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Background: There is debate as to whether recurrent biliary complications are more common in patients who do not have elective cholecystectomy after endoscopic retrograde cholangiopancreatography (ERCP) management of common bile duct (CBD) stones. The aim of this study was to determine the fate of patients with intact gallbladders who have had CBD stones removed at ERCP, and to assess their risk of recurrent biliary symptoms.Methods: We retrospectively identified all patients in our large tertiary center population with intact gallbladders who had an ERCP for CBD stones from December 1999 to March 2002. We determined which patients had subsequent elective cholecystectomy, and the outcomes of patients who did not have elective surgery.Results: 309 patients had CBD stones at ERCP during the study period, of which 139 had intact gallbladders at the time of ERCP. Of these 139 patients 59 had subsequent elective cholecystectomy, 11 by open operation and 48 laparoscopically. Of these 139 patients, 27 had cholecystectomy planned; 47 patients were managed with a wait-and-see strategy, 30 of whom were poor surgical candidates. Of these 47 patients in whom a wait-and-see policy was adopted, 9 (19%) developed complications including recurrent pain and/or abnormal liver function tests (LFTs), recurrent biliary colic, and pancreatitis. Eight of these nine patients were from the poor surgical candidate group. Sphincterotomy had been performed at initial ERCP in all patients.Conclusions: Over half of our population of 139 patients with CBD stones at ERCP and intact gallbladders had actual or planned elective cholecystectomy. For those patients in whom a decision to wait-and-see was made, almost 20% developed complications. Elective cholecystectomy after a finding of choledocholithiasis is supported by many and is a common strategy in our experience. Recurrent biliary complications are relatively common in those who do not undergo elective cholecystectomy, especially those patients who represent a high operative risk. [ABSTRACT FROM AUTHOR]

Methane pyrolysis is known to produce hydrogen and solid carbon in a variety of thermal processes. However, the generated carbon product typically belongs to a low-value amorphous type. Here, we elucidate the thermochemical mechanisms of a reaction that produces high-quality graphite via direct solar methane pyrolysis on a porous substrate. By comparing graphite deposition rates and local reaction zone temperatures of exposed and shadowed regions from the same experiment, we clarify the effects of thermolysis and photolysis in this emission-free process that both decarbonizes a fuel and produces a critical material for the sustainable energy transition., Competing Interests: The authors declare the following competing financial interest(s): Timothy S. Fisher and R. Mitchell Spearrin are co-founders of SolGrapH, Inc., a company specializing in solar-thermal material synthesis. This submitted work is an independent academic study and is not associated with commercial endeavors or intended as a promotion. The other authors have no competing interests to disclose., (© 2024 The Authors. Published by American Chemical Society.)

Recent advancements in DNA techniques, metabarcoding, and bioinformatics could help expand the use of benthic diatoms in monitoring and assessment programs by providing relatively quick and increasingly cost-effective ways to quantify diatom diversity in environmental samples. However, such applications of DNA-based approaches are relatively new, and in the United States, unknowns regarding their applications at large scales exist because only a few small-scale studies have been done. Here, we present results from the first nationwide survey to use DNA metabarcoding (rbcL) of benthic diatoms, which were collected from 1788 streams and rivers across nine ecoregions spanning the conterminous USA. At the national scale, we found that diatom assemblage structure (1) was strongly associated with total phosphorus and total nitrogen concentrations, conductivity, and pH and (2) had clear patterns that corresponded with differences in these variables among the nine ecoregions. These four variables were strong predictors of diatom assemblage structure in ecoregion-specific analyses, but our results also showed that diatom-environment relationships, the importance of environmental variables, and the ranges of these variables within which assemblage changes occurred differed among ecoregions. To further examine how assemblage data could be used for biomonitoring purposes, we used indicator species analysis to identify ecoregion-specific taxa that decreased or increased along each environmental gradient, and we used their relative abundances of gene reads in samples as metrics. These metrics were strongly correlated with their corresponding variable of interest (e.g., low phosphorus diatoms with total phosphorus concentrations), and generalized additive models showed how their relationships compared among ecoregions. These large-scale national patterns and nine sets of ecoregional results demonstrated that diatom DNA metabarcoding is a robust approach that could be useful to monitoring and assessment programs spanning the variety of conditions that exist throughout the conterminous United States., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Nathan J. Smucker, Erik M. Pilgrim, Christopher T. Nietch, Leslie Gains-Germain, Charlie Carpenter, John A. Darling, Lester L. Yuan, Richard M. Mitchell, Amina I. Pollard., (Published by Elsevier B.V.)

Nutrient concentrations in streams vary strongly with flow conditions, and routinely gathered field measurements of nutrients reflect this variability. Diatom assemblage composition has been used in previous studies to infer nutrient concentrations, and because diatoms integrate nutrient concentrations over longer periods of time, diatom inferences may be less susceptible to fluctuations in streamflow. We tested this hypothesis by leveraging differences in the flashiness of streams across a large continental data set. More specifically, we tested whether the variabilities of direct measurements and diatom inferences of dissolved phosphorus and nitrate were greater in flashy versus non-flashy streams. We further considered whether models linking landscape predictor variables to nutrient concentrations yielded consistent results across flashy and non-flashy streams. Our analysis indicated that measured nutrient concentrations were more variable in flashy compared to non-flashy streams and that landscape models identified different important predictors of nutrient concentrations when fit using data from flashy vs. non-flashy streams. In contrast, variabilities of diatom-inferred nutrient concentrations were similar among stream types, as were the important predictor variables (e.g., manure application rates for nitrate and number of wet days for dissolved phosphorus). These analyses indicate that use of diatom-inferred nutrient concentrations can potentially improve efforts to quantify stream nutrient concentrations., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Published by Elsevier B.V.)

Antimicrobial resistance (AMR) is a world-wide public health threat that is projected to lead to 10 million annual deaths globally by 2050. The AMR public health issue has led to the development of action plans to combat AMR, including improved antimicrobial stewardship, development of new antimicrobials, and advanced monitoring. The National Antimicrobial Resistance Monitoring System (NARMS) led by the United States (U.S) Food and Drug Administration along with the U.S. Centers for Disease Control and U.S. Department of Agriculture has monitored antimicrobial resistant bacteria in retail meats, humans, and food animals since the mid 1990's. NARMS is currently exploring an integrated One Health monitoring model recognizing that human, animal, plant, and environmental systems are linked to public health. Since 2020, the U.S. Environmental Protection Agency has led an interagency NARMS environmental working group (EWG) to implement a surface water AMR monitoring program (SWAM) at watershed and national scales. The NARMS EWG divided the development of the environmental monitoring effort into five areas: (i) defining objectives and questions, (ii) designing study/sampling design, (iii) selecting AMR indicators, (iv) establishing analytical methods, and (v) developing data management/analytics/metadata plans. For each of these areas, the consensus among the scientific community and literature was reviewed and carefully considered prior to the development of this environmental monitoring program. The data produced from the SWAM effort will help develop robust surface water monitoring programs with the goal of assessing public health risks associated with AMR pathogens in surface water (e.g., recreational water exposures), provide a comprehensive picture of how resistant strains are related spatially and temporally within a watershed, and help assess how anthropogenic drivers and intervention strategies impact the transmission of AMR within human, animal, and environmental systems., Competing Interests: Conflict of interest 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.

Patient-reported outcomes (PROs) are increasingly used in healthcare research to provide evidence of the benefits and risks of interventions from the patient perspective and to inform regulatory decisions and health policy. The use of PROs in clinical practice can facilitate symptom monitoring, tailor care to individual needs, aid clinical decision-making and inform value-based healthcare initiatives. Despite their benefits, there are concerns that the potential burden on respondents may reduce their willingness to complete PROs, with potential impact on the completeness and quality of the data for decision-making. We therefore conducted an initial literature review to generate a list of candidate recommendations aimed at reducing respondent burden. This was followed by a two-stage Delphi survey by an international multi-stakeholder group. A consensus meeting was held to finalize the recommendations. The final consensus statement includes 19 recommendations to address PRO respondent burden in healthcare research and clinical practice. If implemented, these recommendations may reduce PRO respondent burden., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Restoration efforts often focus on changing the composition and structure of invaded plant communities, with two implicit assumptions: (1) functional interactions with species of other trophic levels, such as pollinators, will reassemble automatically when native plant diversity is restored and (2) restored communities will be more resilient to future stressors. However, the impact of restoration activities on pollinator richness, plant-pollinator interaction network structure, and network robustness is incompletely understood. Leveraging a restoration chronosequence in Pacific Northwest prairies, we examined the effects of restoration-focused prescribed fire and native forb replanting on floral resources, pollinator visitation, and plant-pollinator network structure. We then simulated the effects of plant species loss/removal scenarios on secondary extinction cascades in the networks. Specifically, we explored three management-relevant plant loss scenarios (removal of an abundant exotic forb, removal of an abundant forb designated a noxious weed, and loss of the rarest native forb) and compared them to control scenarios. Pyrodiversity and proportion of area recently burned increased the abundance and diversity of floral resources, with concomitant increases in pollinator visitation and diversity. Pyrodiversity also decreased network connectance and nestedness, increased modularity, and buffered networks against secondary extinction cascades. Rare forbs contributed disproportionately to network robustness in less restored prairies, while removal of typical "problem" plants like exotic and noxious species had relatively small impacts on network robustness, particularly in prairies with a long history of restoration activities. Restoration actions aimed mainly at improving the diversity and abundance of pollinator-provisioning plants may also produce plant-pollinator networks with increased resilience to plant species losses., (© 2023 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Blackwater rivers and streams have stained or tea-colored water from tannins released by decaying plant matter. Natural conditions in these waters often differ from non-blackwater systems. For example, the pH and oxygen levels in waters can be very low, but completely natural. We examined an existing USEPA data set and found that blackwaters existed across the contiguous United States but were most common in the east. Water chemistry showed differences between blackwater and non-blackwater sites, but differences were not consistent across ecoregions making national scale generalizations difficult. Physical habitat data analysis did not show dramatic differences between blackwater and non-blackwater sites. Blackwater typically arises from streams that drain tannin-rich bogs/muskeg and wetlands, so as expected blackwater sites had a shorter Euclidean distance to wetlands than non-blackwater sites and existed in watersheds with a higher percentage of wetland habitat. Blackwaters in Northern and Temperate Plains tended to have higher acid neutralizing capacity, conductivity, and lower True Color; a visual color scale used for water purity. We posit that differences were because Color and Dissolved Organic Carbon at these sites were from buried wetland deposits rather than contemporary wetland habitats. Research needs that may increase our understanding and management of blackwaters include development of an operational definition that includes a classification framework and reference conditions for different blackwater types, identification of stressors and their associated dynamics that negatively impact blackwater systems, and development of data-driven, consistent, and repeatable assessment methods, including development of targets, protective of unique conditions in blackwater rivers and streams., Competing Interests: Conflict of Interest The authors declare no conflicts of interest relevant to this study.

Diet is a key lifestyle component that influences metabolic health through several factors, including total energy intake and macronutrient composition. While the impact of caloric intake on gene expression and physiological phenomena in various tissues is well described, the influence of dietary macronutrient composition on these parameters is less well studied. Here, we use the Nutritional Geometry framework to investigate the role of macronutrient composition on metabolic function and gene regulation in adipose tissue. Using ten isocaloric diets that vary systematically in their proportion of energy from fat, protein, and carbohydrates, we find that gene expression and splicing are highly responsive to macronutrient composition, with distinct sets of genes regulated by different macronutrient interactions. Specifically, the expression of many genes associated with Bardet-Biedl syndrome is responsive to dietary fat content. Splicing and expression changes occur in largely separate gene sets, highlighting distinct mechanisms by which dietary composition influences the transcriptome and emphasizing the importance of considering splicing changes to more fully capture the gene regulation response to environmental changes such as diet. Our study provides insight into the gene regulation plasticity of adipose tissue in response to macronutrient composition, beyond the already well-characterized response to caloric intake., (© 2024. The Author(s).)

A four-dimensional (4D) mid-infrared laser absorption imaging technique has been developed and demonstrated for quantitative, time-resolved, volumetric measurements of temperature and species concentration in dynamic combustion flows. This technique employs a dual high-speed infrared camera setup to capture turnable radiation from a quantum cascade laser near 4.85 µm to resolve rovibrational absorption transitions of carbon monoxide at two orthogonal projection angles. The laser is modulated with a customized waveform to adaptively resolve two target transitions with an increased density of data samples in proximity to the transition peaks, therefore ensuring accurate and quantitative spectral interpretation while minimizing the required frame rate. A 3D masked Tikhonov regularized inversion was performed to reconstruct spectrally resolved absorbance at every grid point of each frame, which enables subsequent interpretation of local gas properties in time. These methods are applied to achieve quantitative 4D cinematography of temperature and carbon monoxide in a propagating C 2 H 4 /O 2 flame with a spatial pixel resolution of ∼70 µm and a temporal resolution of 2 kHz.

Stream macroinvertebrate assemblages are shaped by natural and human-related factors that operate through complex hierarchical pathways. Quantifying these relationships can provide additional insights into stream ecological assessment. We applied a structural equation modeling framework to evaluate hypothesized pathways by which watershed, riparian, and in-stream factors affect benthic macroinvertebrate condition in the Western Mountains (WMT) and Xeric (XER) ecoregions in the United States. We developed a conceptual model grounded in theory, empirical evidence, and expert opinion to evaluate the following hypotheses: (1) macroinvertebrate assemblages are primarily driven by proximal, in-stream factors (e.g., water quality and physical habitat); (2) anthropogenic land uses affect macroinvertebrates indirectly by altering in-stream characteristics; and (3) riparian vegetation cover attenuates land use effects. We tested our model separately on three measures of benthic macroinvertebrate assemblage condition: ratio of observed-to-expected taxonomic richness (O/E); a multimetric index (MMI); and richness of Ephemeroptera, Plecoptera, and Trichoptera taxa (EPT). In the WMT, site-level riparian cover, in-stream physical habitat (relative bed stability), and water chemistry (total nitrogen) were the top three predictors of macroinvertebrate assemblages, each having over two times the magnitude of effect on macroinvertebrates compared with watershed-level predictors. In the arid XER, annual precipitation and stream flow characteristics were top predictors of macroinvertebrate assemblages and had similar magnitudes of effect as in-stream water chemistry. Path analyses revealed that land use activities in the watershed and at the stream site degraded macroinvertebrate assemblages indirectly by altering relative bed stability, water quality, and riparian cover/complexity. Increased riparian cover was associated with greater macroinvertebrate condition by reducing land use impacts on stream flow, streambed substrate, and water quality, but the pathways differed among ecoregions. In the WMT, site-level riparian cover affected macroinvertebrate assemblages partly through indirect pathways associated with greater streambed stability and reduced total nitrogen concentrations. In contrast, in the XER, watershed-level riparian cover affected macroinvertebrate assemblages through greater specific stream power. Identifying the relative effects of and pathways by which natural and anthropogenic factors affect macroinvertebrates can serve as a framework for prioritizing management and conservation efforts., Competing Interests: CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest.

Both native and non-native taxa richness patterns are useful for evaluating areas of greatest conservation concern. To determine those patterns, we analyzed fish and macroinvertebrate taxa richness data obtained at 3475 sites collected by the USEPA's National Rivers and Streams Assessment. We also determined which natural and anthropogenic variables best explained patterns in regional richness. Macroinvertebrate and fish richness increased with the number of sites sampled per region. Therefore, we determined residual taxa richness from the deviation of observed richness from predicted richness given the number of sites per region. Regional richness markedly exceeded average site richness for both macroinvertebrates and fish. Predictors of macroinvertebrate-genus and fish-species residual-regional richness differed. Air temperature was an important predictor in both cases but was positive for fish and negative for macroinvertebrates. Both natural and land use variables were significant predictors of regional richness. This study is the first to determine mean site and regional richness of both fish and aquatic macroinvertebrates across the conterminous USA, and the key anthropogenic drivers of regional richness. Thus, it offers important insights into regional USA biodiversity hotspots., Competing Interests: Conflict of interest The authors declare no competing interests.

Background & Aims: Thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate)., Methods: This was a nationwide observational cohort study conducted from August 2017 until June 2021., Results: We accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings >9.6kPa (P < .05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P < .001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P < .001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P = .121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline., Conclusion: Across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The Ras GTPase-activating protein SYNGAP1 plays a central role in synaptic plasticity, and de novo SYNGAP1 mutations are among the most frequent causes of autism and intellectual disability. How SYNGAP1 is regulated during development and how to treat SYNGAP1-associated haploinsufficiency remain challenging questions. Here, we characterize an alternative 3' splice site (A3SS) of SYNGAP1 that induces nonsense-mediated mRNA decay (A3SS-NMD) in mouse and human neural development. We demonstrate that PTBP1/2 directly bind to and promote SYNGAP1 A3SS inclusion. Genetic deletion of the Syngap1 A3SS in mice upregulates Syngap1 protein and alleviates the long-term potentiation and membrane excitability deficits caused by a Syngap1 knockout allele. We further report a splice-switching oligonucleotide (SSO) that converts SYNGAP1 unproductive isoform to the functional form in human iPSC-derived neurons. This study describes the regulation and function of SYNGAP1 A3SS-NMD, the genetic rescue of heterozygous Syngap1 knockout mice, and the development of an SSO to potentially alleviate SYNGAP1-associated haploinsufficiency., Competing Interests: Declaration of interests A provisional patent on splice-switching oligonucleotides described in this study has been filed on behalf of X.Z. and R.Y., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Changes in phosphorus concentrations affect periphytic diatom composition in streams, yet we rarely observe strong relationships between diatom richness and phosphorus. In contrast, changes in conductivity are strongly associated with differences in both diatom composition and richness. We hypothesised that we could better understand the mechanisms that control the phosphorus-richness relationship by examining relationships between phosphorus and the occurrence of individual diatom taxa, comparing these with relationships between conductivity and taxon occurrence, and documenting how niche breadths of taxa affect richness patterns. We estimated relationships between phosphorus and taxon occurrence using DNA metabarcoding data of diatoms collected from 1,811 sites distributed across the conterminous U.S.A. and contrasted patterns in these relationships with those between conductivity and taxon occurrence. The distribution of taxon optima for phosphorus was bimodal, with most optima located at either the maximum or minimum observed phosphorus concentration. The distribution of taxon optima for conductivity was unimodal. Niche breadths of taxa for phosphorus and for conductivity both generally increased with optimum values. The distribution of conductivity optima gave rise to a prominent hump-shaped relationship between richness and conductivity. The relationship between richness and phosphorus was also slightly hump-shaped, but this relationship would not be expected from the bimodal distribution of optima. Instead, we determined that broad niche breadths caused the hump-shaped relationship between richness and phosphorus. Our results highlight the nuanced effects that increased P loadings exert on diatom assemblages in rivers and streams and identify reasons that weak relationships between taxon richness and increased phosphorus have been observed. These findings allow us to better describe how excess phosphorus and subsets of taxa and their niche breadths contribute to patterns of taxa richness in diatom assemblages, and to improve the tools used to manage phosphorus pollution.

A multi-MHz laser absorption sensor at 777.2 nm (12,863 c m -1 ) is developed for simultaneous sensing of (1)  O ( 5 S 0 ) number density, (2) electron number density, and (3) translational temperature at conditions relevant to high-speed entry conditions and molecular dissociation. This sensor leverages a bias tee circuit with a distributed feedback diode laser and an optimization of the laser current modulation waveform to enable temporal resolution of sub-microsecond kinetics at electronvolt temperatures. In shock-heated O 2 , the precision of the temperature measurement is tested at 5 MHz and is found to be within ±5 % from 6000 to 12,000 K at pressures from 0.1 to 1 atm. The present sensor is also demonstrated in a CO:Ar mixture, in parallel with a diagnostic for CO rovibrational temperature, providing an additional validation across 7500-9700 K during molecular dissociation. A demonstration of the electron number density measurement near 11,000 K is performed and compared to a simplified model of ionization. Finally, as an illustration of the utility of this high-speed diagnostic, the measurement of the heavy particle excitation rate of O ( 5 S 0 ) is extended beyond the temperatures available in the literature and is found to be well represented by k ( 3 P → 5 S 0 )=2.7×10 -14 T 0.5 exp ⁡(-1.428×10 4 / T ) c m 3 ⋅ s -1 from 5400 to 12,200 K.

Background: Detection of malaria parasitaemia in samples that are negative by rapid diagnostic tests (RDTs) requires resource-intensive molecular tools. While pooled testing using a two-step strategy provides a cost-saving alternative to the gold standard of individual sample testing, statistical adjustments are needed to improve accuracy of prevalence estimates for a single step pooled testing strategy., Methods: A random sample of 4670 malaria RDT negative dried blood spot samples were selected from a mass testing and treatment trial in Asembo, Gem, and Karemo, western Kenya. Samples were tested for malaria individually and in pools of five, 934 pools, by one-step quantitative polymerase chain reaction (qPCR). Maximum likelihood approaches were used to estimate subpatent parasitaemia (RDT-negative, qPCR-positive) prevalence by pooling, assuming poolwise sensitivity and specificity was either 100% (strategy A) or imperfect (strategy B). To improve and illustrate the practicality of this estimation approach, a validation study was constructed from pools allocated at random into main (734 pools) and validation (200 pools) subsets. Prevalence was estimated using strategies A and B and an inverse-variance weighted estimator and estimates were weighted to account for differential sampling rates by area., Results: The prevalence of subpatent parasitaemia was 14.5% (95% CI 13.6-15.3%) by individual qPCR, 9.5% (95% CI (8.5-10.5%) by strategy A, and 13.9% (95% CI 12.6-15.2%) by strategy B. In the validation study, the prevalence by individual qPCR was 13.5% (95% CI 12.4-14.7%) in the main subset, 8.9% (95% CI 7.9-9.9%) by strategy A, 11.4% (95% CI 9.9-12.9%) by strategy B, and 12.8% (95% CI 11.2-14.3%) using inverse-variance weighted estimator from poolwise validation. Pooling, including a 20% validation subset, reduced costs by 52% compared to individual testing., Conclusions: Compared to individual testing, a one-step pooled testing strategy with an internal validation subset can provide accurate prevalence estimates of PCR-positivity among RDT-negatives at a lower cost., (© 2022. The Author(s).)

Anthropogenic alteration of physical habitat structure in streams and rivers is increasingly recognized as a major cause of impairment worldwide. As part of their assessment of the status and trends in the condition of rivers and streams in the U.S., the U.S. Environmental Protection Agency's (USEPA) National Aquatic Resource Surveys (NARS) quantify and monitor channel size and slope, substrate size and stability, instream habitat complexity and cover, riparian vegetation cover and structure, anthropogenic disturbance activities, and channel-riparian interaction. Like biological assemblages and water chemistry, physical habitat is strongly controlled by natural geoclimatic factors that can obscure or amplify the influence of human activities. We developed a systematic approach to estimate the deviation of observed river and stream physical habitat from that expected in least-disturbed reference conditions. We applied this approach to calculate indices of anthropogenic alteration of three aspects of physical habitat condition in the conterminous U.S. (CONUS): streambed sediment size and stability, riparian vegetation cover, and instream habitat complexity. The precision and responsiveness of these indices led the USEPA to use them to evaluate physical habitat condition in CONUS rivers and streams. The scores of these indices systematically decreased with greater anthropogenic disturbance at river and stream sites in the CONUS and within ecoregions, which we interpret as a response of these physical habitat indices to anthropogenic influences. Although anthropogenic activities negatively influenced all three physical habitat indices in the least-disturbed sites within most ecoregions, natural geoclimatic and geomorphic factors were the dominant influences. For sites over the full range of anthropogenic disturbance, analyses of observed/expected sediment characteristics showed augmented flood flows and basin and riparian agriculture to be the leading predictors of streambed instability and excess fine sediments. Similarly, basin and riparian agriculture and non-agricultural riparian land uses were the leading predictors of reduced riparian vegetation cover complexity in the CONUS and within ecoregions. In turn, these reductions in riparian vegetation cover and complexity, combined with reduced summer low flows, were the leading predictors of instream habitat simplification. We conclude that quantitative measures of physical habitat structure are useful and important indicators of the impacts of human activities on stream and river condition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Rigorous assessments of the ecological condition of water resources and the effect of human activities on those waters require quantitative physical, chemical, and biological data. The U.S. Environmental Protection Agency's river and stream surveys quantify river and stream bed particle size and stability, instream habitat complexity and cover, riparian vegetation cover and structure, and anthropogenic disturbance activities. Physical habitat is strongly controlled by natural geoclimatic factors that co-vary with human activities. We expressed the anthropogenic alteration of physical habitat as O/E ratios of observed habitat metric values divided by values expected under least-disturbed reference conditions, where site-specific expected values vary given their geoclimatic and geomorphic context. We set criteria for good, fair, and poor condition based on the distribution of O/E values in regional least-disturbed reference sites. Poor conditions existed in 22-24% of the 1.2 million km of streams and rivers in the conterminous U.S. for riparian human disturbance, streambed sediment and riparian vegetation cover, versus 14% for instream habitat complexity. Based on the same four indicators, the percentage of stream length in poor condition within 9 separate U.S. ecoregions ranged from 4% to 42%. Associations of our physical habitat indices with anthropogenic pressures demonstrate the scope of anthropogenic habitat alteration; habitat condition was negatively related to the level of anthropogenic disturbance nationally and in nearly all ecoregions. Relative risk estimates showed that streams and rivers with poor sediment, riparian cover complexity, or instream habitat cover conditions were 1.4 to 2.6 times as likely to also have fish or macroinvertebrate assemblages in poor condition. Our physical habitat condition indicators help explain deviations in biological conditions from those observed among least-disturbed sites and inform management actions for rehabilitating impaired waters and mitigating further ecological degradation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Vaginal Lactobacillus is considered protective of some adverse reproductive health outcomes, including preterm birth. However, factors that increase or decrease the likelihood of harboring Lactobacillus in the vaginal microbiome remain largely unknown. In this study, we sought to identify risk and protective factors associated with vaginal Lactobacillus predominance within a cohort of pregnant African American women. Materials and Methods: Vaginal microbiome samples were self-collected by African American women ( N  = 436) during their 8-14th week of pregnancy. Sociodemographic information and measures of health behaviors, including substance use, antibiotic exposure, sexual practices, frequency of vaginal intercourse, and the use of vaginal products, were collected through participant self-report. The V3-V4 region of the 16S rRNA gene was targeted for amplification and sequencing using Illumina HiSeq, with bacterial taxonomy assigned using the PECAN classifier. Univariate and a series of multivariate logistic regression models identified factors predictive of diverse vaginal microbiota or Lactobacillus predominance. Results: Participants who used marijuana in the past 30 days (aOR 1.80, 95% CI 1.08-2.98) were more likely to have diverse non- Lactobacillus -predominant vaginal microbiota, as were women not living with their partners (aOR 1.90, 95% CI 1.20-3.01). Cohabitating or marijuana usage were not associated with type of Lactobacillus (non- iners Lactobacillus vs. Lactobacillus iners ) predominance (aOR 1.11, 95% CI 0.52-2.38 and aOR 0.56, 95% CI 0.21-1.47, respectively). Conclusions: Living with a partner is conducive to vaginal Lactobacillus predominance. As such, cohabitation may be in important covariate to consider in vaginal microbiome studies.

Benthic diatom assemblages are known to be indicative of water quality but have yet to be widely adopted in biological assessments in the United States due to several limitations. Our goal was to address some of these limitations by developing regional multi-metric indices (MMIs) that are robust to inter-laboratory taxonomic inconsistency, adjusted for natural covariates, and sensitive to a wide range of anthropogenic stressors. We aggregated bioassessment data from two national-scale federal programs and used a data-driven analysis in which all-possible combinations of 2-7 metrics were compared for three measures of performance. After ranking the best-performing MMIs, we selected the final MMIs by evaluating stress-response relations in independent regional datasets of diatom samples paired with measures of several water-quality stressors, including herbicides and streamflow flashiness. Each regional MMI performed well at calibration sites and represented diverse aspects of the structure and function of diatom communities. Most metrics included in the best MMIs were modeled to account for natural variation including climate, topography, soil characteristics, lithology, and groundwater influence on streamflow. MMI performance improved with higher numbers of component metrics, but this effect diminished beyond six metrics. Component metrics of MMIs were associated with a broad suite of measured stressors in every region, including salinity, nutrients, herbicides, and streamflow flashiness. We provide a web-based software application that allows users in the conterminous United States to apply our MMIs to their own datasets and compare MMI scores from their sites to a broader regional context., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: There has been limited research on how the variance of force affects manual therapy outcomes and what the best practices should be. No specific force threshold necessary to achieve a predetermined translational distance within the joint has been quantified within the literature., Purpose: To quantify the amount of force necessary to perform an inferior glide to the glenohumeral joint and reach to end range. A secondary aim was to determine the impact of co-variables, such as gender, height, weight, and age, on the amount of force required to translate the humeral head within the glenohumeral joint., Methods: A convenience sample of 64 healthy subjects were recruited. Musculoskeletal ultrasound imaging using the GE LogiQe was used to measure the translation of the humeral head. The manipulation force was measured using the novel pliance glove device and software. The ANOVA was used to determine if there was a difference in translation distance and force between trials. The Pearson's correlation was used to correlate translation and force and between covariables., Results: There was no significant difference in translation distance between trials (p = .14). There was no significant difference in the mean force for this translation (p = .45). There was a poor correlation between age and force (r = 0.28) and weight and force (r = 0.12)., Conclusion: An average force of 14.27 N (n = 61) was needed to displace the humeral head to reach end range. This was the first study using the combination of a flexible force sensor technology and real-time ultrasound imaging to measure humeral head translation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A high-speed laser absorption technique is employed to resolve spectral transitions of CO 2 in the mid-infrared at MHz rates to infer non-equilibrium populations/temperatures of translation, rotation and vibration in shock-heated CO 2 - Ar mixtures. An interband cascade laser (DFB-ICL) resolves 4 transitions within the CO 2 asymmetric stretch fundamental bands ( Δ v 3 = 1) near 4.19 μ m . The sensor probes a wide range of rotational energies as well as two vibrational states (00 0 0 and 01 1 0). The sensor is demonstrated on the UCLA high enthalpy shock tube, targeting temperatures between 1250 and 3100 K and sub-atmospheric pressures (up to 0.2 atm). The sensor is sensitive to multiple temperatures over a wide range of conditions relevant to Mars entry radiation. Vibrational relaxation times are resolved and compared to existing models of thermal non-equilibrium. Select conditions highlight the shortcomings of modeling CO 2 non-equilibrium with a single vibrational temperature., (© The Author(s) 2022.)

Abstract: Stridor is a common presenting symptom for children in emergency departments (EDs) and usually represents an infectious process, such as croup, or aspiration of a foreign body. We present the case of an otherwise healthy 5-year-old girl with episodic increased work of breathing for several months that was initially diagnosed as asthma by her primary care physician. She subsequently presented to the ED with acutely worsening noisy breathing and dyspnea. Patient and parent denied any recent foreign body ingestions or choking episodes. We gave multiple doses of racemic epinephrine in the ED without symptom improvement. A lateral neck x-ray showed an occlusive subglottic airway mass. Otolaryngology (ENT) evaluation demonstrated an 85% airway occlusion. The mass was partially resected, resolving all of her respiratory symptoms. Although primary airway tumors in children are rare, they must be considered on the differential diagnosis of new noisy breathing or respiratory distress. Failure to diagnose these tumors in a timely manner can be life-threatening., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Head and neck lymphatic malformations (HNLM) are caused by gain-of-function somatic mutations in PIK3CA. Acetylsalicylic acid (ASA/aspirin) is thought to limit growth in PIK3CA-mutated neoplasms through PI3K pathway suppression. We sought to determine if ASA could be beneficial for HNLM., Methods: Retrospective case series of patients (0-18 years) offered ASA (3-5 mg/kg/day) for HNLM treatment (2010-2018). Clinical and treatment characteristics, patient-reported symptom improvement, medication tolerance, compliance, and complications were recorded. Treatment response was determined by change in patient/caregiver-reported symptoms, or HNLM size [complete (resolved), partial (decreased), or stable]., Results: Fifty-three patients were offered ASA, 23 (43%) accepted (median age 10 years, IQR 6-14). Compared to patients who declined, patients receiving ASA were more likely to have extensive malformations: ex-utero intrapartum treatment procedure, bilateral malformations, oral cavity location, ≥2 invasive treatments, or tracheotomy (p < 0.05). All patients with tissue available had PIK3CA mutations (13/23). Treatment indications included oral pain/blebs (12, 52%), recurrent pain/swelling (6, 26%), or sudden/persistent swelling (5, 22%). Treatment plan was commonly one 81 mg tablet daily (19, 83%) for 3-12 months (8, 42%). Therapeutic adherence was reported by 18 patients (78%). Symptoms improved in 18 patients [78%; decreased pain (9, 39%) and swelling (8, 35%)]. Treatment resulted in partial (14, 61%) or complete response (4, 17%). Three patients developed oral bleb bleeding, which resolved with medication discontinuation., Conclusion: ASA seems to be a well-tolerated, low-risk medication for HNLM treatment. This pilot study suggests that it often improves symptoms and reduces HNLM size. Further prospective, randomized studies are warranted to comprehensively assess indications, safety, and efficacy., Level of Evidence: Level 4., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission to health care workers during myringotomy and tympanostomy tube (MT) insertion is unknown. To determine the need for enhanced precautions to prevent potential spread via aerosolized particles, we used an optical particle sizer to measure aerosol generation intraoperatively during a case series of MT insertion. We also discuss our institutional experience with safe pandemic-era perioperative practices. There was no measured increase in aerosol particle number during the procedure at a distance of 30 cm from the external auditory canal. These initial data are reassuring regarding the risk of SARS-CoV-2 transmission to the operating room team due to aerosol generation, but further study is necessary before making definitive recommendations.

Introduction: Ivacaftor was the first therapy licensed to address the underlying defect in cystic fibrosis (CF). The improvements in lung function, nutritional status and pulmonary exacerbations in patients carrying a Gly551Asp mutation were greater than previously seen in clinical trials for other therapies. Limited data are available regarding long-term outcomes and adherence to ivacaftor outside clinical trials., Methods: We conducted a 5-year single-centre retrospective study of people with CF carrying the Gly 551 Asp mutation who received ivacaftor. Clinical outcome data were extracted from medical notes and databases. Drug delivery data were used to assess medicine possession ratio (MPR)., Results: 35 people were included. After commencing ivacaftor, FEV 1 improved by 9.6% (SE±1.59%) predicted by 6 months. Thereafter, FEV 1 declined, and at 5 years had returned to pre-ivacaftor baseline. Ivacaftor did not alter annual rate of FEV 1 decline (1.57% pre vs 1.82% post, p=0.74). Body mass index (BMI) increased for 4 years. There was a significant reduction in inpatient and total intravenous antibiotic days sustained over 5 years. MPR remained high but declined over time (-2.5±0.9% per year, p=0.007). FEV 1 was better maintained in patients with higher MPRs., Conclusion: The addition of ivacaftor provides acute benefits for people with the Gly551Asp mutation and established lung disease. We report a sustained reduction in intravenous antibiotic use but following acute improvement in lung function, decline continues, and patients will continue to require medical observation and optimisation. Strategies to maintain high adherence should be a priority to prolong the benefits of ivacaftor., Competing Interests: Competing interests: PJB has received consultancy fees, lecture fees from Vertex pharmaceuticals; their institution has received a grant to organise an educational event and PJB is the local principal investigator on trials sponsored by Vertex pharmaceuticals. RMM, AMJ, KS and PF have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The precipice response in Caenorhabditis elegans is a little-understood phenomenon in which worms move rapidly away from edges. We hypothesized that mechanosensation underlies the precipice response and that mechanosensory mutants would exhibit the precipice response less often than N2 wild type worms. We found that mec-3 mutants, with severe loss of mechanosensation, exhibited the precipice response at a lower rate than N2, but mec-10 and trp-4 mutants, with partial loss of response to mechanical stimuli, responded at a similar rate to N2. These results provide a characterization of the precipice response and implicate a role for mechanosensation in this behavior., (Copyright: © 2021 by the authors.)

Background and Aims: Understanding impacts of altered disturbance regimes on community structure and function is a key goal for community ecology. Functional traits link species composition to ecosystem functioning. Changes in the distribution of functional traits at community scales in response to disturbance can be driven not only by shifts in species composition, but also by shifts in intraspecific trait values. Understanding the relative importance of these two processes has important implications for predicting community responses to altered disturbance regimes., Methods: We experimentally manipulated fire return intervals in replicated blocks of a fire-adapted, longleaf pine (Pinus palustris) ecosystem in North Carolina, USA and measured specific leaf area (SLA), leaf dry matter content (LDMC) and compositional responses along a lowland to upland gradient over a 4 year period. Plots were burned between zero and four times. Using a trait-based approach, we simulate hypothetical scenarios which allow species presence, abundance or trait values to vary over time and compare these with observed traits to understand the relative contributions of each of these three processes to observed trait patterns at the study site. We addressed the following questions. (1) How do changes in the fire regime affect community composition, structure and community-level trait responses? (2) Are these effects consistent across a gradient of fire intensity? (3) What are the relative contributions of species turnover, changes in abundance and changes in intraspecific trait values to observed changes in community-weighted mean (CWM) traits in response to altered fire regime?, Key Results: We found strong evidence that altered fire return interval impacted understorey plant communities. The number of fires a plot experienced significantly affected the magnitude of its compositional change and shifted the ecotone boundary separating shrub-dominated lowland areas from grass-dominated upland areas, with suppression sites (0 burns) experiencing an upland shift and annual burn sites a lowland shift. We found significant effects of burn regimes on the CWM of SLA, and that observed shifts in both SLA and LDMC were driven primarily by intraspecific changes in trait values., Conclusions: In a fire-adapted ecosystem, increased fire frequency altered community composition and structure of the ecosystem through changes in the position of the shrub line. We also found that plant traits responded directionally to increased fire frequency, with SLA decreasing in response to fire frequency across the environmental gradient. For both SLA and LDMC, nearly all of the observed changes in CWM traits were driven by intraspecific variation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Simultaneous infection with multiple malaria parasite strains is common in high transmission areas. Quantifying the number of strains per host, or the multiplicity of infection (MOI), provides additional parasite indices for assessing transmission levels but it is challenging to measure accurately with current tools. This paper presents new laboratory and analytical methods for estimating the MOI of Plasmodium falciparum., Methods: Based on 24 single nucleotide polymorphisms (SNPs) previously identified as stable, unlinked targets across 12 of the 14 chromosomes within P. falciparum genome, three multiplex PCRs of short target regions and subsequent next generation sequencing (NGS) of the amplicons were developed. A bioinformatics pipeline including B4Screening pathway removed spurious amplicons to ensure consistent frequency calls at each SNP location, compiled amplicons by SNP site diversity, and performed algorithmic haplotype and strain reconstruction. The pipeline was validated by 108 samples generated from cultured-laboratory strain mixtures in different proportions and concentrations, with and without pre-amplification, and using whole blood and dried blood spots (DBS). The pipeline was applied to 273 smear-positive samples from surveys conducted in western Kenya, then providing results into StrainRecon Thresholding for Infection Multiplicity (STIM), a novel MOI estimator., Results: The 24 barcode SNPs were successfully identified uniformly across the 12 chromosomes of P. falciparum in a sample using the pipeline. Pre-amplification and parasite concentration, while non-linearly associated with SNP read depth, did not influence the SNP frequency calls. Based on consistent SNP frequency calls at targeted locations, the algorithmic strain reconstruction for each laboratory-mixed sample had 98.5% accuracy in dominant strains. STIM detected up to 5 strains in field samples from western Kenya and showed declining MOI over time (q < 0.02), from 4.32 strains per infected person in 1996 to 4.01, 3.56 and 3.35 in 2001, 2007 and 2012, and a reduction in the proportion of samples with 5 strains from 57% in 1996 to 18% in 2012., Conclusion: The combined approach of new multiplex PCRs and NGS, the unique bioinformatics pipeline and STIM could identify 24 barcode SNPs of P. falciparum correctly and consistently. The methodology could be applied to field samples to reliably measure temporal changes in MOI.

Epidemic preparedness depends on our ability to predict the trajectory of an epidemic and the human behavior that drives spread in the event of an outbreak. Changes to behavior during an outbreak limit the reliability of syndromic surveillance using large-scale data sources, such as online social media or search behavior, which could otherwise supplement healthcare-based outbreak-prediction methods. Here, we measure behavior change reflected in mobile-phone call-detail records (CDRs), a source of passively collected real-time behavioral information, using an anonymously linked dataset of cell-phone users and their date of influenza-like illness diagnosis during the 2009 H1N1v pandemic. We demonstrate that mobile-phone use during illness differs measurably from routine behavior: Diagnosed individuals exhibit less movement than normal (1.1 to 1.4 fewer unique tower locations; [Formula: see text]), on average, in the 2 to 4 d around diagnosis and place fewer calls (2.3 to 3.3 fewer calls; [Formula: see text]) while spending longer on the phone (41- to 66-s average increase; [Formula: see text]) than usual on the day following diagnosis. The results suggest that anonymously linked CDRs and health data may be sufficiently granular to augment epidemic surveillance efforts and that infectious disease-modeling efforts lacking explicit behavior-change mechanisms need to be revisited., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Generalizing the effect of traits on performance across species may be achievable if traits explain variation in population fitness. However, testing relationships between traits and vital rates to infer effects on fitness can be misleading. Demographic trade-offs can generate variation in vital rates that yield equal population growth rates, thereby obscuring the net effect of traits on fitness. To address this problem, we describe a diversity of approaches to quantify intrinsic growth rates of plant populations, including experiments beyond range boundaries, density-dependent population models built from long-term demographic data, theoretical models, and methods that leverage widely available monitoring data. Linking plant traits directly to intrinsic growth rates is a fundamental step toward rigorous predictions of population dynamics and community assembly., (Copyright © 2020 Elsevier Ltd. All rights reserved.)