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CRISPR-Cas9 genome engineering has revolutionised high-throughput functional genomic screens. However, recent work has raised concerns regarding the performance of CRISPR-Cas9 screens using TP53 wild-type human cells due to a p53-mediated DNA damage response (DDR) limiting the efficiency of generating viable edited cells. To directly assess the impact of cellular p53 status on CRISPR-Cas9 screen performance, we carried out parallel CRISPR-Cas9 screens in wild-type and TP53 knockout human retinal pigment epithelial cells using a focused dual guide RNA library targeting 852 DDR-associated genes. Our work demonstrates that although functional p53 status negatively affects identification of significantly depleted genes, optimal screen design can nevertheless enable robust screen performance. Through analysis of our own and published screen data, we highlight key factors for successful screens in both wild-type and p53-deficient cells., Competing Interests: AB, DM, MS, MA, NL, JT, SJ No competing interests declared, (© 2020, Bowden et al.)

Background: Adherence to antiretroviral therapy is critical to the achievement of the third target of the UNAIDS Fast-Track Initiative goals of 2020-2030. Reliable, valid and accurate measurement of adherence are important for correct assessment of adherence and in predicting the efficacy of ART. The Simplified Medication Adherence Questionnaire is a six-item scale which assesses the perception of persons living with HIV about their adherence to ART. Despite recent widespread use, its measurement properties have yet to be carefully documented beyond the original study in Spain. The objective of this paper was to conduct internal consistency reliability, concurrent validity and measurement invariance tests for the SMAQ., Methods: HIV-positive women who were receiving ART services from 51 service providers in two sub-cities of Addis Ababa, Ethiopia completed the SMAQ in a HIV treatment referral network study between 2011 and 2012. Two cross-sections of 402 and 524 female patients of reproductive age, respectively, from the two sub-cities were randomly selected and interviewed at baseline and follow-up. We used Cronbach's coefficient alpha (α) to assess internal consistency reliability, Pearson product-moment correlation (r) to assess concurrent validity and multiple-group confirmatory factor analysis to analyze factorial structure and measurement invariance of the SMAQ., Results: All participants were female with a mean age of 33; median: 34 years; range 18-45 years. Cronbach's alphas for the six items of the SMAQ were 0.66, 0.68, 0.75 and 0.75 for T1 control, T1 intervention, T2 control, and T2 intervention groups, respectively. Pearson correlation coefficients were 0.78, 0.49, 0.52, 0.48, 0.76 and 0.80 for items 1 to 6, respectively, between T1 compared to T2. We found invariance for factor loadings, observed item intercepts and factor variances, also known as strong measurement invariance, when we compared latent adherence levels between and across patient-groups., Conclusions: Our results show that the six-item SMAQ scale has adequate reliability and validity indices for this sample, in addition to being invariant across comparison groups. The findings of this study strengthen the evidence in support of the increasing use of SMAQ by interventionists and researchers to examine, pool and compare adherence scores across groups and time periods.

In 2016, the proportion of Neisseria gonorrhoeae isolates with reduced susceptibility to azithromycin rose to 3.6%. A phylogenetic analysis of 334 N. gonorrhoeae isolates collected in 2016 revealed a single, geographically diverse lineage of isolates with MICs of 2 to 16 μg/ml that carried a mosaic-like mtr locus, whereas the majority of isolates with MICs of ≥16 μg/ml appeared sporadically and carried 23S rRNA mutations. Continued molecular surveillance of N. gonorrhoeae isolates will identify new resistance mechanisms., (Copyright © 2020 American Society for Microbiology.)

The 1+/n+ method, based on an ECRIS charge breeder (CB) originally developed at the LPSC laboratory, is now implemented at GANIL for the production of Radioactive Ion Beams (RIBs). Prior to its installation in the middle of the low energy beam line of the SPIRAL1 facility, the 1+/n+ system CB has been modified based on the experiments performed on the CARIBU Facility at Argone National Laboratory. Later, it has been tested at the 1+/n+ LPSC test bench to validate its operation performances. Charge breeding efficiencies as well as charge breeding times have been measured for noble gases and alkali elements. The commissioning phase started at GANIL in the second half-year of 2017. It consisted of a stepwise process to test the upgrade of the SPIRAL1 facility from simple validation [operation of Charge Breeder (CB) as a stand-alone source] up to the production of the first 1+/n+ RIB. Thus, this year, a 38m K/ 38 K RIB has been successfully delivered to a physics experiment over a period of 1 week. The yields on the physics target were in the range of ∼2-4 × 10 6 pps at 9 MeV/u. The target ion source system (TISS) was made of a FEBIAD ion source connected to a hot graphite target. This is the first time a RIB is accelerated with a cyclotron with the 1+/n+ method. Moreover, a production test with the FEBIAD TISS has confirmed the yields measured previously, which validates the extension of the GANIL/SPIRAL1 catalog for a number of isotopes. In parallel, R&D is being performed on new TISSs (e.g., a fast release one, using surface ionization source). Targets are also a subject of ongoing R&D for yield and release time optimization. This contribution will present the new acceleration scheme of the SPIRAL1 facility, which largely extends the palette of RIBs available for nuclear physicists. It will be compared to the ones used at similar ISOL facilities. This facility is more than a simple ISOL facility, and an overview of the new opportunities offered by the upgraded installation will be also discussed.

Over the last 40 years, vast changes have occurred in the care of children with open neural tube defects. Not only has newborn survival dramatically improved but survival into adulthood has improved as well. Now, the ability to accurately identify and repair myelomeningocele (MMC) lesions before birth has become a reality. Pioneering efforts at several institutions in the United States paved the way for such advancements in care. Substantial data now exist to support the positive benefits of fetal MMC repair from a neurosurgical standpoint, chiefly the significant reduction in hindbrain herniation, decrease in shunt-dependent hydrocephalus, and improvement in lower-extremity motor function. However, until only recently, the urological impact of fetal repair has not been nearly as positive overall. Multiple retrospective reports of newborn bladder function from the United States suggest that prenatal repair has provided neither short-term nor long-term improvements in bladder function. Yet, the retrospective nature of these data and their focus upon urodynamic studies (UDS) parameters have hampered the ability to draw conclusions. Recently, published data from the landmark Management of Myelomeningocele Study indicate that fetal repair may improve certain aspects of bladder function when compared with conventional repair. This review provides an overview of the history and timeline of fetal repair in the United States and brings the reader quickly up to date on the current impact of repair on both neurosurgical and urological outcomes., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective : The purpose of this study was to investigate the decision-making processes of physical therapists relating to evaluation and categorization of patients with headaches, including consistency with criteria proposed by the International Headache Society (IHS). Methods : A national online survey was distributed in cooperation with the Academy of Orthopaedic Physical Therapy of the American Physical Therapy Association. Three hypothetical patient case vignettes featuring headache disorders were used as assessment instruments. Additionally, data on physical therapist education, clinical experience, manual therapy training, self-efficacy, and familiarity & consistency with IHS criteria were collected. Physical therapist identification and valuation of clinical features of headache disorders were also examined in the decision-making processes. Results : Among the 384 respondents, 32.3% classified the tension-type headache case consistent with IHS criteria. The cervicogenic and migraine headache cases were classified at 54.8% and 41.7% consistent with IHS categories, respectively. Experienced clinicians and those with formal manual training categorized patient presentations with greater consistency. Clinician familiarity with IHS classification criteria was low with 73.6% collectively somewhat and not familiar, while 26.4% of physical therapists were self-described as very or moderately familiar. Discussion : Clinicians' headache categorization was significantly affected by symptom misattribution and weighting of individual examination findings. Weighting by practitioners of clinical features varied markedly with greatest emphasis being placed on detailed manual examination procedures, including passive intervertebral movements. Inconsistencies in valuation of clinical features in headache categorization suggest a need for further formal education in physical therapy educational curricula and in post-graduate education, including of IHS criteria and classification. Level of Evidence : 2a.

The chicken gastrointestinal tract harbors microorganisms that play a role in the health and disease status of the host. The cecum is the part of the gut that carries the highest microbial densities, has the longest residence time of digesta, and is a vital site for urea recycling and water regulation. Therefore, the cecum provides a rich environment for bacteria to horizontally transfer genes between one another via mobile genetic elements such as plasmids and bacteriophages. In this study, we used broiler chicken cecum as a model to investigate antibiotic resistance genes that can be transferred in vitro from cecal flora to Salmonella enterica serovar Heidelberg. We used whole-genome sequencing and resistome enrichment to decipher the interactions between S Heidelberg, the gut microbiome, and acquired antibiotic resistance. After 48 h of incubation of ceca under microaerophilic conditions, we recovered one S Heidelberg isolate with an acquired IncK2 plasmid (88 kb) carrying an extended-spectrum-β-lactamase gene ( bla CMY-2 ). In vitro , this plasmid was transferable between Escherichia coli and S Heidelberg strains but transfer was unsuccessful between S Heidelberg strains. An in-depth genetic characterization of transferred plasmids suggests that they share significant homology with P1-like phages. This study contributes to our understanding of horizontal gene transfer between an important foodborne pathogen and the chicken gut microbiome. IMPORTANCE S. Heidelberg is a clinically important serovar, linked to foodborne illness and among the top 5 serovars isolated from poultry in the United States and Canada. Acquisition of new genetic material from the microbial flora in the gastrointestinal tract of food animals, including broilers, may contribute to increased fitness of pathogens like S. Heidelberg and may increase their level of antibiotic tolerance. Therefore, it is critical to gain a better understanding of the interactions that occur between important pathogens and the commensals present in the animal gut and other agroecosystems. In this report, we show that the native flora in broiler ceca were capable of transferring mobile genetic elements carrying the AmpC β-lactamase ( bla CMY-2 ) gene to an important foodborne pathogen, S Heidelberg. The potential role for bacteriophage transduction is also discussed.

Background: Triatomine bugs are vectors of the protozoan parasite Trypanosoma cruzi, which causes Chagas disease. Rhodnius pallescens is a major vector of Chagas disease in Panama. Understanding the microbial ecology of disease vectors is important in the development of vector management strategies that target vector survival and fitness. In this study we examined the whole-body microbial composition of R. pallescens from three locations in Panama., Methods: We collected 89 R. pallescens specimens using Noireau traps in Attalea butyracea palms. We then extracted total DNA from whole-bodies of specimens and amplified bacterial microbiota using 16S rRNA metabarcoding PCR. The 16S libraries were sequenced on an Illumina MiSeq and analyzed using QIIME2 software., Results: We found Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes to be the most abundant bacterial phyla across all samples. Geographical location showed the largest difference in microbial composition with northern Veraguas Province having the most diversity and Panama Oeste Province localities being most similar to each other. Wolbachia was detected in high abundance (48-72%) at Panama Oeste area localities with a complete absence of detection in Veraguas Province. No significant differences in microbial composition were detected between triatomine age class, primary blood meal source, or T. cruzi infection status., Conclusions: We found biogeographical regions differ in microbial composition among R. pallescens populations in Panama. While overall the microbiota has bacterial taxa consistent with previous studies in triatomine microbial ecology, locality differences are an important observation for future studies. Geographical heterogeneity in microbiomes of vectors is an important consideration for future developments that leverage microbiomes for disease control.

Purpose: We investigated longer term urological outcomes in patients enrolled in the Management of Myelomeningocele Study (MOMS)., Materials and Methods: Women who participated in the original trial were asked for consent for followup for their child at age 6 years or older in a single comprehensive study visit to a MOMS center. Participating children underwent urological and radiologic procedures to provide objective evidence of current bladder functioning. Primary urological outcome was defined as any among need for clean intermittent catheterization, vesicostomy, urethral dilatation or augmentation cystoplasty., Results: A total of 156 children were evaluated, with a mean age of 7.4 years. Overall 62% vs 87% in the prenatal and postnatal surgery groups, respectively, were placed on clean intermittent catheterization (RR 0.71, 95% CI 0.58-0.86, p <0.001). Voiding status was significantly different between the groups (p <0.001) as 24% in the prenatal group vs 4% in the postnatal group (RR 5.8, 95% CI 1.8-18.7) were reported to be voiding volitionally. Augmentation cystoplasty, vesicostomy and urethral dilation did not differ between the 2 groups. Aside from a larger post-void residual urodynamic catheterization volume, there were no other statistical differences in videourodynamic data or findings on renal/bladder ultrasound., Conclusions: Prenatal closure of myelomeningocele resulted in less reported clean intermittent catheterization at school age and the mechanism for this is unclear. Although most children are in diapers or on clean intermittent catheterization, parental reports showed children who underwent prenatal closure may be more likely to void volitionally than the postnatal group. Despite these findings, urological outcomes alone should not be the sole impetus to perform in utero closure in children with spina bifida.

DHX8 is a crucial DEAH-box RNA helicase involved in splicing and required for the release of mature mRNA from the spliceosome. Here, we report the biochemical characterisation of full-length human DHX8 and the catalytically active helicase core DHX8Δ547, alongside crystal structures of DHX8Δ547 bound to ADP and a structure of DHX8Δ547 bound to poly(A) 6 single-strand RNA. Our results reveal that DHX8 has an in vitro binding preference for adenine-rich RNA and that RNA binding triggers the release of ADP through significant conformational flexibility in the conserved DEAH-, P-loop and hook-turn motifs. We demonstrate the importance of R620 and both the hook-turn and hook-loop regions for DHX8 helicase activity and propose that the hook-turn acts as a gatekeeper to regulate the directional movement of the 3' end of RNA through the RNA-binding channel. This study provides an in-depth understanding of the activity of DHX8 and contributes insights into the RNA-unwinding mechanisms of the DEAH-box helicase family., (© 2019 The Author(s).)

Background: In 2006, the Government of India launched the accredited social health activist (ASHA) program, with the goal to connect marginalized communities to the health care system. We assessed the effect of the ASHA program on the utilization of maternity services., Methods: We used data from Indian Human Development Surveys done in 2004-2005 and in 2011-2012 to assess demographic and socioeconomic factors associated with the receipt of ASHA services, and used difference-in-difference analysis with cluster-level fixed effects to assess the effect of the program on the utilization of at least one antenatal care (ANC) visit, four or more ANC visits, skilled birth attendance (SBA), and giving birth at a health facility., Results: Substantial variations in the receipt of ASHA services were reported with 66% of women in northeastern states, 30% in high-focus states, and 16% of women in other states. In areas where active ASHA activity was reported, the poorest women, and women belonging to scheduled castes and other backward castes, had the highest odds of receiving ASHA services. Exposure to ASHA services was associated with a 17% (95% CI 11.8-22.1) increase in ANC-1, 5% increase in four or more ANC visits (95% CI - 1.6-11.1), 26% increase in SBA (95% CI 20-31.1), and 28% increase (95% CI 22.4-32.8) in facility births., Conclusions: Our results suggest that the ASHA program is successfully connecting marginalized communities to maternity health services. Given the potential of the ASHA in impacting service utilization, we emphasize the need to strengthen strategies to recruit, train, incentivize, and retain ASHAs.

The angular weighting coefficient is key to accurate particle size distribution (PSD) measurement using multiangle dynamic light scattering (MDLS). However, determining the weighting coefficient is affected by the noise in the measured MDLS data. In this paper, a novel successive updating of the angular weighting (AWSU) method is proposed. By using information character weighting, the angular weighting coefficient and the character weighting matrix are updated once with each additional angle. The effect of autocorrelation function (ACF) denoising and information extraction is improved by using information character weighting step-by-step. The results for broad unimodal and closely-spaced bimodal PSDs demonstrate the effectiveness of this method. Compared with another routinely used inversion method, it is found that the increase in PSD information retrieved from MDLS depends not only on increasing the number of angles, but also on the calculation of the angular weightings. An accurate weighting algorithm can reduce the number of scattering angles required. Using the AWSU method for PSD recovery with 4 scattering angles can give better results than the usual method with 6 scattering angles. It is also found that the AWSU method not only improves the accuracy of the weightings, but it also contributes directly to the PSD recovery by reconstructing the ACF with the PSD obtained by the weighted inversion. The combination of these two contributions not only reduces the number of scattering angles needed, but also keeps the PSD recovery results from getting worse because of excessive scattering angles.

Background: Given the lack of new antimicrobials or a vaccine, understanding the evolutionary dynamics of Neisseria gonorrhoeae is a significant public and global health priority. We investigated the emergence and spread of gonococcal strains with decreased susceptibility to cephalosporins and azithromycin using detailed genomic analyses of gonococcal isolates collected in the United States, 2014-2016., Methods: We sequenced genomes of 649 isolates collected through the Gonococcal Isolate Surveillance Project. We examined the genetic relatedness of isolates and assessed associations between clades and various genotypic and phenotypic combinations., Results: We identified a large and clonal lineage of strains (MLST ST9363) associated with elevated azithromycin minimum inhibitory concentration (AZIem), characterized by a mosaic mtr locus (C substitution in the mtrR promoter, mosaic mtrR and mtrD). Mutations in 23S rRNA were sporadically distributed among AZIem strains. Another clonal group (MLST ST1901) possessed 7 unique PBP2 patterns, and it shared common mutations in other genes associated with cephalosporin resistance., Conclusions: Whole-genome sequencing methods can enhance monitoring of antimicrobial resistant gonococcal strains by identifying gonococcal populations containing mutations of concern. These methods could inform the development of point-of-care diagnostic tests designed to determine the specific antibiotic susceptibility profile of a gonococcal infection in a patient., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Prenatal social stress "programs" offspring immune activity in animal models, but how the prenatal social environment affects human offspring inflammation is not known. Here, we test associations between prenatal partner support quality, i.e. positive/helpful support, negative/upsetting support, and their interaction, and infant inflammatory markers. A sample of 113 women from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort were followed from early pregnancy to 3-months postpartum. Partner support quality was measured during pregnancy and the postpartum period. Three-month-old infant blood samples were assayed for inflammatory markers, i.e., adaptive immune markers IFNγ, IL12p70 and IL10. The prenatal positive-by-negative partner support interaction predicted infant IFNγ, IL12p70, and IL10, p's<.035, independent of covariates and postpartum partner support. When negative partner support was high, high positive support predicted higher infant IFNγ, IL12p70, and IL10. As such, partner support during pregnancy that is both highly negative/upsetting and also highly positive/helpful predicted adaptive immunity markers in infants at 3 months of age., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Context: The link between testing for HIV and obtaining antiretroviral therapy (ART) is central to the HIV/AIDS control strategies of UNAIDS (the "90-90-90" goals) and the International Association of Providers of AIDS Care ("Test and Start"). To ensure that 90% of those diagnosed with HIV/AIDS begin ART and 90% of those on ART achieve viral suppression, service providers not providing all services need to refer patients to other organizations., Setting: Homa Bay, Kenya., Objective: Homa Bay county's HIV/AIDS prevalence is one of the country's highest. We identified the organizations providing some aspect of HIV/AIDS care and investigated ways in which they work together, or do not, to cover the comprehensive needs of those they serve., Design and Participants: We identified 56 organizations and interviewed a representative from each about his or her organization's services and its connections with the other 55, with particular interest in referrals from sites that test for HIV but do not treat infections to sites that do treat infections., Main Outcome Measure: Referral connections., Results: Referral connections among the 56 in the past 30 days were relatively rare, averaging fewer than 2; 13 organizations made no referrals at all. Notably, 5 facilities that test for HIV did not refer their clients to an ART provider. We found 2 distinct clusters of connected organizations: one in Homa Bay Township and the other in Rangwe subcounty. When we convened the organizations and presented our results to them, they expressed interest in establishing better connections and referrals., Conclusions: Homa Bay has an opportunity to improve care for people with HIV/AIDS, in particular ensuring that those testing positive receive treatment, simply by making better use of the services already available. This can be achieved by informing each organization of the services provided by each of the others and by bringing the organizations together to plan and monitor the services' coordination. These steps could be implemented separately in each of the 2 organizational clusters.

Introduction: Testicular torsion is a urological emergency; as the testicular salvage rate decreases with time, prompt intervention is required to restore the blood flow. Interhospital transfers and ultrasound examinations, while clinically essential to proper treatment and diagnosis, may adversely affect outcomes by delaying surgical intervention. Patients transferred to another institution for treatment of testicular torsion may experience a further time delay by undergoing two ultrasound examinations: one at the initial admitting institution and one at the receiving institution. To the knowledge of the authors, no study has yet explored the time delays and outcomes associated with these repeat ultrasounds., Objective: The objective was to investigate the impact of repeat ultrasound imaging on time to treatment and patient outcomes in patients with testicular torsion., Study Design: A retrospective chart review of 133 patients, aged 0-20 years, treated at the authors' institution for testicular torsion was conducted. Neonate patients and patients who did not receive ultrasound were excluded. Demographic and clinical variables were collected from the electronic medical record. Pearson Chi-squared and t-tests were used for univariate comparisons, and multivariate logistic regression analysis was performed to measure the relationships between variables., Results: Forty-nine percent of patients were primary patients, and 51% were transfer patients. Fifty-two percent of transfer patients received repeat ultrasounds. In comparison to salvaged patients, those who underwent orchiectomy experienced a greater delay between presentation at the institution and surgical intervention (229 min vs 177 min, p = 0.048). The transfer status does not appear to be related to the outcome, i.e. orchiectomy versus salvage. Patients who underwent orchiectomy were more likely than salvaged patients to have received repeat ultrasounds (p = 0.008). Repeat ultrasound patients had three times the likelihood of orchiectomy of single ultrasound patients. In a subset analysis of transfer patients, repeat ultrasound patients were more likely than single ultrasound patients to receive an orchiectomy (p = 0.03)., Discussion: In agreement with previous studies, patients who underwent orchiectomy were found to experience greater treatment delays and trend toward transfer. Specifically, repeat ultrasound and time between presentation and intervention appear to influence patient outcomes. The effect of repeat ultrasound on outcomes appears to be independent of the transfer status. The study was limited by its retrospective nature and small sample size., Conclusion: The analysis suggests that efforts to prevent repeat ultrasounds and minimize the time between presentation and intervention would improve patient outcomes. It is proposed that standardized clinical decision-making procedures, such as the TWIST scoring system, be incorporated into hospital protocols., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Biologic products encounter various types of interfacial stress during development, manufacturing, and clinical administration. When proteins come in contact with vapor-liquid, solid-liquid, and liquid-liquid surfaces, these interfaces can significantly impact the protein drug product quality attributes, including formation of visible particles, subvisible particles, or soluble aggregates, or changes in target protein concentration due to adsorption of the molecule to various interfaces. Protein aggregation at interfaces is often accompanied by changes in conformation, as proteins modify their higher order structure in response to interfacial stresses such as hydrophobicity, charge, and mechanical stress. Formation of aggregates may elicit immunogenicity concerns; therefore, it is important to minimize opportunities for aggregation by performing a systematic evaluation of interfacial stress throughout the product development cycle and to develop appropriate mitigation strategies. The purpose of this white paper is to provide an understanding of protein interfacial stability, explore methods to understand interfacial behavior of proteins, then describe current industry approaches to address interfacial stability concerns. Specifically, we will discuss interfacial stresses to which proteins are exposed from drug substance manufacture through clinical administration, as well as the analytical techniques used to evaluate the resulting impact on the stability of the protein. A high-level mechanistic understanding of the relationship between interfacial stress and aggregation will be introduced, as well as some novel techniques for measuring and better understanding the interfacial behavior of proteins. Finally, some best practices in the evaluation and minimization of interfacial stress will be recommended.

The phosphaturic hormone FGF23 is elevated in chronic kidney disease (CKD). The risk of premature death is substantially higher in the CKD patient population, with cardiovascular disease (CVD) as the leading mortality cause at all stages of CKD. Elevated FGF23 in CKD has been associated with increased odds for all-cause mortality; however, whether FGF23 is associated with positive adaptation in CKD is unknown. To test the role of FGF23 in CKD phenotypes, a late osteoblast/osteocyte conditional flox-Fgf23 mouse (Fgf23fl/fl/Dmp1-Cre+/-) was placed on an adenine-containing diet to induce CKD. Serum analysis showed casein-fed Cre+ mice had significantly higher serum phosphate and blood urea nitrogen (BUN) versus casein diet and Cre- genotype controls. Adenine significantly induced serum intact FGF23 in the Cre- mice over casein-fed mice, whereas Cre+ mice on adenine had 90% reduction in serum intact FGF23 and C-terminal FGF23 as well as bone Fgf23 mRNA. Parathyroid hormone was significantly elevated in mice fed adenine diet regardless of genotype, which significantly enhanced midshaft cortical porosity. Echocardiographs of the adenine-fed Cre+ hearts revealed profound aortic calcification and cardiac hypertrophy versus diet and genotype controls. Thus, these studies demonstrate that increased bone FGF23, although associated with poor outcomes in CKD, is necessary to protect against the cardio-renal consequences of elevated tissue phosphate.

Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children's behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children's behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children's behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children's internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children's behavioural psychopathology.

Introduction: Pelvic Floor Biofeedback Therapy (PFBT) can be an effective treatment for pediatric lower urinary tract symptoms (LUTS). Due to differing perceptions of efficacy and practice patterns, we sought to further evaluate PFBT in our practice. We hypothesized that PFBT results in quiescence of EMG activity during voiding and improves questionnaire scores in patients with LUTS., Methods: We retrospectively reviewed all patients undergoing PFBT and refined the analysis to females ≥6 years old with ≥2 sessions with completed voiding questionnaires pre- and post-treatment, active EMG during voiding, with non-neurogenic urinary tract complaints refractory to standard urotherapy. Validated Bladder Bowel Dysfunction (BBD) questionnaires were collected at each visit. Quiescence of EMG activity and changes in BBD score were the primary outcomes., Results: 229 patients underwent ≥1 PFBT session, of which 64 females ≥6 years of age with ≥2 PFBT sessions and completed pre and post PFBT voiding questionnaires were identified. In this group, mean age at PFBT start was 10.1 (6.2-17.0). Patients completed 3.1 sessions (2-6). No difference was seen in post-void residual (PVR) between first and last session (23.8 vs 22.6 mL, P = 0.55). Median questionnaire score decreased from 18 (4-42) before to 13 (2-28) following PFBT (P < 0.0001). Responders, characterized by silencing of the EMG after PFBT, occurred in 31% (20/64). Non-responders were younger (P = 0.007) with higher pre-PFBT questionnaire scores., Conclusion: The use of PFBT appears to result in a significant reduction in symptom scores, though quiescence of EMG was observed following therapy in less than 1/3 of patients., (© 2018 Wiley Periodicals, Inc.)

Background: Altering rotavirus vaccine schedules may improve vaccine performance in low- and middle-income countries. We analyzed data from clinical trials of the monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in low- and middle-income countries to understand the association between vaccine dose timing and severe rotavirus gastroenteritis incidence., Methods: We assessed the association between variations in rotavirus vaccine administration schedules and severe rotavirus gastroenteritis risk. We used the complement of the Kaplan-Meier survival estimator to estimate risk differences for different schedules. To adjust risk differences (RDs) for confounding, we calibrated estimates in the vaccinated arm using estimates from the placebo arm., Results: There were 3,114 and 7,341 children included from the RV1 and RV5 trials, respectively. The 18-month adjusted severe rotavirus gastroenteritis risk was 4.0% (95% confidence interval [CI] = 1.1, 7.1) higher for those receiving their first RV5 dose at <6 versus ≥6 weeks. For RV1, there was a 4.0% (95% CI = 0.0, 8.2) increase in 12-month adjusted risk for a 4- versus 6-week interval between doses. Further analysis revealed those receiving their first RV5 dose at 3-4 and 5-7 weeks had 2.9% (95% CI = 0.8, 5.3) and 1.3% (95% CI = -0.3, 3.0), respectively, higher risk compared with those at 9-12 weeks. Those receiving their first dose at 8 weeks had the lowest risk (RD: -2.6% [95% CI = -5.4, -0.1]) compared with those at 9-12 weeks., Conclusions: A modest delay in rotavirus vaccination start and increase in interval between doses may be associated with lower severe rotavirus gastroenteritis risk in low- and middle-income countries.

Site-specific and regional analysis of time-series hydrologic and geochemical data collected from 15 monitoring wells in the Piceance Basin indicated that a leaking gas well contaminated shallow groundwater with thermogenic methane. The gas well was drilled in 1956 and plugged and abandoned in 1990. Chemical and isotopic data showed the thermogenic methane was not from mixing of gas-rich formation water with shallow groundwater or natural migration of a free-gas phase. Water-level and methane-isotopic data, and video logs from a deep monitoring well, indicated that a shale confining layer ~125m below the zone of contamination was an effective barrier to upward migration of water and gas. The gas well, located 27m from the contaminated monitoring well, had ~1000m of uncemented annular space behind production casing that was the likely pathway through which deep gas migrated into the shallow aquifer. Measurements of soil gas near the gas well showed no evidence of methane emissions from the soil to the atmosphere even though methane concentrations in shallow groundwater (16 to 20mg/L) were above air-saturation levels. Methane degassing from the water table was likely oxidized in the relatively thick unsaturated zone (~18m), thus rendering the leak undetectable at land surface. Drilling and plugging records for oil and gas wells in Colorado and proxies for depth to groundwater indicated thousands of oil and gas wells were drilled and plugged in the same timeframe as the implicated gas well, and the majority of those wells were in areas with relatively large depths to groundwater. This study represents one of the few detailed subsurface investigations of methane leakage from a plugged and abandoned gas well. As such, it could provide a useful template for prioritizing and assessing potentially leaking wells, particularly in cases where the leakage does not manifest itself at land surface., (Published by Elsevier B.V.)

Supportive social relationships can reduce both psychological and physiological responses to stressful experiences. Recently, studies have also assessed the potential for social relationships to buffer the intergenerational transmission of stress. The majority of these studies, however, have focussed on social learning as a mechanism responsible for the intergenerational transmission of stress. Evidence of biological mechanisms is lacking. The objective of the current study was, therefore, to determine whether the association between maternal adverse childhood experiences (ACEs) and infant hypothalamic-pituitary-adrenal (HPA) axis function is mediated by maternal HPA axis function during pregnancy and moderated by social support. Data were from 243 mother-infant dyads enrolled in a prospective longitudinal cohort (the Alberta Pregnancy Outcomes and Nutrition Study). Maternal history of ACEs was retrospectively assessed while maternal perceived social support and salivary cortisol were assessed prospectively at 6-22 weeks gestation (Time 1) and 27-37 weeks gestation (Time 2), and infant cortisol reactivity to a laboratory stressor and maternal perceived social support were assessed at 5-10 months postnatal (Time 3). Results revealed that maternal HPA axis function during pregnancy mediated the effects of maternal ACEs on infant HPA axis reactivity, suggesting that the maternal HPA axis is a mechanism by which maternal early life stress is transmitted to offspring. Furthermore, social support in the prenatal and postnatal periods moderated the cascade from maternal ACEs to infant HPA axis reactivity. Specifically, prenatal social support moderated the association between ACEs and maternal HPA axis function during pregnancy, and postnatal social support moderated the association between maternal HPA axis function and infant cortisol reactivity. These findings highlight the social sensitivity of the HPA axis and suggest the utility of social relationships as an intervention target to reduce the effects of maternal early life stress on infant outcomes.

The WHO recommends antiretroviral therapy (ART) initiation immediately after HIV diagnosis. When HIV services are fragmented and poorly coordinated, initiation of ART can be delayed. MEASURE Evaluation conducted an organizational network intervention in Addis Ababa, Ethiopia, which increased referral network density and client satisfaction in the intervention versus control networks. The objective of our study was to extend the parent study by assessing effects of network density on the speed of ART initiation and adherence to ART. Measures of client-time since HIV diagnosis, use of ART, satisfaction with HIV-related services, and adherence were obtained from cross-sectional interviews with female service recipients with HIV/AIDS at baseline (T1, 402) and at 18-month follow-up (T2, 524) and compared between network sites. We used weighted least squares estimation with probit regression techniques in a structural equation modeling framework for analyses. On average at follow-up, clients in the intervention network were more likely to have quicker ART initiation, and were initiated on ART 15 days faster than clients in the control network. Moreover, quicker ART initiation was associated with higher adherence. A unit increase in speed of ART initiation was associated with 0.5 points increase in latent adherence score in the intervention group (p < .05). Satisfaction with care positively predicted adherence to ART. Network density had no direct effect on ART adherence. This quasi-experiment demonstrated that increased referral network density, through improved HIV client referrals, can enhance speed of ART initiation, resulting in improved adherence.

Retention in care remains an important issue for prevention of mother-to-child transmission (PMTCT) programs according to WHO guidelines, formerly called the "Option B+" approach. The objective of this study was to examine how poverty, gender, and health system factors interact to influence women's participation in PMTCT services. We used qualitative research, literature, and hypothesized variable connections to diagram causes and effects in causal loop models. We found that many factors, including antiretroviral therapy (ART) use, service design and quality, stigma, disclosure, spouse/partner influence, decision-making autonomy, and knowledge about PMTCT, influence psychosocial health, which in turn affects women's participation in PMTCT services. Thus, interventions to improve psychosocial health need to address many factors to be successful. We also found that the design of PMTCT services, a modifiable factor, is important because it affects several other factors. We identified 66 feedback loops that may contribute to policy resistance-that is, a policy's failure to have its intended effect. Our findings point to the need for a multipronged intervention to encourage women's continued participation in PMTCT services and for longitudinal research to quantify and test our causal loop model., Competing Interests: The authors declare no conflicts of interest. JY’s affiliation with ICF does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: Urodynamic findings often guide treatment for neuropathic bladder and are reported as objective data points in multi-institutional trials. However, urodynamic interpretation can be variable. In a pilot study pediatric urologists interpreting videourodynamics exhibited only moderate agreement despite similar training and practice patterns. We hypothesized the pilot study variability would be replicated in a multi-institutional study., Materials and Methods: We developed an anonymous electronic survey that contained 20 scenarios, each with a brief patient history, 1 urodynamic tracing and fluoroscopic imagery. All videourodynamics were completed during routine care of patients with neuropathic bladder at a single institution. Pediatric urologists from Centers for Disease Control and Prevention Urologic Protocol sites were invited to complete an interpretation instrument for each scenario. Fleiss kappa and 95% confidence limits were reported, with Fleiss kappa 1.00 corresponding to perfect agreement., Results: The survey was completed by 14 pediatric urologists at 7 institutions. Substantial agreement was seen for assessment of fluoroscopic bladder shape (Fleiss kappa 0.73), while moderate agreement was observed for assessment of bladder safety, end filling detrusor pressure and bladder capacity (Fleiss kappa 0.50, 0.56 and 0.54, respectively). Fair agreement was seen for electromyographic synergy and presence of detrusor overactivity (Fleiss kappa 0.21 and 0.35, respectively)., Conclusions: Experienced pediatric urologists demonstrate variability during interpretation of videourodynamic tracings. Subjectivity of assessment of electromyographic activity and detrusor overactivity was confirmed in this expanded study. Future work to improve the reliability of videourodynamic interpretation would improve the quality of clinical care and the quality of multi-institutional studies that use urodynamic data points as outcomes., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The accuracy of the particle size distribution (PSD) recovered from laser diffraction measurements by the Chin-Shifrin integral transform algorithm is reduced unless the proper angular parameters, including the lower and upper angular integration limits (θ max and θ min ) and the angular resolution (Δθ), are used. To determine the selection criteria for these parameters, we use two metrics: the inversion error of the non-negative PSD, ε 1 , and the fitting error of the scattered laser light, ε 2 . By studying the variation of the minimum θ max and ε 2 with the particle size at different inversion errors, and by analyzing the inversion error, as θ min and Δθ are varied, the optimized selection criteria for the minimum θ max , θ min and Δθ are obtained respectively. The inversion errors of the Chin-Shifrin algorithm with different selection criteria are compared, the different PSDs are recovered, and the optimal pixel selection range of the linear charge-coupled-device (CCD) array is determined according to the optimized selection criteria. Simulation results show that the optimized selection criteria for the angular parameters make the PSDs retrieved with the Chin-Shifrin algorithm more accurate.

Delays in rotavirus vaccine schedule could improve performance in low- and middle-income countries (LMICs). However, delaying the first dose could be detrimental if infants experience severe rotavirus gastroenteritis (RVGE) early in life. Our objective was to describe the timing and predictors of severe RVGE in unvaccinated children in LMICs. We analysed the placebo arms from two clinical trials (cohort 1: NCT00241644; cohort 2: NCT00362648). We estimated the rate, cumulative incidence (per 1000 infants) and age distribution of severe RVGE episodes. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between baseline factors and severe RVGE. Cumulative incidence at 6 months of age was 23/1000 (95% CI 15-30) in cohort 1 and 6/1000 (95% CI 3-8) in cohort 2. Early antibiotic use (compared with no use) was associated with 2.03 (95% CI 1.18-3.48) and 1.41 (95% CI 0.80-2.51) times the rate of severe RVGE in cohorts 1 and 2, respectively. The cumulative incidence of severe RVGE was low at 6 months of age, suggesting that a 4-week delay in the vaccination schedule may not result in a large number of severe RVGE episodes prior to vaccine receipt.

We use simple acid-base chemistry to control the valency in self-assembled monolayers of two different carboranedithiol isomers on Au{111}. Monolayer formation proceeds via Au-S bonding, where manipulation of pH prior to or during deposition enables the assembly of dithiolate species, monothiol/monothiolate species, or combination. Scanning tunneling microscopy (STM) images identify two distinct binding modes in each unmodified monolayer, where simultaneous spectroscopic imaging confirms different dipole offsets for each binding mode. Density functional theory calculations and STM image simulations yield detailed understanding of molecular chemisorption modes and their relation with the STM images, including inverted contrast with respect to the geometric differences found for one isomer. Deposition conditions are modified with controlled equivalents of either acid or base, where the coordination of the molecules in the monolayers is controlled by protonating or deprotonating the second thiol/thiolate on each molecule. This control can be exercised during deposition to change the valency of the molecules in the monolayers, a process that we affectionately refer to as the "can-can." This control enables us to vary the density of molecule-substrate bonds by a factor of 2 without changing the molecular density of the monolayer.

Lattice-matched graphene on hexagonal boron nitride is expected to lead to the formation of a band gap but requires the formation of highly strained material and has not hitherto been realized. We demonstrate that aligned, lattice-matched graphene can be grown by molecular beam epitaxy using substrate temperatures in the range 1600-1710 °C and coexists with a topologically modified moiré pattern with regions of strained graphene which have giant moiré periods up to ∼80 nm. Raman spectra reveal narrow red-shifted peaks due to isotropic strain, while the giant moiré patterns result in complex splitting of Raman peaks due to strain variations across the moiré unit cell. The lattice-matched graphene has a lower conductance than both the Frenkel-Kontorova-type domain walls and also the topological defects where they terminate. We relate these results to theoretical models of band gap formation in graphene/boron nitride heterostructures.

In particle size measurement with dynamic light scattering (DLS), it is difficult to get an accurate recovery of a bimodal particle size distribution (PSD) with a peak position ratio less than ~2:1, especially when large particles (>350nm) are present. This is due to the inherent noise in the autocorrelation function (ACF) data and the scarce utilization of PSD information during the inversion process. In this paper, the PSD information distribution in the ACF data is investigated. It was found that the initial decay section of the ACF contains more information, especially for a bimodal PSD. Based on this, an information-weighted constrained regularization (IWCR) method is proposed in this paper and applied in multiangle DLS analysis for bimodal PSD recovery. By using larger (or smaller) coefficients for weighting the ACF data, more (or less) weight can then be given to the initial part of the ACF. In this way, the IWCR method can enhance utilization of the PSD information in the ACF data, and effectively weaken the effect of noise at large delay time on PSD recovery. Using this method, bimodal PSDs (with nominal diameters of 400:608 nm, 448:608 nm, 500:600 nm) were recovered successfully from simulated data and it appears that the IWCR method can improve the recovery resolution for closely spaced bimodal particles. Results of the PSD recovery from experimental DLS data confirm the performance of this method.

Background: Lay support has been associated with improved breastfeeding practices, but studies of programs that engage men in breastfeeding support have shown mixed results and most are from high-income countries. The purpose of our research is to review strategies to engage men in exclusive breastfeeding (EBF) promotion or support in 28 project areas across 20 low- and middle-income countries. This information may be used to inform program implementers and policymakers seeking to increase EBF., Methods: We tested the difference between baseline and final EBF proportions using Pearson's chi-square (a = 0.05) and identified project areas with a significant increase. We categorized male engagement strategies as low- and high-intensity, using information from project reports. We looked for patterns by intensity and geography and described strategies used to engage men in different places., Results: Twenty-eight projects were reviewed; 21 (75%) were in areas where a statistically significant increase in EBF was observed between the beginning and end of the project. A variety of high- and low-intensity male engagement strategies was used in areas with an increase in EBF prevalence and in all geographic regions. High-intensity strategies engaged men directly during home or health visits by forming men's groups and by working with male community leaders or members to promote EBF. Low-intensity strategies included large community meetings that included men, and radio messages, and other behavior change materials directed towards men., Conclusion: Male engagement strategies took many forms in these project areas. We did not find consistent associations between the intensities or types of male engagement strategies and increases in EBF proportions. There is a gap in understanding how gender norms might impact male involvement in women's health behaviors. This review does not support the broad application of male engagement to improve EBF practices, and we recommend considering local gender norms when designing programs to support women to EBF.

At the turn of the century, several major efforts were initiated to combat HIV/AIDS and other major epidemics affecting low- and middle-income countries (LMICs). They were accompanied by initiatives to enable recipient countries to collect and use data to guide their public health programmes. These health information systems (HIS) typify systems in that they have multiple interacting components, and they are embedded within larger systems. Components of a larger system act as the context for all lower-level systems. Their effects can be pervasive, and thus be taken for granted or regarded as unchangeable. We identify four contextual factors that affect efforts to strengthen HIS: hierarchical roles, aid funding, corruption, and competing priorities. We provide examples of each as experienced by those working to strengthen HIS in LMICs. Each of these contextual factors can seriously diminish the effectiveness of HIS strengthening efforts and their long-term sustainability. We propose research questions about each that would enable those engaged in HIS strengthening to work effectively and sustainably.

A study of operator knowledge, attitudes and practices (KAP) in red meat slaughter premise operations in northern Laos was conducted and compared with international best practice, to inform future industry development. The survey interviewed 68 (of 94 possible participants) employees from all ten commercial slaughter premises in six districts in three northern Laos provinces. This was supported by observations of slaughter premises, processes and the conduct of personnel. Descriptive analysis and linear regression modelling identified significant KAP predictor factors, and a gap analysis supported or rejected inferences from the generally low KAP scores for human and animal health, animal welfare, good manufacturing practices (GMP), work conditions and economics. The median proportion of correctly/desirably answered knowledge-related questions was 35.2% (interquartile range [IQR] = 22.2-51.9%) with 27.3% (IQR = 15.9-31.8%) for the attitude-related questions and 21.4% (IQR = 14.3-35.7%) for the practice-related questions. Two districts had significantly lower KAP scores than other districts, and staff had the lowest and meat inspectors had the highest scores. This study indicates that the current KAP for red meat processing falls short of international standards and that training programmes on disease risks and prevention are important in facilitating red meat industry development.

Metaldehyde is a common molluscicide, used to control slugs in agriculture and horticulture. It is resistant to breakdown by current water treatment processes, and its accumulation in drinking water sources leads to regular regulatory failures in drinking water quality. To address this problem, we isolated metaldehyde-degrading microbes from domestic soils. Two distinct bacterial isolates were cultured, that were able to grow prototrophically using metaldehyde as sole carbon and energy source. One isolate belonged to the genus Acinetobacter (strain designation E1) and the other isolate belonged to the genus Variovorax (strain designation E3). Acinetobacter E1 was able to degrade metaldehyde to a residual concentration < 1 nM, whereas closely related Acinetobacter strains were completely unable to degrade metaldehyde. Variovorax E3 grew and degraded metaldehyde more slowly than Acinetobacter E1, and residual metaldehyde remained at the end of growth of the Variovorax E3 strain. Biological degradation of metaldehyde using these bacterial strains or approaches that allow in situ amplification of metaldehyde-degrading bacteria may represent a way forward for dealing with metaldehyde contamination in soils and water., (© 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

A second species of protorhyssaline wasps (Braconidae) is described and figured from inclusions in Upper Cretaceous (Turonian) amber of the Raritan Formation in New Jersey, USA. Rhetinorhyssalites emersoni , gen. n., sp. n. , is distinguished from other protorhyssalines, particularly the contemporaneous Protorhyssalus goldmani .

Although respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and young children, attempts to develop an effective therapy have so far proved unsuccessful. Here we report the preclinical profiles of PC786, a potent nonnucleoside RSV L protein polymerase inhibitor, designed for inhalation treatment of RSV infection. PC786 demonstrated a potent and selective antiviral activity against laboratory-adapted or clinical isolates of RSV-A (50% inhibitory concentration [IC 50 ], <0.09 to 0.71 nM) and RSV-B (IC 50 , 1.3 to 50.6 nM), which were determined by inhibition of cytopathic effects in HEp-2 cells without causing detectable cytotoxicity. The underlying inhibition of virus replication was confirmed by PCR analysis. The effects of PC786 were largely unaffected by the multiplicity of infection (MOI) and were retained in the face of established RSV replication in a time-of-addition study. Persistent anti-RSV effects of PC786 were also demonstrated in human bronchial epithelial cells. In vivo intranasal once daily dosing with PC786 was able to reduce the virus load to undetectable levels in lung homogenates from RSV-infected mice and cotton rats. Treatment with escalating concentrations identified a dominant mutation in the L protein (Y1631H) in vitro In addition, PC786 potently inhibited RSV RNA-dependent RNA polymerase (RdRp) activity in a cell-free enzyme assay and minigenome assay in HEp-2 cells (IC 50 , 2.1 and 0.5 nM, respectively). Thus, PC786 was shown to be a potent anti-RSV agent via inhibition of RdRp activity, making topical treatment with this compound a novel potential therapy for the treatment of human RSV infections., (Copyright © 2017 Coates et al.)

In particle size measurement using dynamic light scattering (DLS), noise makes the estimation of the particle size distribution (PSD) from the autocorrelation function data unreliable, and a regularization technique is usually required to estimate a reasonable PSD. In this paper, we propose an Lp-norm-residual constrained regularization model for the estimation of the PSD from DLS data based on the Lp norm of the fitting residual. Our model is a generalization of the existing, commonly used L2-norm-residual-based regularization methods such as CONTIN and constrained Tikhonov regularization. The estimation of PSDs by the proposed model, using different Lp norms of the fitting residual for p=1, 2, 10, and ∞, is studied and their performance is determined using simulated and experimental data. Results show that our proposed model with p=1 is less sensitive to noise and improves stability and accuracy in the estimation of PSDs for unimodal and bimodal systems. The model with p=1 is particularly applicable to the noisy or bimodal PSD cases.

Proper management of turfgrass systems is critical for reducing the risk of nutrient loss and protecting urban surface waters. In the southern United States, irrigation can be the most significant management practice regulating the biogeochemical and hydrological cycles of turfgrass systems. A turfgrass runoff research facility was used to assess the effects of deficit irrigation and fertilizer applications on turfgrass canopy cover and nitrate-N (NO-N) exports in runoff from St. Augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze] turf over a 2-yr period. Treatments were arranged as a randomized complete block design having eight combinations of irrigation (100, 75, or 50% of estimated turfgrass water requirements) and fertility level (0, 88, and 176 kg N ha yr). Runoff from 31 rainfall events and one irrigation excess event were used to estimate annual and seasonal NO-N exports. The majority of annual NO-N exports occurred during the late winter and spring. Deficit irrigation reduced summer and early autumn runoff volumes. Lower summer and autumn runoff volumes (from deficit irrigation) coincided with reduced NO-N exports from runoff during Year 1. Deficit irrigation combined with fertilizer applications increased runoff [NO-N] in Year 2, suggesting that the previous year's export reduction contributed to higher N accumulation in the system and thus a higher N loss potential. These findings suggest that deficit irrigation can be a tool for reducing seasonal nutrient exports from St. Augustinegrass lawns so long as fertilizer inputs are moderate., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

Background: A country will trust, value, and use, its health information system (HIS) to the extent it has had a role in its creation and maintenance. A sense of ownership contributes in turn to the long-term sustainability of the HIS, and thus the country's ability to monitor and evaluate population health and health services. To facilitate progress toward greater ownership, we developed and tested a tool to measure the country's ownership of its monitoring and evaluation (M&E) system., Methods: Through a systematic review of the literature, we identified four dimensions of country ownership of an M&E system: partnership, commitment and responsibility, capacity, and accountability. We identified relevant indicators of the dimensions already in use in other tools used to assess M&E systems. We tested the data collection tool with 95 stakeholders of the Tanzanian HIS for HIV/AIDS control., Results: We identified 56 items that addressed elements of the four dimensions. The respondents found our tool for assessing country ownership of an HIS to be clear and relevant, leading to the identification of important issues to be discussed. For example, all stakeholder groups affirmed that the Tanzanian Commission for AIDS is "playing a leadership role in addressing HIV through collaborative partnerships and work across borders to achieve greater impact." While many respondents disagreed with the statement, "There is an adequate number of government monitoring and evaluation posts at the sub-national level.", Conclusions: Stakeholders found the M&E country ownership tool to address relevant questions clearly. It enabled them to identify successes and challenges within four dimensions of country ownership. It thus holds the potential to lead to an agenda for strengthening country ownership. If implemented every few years, the tool can provide a means of monitoring progress through a set of standardized indicators. As country ownership of M&E increases, so will the long-term sustainability of the HIS.

The development of novel non-nucleoside inhibitors of the RSV polymerase complex is of significant clinical interest. Compounds derived from the benzothienoazepine core, such as AZ-27, are potent inhibitors of RSV viruses of the A-subgroup, but are only moderately active against the B serotype and as yet have not demonstrated activity in vivo. Herein we report the discovery of several novel families of C-2 arylated benzothienoazepine derivatives that are highly potent RSV polymerase inhibitors and reveal an exemplary structure, compound 4a, which shows low nanomolar activity against both RSV A and B viral subtypes. Furthermore, this compound is effective at suppressing viral replication, when administered intranasally, in a rodent model of RSV infection. These results suggest that compounds belonging to this chemotypes have the potential to provide superior anti-RSV agents than those currently available for clinical use., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Whereas significant advances have been made in understanding how exposure to early adversity "gets under the skin" of children to result in long term changes in developmental outcomes, the processes by which positive social relationships become biologically embedded remain poorly understood. The aim of this study was to understand the pathways by which maternal and infant social environments become biologically embedded in infant cortisol reactivity. Two hundred seventy-two pregnant women and their infants were prospectively assessed during pregnancy and at 6 months postpartum. In serial mediation analyses, higher perceived social support from partners during pregnancy was associated with lower infant cortisol reactivity or larger decreases in cortisol in response to a stressor at 6 months of age via lower self-reported prenatal maternal depression and higher mother-infant interaction quality. The findings add to our understanding of how perinatal social relationships become biologically embedded in child development., (© 2017 Wiley Periodicals, Inc.)

Emotion regulation is essential to cognitive, social, and emotional development and difficulties with emotion regulation portend future socioemotional, academic, and behavioral difficulties. There is growing awareness that many developmental outcomes previously thought to begin their development in the postnatal period have their origins in the prenatal period. Thus, there is a need to integrate evidence of prenatal influences within established postnatal factors, such as infant temperament and maternal sensitivity. In the current study, prenatal depression, pregnancy anxiety, and diurnal cortisol patterns (i.e., the cortisol awakening response (CAR) and diurnal slope) were assessed in 254 relatively low-risk mother-infant pairs (primarily White, middle-class) in early (M = 15 weeks) and late pregnancy (M = 33 weeks). Mothers reported on infant temperamental negativity (Infant Behavior Questionnaire-Revised) at 3 months. At 6 months, maternal sensitivity (Parent Child Interaction Teaching Scale) and infant emotion regulation behavior (Laboratory Temperament Assessment Battery) were assessed. Greater pregnancy anxiety in early pregnancy and a blunted CAR in late pregnancy predicted higher infant temperamental negativity at 3 months, and those infants with higher temperamental negativity used fewer attentional regulation strategies and more avoidance (i.e., escape behavior) at 6 months. Furthermore, this indirect effect was moderated by maternal sensitivity whereby infants with elevated negativity demonstrated maladaptive emotion regulation at below average levels of maternal sensitivity. These findings suggest that the development of infant emotion regulation is influenced by the ways that prenatal exposures shape infant temperament and is further modified by postnatal caregiving. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Purpose: We previously reported catheterizable channel associated outcomes and concluded that the incidence of postoperative complications was greatest in the first 2 years after surgery. At that time our followup was short. In this series we sought to determine whether complications continued to accumulate with longer followup in an updated cohort of patients., Materials and Methods: We comprehensively reviewed the outcomes in 81 consecutive patients who underwent construction of a MACE (Malone antegrade continence enema) and/or a Mitrofanoff channel in association with complex genitourinary reconstruction. Mean followup was 80.1 months. Outcomes of these 119 stomas were classified by Clavien-Dindo grade and time to complication., Results: The 48 unique, channel related events (40.3%) necessitated a total of 70 interventions with a mean 24.2 months to the first event. Difficult catheterization was the most common event, occurring in 20.1% of channels an average of 29.9 months after surgery. Stomal stenosis was also common, developing in 12.6% of channels at an average of 19.9 months after surgery. Unique complications clustered in the first 2 years, after which there was a statistically significant decline (p = 0.0013). High grade complications similarly clustered (p <0.0001). Channel composition was significantly associated with rates of difficult catheterization events., Conclusions: Compared to our previous cohort of patients with similar volume but shorter followup, our assumption that channel associated complications cluster postoperatively and then decrease significantly was correct. Our current and more detailed series demonstrates that the rate of postoperative complications decreases with time. However, with longer followup patients continue to experience lower grade events requiring fewer interventions., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Urodynamic studies are crucial to neuropathic bladder management and they often determine surgical intervention. However, current evidence indicates that interpretations show poor agreement across physicians. We sought to determine the interrater reliability of urodynamic interpretation in our practice. We hypothesized that there would be strong correlation among pediatric urologists of similar training in a single academic practice., Materials and Methods: We retrospectively identified patients with neuropathic bladder who underwent urodynamics at our institution between 2014 and 2015. An anonymous electronic survey (phase I) was developed with 20 clinical scenarios, each containing a brief history, a single urodynamic tracing and an accompanying fluoroscopic image. Faculty members assessed each tracing by an online instrument developed using urodynamic reports and published literature. The primary outcome was statistical correlation across raters as measured by the Spearman correlation coefficient. In a followup study (phase II) we investigated the sources of variability in urodynamic interpretations., Results: Six faculty members completed the study with a response rate of 100%. In comparing urodynamic interpretation across raters, the faculty demonstrated a weak to strong correlation (r s 0.39-0.61, p <0.001). A strong correlation was found for fluoroscopic and clinical decision making variables, while electromyography synergy and detrusor overactivity demonstrated weaker correlation across physicians., Conclusions: Faculty interpretations of urodynamic tracings showed only moderate agreement despite a close working relationship and similar training at a single institution. Variability in interpretation can strongly impact patient treatment. Therefore, further work is needed to standardize the reporting and interpretation of urodynamic studies to optimize patient care., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)