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As the native regenerative potential of adult cardiac tissue is limited post-injury, stimulating endogenous repair mechanisms in the mammalian myocardium is a potential goal of regenerative medicine therapeutics. Injection of myocardial matrix hydrogels into the heart post-myocardial infarction (MI) has demonstrated increased cardiac muscle and promotion of pathways associated with cardiac development, suggesting potential promotion of cardiomyocyte turnover. In this study, the myocardial matrix hydrogel was shown to have native capability as an effective reactive oxygen species scavenger and protect against oxidative stress induced cell cycle inhibition in vitro. Encapsulation of cardiomyocytes demonstrated an enhanced turnover in in vitro studies, and in vivo assessments of myocardial matrix hydrogel treatment post-MI showed increased thymidine analog uptake in cardiomyocyte nuclei compared to saline controls. Overall, this study provides evidence that properties of the myocardial matrix material provide a microenvironment mitigating oxidative damage and supportive of cardiomyocytes undergoing DNA synthesis, toward possible DNA repair or cell cycle activation. Loss of adult mammalian cardiomyocyte turnover is influenced by shifts in oxidative damage, which represents a potential mechanism for improving restoration of cardiac muscle after myocardial infarction (MI). Injection of a myocardial matrix hydrogel into the heart post-MI previously demonstrated increased cardiac muscle and promotion of pathways associated with cardiac development, suggesting potential in promoting proliferation of cardiomyocytes. In this study, the myocardial matrix hydrogel was shown to protect cells from oxidative stress and increase proliferation in vitro. In a rat MI model, greater presence of tissue free thiol content spared from oxidative damage, lesser mitochondrial superoxide content, and increased thymidine analog uptake in cardiomyocytes was found in matrix injected animals compared to saline controls. Overall, this study provides evidence that properties of the myocardial matrix material provide a microenvironment supportive of cardiomyocytes undergoing DNA synthesis, toward possible DNA repair or cell cycle activation. [Display omitted] [ABSTRACT FROM AUTHOR]

Restoration of muscular strength is predicated on restoration of muscle length. The purpose of this study was to describe infraspinatus and deltoid length preoperative to reverse total shoulder arthroplasty (RTSA) to guide distalization and lateralization to restore preoperative muscle length. This was a retrospective radiographic study. We measured the infraspinatus length on preoperative computed tomographic images and the deltoid length on preoperative radiographs. For all measurements, reliability was first established by comparing measurements between 2 observers, and intraclass correlation coefficients (ICCs) were calculated. We then calculated descriptive statistics for these muscle lengths and developed a formula to predict these muscle lengths from patient demographics. We measured infraspinatus length in 97 patients and deltoid length in 108 patients. Inter-rater reliability was excellent, with all ICCs >0.886. The mean infraspinatus length was 15.5 cm (standard deviation 1.3) and ranged from 12.6-18.9 cm, whereas the deltoid length was 16.2±1.7 cm and ranged from 12.5-20.2 cm. Both infraspinatus (r = 0.775, P <.001) and deltoid length (r = 0.717, P <.001) were highly correlated with patient height but did not differ between diagnoses. Formulae developed through linear regression allowed prediction of muscle length to within 1 cm in 78% and within 2 cm in 100% for the infraspinatus and 60% and 88% for the deltoid. Deltoid and infraspinatus length are variable but highly correlated with patient height. To maintain tension, 2 mm of lateralization and distalization should be added for every 6 inches (∼15 cm) of height above average for a Grammont-style RTSA. [ABSTRACT FROM AUTHOR]

Vascular calcification is a commonly occurring pathological process and is recognized as an independent prognostic marker for cardiovascular morbidity and mortality. Recent progress in developing novel therapies to modify vascular calcification is critically hampered due to the lack of reliable in vitro experimental models that recapitulate the structural and mechanical attributes of calcified arteries. In this study, we show the ability to model the behavior of diffuse vascular calcification in vitro using biologically-engineered grafts approximating the composition, structure, and mechanical properties of arteries. Transmural calcification was achieved by exposing the acellular grafts of collagenous ECM to complete medium containing elevated Calcium (Ca) and Phosphate (P) concentrations. It was found that increasing the serum concentration from 2% to 10% increased the extent and degree of calcification based on histochemical, ultrastructural, chemical and thermal analyses. The presence of variably-sized spherical calcific deposits within the matrix further confirmed its morphological similarity to pathologic calcification. Mechanical testing demonstrated up to a 16-fold decrease in compliance due to the calcification, consistent with prior reports for calcified arteries. The model developed thus has potential to improve the design and development of interventional devices and therapies for the diagnosis and treatment of arterial calcification. The presence of extensive vascular calcification makes angiographic/interventional procedures difficult due to reduced arterial compliance. Current attempts to develop safe and effective non-surgical adjunctive techniques to treat calcified arteries are largely limited by the lack of a physiologically relevant testing platform that mimics the structural and mechanical features of vascular calcification. Herein, we developed an off-the-shelf calcified artery model, with the goal to accelerate the pre-clinical development of novel therapies for the management of arterial calcification. To the extent of our knowledge, this is the first report of an in vitro tissue-engineered model of diffuse arterial calcification. Image, graphical abstract [ABSTRACT FROM AUTHOR]

With the increased awareness that cancer and its treatments may have a substantial impact upon quality of life before, during, and after therapy, fertility preservation is now widely recognized as an essential component of care for all patients with a new cancer diagnosis. The emergence of formal fertility preservation guidelines from multiple professional societies has provided a framework for incorporating fertility preservation into clinical practice. Providers should discuss fertility considerations with new cancer patients at the earliest possible opportunity, prior to initiation of potentially gonadotoxic cancer treatments. Sperm banking via masturbation remains the easiest and most reliable method for fertility preservation, though a variety of alternatives exist for adolescents and adult males with azoospermia or those who are unable to provide a sample. Ultimately, care can be optimally delivered through a formal fertility preservation program that includes providers from multiple disciplines with the resources to provide comprehensive and expedient care. [ABSTRACT FROM AUTHOR]

One way pharmacy students contribute to their community while simultaneously practicing critical skills is by providing community blood pressure (BP) and blood glucose (BG) screenings. Instruction on correct techniques ensures student participants obtain accurate results and develop confidence. Previously, community event training had been held live and in person, but due to a curriculum change, an asynchronous online training program was piloted. The purpose of this study was to determine if the online training provides similar confidence, convenience, and knowledge when compared to live training. Three online training modules (BP, BG, and event procedures) were built into a web-based course management system. Each online module consisted of an educational slideshow, an instructional video, and a short quiz. A 10-question anonymous survey was given both before and after the live training in 2017, as well as before and after the asynchronous, online training in 2018. Data were compared using descriptive statistics to see if the increase in knowledge and confidence was similar. The live training event had 69 participants; the online training had 77 participants. Both the live and online training had 99 to 100% successful completion, based upon skill demonstration (live), or quiz (online). Both the live and online training had increases in reported student confidence. Both formats were rated as convenient by participants (9.7/10 for live, 9.6/10 for online). The use of an online, asynchronous training program is an effective alternative for student training to prepare for participation in community screening events. [ABSTRACT FROM AUTHOR]

Normal epithelium exists within a dynamic extracellular matrix (ECM) that is tuned to regulate tissue specific epithelial cell function. As such, ECM contributes to tissue homeostasis, differentiation, and disease, including cancer. Though it is now recognized that the functional unit of normal and transformed epithelium is the epithelial cell and its adjacent ECM, we lack a basic understanding of tissue-specific ECM composition and abundance, as well as how physiologic changes in ECM impact cancer risk and outcomes. While traditional proteomic techniques have advanced to robustly identify ECM proteins within tissues, methods to determine absolute abundance have lagged. Here, with a focus on tissues relevant to breast cancer, we utilize mass spectrometry methods optimized for absolute quantitative ECM analysis. Employing an extensive protein extraction and digestion method, combined with stable isotope labeled Quantitative conCATamer (QconCAT) peptides that serve as internal standards for absolute quantification of protein, we quantify 98 ECM, ECM-associated, and cellular proteins in a single analytical run. In rodent models, we applied this approach to the primary site of breast cancer, the normal mammary gland, as well as a common and particularly deadly site of breast cancer metastasis, the liver. We find that mammary gland and liver have distinct ECM abundance and relative composition. Further, we show mammary gland ECM abundance and relative compositions differ across the reproductive cycle, with the most dramatic changes occurring during the pro-tumorigenic window of weaning-induced involution. Combined, this work suggests ECM candidates for investigation of breast cancer progression and metastasis, particularly in postpartum breast cancers that are characterized by high metastatic rates. Finally, we suggest that with use of absolute quantitative ECM proteomics to characterize tissues of interest, it will be possible to reconstruct more relevant in vitro models to investigate tumor-ECM dynamics at higher resolution. [ABSTRACT FROM AUTHOR]

Extracellular matrix is a key component of many products in regenerative medicine. Multiple regenerative medicine products currently in the clinic are comprised of human or xenogeneic extracellular matrix. In addition, whole-organ regeneration exploits decellularized native organs as scaffolds for organotypic cell culture. However, precise understanding of the constituents of such extracellular matrix-based implants and scaffolds has sorely lagged behind their use. We present here an advanced protein extraction method using known quantities of proteotypic 13 C-labeled peptides to quantify matrix proteins in native and decellularized lung tissues. Using quantitative proteomics that produce picomole-level measurements of a large number of matrix proteins, we show that a mild decellularization technique (“Triton/SDC”) results in near-native retention of laminins, proteoglycans, and other basement membrane and ECM-associated proteins. Retention of these biologically important glycoproteins and proteoglycans is quantified to be up to 27-fold higher in gently-decellularized lung scaffolds compared to scaffolds generated using a previously published decellularization regimen. Cells seeded onto this new decellularized matrix also proliferate robustly, showing positive staining for proliferating cell nuclear antigen (PCNA). The high fidelity of the gently decellularized scaffold as compared to the original lung extracellular matrix represents an important step forward in the ultimate recapitulation of whole organs using tissue-engineering techniques. This method of ECM and scaffold protein analysis allows for better understanding, and ultimately quality control, of matrices that are used for tissue engineering and human implantation. These results should advance regenerative medicine in general, and whole organ regeneration in particular. Statement of Significance The extracellular matrix (ECM) in large part defines the biochemical and mechanical properties of tissues and organs; these inherent cues make acellular ECM scaffolds potent substrates for tissue regeneration. As such, they are increasingly prevalent in the clinic and the laboratory. However, the exact composition of these scaffolds has been difficult to ascertain. This paper uses targeted proteomics to definitively quantify 71 proteins present in acellular lung ECM scaffolds. We use this technique to compare two decellularization methods and demonstrate superior retention of ECM proteins important for cell adhesion, migration, proliferation, and differentiation in scaffolds treated with low-concentration detergent solutions. In the long term, the ability to acquire quantitative biochemical data about biological substrates will facilitate the rational design of engineered tissues and organs based on precise cell-matrix interactions. [ABSTRACT FROM AUTHOR]

Murine norovirus (MNoV) is a model for human norovirus and for interrogating mechanisms of viral tropism and persistence. We previously demonstrated that the persistent strain MNoVCR6 infects tuft cells, which are dispensable for the non-persistent strain MNoVCW3. We now show that diverse MNoV strains require tuft cells for chronic enteric infection. We also demonstrate that interferon-λ (IFN-λ) acts directly on tuft cells to cure chronic MNoVCR6 infection and that type I and III IFNs signal together via STAT1 in tuft cells to restrict MNoVCW3 tropism. We then develop an enteroid model and find that MNoVCR6 and MNoVCW3 similarly infect tuft cells with equal IFN susceptibility, suggesting that IFN derived from non-epithelial cells signals on tuft cells in trans to restrict MNoVCW3 tropism. Thus, tuft cell tropism enables MNoV persistence and is determined by tuft cell-intrinsic factors (viral receptor expression) and -extrinsic factors (immunomodulatory signaling by non-epithelial cells). [Display omitted] • Diverse persistent MNoV strains require tuft cells for enteric infection • Serial infection of short-lived tuft cells enables MNoV immune escape • Tuft-cell-intrinsic STAT1 restricts tropism of non-persistent MNoVCW3 • Type I and III interferons signal on tuft cells in trans to restrict MNoVCW3 tropism Strine et al. interrogate the determinants and consequences of tuft cell tropism on murine norovirus infection. Using enteroid and mouse models, they show that tuft cells are required for persistent enteric infection and that non-epithelial cells restrict tuft cell tropism via combinatorial type I and III interferon signaling on tuft cells. [ABSTRACT FROM AUTHOR]

Suicide is one of the leading causes of death among post-secondary students. It is, therefore, imperative that we identify behavioral risk factors that can have protective effects in preventing against suicide. This study examined whether different combinations of adherence to the Canadian 24-Hour Movement Guidelines for Adults (i.e., physical activity, sedentary behavior, sleep) were associated with reduced odds of suicidal ideation and planning among emerging adults attending post-secondary education. This cross-sectional observational study used data from the first cycle of the Canadian Campus Wellbeing Survey, which included a total of 17,633 students (Mean age = 21.7 ± 2.92 years; 67.1% female, 31.5% male, 1.4% other) enrolled in 20 Canadian post-secondary institutions. Logistic regression models with covariate balanced propensity score weighting were computed. Suicidal ideation and suicidal planning were reported by 14.4% and 4.9% of students, respectively. Adherence to the sleep (OR = 0.71; 95% CI: 0.58–0.86), physical activity and sleep (OR = 0.74; 95% CI: 0.62–0.88), sedentary behavior and sleep guidelines (OR = 0.64; 95% CI: 0.45–0.90) as well as concurrent adherence to all three guidelines (OR = 0.58; 95% CI: 0.44–0.75) were associated with significantly reduced odds of suicidal ideation. Among students who reported suicidal ideation, only adherence to the physical activity and sleep guidelines (OR = 0.67; 95% CI: 0.48–0.96) was associated with suicidal planning. Collectively, findings suggest the promotion of healthy movement behavior patterns may be a promising avenue for broad suicide and mental health prevention efforts on campus, although the potency of these effects may not extend to more severe suicidal thoughts. • 42% lower odds of suicidal ideation when meeting all 24-hr movement guidelines. • Sleep appears to be the strongest determinant of lower suicidal ideation. • Meeting all three 24-hr movement guidelines was not associated with suicidal planning. • Coding decisions for non-response on suicide-related items can influence associations. [ABSTRACT FROM AUTHOR]

• Genus-level, trait-based diatom indices were developed for the conterminous U.S. • Diatom indices had strong ability to separate least- from most-disturbed sites. • Using diatoms traits can circumvent the problem of taxonomic inconsistencies. • Trait approach is cost-effective that could benefit programs with limited resources. • Trait-based indices can be used in large-scale, river and stream assessments. Taxonomic inconsistency in species-level identifications has constrained use of diatoms as biological indicators in aquatic assessments. We addressed this problem by developing diatom multimetric indices (MMIs) of ecological condition using genus-level taxonomy and trait-based autecological information. The MMIs were designed to assess river and stream chemical, physical and biological condition across the conterminous United States. Trait-based approaches have the advantage of using both species-level and genus-level data, which require less effort and expense to acquire than traditional species-based approaches and eliminate the persistent taxonomic biases introduced over vast geographic extents. For large-extent assessment programs that require multiple taxonomic laboratories to process samples, such as the United States Environmental Protection Agency's (U.S. EPA's) National Rivers and Streams Assessment (NRSA), the trait approach can eliminate discrepancies in species-level identification or nomenclature that hinder diatom data interpretation. We developed trait-based MMIs using NRSA data for each of the three large ecoregions across the U.S. - the East, Plains, and West. All three MMIs performed well in discriminating least-disturbed from most-disturbed sites. The MMI for the East had the greatest discrimination ability, followed by MMIs for the Plains and West, respectively. The performance of the MMIs was comparable to that observed in existing NRSA fish and macroinvertebrate MMIs. Our research shows that trait-based diatom indices constructed on genus-level taxonomy can be effective for large-scale assessments, and may also allow programs such as NRSA to assess trends in freshwater condition retrospectively, by revisiting older diatom datasets. Moreover, our genus-based approach facilitates including of diatoms into other assessment programs that have limited monitoring resources. [ABSTRACT FROM AUTHOR]

Abstract: Motor vehicle crashes are the leading cause of work-related fatality in the U.S. as well as in the oil and gas extraction industry. This study describes the characteristics of motor vehicle-related fatalities in the oil and gas extraction industry using data from the U.S. Bureau of Labor Statistics’ Census of Fatal Occupational Injuries. It compares the risk of dying in a motor vehicle crash in this industry to other major industries and among different types and sizes of oil and gas extraction companies. There were 202 oil and gas extraction workers who died in a work-related motor vehicle crash from 2003 to 2009. The motor vehicle fatality rate for workers in this industry was 8.5 times that of all private wage and salary workers (7.6 vs. 0.9, p <.0001). Workers from small oil and gas establishments (<20 workers) and workers from well-servicing companies were at greatest risk of dying in a motor vehicle crash. Pick-up trucks were the most frequent type of vehicle occupied by the fatally injured worker (n =104, 51.5%). Safety belt non-use was identified in 38.1% (n =77) of the cases. Increased focus on motor vehicle safety in this industry is needed, in particular among small establishments. Extraction workers who drive light duty vehicles need to be a specific focus. [Copyright &y& Elsevier]

Abstract: This paper reviews empirical evidence of the association between suicide-related behaviors and anxiety among children and adolescents. It begins with a review of suicide-related behaviors and anxiety, discusses methodological issues related to measurement, and reviews empirical findings published since the last review of this topic in 1988. Evidence is summarized on four criteria necessary to establish anxiety as a causal risk factor for suicide-related behaviors among children and adolescents. There is consistent evidence for a significant association between anxiety and suicide-related behaviors (Criterion 1). Evidence that the influence of anxiety on suicide-related behaviors is not due to a third variable (Criterion 2) is mixed and hindered by methodological limitations. The literature is also unclear as to whether anxiety temporally precedes suicide-related behaviors (Criterion 3). Finally, this review found no evidence to support or refute anxiety''s stability independent of and across instances of suicide-related behaviors (Criterion 4). Theoretical and clinical implications of these findings and directions for future research are discussed. [Copyright &y& Elsevier]

Obesity and knee osteoarthritis adversely affect activities of daily living in older adults. Together, the complexities of their interaction on mobility, including stair negotiation, are unresolved. The purpose of this study was to determine the relationship between obesity, pain, and stair negotiation in older adults with knee osteoarthritis. Older adults with symptomatic knee osteoarthritis and overweight or obesity participated in the study (n = 28; age range = 57.0–78.0 yrs.; body mass index range = 26.6–42.8 kg•m−2). The Western Ontario and McMaster Universities Osteoarthritis Index pain subscale was used to measure knee pain. Measurements included a three-dimensional biomechanical analysis during descent on a set of force plate-instrumented stairs and a timed stair descent test. Pearson's r was used to determine associations between body mass index and pain, stair descent weight-acceptance phase vertical ground reaction force (vGRF) variables and lower extremity joint kinematics and kinetics, and timed stair descent performance. Significant correlations existed between body mass index and pain (r = 0.41; p = 0.03), peak vGRF (r = 0.39; p = 0.04), vertical impulse (r = 0.49; p = 0.008), and peak ankle plantar flexor moments (r = 0.50; p = 0.007) in older adults with knee osteoarthritis. Greater obesity in older adults with knee osteoarthritis was associated with greater knee pain and higher ankle joint loads during stair descent. These results support the recommendations of osteoarthritis treatment guidelines for weight-loss as a first-line of treatment for older adults with obesity and knee osteoarthritis. • Obesity predicts pain in older adults with knee osteoarthritis. • Obesity predicts stair descent forces in older adults with knee osteoarthritis. • Obesity predicts stair descent ankle-joint load in people with knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Theory and research document the role of perceived burdensomeness in the development of suicide ideation, including in youth. There is a critical need to identify and evaluate variables that foster perceived burdensomeness in youth, with an eye toward advancing etiological models and informing prevention approaches for at-risk youth who are not yet actively suicidal. The current study examined and replicated a conceptual model wherein the association between low parental warmth and burdensomeness is moderated by youth impairment. Participants were 75 and 150 clinic referred youths in Study 1 and Study 2, respectively, with anxiety-related difficulties. Youth impairment significantly moderated the association between low parental warmth and youth perceived burdensomeness such that the association was negative and statistically significant at high levels of impairment, but not at low levels of impairment. The moderation effect was statistically significant in both studies while controlling for anxiety and depressive symptoms. These findings provide insight into variables that are associated with a sense of burdensomeness toward others in youth, and identify potential targets for preventing or intervening to reduce perceived burdensomeness in clinic-referred youth. [ABSTRACT FROM AUTHOR]

The current study examined the indirect effect of the use of behavioral parenting skills following the Infant Behavior Program, a brief, home-based adaptation of the child-directed interaction phase of parent-child interaction therapy, on infant language production. Participants were 60 infants (55% male, mean age 13.47 ± 1.31 months) and their caregivers, who were recruited at a large urban pediatric primary care clinic and were included if their scores exceeded the 75th percentile on a brief screener of early behavior problems. Families were randomly assigned to receive the infant behavior program or standard pediatric primary care. Results demonstrated a significant indirect effect of caregivers' use of positive parenting skills (i.e., praise, reflections, and behavior descriptions) on the relation between group and infant total utterances at the 6-month follow-up, such that infants whose caregivers increased their use of positive parenting skills following the intervention showed greater increases in language production. These findings extend previous research examining parenting skills as a mechanism of change in infant language production, and highlight the potential for an early parenting intervention to target behavior and language simultaneously during a critical period in language development. [ABSTRACT FROM AUTHOR]

Abstract Watersheds provide a range of services valued by society, incorporating biotic and abiotic functions within their boundaries. Recently, an operational definition of watershed integrity was applied and indices of watershed integrity (IWI) and catchment integrity (ICI) were developed and mapped for the conterminous United States. However, these indices were originally derived using equally-weighted first-order approximations of relationships between anthropogenic stressors (obtained from the U.S. EPA's StreamCat dataset) and six watershed functions. In addition, the original calculations of the IWI and ICI did not standardize metrics across these differing scales, resulting in IWI and ICI values that are not directly comparable. We provide an example of how to iteratively update the stressor-watershed function relationships using random forest models and a nationwide response metric representative of one of the six watershed functions. Specifically, we focused on the chemical regulation function (CHEM) of IWI and ICI by relating a composite metric of chemical water quality from 1914 samples to land use metrics explicit to CHEM to refine the nature of these relationships (e.g., non-linear versus linear). The rate of nitrogen fertilizer, agricultural land use, and urban land use were found to be the three most important stressors predicting the national water quality response metric. Revision of CHEM values improved the prediction of several regional- to national-scale water quality indicators. In all cases, exponential decay curves replaced the original negative linear relationship for CHEM. Therefore, the original IWI and ICI values are probably over-estimates of the actual integrity of the Nation's watersheds and catchments. With these revisions, we provide updated national maps of IWI and ICI. The methods outlined here can be implemented iteratively as more and better data become available for all six of the watershed functions to elevate the accuracy and applicability of these indices to various land management issues. Graphical abstract Unlabelled Image Highlights • Indices of catchment and watershed integrity aid in management decisions. • This study makes these previously developed indices directly comparable. • Data-driven revision of the national maps of watershed and catchment integrity • Models revealed non-linear relationships between stressors and water quality metric. • Methods outlined can be implemented iteratively with new or improved data. [ABSTRACT FROM AUTHOR]

Field-based methods increase relevance and realism when setting water quality criteria. They also pose challenges. To enable a consistent process, a flow chart was developed for choosing between two field-based methods and then selecting among candidate results. The two field-based methods estimated specific conductivity (SC) levels likely to extirpate 5% of benthic invertebrate genera: an extirpation concentration distribution (XCD) method and a background-to-criterion (B-C) model developed by the U.S. Environmental Protection Agency. The B-C model is a least squares regression of the 5th centile of XCD (XCD 05 ) values against estimates of background SC. Selection of an XCD 05 from the flowchart is determined by characteristics of the paired chemical and biological data sets and method for estimating the XCD 05 values. Confidence in these example SC XCD 05 values is based on the size of the data sets and ecoregional SC disturbance. The level of ecoregional SC disturbance was judged by comparing the background SC (the 25th centile of the data set used to calculate a XCD 05 ) and an estimate of natural base-flow SC modeled from geophysical attributes in the region. The B-C approach appears to be a viable option for estimating a SC benchmark with inexpensive estimates of SC background while the XCD method is used when the data are abundant. To illustrate the use of the flow chart, example SC XCD 05 values were calculated for 63 of 86 Level III ecoregions in the conterminous United States of America. [ABSTRACT FROM AUTHOR]

Watershed integrity is the capacity of a watershed to support and maintain the full range of ecological processes and functions essential to sustainability. Using information from EPA’s StreamCat dataset, we calculated and mapped an Index of Watershed Integrity (IWI) for 2.6 million watersheds in the conterminous US with first-order approximations of relationships between stressors and six watershed functions: hydrologic regulation, regulation of water chemistry, sediment regulation, hydrologic connectivity, temperature regulation, and habitat provision. Results show high integrity in the western US, intermediate integrity in the southern and eastern US, and the lowest integrity in the temperate plains and lower Mississippi Valley. Correlation between the six functional components was high ( r = 0.85–0.98). A related Index of Catchment Integrity (ICI) was developed using local drainages of individual stream segments (i.e., excluding upstream information). We evaluated the ability of the IWI and ICI to predict six continuous site-level indicators with regression analyses – three biological indicators and principal components derived from water quality, habitat, and combined water quality and habitat variables – using data from EPA’s National Rivers and Streams Assessment. Relationships were highly significant, but the IWI only accounted for 1–12% of the variation in the four biological and habitat variables. The IWI accounted for over 25% of the variation in the water quality and combined principal components nationally, and 32–39% in the Northern and Southern Appalachians. We also used multinomial logistic regression to compare the IWI with the categorical forms of the three biological indicators. Results were consistent: we found positive associations but modest results. We compared how the IWI and ICI predicted the water quality PC relative to agricultural and urban land use. The IWI or ICI are the best predictors of the water quality PC for the CONUS and six of the nine ecoregions, but they only perform marginally better than agriculture in most instances. However, results suggest that agriculture would not be appropriate in all parts of the country, and the index is meant to be responsive to all stressors. The IWI in its present form (available through the StreamCat website; https://www.epa.gov/national-aquatic-resource-surveys/streamcat ) could be useful for management efforts at multiple scales, especially when combined with information on site condition. The IWI could be improved by incorporating empirical or literature-derived relationships between functional components and stressors. However, limitations concerning the absence of data for certain stressors should be considered. [ABSTRACT FROM AUTHOR]

Given the strong association between early behavior problems and language impairment, we examined the effect of a brief home-based adaptation of Parent-child Interaction Therapy on infant language production. Sixty infants (55% male; mean age 13.47±1.31 months) were recruited at a large urban primary care clinic and were included if their scores exceeded the 75th percentile on a brief screener of early behavior problems. Families were randomly assigned to receive the home-based parenting intervention or standard pediatric primary care. The observed number of infant total (i.e., token) and different (i.e., type) utterances spoken during an observation of an infant-led play and a parent-report measure of infant externalizing behavior problems were examined at pre- and post-intervention and at 3- and 6-month follow-ups. Infants receiving the intervention demonstrated a significantly higher number of observed different and total utterances at the 6-month follow-up compared to infants in standard care. Furthermore, there was an indirect effect of the intervention on infant language production, such that the intervention led to decreases in infant externalizing behavior problems from pre- to post-intervention, which, in turn, led to increases in infant different utterances at the 3- and 6-month follow-ups and total utterances at the 6-month follow-up. Results provide initial evidence for the effect of this brief and home-based intervention on infant language production, including the indirect effect of the intervention on infant language through improvements in infant behavior, highlighting the importance of targeting behavior problems in early intervention. [ABSTRACT FROM AUTHOR]

Magnetoencephalography (MEG) measures human brain function via assessment of the magnetic fields generated by electrical activity in neurons. Despite providing high-quality spatiotemporal maps of electrophysiological activity, current MEG instrumentation is limited by cumbersome field sensing technologies, resulting in major barriers to utility. Here, we review a new generation of MEG technology that is beginning to lift many of these barriers. By exploiting quantum sensors, known as optically pumped magnetometers (OPMs), 'OPM-MEG' has the potential to dramatically outperform the current state of the art, promising enhanced data quality (better sensitivity and spatial resolution), adaptability to any head size/shape (from babies to adults), motion robustness (participants can move freely during scanning), and a less complex imaging platform (without reliance on cryogenics). We discuss the current state of this emerging technique and describe its far-reaching implications for neuroscience. Magnetoencephalography (MEG) allows noninvasive electrophysiological imaging of human brain activity. However, current MEG technology has significant limitations. Optically pumped magnetometers (OPM)-MEG is a new type of MEG instrumentation, promising several advantages compared with conventional scanners: higher signal sensitivity, better spatial resolution, more uniform coverage, lifespan compliance, free movement of participants during scanning, and lower system complexity. We describe the principles underlying OPM-MEG and its components, including noncryogenic field sensors and magnetic shielding technologies. We discuss how the OPM-MEG technology is impacting neuroscience, enabling researchers to overcome limitations of conventional human imaging techniques and tackle new types of research questions. [ABSTRACT FROM AUTHOR]

Primary cell culture in vitro suffers from cellular senescence. We hypothesized that expansion on decellularized extracellular matrix (dECM) deposited by simian virus 40 large T antigen (SV40LT) transduced autologous infrapatellar fat pad stem cells (IPFSCs) could rejuvenate high-passage IPFSCs in both proliferation and chondrogenic differentiation. In the study, we found that SV40LT transduced IPFSCs exhibited increased proliferation and adipogenic potential but decreased chondrogenic potential. Expansion on dECMs deposited by passage 5 IPFSCs yielded IPFSCs with dramatically increased proliferation and chondrogenic differentiation capacity; however, this enhanced capacity diminished if IPFSCs were grown on dECM deposited by passage 15 IPFSCs. Interestingly, expansion on dECM deposited by SV40LT transduced IPFSCs yielded IPFSCs with enhanced proliferation and chondrogenic capacity but decreased adipogenic potential, particularly for the dECM group derived from SV40LT transduced passage 15 cells. Our immunofluorescence staining and proteomics data identify matrix components such as basement membrane proteins as top candidates for matrix mediated IPFSC rejuvenation. Both cell proliferation and differentiation were endorsed by transcripts measured by RNASeq during the process. This study provides a promising model for in-depth investigation of the matrix protein influence on surrounding stem cell differentiation. [ABSTRACT FROM AUTHOR]

Objective: To describe the test construction procedure and evaluate the internal consistency, criterion-referenced validity, and diagnostic accuracy of the Child/Adolescent Self-Report Version of the UCLA PTSD Reaction Index for DSM-5 (RI-5) across 2 independent samples.Method: Study 1 examined the clarity, developmental appropriateness, acceptability of individual RI-5 items, and internal consistency and criterion-referenced validity of the full test. The study 1 sample included 486 youth recruited from 2 major US cities who completed the RI-5 and a measure of depression. Study 2 evaluated the reliability and diagnostic accuracy of the RI-5 in 41 treatment-seeking youth who completed the RI-5 and a "gold standard" structured diagnostic interview, the Clinician-Administered PTSD Scale for DSM-5-Child/Adolescent Version.Results: RI-5 total scale scores showed excellent internal consistency in the 2 samples. Study 1 provided evidence of criterion-referenced validity, in that total scale scores correlated positively with depressive symptoms. Study 2 provided evidence of diagnostic accuracy (including discriminant-groups validity). RI-5 total scores discriminated youth with from youth without PTSD as benchmarked against the structured diagnostic interview. Further, receiver operating characteristic analyses using a total score of 35 provided excellent diagnostic classification accuracy (area under the curve 0.94).Conclusion: The developmental appropriateness and diagnostic accuracy of the RI-5 support its utility for clinical assessment, case conceptualization, and treatment planning in different child-serving systems, including schools, juvenile justice, child welfare, and mental health. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Alaska had the highest work-related fatality rate of any state during 1980–1989. The National Institute for Occupational Safety and Health established the Alaska Field Station (AFS) to address this problem. Methods: AFS established surveillance systems to provide scientific assessments of occupational hazards. Interventions were developed in collaboration with partners and evaluated. Results: During 2000–2009, Alaska experienced a 42.5% decline in work-related fatalities over the previous decade of 1990–1999. In 2009, the workplace fatality rate for Alaska was 5.6/100,000 workers. Commercial pilot deaths were reduced by 50% and Bering Sea crab fishing death rates were reduced by 60%. Building on this success, AFS established national programs to improve safety in the commercial fishing and oil and gas extraction industries. Impact on Industry: A focused, epidemiological approach to reducing fatalities in high-risk occupations is effective. Ongoing commitment to this type of approach will assist in continued success in Alaska and elsewhere. [Copyright &y& Elsevier]

Excess nitrate in drinking water is a human health concern, especially for young children. Public drinking water systems in violation of the 10 mg nitrate-N/L maximum contaminant level (MCL) must be reported in EPA's Safe Drinking Water Information System (SDWIS). We used SDWIS data with random forest modeling to examine the drivers of nitrate violations across the conterminous U.S. and to predict where public water systems are at risk of exceeding the nitrate MCL. As explanatory variables, we used land cover, nitrogen inputs, soil/hydrogeology, and climate variables. While we looked at the role of nitrate treatment in separate analyses, we did not include treatment as a factor in the final models, due to incomplete information in SDWIS. For groundwater (GW) systems, a classification model correctly classified 79% of catchments in violation and a regression model explained 43% of the variation in nitrate concentrations above the MCL. The most important variables in the GW classification model were % cropland, agricultural drainage, irrigation-to-precipitation ratio, nitrogen surplus, and surplus precipitation. Regions predicted to have risk for nitrate violations in GW were the Central California Valley, parts of Washington, Idaho, the Great Plains, Piedmont of Pennsylvania and Coastal Plains of Delaware, and regions of Wisconsin, Iowa, and Minnesota. For surface water (SW) systems, a classification model correctly classified 90% of catchments and a regression model explained 52% of the variation in nitrate concentration. The variables most important for the SW classification model were largely hydroclimatic variables including surplus precipitation, irrigation-to-precipitation ratio, and % shrubland. Areas at greatest risk for SW nitrate violations were generally in the non-mountainous west and southwest. Identifying the areas with possible risk for future violations and potential drivers of nitrate violations across U.S. can inform decisions on how source water protection and other management options could best protect drinking water. Unlabelled Image • Random forest models assess risk for nitrate in drinking water. • Groundwater nitrate drivers were cropland, nitrogen surplus, and precipitation. • Surface water nitrate drivers were hydroclimatic variables. • Nitrate risk greatest in parts of southwest, great plains, upper midwestern U.S. • Small changes in certain variables cause rapid increases or decreases in risk. [ABSTRACT FROM AUTHOR]

Cartilage repair in clinics is a challenge owing to the limited regenerative capacities of cartilage. Synovium-derived stem cells (SDSCs) are suggested as tissue-specific stem cells for chondrogenesis. In this study, we hypothesize that decellularized extracellular matrix (dECM) deposited by SDSCs could provide a superior tissue-specific matrix microenvironment for optimal rejuvenation of adult SDSCs for cartilage regeneration. dECMs were deposited by adult stem cells with varying chondrogenic capacities; SDSCs (strong) (SECM), adipose-derived stem cells (weak) (AECM) and dermal fibroblasts (weak) (DECM), and urine-derived stem cells (none) (UECM). Plastic flasks (Plastic) were used as a control substrate. Human SDSCs were expanded on the above substrates for one passage and examined for chondrogenic capacities. We found that each dECM consisted of unique matrix proteins and exhibited varied stiffnesses, which affected cell morphology and elasticity. Human SDSCs grown on dECMs displayed a significant increase in cell proliferation and unique surface phenotypes. Under induction media, dECM expanded cells yielded pellets with a dramatically increased number of chondrogenic markers. Interestingly, SECM expanded cells had less potential for hypertrophy compared to those grown on other dECMs, indicating that a tissue-specific matrix might provide a superior microenvironment for stem cell chondrogenic differentiation. [ABSTRACT FROM AUTHOR]