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.

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.

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.

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.

Assessing Near-Infrared Spectroscopy (NIRS) for Evaluation of Aedes aegypti Population Age Structure.

Given that older Aedes aegypti (L.) mosquitoes typically pose the greatest risk of pathogen transmission, the capacity to age grade wild Ae. aegypti mosquito populations would be a valuable tool in monitoring the potential risk of arboviral transmission. Here, we compared the effectiveness of near-infrared spectroscopy (NIRS) to age grade field-collected Ae. aegypti with two alternative techniques-parity analysis and transcript abundance of the age-associated gene SCP1. Using lab-reared mosquitoes of known ages from three distinct populations maintained as adults under laboratory or semi-field conditions, we developed and validated four NIRS models for predicting the age of field-collected Ae. aegypti. To assess the accuracy of these models, female Ae. aegypti mosquitoes were collected from Maricopa County, AZ, during the 2017 and 2018 monsoon season, and a subset were age graded using the three different age-grading techniques. For both years, each of the four NIRS models consistently graded parous mosquitoes as significantly older than nulliparous mosquitoes. Furthermore, a significant positive linear association occurred between SCP1 and NIRS age predictions in seven of the eight year/model combinations, although considerable variation in the predicted age of individual mosquitoes was observed. Our results suggest that although the NIRS models were not adequate in determining the age of individual field-collected mosquitoes, they have the potential to quickly and cost effectively track changes in the age structure of Ae. aegypti populations across locations and over time.

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.

The Complex Epidemiological Relationship between Flooding Events and Human Outbreaks of Mosquito-Borne Diseases: A Scoping Review.

BACKGROUND: Climate change is expected to increase the frequency of flooding events. Although rainfall is highly correlated with mosquito-borne diseases (MBD) in humans, less research focuses on understanding the impact of flooding events on disease incidence. This lack of research presents a significant gap in climate change-driven disease forecasting. OBJECTIVES: We conducted a scoping review to assess the strength of evidence regarding the potential relationship between flooding and MBD and to determine knowledge gaps. METHODS: PubMed, Embase, and Web of Science were searched through 31 December 2020 and supplemented with review of citations in relevant publications. Studies on rainfall were included only if the operationalization allowed for distinction of unusually heavy rainfall events. Data were abstracted by disease (dengue, malaria, or other) and stratified by post-event timing of disease assessment. Studies that conducted statistical testing were summarized in detail. RESULTS: From 3,008 initial results, we included 131 relevant studies (dengue n=45, malaria n=61, other MBD n=49). Dengue studies indicated short-term (<1 month) decreases and subsequent (1-4 month) increases in incidence. Malaria studies indicated post-event incidence increases, but the results were mixed, and the temporal pattern was less clear. Statistical evidence was limited for other MBD, though findings suggest that human outbreaks of Murray Valley encephalitis, Ross River virus, Barmah Forest virus, Rift Valley fever, and Japanese encephalitis may follow flooding. DISCUSSION: Flooding is generally associated with increased incidence of MBD, potentially following a brief decrease in incidence for some diseases. Methodological inconsistencies significantly limit direct comparison and generalizability of study results. Regions with established MBD and weather surveillance should be leveraged to conduct multisite research to a) standardize the quantification of relevant flooding, b) study nonlinear relationships between rainfall and disease, c) report outcomes at multiple lag periods, and d) investigate interacting factors that modify the likelihood and severity of outbreaks across different settings. https://doi.org/10.1289/EHP8887.

Stress interventions and hypertension in Black women.

Hypertension is a risk factor for cardiovascular disease. Black women have high rates of hypertension compared to women of other racial or ethnic groups and are disproportionately affected by psychosocial stressors such as racial discrimination, gender discrimination, and caregiving stress. Evidence suggests that stress is associated with incident hypertension and hypertension risk. Stress management is associated with improvements improved blood pressure outcomes. The purpose of this review is to synthesize evidence on effects of stress management interventions on blood pressure in Black women. A comprehensive search of scientific databases was conducted. Inclusion criteria included studies that were: (1) primary research that tested an intervention; (2) in the English language; (3) included African-American women; (4) incorporated stress in the intervention; (5) included blood pressure as an outcome; and (6) were US based. Eighteen studies met inclusion criteria. Ten (56%) studies tested meditation-based interventions, two (11%) tested coping and affirmation interventions, and six (33%) tested lifestyle modification interventions that included stress management content. Thirteen of the studies were randomized controlled trials. Reductions in blood pressure were observed in all of the meditation-based interventions, although the magnitude and statistical significance varied. Comprehensive lifestyle interventions were also efficacious for reducing blood pressure, although the relative contribution of stress management versus behavior modification could not be evaluated. Coping and affirmation interventions did not affect blood pressure. Most of the reviewed studies included small numbers of Black women and did not stratify results by race and gender, so effects remain unclear. This review highlights the urgent need for studies specifically focusing on Black women. Given the extensive disparities in cardiovascular disease morbidity and mortality, whether stress management can lower blood pressure and improve primary and secondary cardiovascular disease prevention among Black women is an important question for future research.

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.

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.

Case-comparison study protocol for gauging effects of neighbourhood trends and sickness: examining the perceptions of transit-Induced gentrification in Prince George's County.

INTRODUCTION: Impoverished neighbourhoods and communities of colour often bear the brunt of unintended transit-oriented development (TOD) impacts. These impacts have been known to come in the form of transit-induced gentrification (TIG), a socioeconomic by-product of TOD defined as a phenomenon that occurs when the provision of transit service, particularly light rail transit (LRT), 'up-scales' nearby neighbourhood(s) and displaces existing residents. Consequently, TIG or even the perception of TIG can impact health outcomes (eg, anxiety) and social determinants of health (SDOH) (eg, crime). METHODS/ANALYSIS: In 2022, the purple line (PL), a 16.2 mile LRT line, is opening in Prince George's County, Maryland, a suburb of Washington, DC, comprised of over 80% African American and Hispanic residents. By taking advantage of this natural experiment, we are proposing the GENTS (Gauging Effects of Neighborhood Trends and Sickness: Examining the Perceptions of Transit-Induced Gentrification in Prince George's County) Study in order to evaluate perceived TIG and associated health outcome and SDOH changes, at two points in time, among Prince George's County adults in a prospective case-comparison design during the pre-PL LRT period. Descriptive analysis and latent growth curve modelling will be used to examine these changes over time. ETHICS AND DISSEMINATION: Ethics approval has been granted by the University of Maryland Institutional Review Board. The GENTS Study will identify temporal changes in perceived TIG, health outcomes and SDOH among case and comparison residents before the completion and operation of the PL LRT, an under researched period of TOD. The dissemination of GENTS Study findings will be able to address research questions and policy issues that are specifically tailored to PG County while also providing more effective procedural solutions for other regions undergoing TOD and TIG risks.

"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.

Development of "Advancing People of Color in Clinical Trials Now!": Web-Based Randomized Controlled Trial Protocol.

BACKGROUND: Participation in clinical trials among people of color remains low, compared with white subjects. This protocol describes the development of "Advancing People of Color in Clinical Trials Now!" (ACT Now!), a culturally tailored website designed to influence clinical trial decision making among people of color. OBJECTIVE: This cluster randomized study aims to test the efficacy of a culturally tailored website to increase literacy, self-efficacy, and willingness to enroll in clinical trials among people of color. METHODS: ACT Now! is a randomized trial including 2 groups: (1) intervention group (n=50) with access to the culturally tailored website and (2) control group (n=50) exposed to a standard clinical recruitment website. Clinical trial literacy and willingness to enroll in a clinical trial will be measured before and after exposure to the website corresponding to their assigned group (intervention or control). Surveys will be conducted at baseline and during the 1-month postintervention and 3-month follow-up. Website architecture and wireframing will be informed by the literature and experts in the field. Statistical analysis will be conducted using a two-tailed t test, with 80% power, at .05 alpha level, to increase clinical trial literacy, self-efficacy, and willingness to enroll in clinical trials 3 months post intervention. RESULTS: We will design a culturally tailored website that will provide leverage for community stakeholders to influence clinical trial literacy, self-efficacy, and willingness to enroll in clinical trials among racial and ethnic groups. ACT Now! applies a community-based participatory research approach through the use of a community steering committee (CSC). The CSC provides input during the research study conception, development, implementation, and enrollment. CSC relationships help foster trust among communities of color. ACT Now! has the potential to fill a gap in clinical trial enrollment among people of color through an accessible web-based website. This study was funded in July 2017 and obtained institutional review board approval in spring 2017. As of December 2019, we had enrolled 100 participants. Data analyses are expected to be completed by June 2020, and expected results are to be published in fall 2020. CONCLUSIONS: ACT Now! has the potential to fill an important gap in clinical trial enrollment among people of color through an accessible web-based website. TRIAL REGISTRATION: ClinicalTrials.gov NCT03243071; https://clinicaltrials.gov/ct2/show/NCT00102401. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17589.

Dbf4-Dependent Kinase (DDK)-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A in Saccharomyces cerevisiae.

The evolutionarily conserved centromeric histone H3 variant (Cse4 in budding yeast, CENP-A in humans) is essential for faithful chromosome segregation. Mislocalization of CENP-A to non-centromeric chromatin contributes to chromosomal instability (CIN) in yeast, fly, and human cells and CENP-A is highly expressed and mislocalized in cancers. Defining mechanisms that prevent mislocalization of CENP-A is an area of active investigation. Ubiquitin-mediated proteolysis of overexpressed Cse4 (GALCSE4) by E3 ubiquitin ligases such as Psh1 prevents mislocalization of Cse4, and psh1Δ strains display synthetic dosage lethality (SDL) with GALCSE4 We previously performed a genome-wide screen and identified five alleles of CDC7 and DBF4 that encode the Dbf4-dependent kinase (DDK) complex, which regulates DNA replication initiation, among the top twelve hits that displayed SDL with GALCSE4 We determined that cdc7-7 strains exhibit defects in ubiquitin-mediated proteolysis of Cse4 and show mislocalization of Cse4 Mutation of MCM5 (mcm5-bob1) bypasses the requirement of Cdc7 for replication initiation and rescues replication defects in a cdc7-7 strain. We determined that mcm5-bob1 does not rescue the SDL and defects in proteolysis of GALCSE4 in a cdc7-7 strain, suggesting a DNA replication-independent role for Cdc7 in Cse4 proteolysis. The SDL phenotype, defects in ubiquitin-mediated proteolysis, and the mislocalization pattern of Cse4 in a cdc7-7psh1Δ strain were similar to that of cdc7-7 and psh1Δ strains, suggesting that Cdc7 regulates Cse4 in a pathway that overlaps with Psh1 Our results define a DNA replication initiation-independent role of DDK as a regulator of Psh1-mediated proteolysis of Cse4 to prevent mislocalization of Cse4.

On the Limit to the Accuracy of Regional-Scale Air Quality Models.

Regional-scale air pollution models are routinely being used world-wide for research, forecasting air quality, and regulatory purposes. It is well recognized that there are both reducible (systematic) and irreducible (unsystematic) errors in the meteorology-atmospheric chemistry modeling systems. The inherent (random) uncertainty stems from our inability to properly characterize stochastic variations in atmospheric dynamics and chemistry, and from the incommensurability associated with comparisons of the volume-averaged model estimates with point measurements. Because these stochastic variations are not being explicitly simulated in the current generation of regional-scale meteorology-air quality models, one should expect to find differences between the model estimates and corresponding observations. This paper presents an observation-based methodology to determine the expected errors from current generation regional air quality models even when the model design, physics, chemistry, and numerical analysis, as well as its input data, were "perfect". To this end, the short-term synoptic-scale fluctuations embedded in the daily maximum 8-hr ozone time series are separated from the longer-term forcing using a simple recursive moving average filter. The inherent uncertainty attributable to the stochastic nature of the atmosphere is determined based on 30+ years of historical ozone time series data measured at various monitoring sites in the contiguous United States. The results reveal that the expected root mean square error at the median and 95th percentile is about 2 ppb and 5 ppb, respectively, even for "perfect" air quality models driven with "perfect" input data. Quantitative estimation of the limit to the model's accuracy will help in objectively assessing the current state-of-the-science in regional air pollution models, measuring progress in their evolution, and providing meaningful and firm targets for improvements in their accuracy relative to ambient measurements.

"He told me it would be extremely selfish of me to even consider [having kids]": The importance of reproductive health to women with spina bifida and the lack of support from their providers.

BACKGROUND: As more women with spina bifida (SB) enter their reproductive years, the number having children is significantly increasing. However, little is known about their understanding of their ability to get pregnant or their experiences in considering, planning, or interacting with providers during a pregnancy. OBJECTIVE: We sought to determine what women have been told and understand about their reproductive health, their attitudes towards having children, and their experiences interacting with providers when seeking reproductive health care. METHODS: In this exploratory study employing qualitative research methods and following Grounded Theory, interviews with women with SB 16 years or older were transcribed verbatim and analyzed by three coders. RESULTS: Interviews of 25 women with SB ages 16-52 (median 26) revealed the following themes about their reproductive health perceptions and experiences: 1) poor understanding of reproductive health and potential, 2) interest in having a family, 3) facing provider's opposition to their reproductive goals, 4) going into pregnancy and delivery unprepared, 5) the importance of provider support for reproductive goals. Five women experienced an unintended pregnancy. CONCLUSIONS: Although having children is important to most women with SB in this study, they report a poor understanding of their reproductive potential with several noting unintended pregnancies. They feel uninformed and unprepared during pregnancy and face discouragement from providers. Those experiencing supportive providers report a more positive experience. This demonstrates the urgent need to educate women with SB about their reproductive health and the providers who care for them how to support and counsel these women.

Legionella pneumophila as a Health Hazard to Miners: A Pilot Study of Water Quality and QMRA.

Legionella pneumophila (L. pneumophila), the causative agent of legionellosis, is an aquatic bacterium that grows in warm water. Humans are only presented with a health risk when aerosolized water containing L. pneumophila is inhaled. In mining operations, aerosolized water is used as dust control and as part of the drilling operations, a currently ignored exposure route. This study characterized L. pneumophila concentrations in the mine's non-potable water and the relationship between L. pneumophila and chlorine concentrations. These concentrations informed a quantitative microbial risk assessment (QMRA) model to estimate the infection risk to miners exposed to aerosolized water containing L. pneumophila. Fourteen water samples were collected from seven locations at a mine and analyzed for temperature, pH, chlorine, and L. pneumophila serogroup. Most samples (93%) tested positive for L. pneumophila cells. The faucet from the sprinkler system on the adit level (entrance to the underground mine levels) showed the highest concentration of L. pneumophila (8.35 × 104 MPN/L). Disability adjusted life years (DALYs) were estimated in the QMRA model and showed that the risk for all miners was significantly lower (p < 0.0001) with the ventilation system on than when the system was off. Our study showed that the use of a ventilation system at the adit level of the mine reduced the risk of infection with aerosolized L. pneumophila.

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.