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Objective: To examine ear and hearing clinical practices across American Cleft Palate-Craniofacial Association (ACPA) approved teams in the United States., Design: Multi-site prospective, observational, longitudinal study., Setting: Seventeen Cleft Palate Teams in the United States., Patients, Participants: Children with cleft palate, with or without cleft lip (CP ± L), born between 2015 and 2022, evaluated by 18 months (n = 1246)., Interventions: None., Main Outcome Measure(s): Standard of care otolaryngology and audiology appointments evaluated in the context of whether otolaryngology and audiology services were provided as embedded care within the team visit or as ancillary services., Results: Over 71% of infants passed newborn hearing screening (NBHS). By age 18 months, only 40% of infants received audiologic follow-up while 93.6% of children received otolaryngology care. Follow-up was significantly better for infants served by teams with embedded providers versus those who refer families for ancillary services; the odds of seeing an audiologist by 18 months were three times as high among participants seen by teams with embedded audiology (OR = 3.25; CI = 2.0, 5.2) while those seen by teams with embedded otolaryngologists had more than double the odds of seeing an otolaryngologist by 18 months (OR = 2.2; CI = 1.5, 3.2)., Conclusions: There is considerable variability across ACPA-approved centers in the US regarding the timing and completion of otolaryngology and audiologic follow-up for children with CP ± L. This study highlights the importance of following established standards of care and the impact that team composition and access to clinical services can have on equity of care., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In 2023, the Obesity Medicine Association (OMA) published "Compounded peptides: An Obesity Medicine Association Position Statement." Since this publication, the use of compounded peptides for the treatment of obesity has continued to evolve, leading to additional confusion and questions from obesity medicine clinicians and their patients., Methods: This frequently asked questions (FAQ) document and "Call for Action" commentary is based upon the existing evidence and practical clinical experiences of the authors., Results: This FAQ is intended to provide insights beyond the original 2023 OMA Position Statement regarding the use of "compounded peptides" for treating obesity. Three obstacles impair patient access to highly effective peptide anti-obesity medications: insufficient production especially during times of high demand, high costs, and lack of clarity surrounding the role of compounded peptides. Solutions to enhance patient access to these medications lie within the existing legal and regulatory framework and Food and Drug Administration policies. Implementing these solutions necessitates dispelling misinformation and providing clear guidance on the appropriate prescribing and administration of compounded peptides, particularly during times of acknowledged shortage., Conclusion: Among stakeholders with aligned priorities, challenges can often be overcome by collaboration and communication. Towards the goal of providing patient-centered care, the OMA calls on applicable stakeholders (e.g., pharmaceutical companies, compounding pharmacy organizations, health insurance companies, and the Food and Drug Administration) to work collaboratively to achieve a consensus that improves patient access to safe anti-obesity medications. The purpose of this "Call to Action" is to ask stakeholders to provide clinicians and their patients clarity regarding the role of compounded peptide anti-obesity medications during times of FDA-acknowledged shortages. Finally, this FAQ review provides clinicians with a simple and practical checklist respective to the potential use of compounded peptides., Competing Interests: HEB's research site institution has received research grants from 89Bio, Allergan, Alon Medtech/Epitomee, Aligos, Altimmune, Amgen, Anji Pharma, Abbvie, AstraZeneca, Bioage, Bionime, Boehringer Ingelheim, Carmot, Chorus/Bioage, Eli Lilly, Esperion, Evidera, Fractyl, GlaxoSmithKline, HighTide, Home Access, Horizon, Ionis, Kallyope, LG-Chem, Madrigal, Merck, Mineralys, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Satsuma, Selecta, Shionogi, Skye/Birdrock, TIMI, Veru, Viking, and Vivus. HEB has served as a consultant/advisor for 89Bio, Altimmune, Amgen, Boehringer Ingelheim, Kiniksa, HighTide, Lilly, Novo Nordisk, Regeneron, Zomagen, ZyVersa. HEB does not serve as a promotional speaker for any pharmaceutical company. AKF has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. CFB has served as a speaker for Eli Lilly, has investments in Eli Lilly and Novo Nordisk. CY is Chief Medical Officer at Journeys Metabolic, founder of Health Partners MD and WellMi. CY has served as a consultant for Redesign Health Real Chemistry’, IRIS, Retool, and Eli Lilly. SMC is a speaker and advisor for Novo Nordisk, speaker for Eli Lilly; advisor for Abbott Nutrition. LCA has consulted for the Novo Nordisk Obesity Advisory Board and is on the Speaker's Bureau for Eli Lilly., (© 2024 The Authors.)

Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant Staphylococcus aureus (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm. These results demonstrate essential roles for PI3Kγ in inflammatory lung disease and support the potential use of PI3Kγ inhibitors to suppress inflammation in severe infectious diseases.

Active matter spans a wide range of time and length scales, from groups of cells and synthetic self-propelled colloids to schools of fish and flocks of birds. The theoretical framework describing these systems has shown tremendous success in finding universal phenomenology. However, further progress is often burdened by the difficulty of determining forces controlling the dynamics of individual elements within each system. Accessing this local information is pivotal for the understanding of the physics governing an ensemble of active particles and for the creation of numerical models capable of explaining the observed collective phenomena. In this work, we present ActiveNet, a machine-learning tool consisting of a graph neural network that uses the collective motion of particles to learn active and two-body forces controlling their individual dynamics. We verify our approach using numerical simulations of active Brownian particles, active particles undergoing underdamped Langevin dynamics, and chiral active Brownian particles considering different interaction potentials and values of activity. Interestingly, ActiveNet can equally learn conservative or nonconservative forces as well as torques. Moreover, ActiveNet has proven to be a useful tool to learn the stochastic contribution to the forces, enabling the estimation of the diffusion coefficients. Therefore, all coefficients of the equation of motion of Active Brownian Particles are captured. Finally, we apply ActiveNet to experiments of electrophoretic Janus particles, extracting the active and two-body forces controlling colloids' dynamics. On the one side, we have learned that the active force depends on the electric field and area fraction. On the other side, we have also discovered a dependence of the two-body interaction with the electric field that leads us to propose that the dominant force between active colloids is a screened electrostatic interaction with a constant length scale. We believe that the proposed methodological tool, ActiveNet, might open a new avenue for the study and modeling of experimental suspensions of active particles.

Climate change is projected to impact river, lake, and wetland hydrology, with global implications for the condition and productivity of aquatic ecosystems. We integrated Sentinel-1 and Sentinel-2 based algorithms to track monthly surface water extent (2017-2021) for 32 sites across the central United States (U.S.). Median surface water extent was highly variable across sites, ranging from 3.9% to 45.1% of a site. To account for landscape-based differences (e.g., water storage capacity, land use) in the response of surface water extents to meteorological conditions, individual statistical models were developed for each site. Future changes to climate were defined as the difference between 2006-2025 and 2061-2080 using MACA-CMIP5 (MACAv2-METDATA) Global Circulation Models. Time series of climate change adjusted surface water extents were projected. Annually, 19 of the 32 sites under RCP4.5 and 22 of the 32 sites under RCP8.5 were projected to show an average decline in surface water extent, with drying most consistent across the southeast central, southwest central, and midwest central U.S. Projected declines under surface water dry conditions at these sites suggest greater impacts of drought events are likely in the future. Projected changes were seasonally variable, with the greatest decline in surface water extent expected in summer and fall seasons. In contrast, many north central sites showed a projected increase in surface water in most seasons, relative to the 2017-2021 period, likely attributable to projected increases in winter and spring precipitation exceeding increases in projected temperature.

Effective mentoring is crucial for early-career researchers, and formal mentor training programs have demonstrated benefits for participating faculty. To determine how mentor training generalizes to different contexts and populations, we delivered mentor training and evaluated its impact on faculty's self-perceived mentoring skills. We also assessed whether mentor experience with diverse mentee populations or mentor gender influences mentors' self-perceived skills and if training interacted with these self-perceptions. We found mentors with more experience with diverse mentees were more likely to rate their mentoring skills higher than mentors with less experience across most areas assessed. Women rated themselves more highly than men at addressing diversity within the mentoring relationship. Mentors with less experience with diverse mentees gained the most training-related benefits in fostering independence skills. Training improved faculty self-perceived mentoring skills in all areas assessed. These results suggest while mentor training can benefit all involved, it can be especially useful for those newer to mentoring.

Streamflow-duration assessment methods (SDAMs) are rapid, indicator-based tools for classifying streamflow duration (e.g., intermittent vs perennial flow) at the reach scale. Indicators are easily assessed stream properties used as surrogates of flow duration, which is too resource intensive to measure directly for many reaches. Invertebrates are commonly used as SDAM indicators because many are not highly mobile, and different species have life stages that require flow for different durations and times of the year. The objectives of this study were to 1) identify invertebrate taxa that can be used as SDAM indicators to distinguish between stream reaches having intermittent and perennial flow, 2) to compare indicator strength across different taxonomic and numeric resolutions, and 3) to assess the relative importance of season and habitat type on the ability of invertebrates to predict streamflow-duration class. We used 2 methods, random forest models and indicator species analysis, to analyze aquatic and terrestrial invertebrate data (presence/absence, density, and biomass) at the family and genus levels from 370 samples collected from both erosional and depositional habitats during both wet and dry seasons. In total, 36 intermittent and 53 perennial reaches were sampled along 31 forested headwater streams in 4 level II ecoregions across the United States. Random forest models for family- and genus-level datasets had stream classification accuracy ranging from 88.9 to 93.2%, with slightly higher accuracy for density than for presence/absence and biomass datasets. Season (wet/dry) tended to be a stronger predictor of streamflow-duration class than habitat (erosional/depositional). Many taxa at the family (58.8%) and genus level (61.6%) were collected from both intermittent and perennial reaches, and most taxa that were exclusive to 1 streamflow-duration class were rarely collected. However, 23 family-level or higher taxa (20 aquatic and 3 terrestrial) and 44 aquatic genera were identified as potential indicators of streamflow-duration class for forested headwater streams. The utility of the potential indicators varied across level II ecoregions in part because of representation of intermittent and perennial reaches in the dataset but also because of variable ecological responses to drying among species. Aquatic invertebrates have been an important field indicator of perennial reaches in existing SDAMs, but our findings highlight how including aquatic and terrestrial invertebrates as indicators of intermittent reaches can further maximize the data collected for streamflow-duration classifications.

This study assists the interpretation of glass and paint evidence by filling an existing gap in the background occurrence that reflects the socioeconomic and demographic circumstances in the United States. The collection was performed in a college US city (Morgantown, West Virginia) to determine the effect of the type of clothing worn at different seasons on the presence of glass and paint. Tape lifts and sole scrapings (1038) were collected from 210 participants and up to six clothing and footwear areas per individual. Glass fragments were analyzed via polarized light microscopy (PLM), refractive index (RI), micro-X-Ray fluorescence (μXRF), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), while paint specimens were examined by light microscopy and infrared spectroscopy (μFTIR). Higher occurrences of glass and paint were found in the winter season. The winter collection yielded 10 glass fragments and 68 paint particles, whereas the summer collection resulted in one glass fragment and 23 paint particles. The percentage of individuals with traces varied between seasons; 7% of individuals in the winter and 0.9% in the summer had glass, whereas 36% of individuals in the winter and 19% in the summer bore paint. Lastly, when considering the overall garment and footwear areas, glass was detected in 1.4% of the winter set, compared to 0.2% in the summer collection; paint was found in 9.2% of the winter collection, whereas only 4.2% was found in the summer set. There were no instances where both glass and paint were detected on the clothing and footwear of the same individual., (© 2023 American Academy of Forensic Sciences.)

Background: Certification of obesity medicine for physicians in the United States occurs mainly via the American Board of Obesity Medicine (ABOM). Obesity medicine is not recognized as a subspecialty by the American Board of Medical Specialties (ABMS) or the American Osteopathic Association (AOA). This review examines the value of specialization, status of current ABOM Diplomates, governing bodies involved in ABMS/AOA Board Certification, and the advantages and disadvantages of an ABMS/AOA recognized obesity medicine subspecialty., Methods: Data for this review were derived from PubMed and appliable websites. Content was driven by the expertise, insights, and perspectives of the authors., Results: The existing ABOM obesity medicine certification process has resulted in a dramatic increase in the number of Obesity Medicine Diplomates. If ABMS/AOA were to recognize obesity medicine as a subspecialty under an existing ABMS Member Board, then Obesity Medicine would achieve a status like other ABMS recognized subspecialities. However, the transition of ABOM Diplomates to ABMS recognized subspecialists may affect the kinds and the number of physicians having an acknowledged focus on obesity medicine care. Among transition issues to consider include: (1) How many ABMS Member Boards would oversee Obesity Medicine as a subspecialty and which physicians would be eligible? (2) Would current ABOM Diplomates be required to complete an Obesity Medicine Fellowship? If not, then what would be the process for a current ABOM Diplomate to transition to an ABMS-recognized Obesity Medicine subspecialist (i.e., "grandfathering criteria")? and (3) According to the ABMS, do enough Obesity Medicine Fellowship programs exist to recognize Obesity Medicine as a subspecialty?, Conclusions: Decisions regarding a transition to an ABMS recognized Obesity Medicine Subspecialty versus retention of the current ABOM Diplomate Certification should consider which best facilitates medical access and care to patients with obesity, and which best helps obesity medicine clinicians be recognized for their expertise., (© 2023 The Authors.)

E-cigarette (E-cig) inhalation affects health status by modulating inflammation profiles in several organs, including the brain, lung, heart, and colon. The effect of flavored fourth-generation pod-based E-cigs (JUUL) on murine gut inflammation is modulated by both flavor and exposure period. Exposure of mice to JUUL mango and JUUL mint for one month upregulated inflammatory cytokines, particularly TNF-α, IL-6, and Cxcl-1 (IL-8). JUUL Mango effects were more prominent than those incurred by JUUL Mint after one month of exposure. However, JUUL Mango reduced the expression of colonic inflammatory cytokines after three months of exposure. In this protocol, we detail the process of RNA isolation from the mouse colon and the use of extracted RNA in profiling the inflammatory milieu. Efficient RNA extraction from the murine colon is the most important step in the evaluation of inflammatory transcripts in the colon., Competing Interests: Competing interestsThe authors declare there is no conflict of interest., (Copyright © 2023 The Authors; This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).)

Introduction: Sorghum ( Sorghum bicolor (L.) Moench) is an agriculturally and economically important staple crop that has immense potential as a bioenergy feedstock due to its relatively high productivity on marginal lands. To capitalize on and further improve sorghum as a potential source of sustainable biofuel, it is essential to understand the genomic mechanisms underlying complex traits related to yield, composition, and environmental adaptations., Methods: Expanding on a recently developed mapping population, we generated de novo genome assemblies for 10 parental genotypes from this population and identified a comprehensive set of over 24 thousand large structural variants (SVs) and over 10.5 million single nucleotide polymorphisms (SNPs)., Results: We show that SVs and nonsynonymous SNPs are enriched in different gene categories, emphasizing the need for long read sequencing in crop species to identify novel variation. Furthermore, we highlight SVs and SNPs occurring in genes and pathways with known associations to critical bioenergy-related phenotypes and characterize the landscape of genetic differences between sweet and cellulosic genotypes., Discussion: These resources can be integrated into both ongoing and future mapping and trait discovery for sorghum and its myriad uses including food, feed, bioenergy, and increasingly as a carbon dioxide removal mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Voelker, Krishnan, Chougule, Alexander, Lu, Olson, Ware, Songsomboon, Ponce, Brenton, Boatwright and Cooper.)

Headwater streams and inland wetlands provide essential functions that support healthy watersheds and downstream waters. However, scientists and aquatic resource managers lack a comprehensive synthesis of national and state stream and wetland geospatial datasets and emerging technologies that can further improve these data. We conducted a review of existing United States (US) federal and state stream and wetland geospatial datasets, focusing on their spatial extent, permanence classifications, and current limitations. We also examined recent peer-reviewed literature for emerging methods that can potentially improve the estimation, representation, and integration of stream and wetland datasets. We found that federal and state datasets rely heavily on the US Geological Survey's National Hydrography Dataset for stream extent and duration information. Only eleven states (22%) had additional stream extent information and seven states (14%) provided additional duration information. Likewise, federal and state wetland datasets primarily use the US Fish and Wildlife Service's National Wetlands Inventory (NWI) Geospatial Dataset, with only two states using non-NWI datasets. Our synthesis revealed that LiDAR-based technologies hold promise for advancing stream and wetland mapping at limited spatial extents. While machine learning techniques may help to scale-up these LiDAR-derived estimates, challenges related to preprocessing and data workflows remain. High-resolution commercial imagery, supported by public imagery and cloud computing, may further aid characterization of the spatial and temporal dynamics of streams and wetlands, especially using multi-platform and multi-temporal machine learning approaches. Models integrating both stream and wetland dynamics are limited, and field-based efforts must remain a key component in developing improved headwater stream and wetland datasets. Continued financial and partnership support of existing databases is also needed to enhance mapping and inform water resources research and policy decisions.

Objective: To evaluate the degree of symmetry of knee osteoarthritis (OA) structural severity and progression of participants with a mean follow-up time of 3.8 years., Design: Participants from the Genetics of Generalized Osteoarthritis (GOGO) study (n = 705) were selected on the basis of radiographic evidence of OA in at least 1 knee, availability of radiographs at baseline and follow-up, and no history of prior knee injury or surgery. Incidence and progression of osteoarthritis were determined by radiographic Kellgren-Lawrence (KL) grade; compartmental OA progression was determined by change in joint space width of lateral and medial tibiofemoral compartments. Total OA progression was the sum of change in KL grade of both knees., Results: Compared with left knees, right knees had more severe KL grades at baseline (p = 0.0002) and follow-up (p = 0.0004), McNemar's χ 2 = 34.16 and 26.08, respectively; however, both knees progressed similarly (p = 0.121, McNemar's χ 2 = 10.09). Compartmental changes were symmetric across knees: medial r = 0.287, p = 0.0002; lateral r = 0.593, p = 0.0002. Change in joint space width in the medial compartment was negatively correlated with change in the lateral compartment of the same knee (left knees: r = -0.293, p = 0.021; right knees: r = -0.195, p = 0.0002)., Conclusions: Although right knees tended to have more severe OA at both baseline and follow-up, radiographic progression did not differ by knee and compartmental progression correlated across knees. Given this trend in generalized OA, the risk of progression for both knees should be considered, even if only one knee has radiographic OA at baseline., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest related to this work.

Watershed resilience is the ability of a watershed to maintain its characteristic system state while concurrently resisting, adapting to, and reorganizing after hydrological (for example, drought, flooding) or biogeochemical (for example, excessive nutrient) disturbances. Vulnerable waters include non-floodplain wetlands and headwater streams, abundant watershed components representing the most distal extent of the freshwater aquatic network. Vulnerable waters are hydrologically dynamic and biogeochemically reactive aquatic systems, storing, processing, and releasing water and entrained (that is, dissolved and particulate) materials along expanding and contracting aquatic networks. The hydrological and biogeochemical functions emerging from these processes affect the magnitude, frequency, timing, duration, storage, and rate of change of material and energy fluxes among watershed components and to downstream waters, thereby maintaining watershed states and imparting watershed resilience. We present here a conceptual framework for understanding how vulnerable waters confer watershed resilience. We demonstrate how individual and cumulative vulnerable-water modifications (for example, reduced extent, altered connectivity) affect watershed-scale hydrological and biogeochemical disturbance response and recovery, which decreases watershed resilience and can trigger transitions across thresholds to alternative watershed states (for example, states conducive to increased flood frequency or nutrient concentrations). We subsequently describe how resilient watersheds require spatial heterogeneity and temporal variability in hydrological and biogeochemical interactions between terrestrial systems and down-gradient waters, which necessitates attention to the conservation and restoration of vulnerable waters and their downstream connectivity gradients. To conclude, we provide actionable principles for resilient watersheds and articulate research needs to further watershed resilience science and vulnerable-water management.

Objective: To evaluate effects of physical activity and food consumption on plasma concentrations of free and total transforming growth factor beta-1 (TGF-β1), beta-2 (TGF-β2), and beta-3 (TGF-β3) in individuals with knee osteoarthritis (OA)., Methods: Participants ( n = 40 in 2 cohorts of 20; mean age 70 years) with radiographic knee OA were admitted overnight for serial blood sampling. Cohorts 1 and 2 assessed the impacts of food intake and activity, respectively, on TGF-β concentrations. Cohort 1 blood draws included 2 hours postprandial the evening of day 1 (T3), fasting before rising on day 2 (T0), nonfasting 1 hour after rising (T1B), and 4 hours after rising (T2). Cohort 2 blood draws included T3, T0, fasting 1 hour after rising and performing activities of daily living (T1A), and nonfasting 2 hours after rising (T1B). By sandwich ELISAs, we quantified plasma free and total TGF-β1 concentrations in all samples, and plasma total TGF-β2 and TGF-β3 in cohort 2., Results: Free TGF-β1 represented a small fraction of the total systemic concentration (mean 0.026%). In cohort 2, free and total TGF-β1 and total TGF-β2 concentration significantly increased in fasting samples collected after an hour (T1A) of activities of daily living (free TGF-β1: P = 0.006; total TGF-β1: P < 0.001; total TGF-β2: P = 0.001). Total TGF-β3 increased nonsignificantly following activity ( P = 0.590) and decreased ( P = 0.035) after food consumption while resting (T1B)., Conclusions: Increased plasma concentrations of TGF-β with physical activity suggests activity should be standardized prior to TGF-β1 analyses.

Objective: To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis., Methods: Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18)., Results: BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain., Conclusions: To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation., (© 2021. The Author(s).)

Severe asthma accounts for almost half the cost associated with asthma. Severe asthma is driven by heterogeneous molecular mechanisms. Conventional clinical trial design often lacks the power and efficiency to target subgroups with specific pathobiological mechanisms. Furthermore, the validation and approval of new asthma therapies is a lengthy process. A large proportion of that time is taken by clinical trials to validate asthma interventions. The National Institutes of Health Precision Medicine in Severe and/or Exacerbation Prone Asthma (PrecISE) program was established with the goal of designing and executing a trial that uses adaptive design techniques to rapidly evaluate novel interventions in biomarker-defined subgroups of severe asthma, while seeking to refine these biomarker subgroups, and to identify early markers of response to therapy. The novel trial design is an adaptive platform trial conducted under a single master protocol that incorporates precision medicine components. Furthermore, it includes innovative applications of futility analysis, cross-over design with use of shared placebo groups, and early futility analysis to permit more rapid identification of effective interventions. The development and rationale behind the study design are described. The interventions chosen for the initial investigation and the criteria used to identify these interventions are enumerated. The biomarker-based adaptive design and analytic scheme are detailed as well as special considerations involved in the final trial design., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

We study a two-dimensional system composed by Active Brownian Particles (ABPs), focusing on the onset of Motility Induced Phase Separation (MIPS), by means of molecular dynamics simulations. For a pure hard-disk system with no translational diffusion, the phase diagram would be completely determined by their density and Péclet number. In our model, two additional effects are present: translational noise and the overlap of particles; we study the effects of both in the phase space. As we show, the second effect can be mitigated if we use, instead of the standard Weeks-Chandler-Andersen potential, a stiffer potential: the pseudo-hard sphere potential. Moreover, in determining the boundary of our phase space, we explore different approaches to detect MIPS and conclude that observing dynamical features, via the non-Gaussian parameter, is more efficient than observing structural ones, such as through the local density distribution function. We also demonstrate that the Vogel-Fulcher equation successfully reproduces the decay of the diffusion as a function of density, with the exception of very high densities. Thus, in this regard, the ABP system behaves similar to a fragile glass.

The Upper Missouri River headwaters (UMH) basin (36 400 km 2 ) depends on its river corridors to support irrigated agriculture and world-class trout fisheries. We evaluated trends (1984-2016) in riparian wetness, an indicator of the riparian condition, in peak irrigation months (June, July and August) for 158 km 2 of riparian area across the basin using the Landsat normalized difference wetness index (NDWI). We found that 8 of the 19 riparian reaches across the basin showed a significant drying trend over this period, including all three basin outlet reaches along the Jefferson, Madison and Gallatin rivers. The influence of upstream climate was quantified using per reach random forest regressions. Much of the interannual variability in the NDWI was explained by climate, especially by drought indices and annual precipitation, but the significant temporal drying trends persisted in the NDWI-climate model residuals, indicating that trends were not entirely attributable to climate. Over the same period we documented a basin-wide shift from 9 % of agriculture irrigated with center-pivot irrigation to 50 % irrigated with center-pivot irrigation. Riparian reaches with a drying trend had a greater increase in the total area with center-pivot irrigation (within reach and upstream from the reach) relative to riparian reaches without such a trend ( p < 0.05). The drying trend, however, did not extend to river discharge. Over the same period, stream gages ( n = 7) showed a positive correlation with riparian wetness ( p < 0.05) but no trend in summer river discharge, suggesting that riparian areas may be more sensitive to changes in irrigation return flows relative to river discharge. Identifying trends in riparian vegetation is a critical precursor for enhancing the resiliency of river systems and associated riparian corridors., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

Switching on high activity in a relatively dense system of active Janus colloids, we observe fast clustering, followed by cluster aggregation towards full phase separation. The phase separation process is however interrupted when large enough clusters start breaking apart. Following the cluster size distribution as a function of time, we identify three successive dynamical regimes. Tracking both the particle positions and orientations, we characterize the structural ordering and alignment in the growing clusters and thereby unveil the mechanisms at play in these regimes. In particular, we identify how alignment between the neighboring particles is responsible for the interruption of the full phase separation. Our large scale quantification of the phase separation kinetics in active colloids points towards the new physics observed when both alignment and short-range repulsions are present.

We describe a collection of aquatic and wetland habitats in an inland landscape, and their occurrence within a terrestrial matrix, as a "freshwater ecosystem mosaic" (FEM). Aquatic and wetland habitats in any FEM can vary widely, from permanently ponded lakes, to ephemerally ponded wetlands, to groundwater-fed springs, to flowing rivers and streams. The terrestrial matrix can also vary, including in its influence on flows of energy, materials, and organisms among ecosystems. Biota occurring in a specific region are adapted to the unique opportunities and challenges presented by spatial and temporal patterns of habitat types inherent to each FEM. To persist in any given landscape, most species move to recolonize habitats and maintain mixtures of genetic materials. Species also connect habitats through time if they possess needed morphological, physiological, or behavioral traits to persist in a habitat through periods of unfavorable environmental conditions. By examining key spatial and temporal patterns underlying FEMs, and species-specific adaptations to these patterns, a better understanding of the structural and functional connectivity of a landscape can be obtained. Fully including aquatic, wetland, and terrestrial habitats in FEMs facilitates adoption of the next generation of individual-based models that integrate the principles of population, community, and ecosystem ecology., (© 2018 The Authors. This article is a U.S. Government work and is in the public domain in the USA.)

Wetlands are often dominant features in low relief, depressional landscapes and provide an array of hydrologically driven ecosystem services. However, contemporary models do not adequately represent the role of spatially distributed wetlands in watershed-scale water storage and flows. Such tools are critical to better understand wetland hydrological, biogeochemical, and biological functions and predict management and policy outcomes at varying spatial scales. To develop a new approach for simulating depressional landscapes, we modified the Soil and Water Assessment Tool (SWAT) model to incorporate improved representations of depressional wetland structure and hydrological processes. Specifically, we refined the model to incorporate: (1) water storage capacity and surface flowpaths of individual wetlands and (2) local wetland surface and subsurface exchange. We utilized this model, termed SWAT-DSF (DSF for Depressional Storage and Flows), to simulate the ~289 km 2 Greensboro watershed within the Delmarva Peninsula of the US Coastal Plain. Model calibration and verification used both daily streamflow observations and remotely sensed surface water extent data (ca. 2-week temporal resolution), allowing us to assess model performance with respect to both streamflow and watershed inundation patterns. Our findings demonstrate that SWAT-DSF can successfully replicate distributed wetland processes and resultant watershed-scale hydrology. SWAT-DSF provides improved temporal and spatial characterization of watershed-scale water storage and flows in depressional landscapes, providing a new tool to quantify wetland functions at broad spatial scales., Competing Interests: Conflict of interest Authors declare no conflict of interest.

Watershed integrity, the capacity of a watershed to support and maintain ecological processes essential to the sustainability of services provided to society, can be influenced by a range of landscape and in-stream factors. Ecological response data from four intensively monitored case study watersheds exhibiting a range of environmental conditions and landscape characteristics across the United States were used to evaluate the performance of a national level Index of Watershed Integrity (IWI) at regional and local watershed scales. Using Pearson's correlation coefficient ( r ), and Spearman's rank correlation coefficient ( r s ), response variables displayed highly significant relationships and were significantly correlated with IWI and ICI (Index of Catchment Integrity) values at all watersheds. Nitrogen concentration and flux-related watershed response metrics exhibited significantly strong negative correlations across case study watersheds, with absolute correlations (| r |) ranging from 0.48 to 0.97 for IWI values, and 0.31 to 0.96 for ICI values. Nitrogen-stable isotope ratios measured in chironomids and periphyton from streams and benthic organic matter from lake sediments also demonstrated strong negative correlations with IWI values, with | r | ranging from 0.47 to 0.92, and 0.35 to 0.89 for correlations with ICI values. This evaluation of the performance of national watershed and catchment integrity metrics and their strong relationship with site level responses provides weight-of-evidence support for their use in state, local and regionally focused applications., Competing Interests: Conflicts of Interest The authors declare no conflict of interest. Co-author Jennifer James’ contribution to this research was supported in part by an appointment to the Research Participation Program for the U.S. EPA, Office of Research and Development, administered by the Oak Ridge Institute for Science and Education through an inter-agency agreement between the U.S. Department of Energy and U.S. EPA. This manuscript has been subjected to Agency review and has been approved for publication. The views expressed in this article are those of the authors and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency. Any mention of trade names, products, or services does not imply an endorsement by the U.S. Government or the U.S. Environmental Protection Agency. The EPA does not endorse any commercial products, services, or enterprises.

Streams, riparian areas, floodplains, alluvial aquifers and downstream waters (e.g., large rivers, lakes, oceans) are interconnected by longitudinal, lateral, and vertical fluxes of water, other materials and energy. Collectively, these interconnected waters are called fluvial hydrosystems. Physical and chemical connectivity within fluvial hydrosystems is created by the transport of nonliving materials (e.g., water, sediment, nutrients, contaminants) which either do or do not chemically change (chemical and physical connections, respectively). A substantial body of evidence unequivocally demonstrates physical and chemical connectivity between streams and riparian wetlands and downstream waters. Streams and riparian wetlands are structurally connected to downstream waters through the network of continuous channels and floodplain form that make these systems physically contiguous, and the very existence of these structures provides strong geomorphologic evidence for connectivity. Functional connections between streams and riparian wetlands and their downstream waters vary geographically and over time, based on proximity, relative size, environmental setting, material disparity, and intervening units. Because of the complexity and dynamic nature of connections among fluvial hydrosystem units, a complete accounting of the physical and chemical connections and their consequences to downstream waters should aggregate over multiple years to decades.

Understanding hydrologic connectivity between wetlands and perennial streams is critical to understanding the reliance of stream flow on inputs from wetlands. We used the isotopic evaporation signal in water and remote sensing to examine wetland-stream hydrologic connectivity within the Pipestem Creek watershed, North Dakota, a watershed dominated by prairie-pothole wetlands. Pipestem Creek exhibited an evaporated-water signal that had approximately half the isotopic-enrichment signal found in most evaporatively enriched prairie-pothole wetlands. Groundwater adjacent to Pipestem Creek had isotopic values that indicated recharge from winter precipitation and had no significant evaporative enrichment, indicating that enriched surface water did not contribute significantly to groundwater discharging into Pipestem Creek. The estimated surface-water area necessary to generate the evaporation signal within Pipestem Creek was highly dynamic, varied primarily with the amount of discharge, and was typically greater than the immediate Pipestem Creek surface-water area, indicating that surficial flow from wetlands contributed to stream flow throughout the summer. We propose a dynamic range of spilling thresholds for prairie-pothole wetlands across the watershed allowing for wetland inputs even during low flow periods. Combining Landsat estimates with the isotopic approach allowed determination of potential (Landsat) and actual (isotope) contributing areas in wetland-dominated systems. This combined approach can give insights into the changes in location and magnitude of surface water and groundwater pathways over time. This approach can be used in other areas where evaporation from wetlands results in a sufficient evaporative isotopic signal.

We reviewed the scientific literature on non-floodplain wetlands (NFWs), freshwater wetlands typically located distal to riparian and floodplain systems, to determine hydrological, physical, and chemical functioning and stream and river network connectivity. We assayed the literature for source, sink, lag, and transformation functions, as well as factors affecting connectivity. We determined NFWs are important landscape components, hydrologically, physically, and chemically affecting downstream aquatic systems. NFWs are hydrologic and chemical sources for other waters, hydrologically connecting across long distances and contributing compounds such as methylated mercury and dissolved organic matter. NFWs reduced flood peaks and maintained baseflows in stream and river networks through hydrologic lag and sink functions, and sequestered or assimilated substantial nutrient inputs through chemical sink and transformative functions. Landscape-scale connectivity of NFWs affects water and material fluxes to downstream river networks, substantially modifying the characteristics and function of downstream waters. Many factors determine the effects of NFW hydrological, physical, and chemical functions on downstream systems, and additional research quantifying these factors and impacts is warranted. We conclude NFWs are hydrologically, chemically, and physically interconnected with stream and river networks though this connectivity varies in frequency, duration, magnitude, and timing.

Geographically isolated wetlands, those entirely surrounded by uplands, provide numerous landscape-scale ecological functions, many of which are dependent on the degree to which they are hydrologically connected to nearby waters. There is a growing need for field-validated, landscape-scale approaches for classifying wetlands on the basis of their expected degree of hydrologic connectivity with stream networks. This study quantified seasonal variability in surface hydrologic connectivity (SHC) patterns between forested Delmarva bay wetland complexes and perennial/intermittent streams at 23 sites over a full-water year (2014-2015). Field data were used to develop metrics to predict SHC using hypothesized landscape drivers of connectivity duration and timing. Connection duration was most strongly related to the number and area of wetlands within wetland complexes as well as the channel width of the temporary stream connecting the wetland complex to a perennial/intermittent stream. Timing of SHC onset was related to the topographic wetness index and drainage density within the catchment. Stepwise regression modelling found that landscape metrics could be used to predict SHC duration as a function of wetland complex catchment area, wetland area, wetland number, and soil available water storage (adj-R 2  = 0.74, p < .0001). Results may be applicable to assessments of forested depressional wetlands elsewhere in the U.S. Mid-Atlantic and Southeastern Coastal Plain, where climate, landscapes, and hydrological inputs and losses are expected to be similar to the study area.

Globally, hydrologic modifications such as ditching and subsurface drainage have significantly reduced wetland water storage capacity (i.e., volume of surface water a wetland can retain) and consequent wetland functions. While wetland area has been well documented across many landscapes and used to guide restoration efforts, few studies have directly quantified the associated wetland storage capacity. Here, we present a novel raster-based approach to quantify both contemporary and potential (i.e., restorable) storage capacities of individual depressional basins across landscapes. We demonstrate the utility of this method by applying it to the Delmarva Peninsula, a region punctuated by both depressional wetlands and drainage ditches. Across the entire peninsula, we estimated that restoration (i.e., plugging ditches) could increase storage capacity by 80%. Focusing on an individual watershed, we found that over 59% of restorable storage capacity occurs within 20 m of the drainage network, and that 93% occurs within 1 m elevation of the drainage network. Our demonstration highlights widespread ditching in this landscape, spatial patterns of both contemporary and potential storage capacities, and clear opportunities for hydrologic restoration. In Delmarva and more broadly, our novel approach can inform targeted landscape-scale conservation and restoration efforts to optimize hydrologically mediated wetland functions.

Freshwater ecosystems are linked at various spatial and temporal scales by movements of biota adapted to life in water. We review the literature on movements of aquatic organisms that connect different types of freshwater habitats, focusing on linkages from streams and wetlands to downstream waters. Here, streams, wetlands, rivers, lakes, ponds, and other freshwater habitats are viewed as dynamic freshwater ecosystem mosaics (FEMs) that collectively provide the resources needed to sustain aquatic life. Based on existing evidence, it is clear that biotic linkages throughout FEMs have important consequences for biological integrity and biodiversity. All aquatic organisms move within and among FEM components, but differ in the mode, frequency, distance, and timing of their movements. These movements allow biota to recolonize habitats, avoid inbreeding, escape stressors, locate mates, and acquire resources. Cumulatively, these individual movements connect populations within and among FEMs and contribute to local and regional diversity, resilience to disturbance, and persistence of aquatic species in the face of environmental change. Thus, the biological connections established by movement of biota among streams, wetlands, and downstream waters are critical to the ecological integrity of these systems. Future research will help advance our understanding of the movements that link FEMs and their cumulative effects on downstream waters.

Interest in connectivity has increased in the aquatic sciences, partly because of its relevance to the Clean Water Act. This paper has two objectives: (1) provide a framework to understand hydrological, chemical, and biological connectivity, focusing on how headwater streams and wetlands connect to and contribute to rivers; and (2) review methods to quantify hydrological and chemical connectivity. Streams and wetlands affect river structure and function by altering material and biological fluxes to the river; this depends on two factors: (1) functions within streams and wetlands that affect material fluxes; and (2) connectivity (or isolation) from streams and wetlands to rivers that allows (or prevents) material transport between systems. Connectivity can be described in terms of frequency, magnitude, duration, timing, and rate of change. It results from physical characteristics of a system, e.g., climate, soils, geology, topography, and the spatial distribution of aquatic components. Biological connectivity is also affected by traits and behavior of the biota. Connectivity can be altered by human impacts, often in complex ways. Because of variability in these factors, connectivity is not constant but varies over time and space. Connectivity can be quantified with field-based methods, modeling, and remote sensing. Further studies using these methods are needed to classify and quantify connectivity of aquatic ecosystems and to understand how impacts affect connectivity.

Wetlands across the globe provide extensive ecosystem services. However, many wetlands - especially those surrounded by uplands, often referred to as geographically isolated wetlands (GIWs) - remain poorly protected. Protection and restoration of wetlands frequently requires information on their hydrologic connectivity to other surface waters, and their cumulative watershed-scale effects. The integration of measurements and models can supply this information. However, the types of measurements and models that should be integrated are dependent on management questions and information compatibility. We summarize the importance of GIWs in watersheds and discuss what wetland connectivity means in both science and management contexts. We then describe the latest tools available to quantify GIW connectivity and explore crucial next steps to enhancing and integrating such tools. These advancements will ensure that appropriate tools are used in GIW decision making and maintaining the important ecosystem services that these wetlands support.

The dependence of downstream waters on upstream ecosystems necessitates an improved understanding of watershed-scale hydrological interactions including connections between wetlands and streams. An evaluation of such connections is challenging when, (1) accurate and complete datasets of wetland and stream locations are often not available and (2) natural variability in surface-water extent influences the frequency and duration of wetland/stream connectivity. The Upper Choptank River watershed on the Delmarva Peninsula in eastern Maryland and Delaware is dominated by a high density of small, forested wetlands. In this analysis, wetland/stream surface water connections were quantified using multiple wetland and stream datasets, including headwater streams and depressions mapped from a lidar-derived digital elevation model. Surface-water extent was mapped across the watershed for spring 2015 using Landsat-8, Radarsat-2 and Worldview-3 imagery. The frequency of wetland/stream connections increased as a more complete and accurate stream dataset was used and surface-water extent was included, in particular when the spatial resolution of the imagery was finer (i.e., <10 m). Depending on the datasets used, 12% to 60% of wetlands by count (21% to 93% of wetlands by area) experienced surface-water interactions with streams during spring 2015. This translated into a range of 50% to 94% of the watershed contributing direct surface water runoff to streamflow. This finding suggests that our interpretation of the frequency and duration of wetland/stream connections will be influenced not only by the spatial and temporal characteristics of wetlands, streams and potential flowpaths, but also by the completeness, accuracy and resolution of input datasets.

When we think about connections in and among aquatic systems, we typically envision clear headwater streams flowing into downstream rivers, river floodwaters spilling out onto adjacent floodplains, or groundwater connecting wetlands to lakes and streams. However, there is another layer of connectivity moving materials among freshwater systems, one with connections that are not always tied to down-gradient flows of surface waters and groundwater. These movements are those of organisms, key components of virtually every freshwater system on the planet. In their movements across the landscape, biota connect aquatic systems in often-overlooked ways.

Ecosystem function in rivers, lakes and coastal waters depends on the functioning of upstream aquatic ecosystems, necessitating an improved understanding of watershed-scale interactions including variable surface-water flows between wetlands and streams. As surface water in the Prairie Pothole Region expands in wet years, surface-water connections occur between many depressional wetlands and streams. Minimal research has explored the spatial patterns and drivers for the abundance of these connections, despite their potential to inform resource management and regulatory programs including the U.S. Clean Water Act. In this study, wetlands were identified that did not intersect the stream network, but were shown with Landsat images (1990-2011) to become merged with the stream network as surface water expanded. Wetlands were found to spill into or consolidate with other wetlands within both small (2-10 wetlands) and large (>100 wetlands) wetland clusters, eventually intersecting a stream channel, most often via a riparian wetland. These surface-water connections occurred over a wide range of wetland distances from streams (averaging 90-1400 m in different ecoregions). Differences in the spatial abundance of wetlands that show a variable surface-water connection to a stream were best explained by smaller wetland-to-wetland distances, greater wetland abundance, and maximum surface-water extent. This analysis demonstrated that wetland arrangement and surface water expansion are important mechanisms for depressional wetlands to connect to streams and provides a first step to understanding the frequency and abundance of these surface-water connections across the Prairie Pothole Region., (© The Author(s) 2016.)

Governments worldwide do not adequately protect their limited freshwater systems and therefore place freshwater functions and attendant ecosystem services at risk. The best available scientific evidence compels enhanced protections for freshwater systems, especially for impermanent streams and wetlands outside of floodplains that are particularly vulnerable to alteration or destruction. New approaches to freshwater sustainability - implemented through scientifically informed adaptive management - are required to protect freshwater systems through periods of changing societal needs. One such approach introduced in the US in 2015 is the Clean Water Rule, which clarified the jurisdictional scope for federally protected waters. However, within hours of its implementation litigants convinced the US Court of Appeals for the Sixth Circuit to stay the rule, and the subsequently elected administration has now placed it under review for potential revision or rescission. Regardless of its outcome at the federal level, policy and management discussions initiated by the propagation of this rare rulemaking event have potential far-reaching implications at all levels of government across the US and worldwide. At this timely juncture, we provide a scientific rationale and three policy options for all levels of government to meaningfully enhance protection of these vulnerable waters. A fourth option, a 'do-nothing' approach, is wholly inconsistent with the well-established scientific evidence of the importance of these vulnerable waters.

We evaluated the current literature, coupled with our collective research expertise, on surface-water connectivity of wetlands considered to be "geographically isolated" ( sensu Tiner Wetlands 23:494-516, 2003a) to critically assess the scientific foundation of grouping wetlands based on the singular condition of being surrounded by uplands. The most recent research on wetlands considered to be "geographically isolated" shows the difficulties in grouping an ecological resource that does not reliably indicate lack of surface water connectivity in order to meet legal, regulatory, or scientific needs. Additionally, the practice of identifying "geographically isolated wetlands" based on distance from a stream can result in gross overestimates of the number of wetlands lacking ecologically important surface-water connections. Our findings do not support use of the overly simplistic label of "geographically isolated wetlands". Wetlands surrounded by uplands vary in function and surface-water connections based on wetland landscape setting, context, climate, and geographic region and should be evaluated as such. We found that the "geographically isolated" grouping does not reflect our understanding of the hydrologic variability of these wetlands and hence does not benefit conservation of the Nation's diverse wetland resources. Therefore, we strongly discourage use of categorizations that provide overly simplistic views of surface-water connectivity of wetlands fully embedded in upland landscapes.

One application of gene flow science is the policy arena. In this article, we describe two examples in which the topic of gene flow has entered into the U.S. national environmental policymaking process: regulation of genetically engineered crops and clarification of the jurisdictional scope of the Clean Water Act. We summarize both current scientific understanding and the legal context within which gene flow science has relevance. We also discuss the process by which scientific knowledge has been synthesized and communicated to decision-makers in these two contexts utilizing the concept of 'boundary work'. Boundary organizations, the work they engage in to bridge the worlds of science, policy, and practice, and the boundary objects they produce to translate scientific knowledge existed in both examples. However, the specific activities and attributes of the objects produced varied based on the needs of the decision-makers. We close with suggestions for how scientists can contribute to or engage in boundary work with policymakers.

Interannual variation in lake extent is well documented in the Prairie Pothole Region, but the role of surface-water expansion, including lake expansion, in merging with and subsuming wetlands across the landscape has been minimally considered. We examined how the expansion of surface-water extent, in particular, the expansion of lakes across parts of the Prairie Pothole Region can alter landscape-level hydrologic connectivity among substantial numbers of previously surficially disconnected wetlands. Temporally static wetland, lake, and stream datasets were fused with temporally varying Landsat-derived surface-water extent maps (1990-2011) to quantify changes in surface-water connectivity. Under deluge conditions, lakes were found to create significantly larger complexes of surficially-connected wetlands relative to non-lake surface-water connections (e.g., only wetlands or wetlands and streams). Analysis of three specific lakes showed that lakes can merge with and subsume wetlands located kilometers to tens of kilometers from the National Wetland Inventory defined lake perimeter. As climate across the Prairie Pothole Region is highly variable, understanding historic patterns of surface-water expansion and contraction under drought-to-deluge conditions will be integral to predicting future effects of climate change on wetland function, loss and influence on other aquatic systems, including downstream waters., (© The Author(s) 2015.)

This review assesses the state of the science on the effects of mountaintop mines and valley fills (MTM-VF) on the physicochemical characteristics of streams in the central Appalachian coalfields of West Virginia, Kentucky, Virginia and Tennessee, USA. We focus on the impacts of mountaintop removal coal mining, which involves removing all - or some portion - of the top of a mountain or ridge to expose and mine one or more coal seams. Excess overburden is disposed in constructed fills in small valleys adjacent to the mining site. MTM-VF leachate persistently increases the downstream concentrations of major ions. Conductivity is a coarse measure of these ions, which are dominated by a distinct mixture of SO(4)(2-), HCO(3)(-), Ca(2+) and Mg(2+), that reflects their source, the oxidation of pyrite to form acid followed by neutralization of the acidity by carbonate minerals within the valley fills. This results in neutral to alkaline pHs, a range at which many metals are relatively insoluble. Other compounds within coal or overburden are solubilized and occur at elevated albeit lower concentrations, including K(+), Na(+), Cl(-), Se and Mn. In terms of physical characteristics, the valley fills act like headwater aquifers, baseflows increase in streams below valley fills and water temperatures exhibit reduced seasonal variation. Peak discharges may be increased in response to intense precipitation events, because of compaction of base surfaces of the MTM-VF areas, but newer approaches to reclamation reduce this compaction and may ameliorate these peak flows. Although the sedimentation pond is intended to capture fine particles that wash downstream from the valley fill, some studies found increased fine sediments in streams downstream from valley fills. However, a proportion of these fines may be eroded from stream banks rather than the valley fills. This is probably a result of the alterations in stream flows., (Published by Elsevier B.V.)

Although potato leafhopper, Empoasca fabae (Harris) (Hemiptera: Cicadellidae), is highly polyphagous, classic host studies do not recognize grapevines (Vitis spp.), as suitable hosts. Recently, injury has been reported and reproduction documented within grape vineyards, suggesting a host expansion for the leafhopper. To document this apparent expansion in host use, we determined whether grape plants were suitable hosts for potato leafhopper reproduction, measured the consequence of feeding injury on gas exchange rates of grape leaves, and compared the susceptibility to feeding injury among cultivars. We found that potato leafhopper adults survived equally well on grape (Vitis vinifera L.), alfalfa (Medicago sativa L.), and fava bean (Vicia faba L.). The total number of offspring was greater on fava bean but did not differ between alfalfa and grape. Injury to grapevines was assessed by measuring gas exchange responses of leaves in field cages and in greenhouse tests. We found marginally significant declines in photosynthesis and transpiration rates in the field (9.6 and 13.2%, respectively), and much stronger effects in greenhouse tests (ranging between 22 and 52%). Our results verify that Vitis is a suitable host, and that potato leafhopper is capable of injuring its gas exchange physiology. We discuss possible explanations for the host expansion, and its potential to damage commercial grapevines.

Plant tolerance to herbivory is a key approach for managing pests. In alfalfa, Medicago sativa, the potato leafhopper, Empoasca fabae, is a major pest as a result of the cascade of plant responses to piercing-sucking injury. To identify tolerance to its injury based on alfalfa physiology, experiments were conducted in the field and greenhouse. In our comparison of the response of field-grown alfalfa cultivars to standardized leafhopper densities, net photosynthesis and transpiration rates of 'Geneva' leaves were reduced by 18 and 21%, respectively, by leafhopper presence compared with a rate change of <1% of resistant 'EverGreen' leaves. Under greenhouse conditions, alfalfa clones varied in their level of gas exchange (net photosynthesis and transpiration) and stem elongation responses to leafhopper injury. For example, in the comparison of seven clones, net photosynthesis declined an average of 40.7% with leafhopper injury, although individual clones varied from 26.6 to 74.3% reduction. Internode elongation after 2 d was 60.3% less on injured stems compared with healthy stems, but again, the individual clones varied from 17.3 to 91.9%. In a time-course study of selected clones, clones varied in their level of injury just after and 3 d after insect removal. Gas exchange responses of all clones recovered by 7 d after cessation of injury. In a choice test, leafhoppers spent similar amounts of time on the susceptible clone and the most tolerant clone; however, their precise feeding behaviors were not measured. Thus, the variable response of clones to injury may be either true physiological tolerance or antixenosis from a change in feeding behavior. This study showed putative tolerance to leafhopper injury among alfalfa genotypes, suggesting that tolerance could be the basis for crop protection in alfalfa from potato leafhopper injury.

An assay using Laurell rocket immunoelectrophoresis has been developed for quantitation of beta-2-microglobulin (beta 2m) and serial levels of beta 2m have been measured in sera obtained daily from 52 patients following renal transplantation. The RIEP assay was performed using 1% low-endosmosis agarose gels containing 4% polyethylene glycol 6000 and the IgG fraction of rabbit antihuman beta 2m. Elevated beta 2m levels pretransplant fell markedly in the first 48 hr posttransplant in all patients with primary functioning grafts. Base-line control values for serum beta 2m were obtained in patients when stable graft function was established. Serum beta 2m levels increased during renal graft rejection, and significant elevations of serum beta 2m were detected at the onset of all graft rejection episodes as compared with control values. It is suggested that serum beta 2m quantitation by rocket immunoelectrophoresis is a simple and valuable assay to assess posttransplant renal graft function.

The circulating levels of pregnancy-specific beta 1-glycoproteins (SP1) were measured in 71 normal pregnant women in Northern Nigeria by immunoelectrophoresis. The levels showed a steady rise up to 34 weeks as in Caucasians and then plateaued with a slight fall just before term. The mean individual values were lower than those found in Caucasians at comparable gestation periods. This was thought to be related to the lower mean fetal weight in the Nigerian women.

Levels of IgG and IgM and complement components C4 and C3 were measured using rate nephelometry and serum levels of beta-2-microglobulin (beta 2m) by rocket immunoelectrophoresis (RIEP) and these assays have been applied serially following cadaveric renal transplantation on 28 patients 14 of whom were treated with cyclosporin A. There were 31 rejection episodes of which 7 were irreversible. Elevated pre-transplant serum beta 2m levels fell rapidly in the first 24-48 hr post-transplant in all patients with primary functioning grafts and the mean base-line control value was 4.5 +/- 1.27 micrograms/ml in patients with stable graft function in the period 5-10 days post-transplant. At the onset of all 31 rejection episodes however the level of beta 2m increased compared to control values and significantly exceeded the 95% confidence limits of +/- 2.0 micrograms/ml. Control values for serum IgG and IgM were significantly lower than paired pre-transplant levels and, whereas IgM increased during rejection episodes with significant differences between paired rejection and control values, no significant changes in IgG levels were detected. In contrast mean control values for C4 and C3 were not significantly different to mean pre-transplant values; however, mean levels of C4 and C3 decreased significantly during rejection episodes compared to both pre-transplant and control values.