Concerted cutting by Spo11 illuminates meiotic DNA break mechanics.

Genetic recombination arises during meiosis through the repair of DNA double-strand breaks (DSBs) that are created by Spo11, a topoisomerase-like protein1,2. Spo11 DSBs form preferentially in nucleosome-depleted regions termed hotspots3,4, yet how Spo11 engages with its DNA substrate to catalyse DNA cleavage is poorly understood. Although most recombination events are initiated by a single Spo11 cut, here we show in Saccharomyces cerevisiae that hyperlocalized, concerted Spo11 DSBs separated by 33 to more than 100 base pairs also form, which we term 'double cuts'. Notably, the lengths of double cuts vary with a periodicity of 10.5 base pairs, which is conserved in yeast and mice. This finding suggests a model in which the orientation of adjacent Spo11 molecules is fixed relative to the DNA helix-a proposal supported by the in vitro DNA-binding properties of the Spo11 core complex. Deep sequencing of meiotic progeny identifies recombination scars that are consistent with repair initiated from gaps generated by adjacent Spo11 DSBs. Collectively, these results revise our present understanding of the mechanics of Spo11-DSB formation and expand on the original concepts of gap repair during meiosis to include DNA gaps that are generated by Spo11 itself.

DNA Polymerase Delta Synthesizes Both Strands during Break-Induced Replication.

Break-induced replication (BIR) is a pathway of homology-directed repair that repairs one-ended DNA breaks, such as those formed at broken replication forks or uncapped telomeres. In contrast to conventional S phase DNA synthesis, BIR proceeds by a migrating D-loop and results in conservative synthesis of the nascent strands. DNA polymerase delta (Pol δ) initiates BIR; however, it is not known whether synthesis of the invading strand switches to a different polymerase or how the complementary strand is synthesized. By using alleles of the replicative DNA polymerases that are permissive for ribonucleotide incorporation, thus generating a signature of their action in the genome that can be identified by hydrolytic end sequencing, we show that Pol δ replicates both the invading and the complementary strand during BIR. In support of this conclusion, we show that depletion of Pol δ from cells reduces BIR, whereas depletion of Pol ε has no effect.

Reducing Vaccination Disparities During a National Emergency Response: The US Mpox Vaccine Equity Pilot Program.

CONTEXT: In response to the first reported mpox cases in May 2022, the US government implemented plans to bring testing, treatment, and vaccines to communities disproportionately affected by mpox-including the population of men who have sex with men (MSM) and Black/African American and Hispanic/Latino men, 2 subpopulations experiencing vaccination disparities. We describe the development and implementation of the US Mpox Vaccine Equity Pilot Program (MVEPP), characteristics of completed vaccination projects, and challenges that occurred. We also discuss opportunities for reducing vaccination disparities in future outbreaks. PROGRAM: To address reported vaccination disparities, the US government launched MVEPP in 2 phases. Phase 1 centered around public events attended by large numbers of gay, bisexual, and other MSM, such as Pride festivals. Phase 2 asked health departments to propose mpox vaccination projects specifically aimed at reducing or eliminating racial/ethnic and other demographic disparities in mpox vaccination. IMPLEMENTATION: MVEPP received 35 vaccination project proposals. We analyzed data from 22 completed projects that resulted in 25 675 doses of JYNNEOS administered. We note 3 innovative strategies that were implemented in several projects: direct collaboration with organizations providing services to MSM and transgender women; implementation of MVEPP projects in unique nonclinical community settings and at venues frequented by MSM and transgender women; and offering an array of services as part of mpox vaccination projects, rather than offering only mpox vaccination. EVALUATION: MVEPP highlighted the importance of recognizing and working to eliminate racial/ethnic and other disparities in access to medical countermeasures during a public health emergency. Jurisdictions developed and implemented innovative strategies to bring mpox vaccination and related services to communities disproportionately affected by mpox-including MSM and the subpopulations of Black/African American and Hispanic/Latino MSM. Lessons learned from MVEPP may inform efforts to reduce disparities during future public health responses.

Tel1(ATM)-mediated interference suppresses clustered meiotic double-strand-break formation.

Meiotic recombination is a critical step in gametogenesis for many organisms, enabling the creation of genetically diverse haploid gametes. In each meiotic cell, recombination is initiated by numerous DNA double-strand breaks (DSBs) created by Spo11, the evolutionarily conserved topoisomerase-like protein, but how these DSBs are distributed relatively uniformly across the four chromatids that make up each chromosome pair is poorly understood. Here we employ Saccharomyces cerevisiae to demonstrate distance-dependent DSB interference in cis (in which the occurrence of a DSB suppresses adjacent DSB formation)--a process that is mediated by the conserved DNA damage response kinase, Tel1(ATM). The inhibitory function of Tel1 acts on a relatively local scale, while over large distances DSBs have a tendency to form independently of one another even in the presence of Tel1. Notably, over very short distances, loss of Tel1 activity causes DSBs to cluster within discrete zones of concerted DSB activity. Our observations support a hierarchical view of recombination initiation where Tel1(ATM) prevents clusters of DSBs, and further suppresses DSBs within the surrounding chromosomal region. Such collective negative regulation will help to ensure that recombination events are dispersed evenly and arranged optimally for genetic exchange and efficient chromosome segregation.

Phosphorylation-dependent assembly and coordination of the DNA damage checkpoint apparatus by Rad4(TopBP1).

The BRCT-domain protein Rad4(TopBP1) facilitates activation of the DNA damage checkpoint in Schizosaccharomyces pombe by physically coupling the Rad9-Rad1-Hus1 clamp, the Rad3(ATR) -Rad26(ATRIP) kinase complex, and the Crb2(53BP1) mediator. We have now determined crystal structures of the BRCT repeats of Rad4(TopBP1), revealing a distinctive domain architecture, and characterized their phosphorylation-dependent interactions with Rad9 and Crb2(53BP1). We identify a cluster of phosphorylation sites in the N-terminal region of Crb2(53BP1) that mediate interaction with Rad4(TopBP1) and reveal a hierarchical phosphorylation mechanism in which phosphorylation of Crb2(53BP1) residues Thr215 and Thr235 promotes phosphorylation of the noncanonical Thr187 site by scaffolding cyclin-dependent kinase (CDK) recruitment. Finally, we show that the simultaneous interaction of a single Rad4(TopBP1) molecule with both Thr187 phosphorylation sites in a Crb2(53BP1) dimer is essential for establishing the DNA damage checkpoint.

CDK and Mec1/Tel1-catalyzed phosphorylation of Sae2 regulate different responses to DNA damage.

Sae2 functions in the DNA damage response by controlling Mre11-Rad50-Xrs2 (MRX)-catalyzed end resection, an essential step for homology-dependent repair of double-strand breaks (DSBs), and by attenuating DNA damage checkpoint signaling. Phosphorylation of Sae2 by cyclin-dependent kinase (CDK1/Cdc28) activates the Mre11 endonuclease, while the physiological role of Sae2 phosphorylation by Mec1 and Tel1 checkpoint kinases is not fully understood. Here, we compare the phenotype of sae2 mutants lacking the main CDK (sae2-S267A) or Mec1 and Tel1 phosphorylation sites (sae2-5A) with sae2Δ and Mre11 nuclease defective (mre11-nd) mutants. The phosphorylation-site mutations confer DNA damage sensitivity, but not to the same extent as sae2Δ. The sae2-S267A mutation is epistatic to mre11-nd for camptothecin (CPT) sensitivity and synergizes with sgs1Δ, whereas sae2-5A synergizes with mre11-nd and exhibits epistasis with sgs1Δ. We find that attenuation of checkpoint signaling by Sae2 is mostly independent of Mre11 endonuclease activation but requires Mec1 and Tel1-dependent phosphorylation of Sae2. These results support a model whereby CDK-catalyzed phosphorylation of Sae2 activates resection via Mre11 endonuclease, whereas Sae2 phosphorylation by Mec1 and Tel1 promotes resection by the Dna2-Sgs1 and Exo1 pathways indirectly by dampening the DNA damage response.

Linking multi-media modeling with machine learning to assess and predict lake Chlorophyll a concentrations.

Eutrophication and excessive algal growth pose a threat on aquatic organisms and the health of the public, environment, and the economy. Understanding what drives excessive algal growth can inform mitigation measures and aid in advance planning to minimize impacts. We demonstrate how simulated data from weather, hydrological, and agroecosystem numerical prediction models can be combined with machine learning (ML) to assess and predict Chlorophyll a (Chl a) concentrations, a proxy for lake eutrophication and algal biomass. The study area is Lake Erie for a 16-year period, 2002-2017. A total of 20 environmental variables from linked and coupled physical models are used as input features to train the ML model with Chl a observations from 16 measuring stations. Included are meteorological variables from the Weather Research and Forecasting (WRF) model, hydrological variables from the Variable Infiltration Capacity (VIC) model, and agricultural management practice variables from the Environmental Policy Integrated Climate (EPIC) agroecosystem model. The consolidation of these variables is conducive to a successful prediction of Chl a. Aside from the synergistic effects that weather, hydrology, and fertilizers have on eutrophication and excessive algal growth, we found that the application of different forms of both P and N fertilizers are highly ranked for the prediction of Chl a concentration. The developed ML model successfully predicts Chl a with a coefficient of determination of 0.81, bias of -0.12 µg/l and RMSE of 4.97 µg/l. The developed ML-based modeling approach can be used for impact assessment of agriculture practices in a changing climate that affect Chl a concentrations in Lake Erie.

"I Tell Them What I Can Feel and How Far My Legs Can Bend": Optimizing Sexual Satisfaction for Women With Spina Bifida.

BACKGROUND: There is a high reported rate of sexual dysfunction among women with spina bifida, but little is known about the etiology of this or how sexual satisfaction could be improved. AIM: To identify, through the words of women with spina bifida, perceived causes of diminished sexual satisfaction and recommendations to optimize partnered sexual encounters. METHODS: In this qualitative study, we conducted semi-structured individual interviews with 22 women with spina bifida (median age 26.5 years, range 16-52 years) who have had a romantic partner. Using Grounded Theory, interviews were independently coded by 3 reviewers. Disagreements were resolved by consensus. OUTCOMES: We identified overlapping themes of issues women experienced during sexual intimacy and strategies they learned to improve sexual encounters. RESULTS: 7 salient themes emerged from the data: (i) fear of rejection with resulting difficulty setting boundaries and the risk of coercion; (ii) conflict between spontaneity and self-care in sexual encounters; (iii) worry about incontinence during sex; (iv) trial and error in learning optimal sexual positions; (v) decreased genital sensation; (vi) safety considerations; and (vii) sharing advice with other women with spina bifida. CLINICAL IMPLICATIONS: As sexual satisfaction is influenced by physical features as well as psychological, interpersonal, and sociocultural factors, optimizing sexual satisfaction of women with spina bifida is best managed with a holistic approach utilizing a biopsychosocial model. STRENGTHS & LIMITATIONS: The sample included women with a diverse range of functional impairments. Women were forthright with their comments and thematic saturation was reached. Recruitment was primarily from a single Midwestern institution, which may have limited sampled perspectives. CONCLUSION: While women with spina bifida encounter challenges during sexual encounters, strategies focused on improving communication with partners and addressing specific physical considerations can potentially enhance their sexual experiences. Streur CS, Schafer CL, Garcia VP, et al. "I Tell Them What I Can Feel and How Far My Legs Can Bend": Optimizing Sexual Satisfaction for Women With Spina Bifida. J Sex Med 2020;17;1694-1704.

"If Everyone Else Is Having This Talk With Their Doctor, Why Am I Not Having This Talk With Mine?": The Experiences of Sexuality and Sexual Health Education of Young Women With Spina Bifida.

INTRODUCTION: Women with spina bifida are sexually active, but most never discuss this topic with providers. AIM: To determine what women with spina bifida understand about their sexual health, how they learned about it, what questions they have, and their experiences with their sexuality. METHODS: For this qualitative study, women with spina bifida ages 16 and older without marked developmental delay were individually interviewed. 25 women with spina bifida participated (mean age 27.1 years, range 16-52). Interviews were independently coded for themes by 3 reviewers, using Grounded Theory, with disagreements resolved by consensus. MAIN OUTCOME MEASURES: We identified overlapping themes regarding the women's perception and experience of their sexuality and sexual health education. RESULTS: 17 of the 25 (68%) participants had been or were currently sexually active. 5 themes emerged regarding their understanding of their sexuality and their sexual experiences: (i) being perceived as asexual, (ii) sources for sex education, (iii) need for spina bifida-specific sex education, (iv) impact of spina bifida-specific features on sexual encounters, and (v) perceived relationship between low sexual self-confidence and risk for sexual assault. CLINICAL IMPLICATIONS: Women with spina bifida are sexual beings, but they are perceived as asexual by providers, which prevents them from getting adequate sexual health education and leaves them with misconceptions and unanswered questions, as well as vulnerable to sexual abuse. STRENGTH & LIMITATIONS: The strengths of this study include the diversity of women interviewed, including their age, severity of disability, and experiences with their sexuality, as well as the ability to reach thematic saturation. The limitation of this study is that most women received treatment at a single Midwestern tertiary referral center in the United States. CONCLUSION: Including sexual health discussions in the usual care of women with spina bifida is critical to enhancing their sexual confidence and experience and preventing sexual abuse. Streur CS, Schafer CL, Garcia VP, et al. "If Everyone Else Is Having This Talk With Their Doctor, Why Am I Not Having This Talk With Mine?": The Experiences of Sexuality and Sexual Health Education of Young Women With Spina Bifida. J Sex Med 2019;16:853-859.

"I Don't Know What I'm Doing I Hope I'm Not Just an Idiot": The Need to Train Pediatric Urologists to Discuss Sexual and Reproductive Health Care With Young Women With Spina Bifida.

INTRODUCTION: Although pediatric urologists have taken responsibility for initiating discussions on sexual and reproductive health with spina bifida patients, research shows that very few girls and women with spina bifida have ever discussed this topic with any physician. AIM: We sought to better understand pediatric urologists' gaps in knowledge and training needs in the sexual and reproductive health education of women with spina bifida with the goal of creating a tool kit to equip providers to have these discussions. METHODS: In this qualitative study, pediatric urologists were interviewed separately about their current practices, perceived barriers, knowledge gaps, and recommendations for the tool kit until thematic saturation was reached. The interviews were recorded and transcribed verbatim, then analyzed using grounded theory by 3 independent reviewers. MAIN OUTCOME MEASURES: To evaluate the perspectives and practices of pediatric urologists, we identified the overlapping themes of the interviews. Consensus on themes was reached. RESULTS: 10 Pediatric urologists participated in the study, including 5 men and 5 women, of whom 4 were fellows and 6 were attending physicians (mean years of practice 18, range 6-31 years). The mean number of patients followed up in the respective spina bifida clinics or by the provider was 434 (range 24-1,500). The following themes regarding pediatric urologists' experience providing sexual and reproductive health education to women with spina bifida emerged. Pediatric urologists': (i) lack of formal training; (ii) knowledge gaps such as spina bifida sexuality, fertility, and pregnancy experience; (iii) barriers to having sexual and reproductive health conversations such as lack of comfort and lack of time; (iv) facilitators of these conversations such as a long-term relationship with the patient and the patient's own initiative; (v) desire to learn and provide competent care; and (vi) recommendations for a web-based tool kit that would include content to address the knowledge gaps and training about how to start sexual and reproductive health conversations. CLINICAL IMPLICATIONS: These findings can provide the beginning concepts for the development of training on providing sexual and reproductive health education for pediatric urologists' care for women with spina bifida. STRENGTHS & LIMITATIONS: This study gives the perspectives of 10 pediatric urologists with a diversity of backgrounds, but all of whom care for a large number of spina bifida patients. This does not give the perspectives of the spina bifida women themselves, which will be evaluated in the next phase of the study. CONCLUSION: Pediatric urologists are not trained and do not feel prepared to provide sexual and reproductive health education for girls and women with spina bifida. However, they do see it as their scope of practice and wish to acquire competence in this area. Streur CS, Schafer CL, Garcia VP, et al. "I Don't Know What I'm Doing… I Hope I'm Not Just an Idiot": The Need to Train Pediatric Urologists to Discuss Sexual and Reproductive Health Care With Young Women With Spina Bifida. J Sex Med 2018;15:1403-1413.

Necrotizing Infundibular Crystalline Folliculitis: An Unusual Clinical Presentation and Demonstration of the Presence of Calcium Palmitate.

Necrotizing infundibular crystalline folliculitis (NICF) is a rare disorder, which was described for the first time by Lucke et al in 1999. NICF is characterized by multiple folliculocentric papules with a predilection for occurring in seborrheic areas in adults and corresponding dilated follicular ostia containing crystalline material. The precise pathogenesis and nature of this crystalline material are currently unknown. Here, we report an unusual case of NICF presented as an uncommon generalized skin rash in an adolescent. In addition, we present analysis using infrared microscopy for improved characterization of this crystalline material. Similar to previous cases, a biopsy revealed a dilated follicular ostium with the appearance of containing crystalline material associated with parakeratosis. Infrared microscopy analysis produced specific spectral features of calcium palmitate.

Bidirectional resection of DNA double-strand breaks by Mre11 and Exo1.

Repair of DNA double-strand breaks (DSBs) by homologous recombination requires resection of 5'-termini to generate 3'-single-strand DNA tails. Key components of this reaction are exonuclease 1 and the bifunctional endo/exonuclease, Mre11 (refs 2-4). Mre11 endonuclease activity is critical when DSB termini are blocked by bound protein--such as by the DNA end-joining complex, topoisomerases or the meiotic transesterase Spo11 (refs 7-13)--but a specific function for the Mre11 3'-5' exonuclease activity has remained elusive. Here we use Saccharomyces cerevisiae to reveal a role for the Mre11 exonuclease during the resection of Spo11-linked 5'-DNA termini in vivo. We show that the residual resection observed in Exo1-mutant cells is dependent on Mre11, and that both exonuclease activities are required for efficient DSB repair. Previous work has indicated that resection traverses unidirectionally. Using a combination of physical assays for 5'-end processing, our results indicate an alternative mechanism involving bidirectional resection. First, Mre11 nicks the strand to be resected up to 300 nucleotides from the 5'-terminus of the DSB--much further away than previously assumed. Second, this nick enables resection in a bidirectional manner, using Exo1 in the 5'-3' direction away from the DSB, and Mre11 in the 3'-5' direction towards the DSB end. Mre11 exonuclease activity also confers resistance to DNA damage in cycling cells, suggesting that Mre11-catalysed resection may be a general feature of various DNA repair pathways.

Homeostatic regulation of meiotic DSB formation by ATM/ATR.

Ataxia-telangiectasia mutated (ATM) and RAD3-related (ATR) are widely known as being central players in the mitotic DNA damage response (DDR), mounting responses to DNA double-strand breaks (DSBs) and single-stranded DNA (ssDNA) respectively. The DDR signalling cascade couples cell cycle control to damage-sensing and repair processes in order to prevent untimely cell cycle progression while damage still persists [1]. Both ATM/ATR are, however, also emerging as essential factors in the process of meiosis; a specialised cell cycle programme responsible for the formation of haploid gametes via two sequential nuclear divisions. Central to achieving accurate meiotic chromosome segregation is the introduction of numerous DSBs spread across the genome by the evolutionarily conserved enzyme, Spo11. This review seeks to explore and address how cells utilise ATM/ATR pathways to regulate Spo11-DSB formation, establish DSB homeostasis and ensure meiosis is completed unperturbed.

The Rad4(TopBP1) ATR-activation domain functions in G1/S phase in a chromatin-dependent manner.

DNA damage checkpoint activation can be subdivided in two steps: initial activation and signal amplification. The events distinguishing these two phases and their genetic determinants remain obscure. TopBP1, a mediator protein containing multiple BRCT domains, binds to and activates the ATR/ATRIP complex through its ATR-Activation Domain (AAD). We show that Schizosaccharomyces pombe Rad4(TopBP1) AAD-defective strains are DNA damage sensitive during G1/S-phase, but not during G2. Using lacO-LacI tethering, we developed a DNA damage-independent assay for checkpoint activation that is Rad4(TopBP1) AAD-dependent. In this assay, checkpoint activation requires histone H2A phosphorylation, the interaction between TopBP1 and the 9-1-1 complex, and is mediated by the phospho-binding activity of Crb2(53BP1). Consistent with a model where Rad4(TopBP1) AAD-dependent checkpoint activation is ssDNA/RPA-independent and functions to amplify otherwise weak checkpoint signals, we demonstrate that the Rad4(TopBP1) AAD is important for Chk1 phosphorylation when resection is limited in G2 by ablation of the resecting nuclease, Exo1. We also show that the Rad4(TopBP1) AAD acts additively with a Rad9 AAD in G1/S phase but not G2. We propose that AAD-dependent Rad3(ATR) checkpoint amplification is particularly important when DNA resection is limiting. In S. pombe, this manifests in G1/S phase and relies on protein-chromatin interactions.

Respiratory hospitalizations in association with fine PM and its components in New York State.

UNLABELLED: Despite observed geographic and temporal variation in particulate matter (PM)-related health morbidities, only a small number of epidemiologic studies have evaluated the relation between PM2.5 chemical constituents and respiratory disease. Most assessments are limited by inadequate spatial and temporal resolution of ambient PM measurements and/or by their approaches to examine the role of specific PM components on health outcomes. In a case-crossover analysis using daily average ambient PM2.5 total mass and species estimates derived from the Community Multiscale Air Quality (CMAQ) model and available observations, we examined the association between the chemical components of PM (including elemental and organic carbon, sulfate, nitrate, ammonium, and other remaining) and respiratory hospitalizations in New York State. We evaluated relationships between levels (low, medium, high) of PM constituent mass fractions, and assessed modification of the PM2.5-hospitalization association via models stratified by mass fractions of both primary and secondary PM components. In our results, average daily PM2.5 concentrations in New York State were generally lower than the 24-hr average National Ambient Air Quality Standard (NAAQS). Year-round analyses showed statistically significant positive associations between respiratory hospitalizations and PM2.5 total mass, sulfate, nitrate, and ammonium concentrations at multiple exposure lags (0.5-2.0% per interquartile range [IQR] increase). Primarily in the summer months, the greatest associations with respiratory hospitalizations were observed per IQR increase in the secondary species sulfate and ammonium concentrations at lags of 1-4 days (1.0-2.0%). Although there were subtle differences in associations observed between mass fraction tertiles, there was no strong evidence to support modification of the PM2.5-respiratory disease association by a particular constituent. We conclude that ambient concentrations of PM2.5 and secondary aerosols including sulfate, ammonium, and nitrate were positively associated with respiratory hospitalizations, although patterns varied by season. Exposure to specific fine PM constituents is a plausible risk factor for respiratory hospitalization in New York State. IMPLICATIONS: The association between ambient concentrations of PM2.5 components has been evaluated in only a small number of epidemiologic studies with refined spatial and temporal scale data. In New York State, fine PM and several of its constituents, including sulfate, ammonium, and nitrate, were positively associated with respiratory hospitalizations. Results suggest that PM species relationships and their influence on respiratory endpoints are complex and season dependent. Additional work is needed to better understand the relative toxicity of PM species, and to further explore the role of co-pollutant relationships and exposure prediction error on observed PM-respiratory disease associations.

Preferences and Demand for Mosquito Control among Dengue-Endemic Communities in Peñuelas, Puerto Rico: An Application of the Best-Worst Choice Model.

Aedes aegypti is the primary vector of dengue virus and threatens 3.9 billion people living in many tropical and subtropical countries. Prevention and reduction of dengue and other Aedes-borne viruses, including Zika and chikungunya, requires control of mosquito populations. Community mobilization and input are essential components of vector control efforts. Many vector control campaigns do not engage communities prior to implementation, leading to program failure. Those that do often conduct basic knowledge, attitude, and practice surveys that are not designed to explicitly elicit preferences. Here, we applied a novel stated preference elicitation tool, best-worst choice, to understand preferences, willingness to participate, and willingness to pay for mosquito control in dengue-endemic communities of Peñuelas, Puerto Rico. Findings revealed that the community preferred mosquito control programs that are 1) applied at the neighborhood level, 2) implemented by the local government, and 3) focused specifically on reducing disease transmission (e.g., dengue) instead of mosquito nuisance. Programs targeting the reduction of disease transmission and higher educational level of participants increased willingness to participate. Participants were willing to pay an average of $72 annually to have a program targeting the reduction of diseases such as dengue. This study serves as a model to engage communities in the design of mosquito control programs and improve stakeholders' decision-making.

A New Approach to Predict Tributary Phosphorus Loads Using Machine Learning- and Physics-Based Modeling Systems.

Tributary phosphorus (P) loads are one of the main drivers of eutrophication problems in freshwater lakes. Being able to predict P loads can aid in understanding subsequent load patterns and elucidate potential degraded water quality conditions in downstream surface waters. We demonstrate the development and performance of an integrated multimedia modeling system that uses machine learning (ML) to assess and predict monthly total P (TP) and dissolved reactive P (DRP) loads. Meteorological variables from the Weather Research and Forecasting (WRF) Model, hydrologic variables from the Variable Infiltration Capacity model, and agricultural management practice variables from the Environmental Policy Integrated Climate agroecosystem model are utilized to train the ML models to predict P loads. Our study presents a new modeling methodology using as testbeds the Maumee, Sandusky, Portage, and Raisin watersheds, which discharge into Lake Erie and contribute to significant P loads to the lake. Two models were built, one for TP loads using 10 environmental variables and one for DRP loads using nine environmental variables. Both models ranked streamflow as the most important predictive variable. In comparison with observations, TP and DRP loads were predicted very well temporally and spatially. Modeling results of TP loads are within the ranges of those obtained from other studies and on some occasions more accurate. Modeling results of DRP loads exceed performance measures from other studies. We explore the ability of both ML-based models to further improve as more data become available over time. This integrated multimedia approach is recommended for studying other freshwater systems and water quality variables using available decadal data from physics-based model simulations.

Self-Reported Symptoms at Last Febrile Illness as a Predictor of Treatment-Seeking in Western Kenya: A Cross-Sectional Study.

Timely treatment-seeking behavior can reduce morbidity and mortality due to infectious diseases. Patterns of treatment-seeking behavior can differ by access to health care, and perceptions of disease severity and symptoms. We evaluated the association between self-reported symptoms at last illness and the level of treatment-seeking behaviors. We analyzed cross-sectional data from 1,037 participants from the lowlands and highlands of Western Kenya from 2015 using logistic regression models. There was considerable heterogeneity in the symptoms and treatment-seeking behaviors reported among individuals who were febrile at their last illness. A greater number of self-reported categories of symptoms tended to be associated with a higher likelihood of treatment-seeking in both sites. Participants were significantly more likely to seek treatment if they reported fever, aches, and digestive symptoms at last illness than just fever and aches or fever alone, but the frequency of treatment-seeking for fever in combination with aches and respiratory symptoms did not follow a consistent pattern. Among those who sought treatment, most used a formal source, but the patterns were inconsistent across sites and by the number of symptoms categories. Understanding the drivers of treatment-seeking behavior after febrile illness is important to control and treat infectious diseases in Kenya.

Construction and validation of a scale of sexual self-concept for the elderly Chilean population.

BACKGROUND: Sexual self-concept has a central role in the life of the elderly population. Indeed, their sexual self-concept has significant and positive relationships with their satisfaction with life, pleasure, and willingness to interact with others. However, social-cultural prejudice means that the elderly are considered asexual individuals, harming their sexual self-concept. This prejudice is prominent in Chile, where the elderly do not have access to clear information about their sexuality. However, research on the Chilean elderly population is still in its infancy and requires more attention. Hence, this research aims to construct and validate a scale of sexual self-concept for the elderly Chilean population to cover this identified gap in the literature. METHODS: Sixty items were integrated into the first version of the scale. Ten external judges were asked to assess the content validity. Twenty-eight items were maintained. Subsequently, an instrumental and cross-sectional design was implemented with a non-probabilistic sampling (N = 188). Items were refined with corrected homogeneity indices and conditional estimates of Cronbach's alpha and Omega coefficient. RESULTS: A final scale of nine items equally distributed in three dimensions was obtained: Sexual self-efficacy (ω = 0.867), Sexual assertiveness (ω = 0.764), and Sexual self-esteem (ω = 0.803). The confirmatory factor analysis reflects that the theoretical model has an adequate fit (CFI = .989; TLI = .984; RMSEA = .086). CONCLUSIONS: The data analyses confirmed that the scale has adequate psychometric properties. This scale can be used for multidimensional measurements of sexual self-concept in the elderly in Chile. Further research can confirm its psychometric properties in different settings within the Spanish language population.

Greening Up For Mosquitoes: A Comparison of Green Stormwater Infrastructure in a Semiarid Region.

Green stormwater infrastructure provides environmental, economic, and health benefits as a strategy for building resilience against climate change impacts. However, it may inadvertently increase vulnerability due to improper design and construction or lack of maintenance. We engaged city stakeholders and a diverse student group to investigate possible maladaptation. After rain events, student interns collected data at green stormwater infrastructure, identified in partnership with city stakeholders, for both water retention and mosquito larvae, if present. During the sampling period in 2018, 24 rain events occurred, with 28 sites visited 212 times including visits to basins (63%), curb cuts (34%), and a bioswale (2%). The largest basin consistently retained water (mean: 3.3 days, SD: 2.3 days) and was a positive site for Culex quinquefasciatus, a West Nile virus vector. We found that while basins can become mosquito breeding habitat, there was no evidence that curb cuts were collecting and retaining water long enough. As cities turn to green stormwater infrastructure to address climate change impacts of increasing drought, flooding, and extreme heat, these findings can help in the selection of appropriate infrastructure design typologies.