of the societal impacts of sustainable remediation. Finally, as was the case for the 2009 white paper, this paper explores how sustainable remediation may evolve over the next 10 years and focuses on the events and drivers that can be significant in the pace of further development of the practice. The events and drivers include transformation impacts, societal influences, and the continued development of new technologies, approaches, and tools by remediation practitioners. The remediation industry has made significant progress in developing the practice of sustainable remediation and has implemented it successfully into hundreds of projects. While progress has been significant, an opportunity exists to implement the tenets of sustainable remediation on many more projects and explore new frontiers to help improve the communication, integration, and derived benefits from implementing sustainable remediation into future remediation projects.

The antibody-drug conjugate enfortumab vedotin is a fully humanized monoclonal antibody targeting Nectin-4 linked to a microtubule-disrupting agent, monomethyl auristatin E, via a protease-cleavable maleimidocaproyl valine-citrulline linker. In this article, we provide a comprehensive review of the preclinical and clinical activity of enfortumab vedotin, which has been recently approved in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have previously received a programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) inhibitor as well as platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. Enfortumab vedotin is the first antibody-drug conjugate approved for patients with urothelial carcinoma.

Abstract Objective. Evoked compound action potential (ECAP) recordings have emerged as a quantitative measure of the neural response during spinal cord stimulation (SCS) to treat pain. However, utilization of ECAP recordings to optimize stimulation efficacy requires an understanding of the factors influencing these recordings and their relationship to the underlying neural activation. Approach. We acquired a library of ECAP recordings from 56 patients over a wide assortment of postures and stimulation parameters, and then processed these signals to quantify several aspects of these recordings (e.g., ECAP threshold (ET), amplitude, latency, growth rate). We compared our experimental findings against a computational model that examined the effect of variable distances between the spinal cord and the SCS electrodes. Main results. Postural shifts strongly influenced the experimental ECAP recordings, with a 65.7% lower ET and 178.5% higher growth rate when supine versus seated. The computational model exhibited similar trends, with a 71.9% lower ET and 231.5% higher growth rate for a 2.0 mm cerebrospinal fluid (CSF) layer (representing a supine posture) versus a 4.4 mm CSF layer (representing a prone posture). Furthermore, the computational model demonstrated that constant ECAP amplitudes may not equate to a constant degree of neural activation. Significance. These results demonstrate large variability across all ECAP metrics and the inability of a constant ECAP amplitude to provide constant neural activation. These results are critical to improve the delivery, efficacy, and robustness of clinical SCS technologies utilizing these ECAP recordings to provide closed-loop stimulation.

Abstract Purpose The treatment landscape of advanced bladder cancer continues to evolve with novel therapeutics approved in recent years and many in the pipeline. Here we review the role of the novel agents enfortumab vedotin and sacituzumab govitecan in treatment of advanced disease. Summary Patients with advanced bladder cancer often first receive platinum-based therapy, while immune checkpoint inhibitors offer a maintenance option following cytotoxic chemotherapy or a second-line option. Despite various first- and second-line options, patients with significant comorbidities and treatment-related adverse events will experience disease progression requiring alternative treatment. Enfortumab vedotin and sacituzumab govitecan are novel antibody-drug conjugates approved in patients with advanced bladder cancer following platinum-based and immune checkpoint inhibitor therapy. Following platinum-based therapy and immunotherapy in patients with advanced bladder cancer, enfortumab vedotin, targeting Nectin-4, improves overall survival while sacituzumab govitecan, targeting Trop-2, is associated with a 27% response rate. With these new approaches to disease management, however, it remains critical to understand safety, efficacy, and operational considerations to optimize outcomes. Conclusion When selecting an antibody-drug conjugate to treat patients with bladder cancer, it is important to note the adverse event profile of each agent to optimize outcomes and safety for patients.

Benign prostatic hyperplasia (BPH) is a common problem among older men. Transurethral resection of the prostate (TURP) is a common surgical procedure for treatment of BPH. Typically, TURP is performed using monopolar electric current and a wire electrode; however, the irrigating solution used during this procedure has the potential to cause transurethral resection (TUR) syndrome. A new technology uses bipolar electrosurgery, which creates less risk of electrical shock, and saline irrigation, which eliminates the risk for TUR syndrome.

AIMS: The aim of our study was to review the surgical literature regarding the relationship between hemoglobin A1c (HbA1c), diagnosis of diabetes mellitus (DM), and risk of postoperative surgical site infection (SSI). METHODS: A librarian-assisted literature search was performed with two goals: (1) identify surgical publications related to SSI and HbA1c values, and (2) identify publications reporting infection risk with DM in spinal cord stimulation (SCS), intrathecal drug delivery systems (IDDS), and cardiovascular implantable electronic device (CIED) implantation surgeries. Published guidelines on perioperative management of DM are reviewed. RESULTS: We identified 30 studies reporting SSI and HbA1c values. The literature review indicated that for many surgical procedures, elevated HbA1c is not correlated to rate of SSI. We identified 16 studies reporting infection rates within DM cohorts following SCS, IDDS, and CIED implantation surgeries. The data reviewed did not indicate DM as an independent risk factor for SSI. CONCLUSION: Preoperative HbA1c levels in patients with a history of DM is not a singularly sufficient tool to estimate risk of perioperative infection in SCS implantation surgery. Published guidelines on perioperative management of DM do not suggest a specific HbA1c above which surgery should be delayed; intentional perioperative glycemic control is recommended.

OBJECTIVE: This prospective longitudinal study compares outcomes between Medicare beneficiaries receiving percutaneous image-guided lumbar decompression (PILD) using the mild® procedure and a control group of patients receiving interspinous spacers for the treatment of lumbar spinal stenosis (LSS) with neurogenic claudication (NC). METHODS: Patients diagnosed with LSS with NC and treated with either the mild procedure or a spacer were identified in the Medicare claims database. The incidence of harms, the rate of subsequent interventions, and the overall combined rate of harms and subsequent interventions during 2-year follow-up after the index procedure were compared between the two groups and assessed for statistical significance with p = 0.05. RESULTS: The study included 2229 patients in the mild group and 3401 patients who were implanted with interspinous spacers. The rate of harms for those treated with the mild procedure was less than half that of patients implanted with a spacer (5.6% vs. 12.1%, respectively; p < 0.0001) during 2-year follow-up. The rate of subsequent interventions was not significantly different between the two groups (24.9% and 26.1% for the mild and spacer groups, respectively; p = 0.7679). The total rate of harms and subsequent interventions for mild was found to be noninferior to spacers (p < 0.0001). CONCLUSIONS: This comprehensive study of real-world Medicare claims data demonstrated a significantly lower rate of harms for the mild procedure compared to interspinous spacers for patients diagnosed with LSS with NC, and a similar rate of subsequent interventions during 2-year follow-up.

The influenza vaccine is critical for preventing influenza-related complications in transplant patients. Previous studies demonstrated de novo donor-specific antibody formation and rejection following the influenza vaccination. This risk has not been adequately assessed in the pediatric population. We performed a single-center retrospective analysis of 187 unique pediatric kidney transplant recipients, transplanted from January 1, 2006, to December 31, 2015, assessing for an association of the influenza vaccination with various transplant outcomes. The influenza vaccine was received by 125 of 187 patients within the first year post-transplant. Using log-rank tests and Kaplan-Meier curves, vaccinated patients had a significantly lower risk of mortality (P = 0.048). There were no differences in death-censored graft survival (P = 0.253), graft survival (P = 0.098), or rejection (P = 0.195) between vaccinated and unvaccinated groups. To address the problem of multiple exposures for a yearly vaccine, Cox proportional hazards regression was utilized with post-transplant vaccination status considered as a time-dependent covariate; analyses were performed using both a 360- and 180-day vaccination period following any post-transplant influenza vaccination. In this model, being vaccinated did not result in a significant difference in mortality (HR 0.90 [0.16, 5.15], P = 0.91), death-censored graft survival (HR 0.70 [0.31, 1.58], P = 0.39), graft survival (HR 0.69 [0.32, 1.49], P = 0.34), or rejection (HR 0.67 [0.37, 1.19], P = 0.17). Eight patients developed de novo donor-specific antibodies following the first post-transplant influenza vaccination; three then developed biopsy-proven rejection. These results suggest influenza vaccination is safe in pediatric kidney transplant recipients, and larger prospective studies are required to conclusively confirm our findings.

Soil wetting agents are commonly used in the golf course industry for managing soil moisture. Recently, there has been an interest in the influence wetting agents have on the firmness characteristics of putting surfaces. To date, there has been no established relationship between wetting agents and surface firmness of putting greens. Research was conducted in St. Paul, MN, to evaluate the surface firmness impacts from 13 commercially available wetting agents applied individually or in combination to a creeping bentgrass ( Agrostis stolonifera L.) research green. Treatments were evaluated as season‐long wetting agent programs with applications every 4 wk. Data collection included surface firmness (Clegg Impact Soil Tester), turfgrass quality (TQ), chlorophyll index (CI), volumetric water content (VWC), and spring water drop penetration tests (WDPT) to assess residual of fall‐applied wetting agents. Firmness measurements were not affected by wetting agent applications in 2014. In 2015, Duplex (15% alcohol ethoxylates, 2% alkyl sulfonate, 7% ethylenediaminetetraacetic acid), Aquicare (100% blend of alkoxylated alcohols), and Primer Select (100% alkoxylated polyols) provided the firmest surfaces. Ratings for TQ and CI demonstrated only minor influence of wetting agent applications, as did VWC measurements. Spring WDPT tests indicated wetting agent residual from late‐fall applications, and persistence was most evident at shallow depths. Revolution (100% modified alkylated polyol) demonstrated the greatest residual, whereas Duplex and Aquiflo (45% poloxanlene, 2‐butoxyethanol, siloxane surfactants) had the least residual. These results indicate that firmness can be influenced by wetting agent applications, and that persistence in the soil through the winter months is possible.

Abstract This reply addresses concerns raised by Schilling (2016, doi:10.1002/2015WR018482) on Gupta et al. (2015a, doi: 10.1002/2015WR017323, 2015b, doi:10.1002/2015WR017323). To this end, we provide additional analysis of the Raccoon River flows in Iowa and show that both annual streamflow and baseflow are mainly controlled by precipitation.