Background Standing genetic variation is important especially in immune response-related genes because of threats to wild populations like the emergence of novel pathogens. Genetic variation at the major histocompatibility complex (MHC), which is crucial in activating the adaptive immune response, is influenced by both natural selection and historical population demography, and their relative roles can be difficult to disentangle. To provide insight into the influences of natural selection and demography on MHC evolution in large populations, we analyzed geographic patterns of variation at the MHC class II DRB exon 2 locus in mule deer ( Odocoileus hemionus ) using sequence data collected across their entire broad range. Results We identified 31 new MHC-DRB alleles which were phylogenetically similar to other cervid MHC alleles, and one allele that was shared with white-tailed deer ( Odocoileus virginianus ). We found evidence for selection on the MHC including high dN/dS ratios, positive neutrality tests, deviations from Hardy–Weinberg Equilibrium (HWE) and a stronger pattern of isolation-by-distance (IBD) than expected under neutrality. Historical demography also shaped variation at the MHC, as indicated by similar spatial patterns of variation between MHC and microsatellite loci and a lack of association between genetic variation at either locus type and environmental variables. Conclusions Our results show that both natural selection and historical demography are important drivers in the evolution of the MHC in mule deer and work together to shape functional variation and the evolution of the adaptive immune response in large, well-connected populations.
Imbalances in mitochondrial and peroxisomal dynamics are associated with a spectrum of human neurological disorders. Mitochondrial and peroxisomal fission both involve dynamin-related protein 1 (DRP1) oligomerisation and membrane constriction, although the precise biophysical mechanisms by which distinct DRP1 variants affect the assembly and activity of different DRP1 domains remains largely unexplored. We analysed four unreported de novo heterozygous variants in the dynamin-1-like gene DNM1L , affecting different highly conserved DRP1 domains, leading to developmental delay, seizures, hypotonia, and/or rare cardiac complications in infancy. Single-nucleotide DRP1 stalk domain variants were found to correlate with more severe clinical phenotypes, with in vitro recombinant human DRP1 mutants demonstrating greater impairments in protein oligomerisation, DRP1-peroxisomal recruitment, and both mitochondrial and peroxisomal hyperfusion compared to GTPase or GTPase-effector domain variants. Importantly, we identified a novel mechanism of pathogenesis, where a p.Arg710Gly variant uncouples DRP1 assembly from assembly-stimulated GTP hydrolysis, providing mechanistic insight into how assembly-state information is transmitted to the GTPase domain. Together, these data reveal that discrete, pathological DNM1L variants impair mitochondrial network maintenance by divergent mechanisms.
Introduction Disparities in surgical management have been documented across a range of disease processes. The objective of this study was to investigate sociodemographic disparities in young females undergoing excision of a breast mass. Methods A retrospective study of females aged 10-21 y who underwent surgery for a breast lesion across eleven pediatric hospitals from 2011 to 2016 was performed. Differences in patient characteristics, workup, management, and pathology by race/ethnicity, insurance status, median neighborhood income, and urbanicity were evaluated with bivariate and multivariable regression analyses. Results A total of 454 females were included, with a median age of 16 y interquartile range (IQR: 3). 44% of patients were nonHispanic (NH) Black, 40% were NH White, and 7% were Hispanic. 50% of patients had private insurance, 39% had public insurance, and 9% had other/unknown insurance status. Median neighborhood income was $49,974, and 88% of patients resided in a metropolitan area. NH Whites have 4.5 times the odds of undergoing preoperative fine needle aspiration or core needle biopsy compared to NH Blacks (CI: 2.0, 10.0). No differences in time to surgery from the initial imaging study, size of the lesion, or pathology were observed on multivariable analysis. Conclusions We found no significant differences by race/ethnicity, insurance status, household income, or urbanicity in the time to surgery after the initial imaging study. The only significant disparity noted on multivariable analysis was NH White patients were more likely to undergo preoperative biopsy than were NH Black patients; however, the utility of biopsy in pediatric breast masses is not well established.
Motivated by applications in natural resource management, risk management, and finance, this paper is focused on an ergodic two-sided singular control problem for a general one-dimensional diffusion process. The control is given by a bounded variation process. Under some mild conditions, the optimal reward value as well as an optimal control policy are derived by the vanishing discount method. Moreover, the Abelian and Cesàro limits are established. Then a direct solution approach is provided at the end of the paper.
Aggregation of flexible loads and power generation of solar photo-voltaic (PV) systems is considered as a valuable power resource in residential demand response (DR). Despite the rapid growth of smart appliances, there are few practical solutions for exploiting their potentials in DR load aggregation. In this paper, we present a practical multi-prosumer framework to enable the aggregator reach a minimum bidding power and participate in the wholesale market. This is attainable through directly rescheduling a large number of smart appliances and utilizing the surplus power generation of residential PVs. An optimization model is designed which maximizes the aggregator’s profit while respecting customers convenience. Fairness is a significant component of this model ensuring fair selection of appliances for shifting by the aggregator and not biased toward customers availability. We investigate the model as a hard instance of the 0–1 Knapsack problem and devise a heuristic algorithm to cope with its time complexity and to improve its scalability. The simulation results of two large-scale case studies are presented and discussed. It is demonstrated that the proposed framework is beneficial to both the aggregator and its customers, leading to a greener environment.
Inverted pavement is considered an unconventional type of flexible pavement structure. In this pavement structure, an unbound aggregate base (UAB) with a low initial modulus is sandwiched (layered) between two stiffer layers, a thinner asphalt concrete layer (AC) and a cement-treated base layer (CTB). This paper presents a comparison study of the rutting performance (permanent deformation) between conventional and inverted pavement structures. In addition, the inverted pavements with different thicknesses of UAB and CTB were studied. The accelerated pavement test (APT) method was conducted on a full-scale pavement consisting of two inverted pavement lanes and one typical three-layer conventional flexible pavement lane as the control section for performance comparison. Significant permanent deformation was observed in all three pavement lanes after the completion of 100,000 passes of APT. Comparisons of the measured total deformations showed that the inverted pavement structure outperformed the conventional pavement. Furthermore, the inverted pavement with a thicker CTB layer exhibited less deformation compared with the inverted pavement with a thicker UAB layer. The stiffness of the UAB layer of the inverted pavement increased with the loading passes. A stiffer UAB could provide a cushion for the thin AC layer, resulting in less deformation in the AC surface compared with that of the conventional pavement. Furthermore, the loading on the pavement surface had a larger affected area in the inverted pavement structure. Based on the overall pavement conditions, the inverted pavement can be regarded as a promising alternative to the conventional flexible pavement, and the asphalt mixture layer thickness can be reduced during the construction.
Objectives This study evaluated the psychometric properties of the Mandarin version of the HeartQoL questionnaire, a core ischemic heart disease (IHD) health-related quality of life (HRQL) instrument, in patients with angina, myocardial infarction (MI), and ischemic heart failure (IHF). Methods The English version of HeartQoL was translated into Mandarin. A cross-sectional study was then conducted in mainland China using the Mandarin HeartQoL, Short Form-12 Health Survey, and Hospital Anxiety and Depression Scale. Factor analysis was used to establish the HeartQoL structure and internal consistency reliability and construct validity were assessed. Results Patients with IHD (n = 412; angina = 112, MI = 151, and IHF = 149) were enrolled. Significantly higher HeartQoL HRQL scores were reported by patients with either angina or MI than by patients with IHF. The 2-factor structure was confirmed by Mokken scale analysis in the total group with strong H coefficients on the global scale (0.64) and both the physical (0.70) and emotional (0.80) subscales. Internal consistency reliability was strong with Cronbach’s α ranging from 0.90 to 0.95. Convergent validity was confirmed with strong correlations between similar physical and mental HeartQoL and Short Form-12 Health Survey subscales ranging from 0.77 to 0.82 with divergent validity confirmed with significantly lower correlations between dissimilar constructs. Discriminative validity was confirmed for 72% of the a priori sociodemographic and clinical hypotheses. Conclusions The Mandarin version of the HeartQoL HRQL questionnaire demonstrates acceptable internal consistency reliability and convergent, divergent, and discriminative validity in patients with IHD and in each diagnostic subgroup. The data support the use of the HeartQoL to assess and compare HRQL in Mandarin-speaking patients with IHD.
The purpose of this cross-sectional study is to examine the causal relationship of maternal education and infants' health outcomes. Using birth certificate data over the years 1970–2004 and exploiting the space-time variation in Minimum Dropout Age laws to solve the endogeneity of education, we find a sizeable effect of mothers' education on their birth outcomes. An additional year of maternal education is associated with a reduction in incidences of low birth weight and preterm birth by 15.2 and 12.7 percent, respectively. The estimates are robust across various specifications and even when allowing mothers’ cohort-of-birth to vary across regions. The results suggest that the candidate mechanisms of impact include improvements in timing, quantity, and quality of prenatal care, lower negative health behavior during pregnancy such as smoking and drinking, and higher spousal education.
Authentic youth engagement is widely recognized as an efficacious strategy to promote adolescent health. The Providers and Teens Communicating for Health (PATCH) Youth Advocacy Fellowship was created to support Wisconsin's Adolescent Health Program. It strives to bring youth voice to the forefront of adolescent health conversations while also providing young people the knowledge, skills, and opportunities to thrive into adulthood. The Fellowship hires and trains Wisconsin youth, aged 12 to 21 years, to be a part of community- and state-based adolescent health conversations. Youth meet regularly as a team for ongoing enrichment and are provided opportunities to consult on adolescent-focused projects and initiatives. They are also responsible for independently completing an advocacy learning series, which culminates in an advocacy plan on a topic of personal interest. The Fellowship has been implemented as an extended 9-month program, as well as an expedited 8-week pilot. An evaluation was conducted to compare the 8-week pilot (summer 2018) with 51 youth and the sequential 9-month Fellowship (2018-2019) with 12 youth. Based on the quantitative analysis of 2 programmatic evaluations (posttraining and postprogram), both program models showed success. Yet, there were distinct differences among self-reported youth outcomes as well as depth and extent of engagement. Across all 14 domains, the 9-month cohort demonstrated consistently higher mean scores. Half of the domains (7) showed statistically significant differences. When considering youth engagement, it is important for practitioners to determine the goals, needs, capacity, and resources of both youth and the organization. Engaging youth for shorter-term commitments may serve as an important health education strategy, providing youth important knowledge and skills. Yet, engaging youth for extended periods of time may result in more meaningful engagement, fruitful projects, and substantial changes in positive youth development.
Youth disclosure (to parents) is an important factor in assessing parental knowledge and can be defined as the frequency with which adolescents share information about their daily activities. Unfortunately, measurement invariance (across time and reporter) is rarely reported in the literature for measures of youth disclosure, even though it is important to establish at least strong invariance before proceeding to further analyses where means are compared. Measurement invariance was examined across three time points (child ages 11, 14, and 17) and across reporter (youth report of disclosure to mother/father, maternal/paternal report of youth disclosure) for one of the primary measures of youth disclosure. The sample consisted of 335 families (youth, mother, father) from an urban center in the northwestern United States, with adolescent respondents being a primarily European American, middle-income sample of approximately equal numbers of boys and girls (51.6% female). Structural equation modeling was utilized to verify weak, strong and strict measurement invariance. Strong invariance was demonstrated in several instances across two time points (e.g., ages 11 and 14) but there was no evidence of strong invariance across the three time points, regardless of reporter. Implications for youth disclosure theory and construct development are discussed.
Ecological forecasting provides a powerful set of methods for predicting short‐ and long‐term change in living systems. Forecasts are now widely produced, enabling proactive management for many applied ecological problems. However, despite numerous calls for an increased emphasis on prediction in ecology, the potential for forecasting to accelerate ecological theory development remains underrealized. Here, we provide a conceptual framework describing how ecological forecasts can energize and advance ecological theory. We emphasize the many opportunities for future progress in this area through increased forecast development, comparison and synthesis. Our framework describes how a forecasting approach can shed new light on existing ecological theories while also allowing researchers to address novel questions. Through rigorous and repeated testing of hypotheses, forecasting can help to refine theories and understand their generality across systems. Meanwhile, synthesizing across forecasts allows for the development of novel theory about the relative predictability of ecological variables across forecast horizons and scales. We envision a future where forecasting is integrated as part of the toolset used in fundamental ecology. By outlining the relevance of forecasting methods to ecological theory, we aim to decrease barriers to entry and broaden the community of researchers using forecasting for fundamental ecological insight.
Lung ultrasound (US) is a well-established imaging tool in the inpatient and critical care setting. It has proven its worth in the rapid bedside diagnosis of a variety of conditions pertaining to the lungs and the thorax. Lung US was initially introduced as a bedside imaging tool to evaluate the size and characteristics of pleural effusion. Over the years, the field of lung ultrasonography has rapidly expanded introducing nuances in image interpretation. Numerous primary and secondary signs have been described in the literature to identify both normal and abnormal findings. The primary signs can help narrow the list of differential diagnoses, whereas the addition of secondary signs help create an imaging pattern facilitating the confirmation of diagnosis or recognition of the underlying disease process. These wide variety of signs and patterns can present a challenge to the learning of lung ultrasonography, particularly to a novice user. We sought to compile a comprehensive list of these findings to serve as a useful resource to aid effortless adoption of lung ultrasonography in clinical practice. In this review, we narrate the evolution of lung US, describe common protocols applied in performance of the lung US, and illustrate a comprehensive list of common lung US signs and patterns along with their differential diagnosis and clinical utility.
Every year, 180 billion tonnes of cellulose are produced by plants as waste biomass after the cultivation of the desired product. One of the smart and effective ways to utilize this biomass rather than burn it is to utilize the biomass to adequately meet the energy needs with the help of microbial cellulase that can catalytically convert the cellulose into simple sugar units. Marine actinobacteria is one of the plentiful gram-positive bacteria known for its industrial application as it can produce multienzyme cellulase with high thermal tolerance, pH stability and high resistant towards metal ions and salt concentration, along with other antimicrobial properties. Highly stable cellulase obtained from marine actinobacteria will convert the cellulose biomass into glucose, which is the precursor for biofuel production. This review will provide a comprehensive outlook of various strategic applications of cellulase from marine actinobacteria which can facilitate the breakdown of lignocellulosic biomass to bioenergy with respect to its characteristics based on the location/environment that the organism was collected and its screening strategies followed by adopted methodologies to mine the novel cellulase genome and enhance the production, thereby increasing the activity of cellulase continued by effective immobilization on novel substrates for the multiple usage of cellulase along with the industrial applications.
Discharged wastewater treatment plant (WWTP) effluent greatly contributes to the generation of complex mixtures of contaminants of emerging concern (CECs) in aquatic environments which often contain neuropharmaceuticals and other emerging contaminants that may impact neurological function. However, there is a paucity of knowledge on the neurological impacts of these exposures to aquatic organisms. In this study, caged fathead minnows (Pimephales promelas) were exposed in situ in a temperate-region effluent-dominated stream (i.e., Muddy Creek) in Coralville, Iowa, USA upstream and downstream of a WWTP effluent outfall. The pharmaceutical composition of Muddy Creek was recently characterized by our team and revealed many compounds there were at a low microgram to high nanogram per liter concentration. Total RNA sequencing analysis on brain tissues revealed 280 gene isoforms that were significantly differentially expressed in male fish and 293 gene isoforms in female fish between the upstream and downstream site. Only 66 (13%) of such gene isoforms overlapped amongst male and female fish, demonstrating sex-dependent impacts on neuronal gene expression. By using a systems biology approach paired with functional enrichment analyses, we identified several potential novel gene biomarkers for treated effluent exposure that could be used to expand monitoring of environmental effects with respect to complex CEC mixtures. Lastly, when comparing the results of this study to those that relied on a single-compound approach, there was relatively little overlap in terms of gene-specific effects. This discovery brings into question the application of single-compound exposures in accurately characterizing environmental risks of complex mixtures and for gene biomarker identification.
Sport-related concussions can result from a single high magnitude impact that generates concussive symptoms, repeated subconcussive head impacts aggregating to generate concussive symptoms, or a combined effect from the two mechanisms. The array of symptoms produced by these mechanisms may be clinically interpreted as a sport-related concussion. It was hypothesized that head impact exposure resulting in concussion is influenced by severity, total number, and frequency of subconcussive head impacts. The influence of total number and magnitude of impacts was previously explored, but frequency was investigated to a lesser degree. In this analysis, head impact frequency was investigated over a new metric called ‘time delta’, the time difference from the first recorded head impact of the day until the concussive impact. Four exposure metrics were analyzed over the time delta to determine whether frequency of head impact exposure was greater for athletes on their concussion date relative to other dates of contact participation. Those metrics included head impact frequency, head impact accrual rate, risk weighted exposure (RWE), and RWE accrual rate. Athletes experienced an elevated median number of impacts, RWE, and RWE accrual rate over the time delta on their concussion date compared to non-injury sessions. This finding suggests elevated frequency of head impact exposure on the concussion date compared to other dates that may precipitate the onset of concussion.
Purpose To evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed <50 years of age) risk overall and by breast cancer (BC) subtype, and whether risk varies by race or socioeconomic position (SEP). Methods Data are from the Young Women’s Health History Study (YWHHS), a population-based case–control study of non-Hispanic Black (NHB) and White (NHW) women, ages 20–49 years (n = 1812 cases, n = 1381 controls) in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010–2015. Lifetime personal cigarette smoking characteristics and YOBC risk by subtype were examined using sample-weighted, multivariable-adjusted polytomous logistic regression. Results YOBC risk associated with ever versus never smoking differed by subtype (Pheterogeneity = 0.01) with risk significantly increased for Luminal A (adjusted odds ratio [aOR] 1.34; 95% confidence interval [CI] 1.06–1.68) and HER2-type (aOR 1.97; 95% CI 1.23–3.16), and no association with Luminal B or Triple Negative subtypes. Additionally, ≥30 years since smoking initiation (versus never) was statistically significantly associated with an increased risk of Luminal A (aOR 1.55; 95% CI 1.07–2.26) and HER2-type YOBC (aOR 2.77; 95% CI 1.32–5.79), but not other subtypes. In addition, among parous women, smoking initiated before first full-term pregnancy (versus never) was significantly associated with an increased risk of Luminal A YOBC (aOR 1.45; 95% CI 1.11–1.89). We observed little evidence for interactions by race and SEP. Conclusion Findings confirm prior reports of a positive association between cigarette smoking and Luminal A YOBC and identify a novel association between smoking and HER2-type YOBC.
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