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We characterized the patterns of agreement variation and consistency in three corpora of child and child-directed US English to better understand preschoolers’ input and to compare preschoolers’ own agreement production. We examined sentences with third-person subjects and tensed forms of be in two large single-family corpora and one cross-sectional corpus collected during a Search-and-Find activity. Caregivers’ agreement variation consistently reflected patterns previously found in adult-to-adult speech. Children's variation was conditioned by many of the same factors (e.g., sentence type, pronoun subject, and order of subject and verb) and clearly demonstrated acquisition of the categorical-variable split. However, some children showed substantially higher rates of nonagreeing forms (There's the cherries) than their caregivers and differed in their ranking of conditioning factors. We suggest that this reflects children's developing production processing abilities: shorter sentence-planning spans may make nonagreement a useful strategy for avoiding early number commitments in verb-first sentences.

PURPOSE CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570 ) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS ≥ 20 populations. RESULTS Among 947 patients randomly assigned, 38.3% had CPS ≥ 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P = .4951) and CPS ≥ 20 (median: 17.6 v 14.6 months; HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469) populations. In patients with CPS ≥ 1, the median OS was 15.7 versus 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97). Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), objective response rate was 34.1% versus 36.0%, and median duration of response was 32.6 versus 7.0 months. Grade 3/4 treatment-related adverse events occurred in 28.2% of patients treated with nivolumab plus ipilimumab versus 70.7% treated with EXTREME. CONCLUSION CheckMate 651 did not meet its primary end points of OS in the all randomly assigned or CPS ≥ 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with R/M SCCHN.

Persistence of symptoms post-COVID-19 infection, commonly known as “long COVID”, is a significant issue, affecting nearly one in five individuals. The aim was to assess whether the persistence of COVID-19 symptoms beyond infection was associated with poorer overall health status. Additionally, The investigators assessed the frequency and severity of the symptoms associated with long COVID in the patient population. They surveyed patients verbally at the Vanderbilt University Medical Center Emergency Department, a Level 1 Urban Trauma Center. The investigators gathered patients’ demographic data and perspectives on their symptoms before, during, and after COVID-19 infection. They enrolled a total of 100 patients and analyzed the data descriptively, proportions with Pearson Goodness-of-fit Test and differences between paired samples with Wilcoxon signed-ranked test. Nearly one-fourth of the local population experienced long COVID symptoms, including shortness of breath and fatigue (p = 0.009372). Additionally, there was a significant difference between patient health rankings before and after testing positive for COVID-19 (p = 1.6 x 10-10), which may suggest COVID-19 has a negative impact on overall health or perception of health in the patient population.

Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. Methods We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria—with no contraindications to influenza vaccination—were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18–64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. Findings Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to

RATIONALE: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. OBJECTIVES: To test differing durations of intravenous antimicrobials for CF exacerbations. METHODS: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7–10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days’ total antimicrobial duration; all others were randomized to 14 or 21 days’ duration. MEASUREMENTS AND MAIN RESULTS: The primary outcome was percent predicted FEV(1) (ppFEV(1)) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV(1) change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI [‒3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV(1) changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. CONCLUSIONS: Among adults with CF with early treatment improvement during exacerbation, ppFEV(1) after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).

As members of the editorial team at Language Acquisition, we read Kidd and Garcia’s target article with enthusiasm. In our commentary, we outline some specific ideas for how journals can help to alleviate the issues raised by Kidd and Garcia, some of which are in progress or in place at Language Acquisition, and some of which we hope to undertake alongside other journals in the field. We focus on concrete steps, acknowledging that systemic changes, too, will be required to ensure that our science reflects the diversity of languages learned.

Research in language development has only recently begun to focus on the inherent variability of language. Previous studies have explored at what age children begin to produce variable linguistic f...

The present study investigates the relationship between discourse integration skills and Spanish copula choice in monolingual Chilean Spanish-speaking children. Previous research has focused on determining the age at which children associateestarto a transitory property andserto an inherent property (Holtheuer, Carolina. 2012. Spanish-speaking children do not always overuse estar.Revista Signos45(78). 3–19, Holtheuer, Carolina & Johanna Rendle-Short. 2013. Ser and estar: Corrective input to children’s errors of the Spanish copula verbs.First Language33(2). 155–167, Schmitt, Cristina & Karen Miller. 2007. Making discourse dependent decisions: The case of the copulas ser and estar in Spanish.Lingua117(11). 1907–1929, Sera, Maria. 1992. To be or to be: Use and acquisition of the Spanish copulas.Journal of Memory and Language31. 408–427, Requena, Pablo, Astrid Román-Hernández & Karen Miller. 2015. Children’s knowledge of the Spanish copulas ser and estar with novel adjectives.Language Acquisition: A Journal of Developmental Linguistics22. 193–207), showing that by 2 years of age children know the categorial distribution of the two copulas, but that at 5 years of age only some children, but not all children, have knowledge of the transitory/inherent distinction that often arises when the same adjective occurs with one or the other copula. The present study seeks to extend the latter research by further investigating the factors that might influence why only some children associateestarto transitory properties at 5 years of age, a question that will not only shed light onwhenthe subtle meaning differences of the copulas are acquired, but alsohowthey are acquired. Maienborn, Claudia (2005. A discourse-based account of Spanish ser/estar.Linguistics43(1). 155–180) notes thatestaris discourse-linked, whileseris not. Specifically, the use ofestarwith an adjectival predicate to compare changes to a person across different stages of their life relies on one’s ability to integrate the larger discourse (i.e., these various stages) into their statement. In the present study, to determine whether Spanish-speaking children’s production of the copulaestarwith adjectival predicates was associated with their discourse integration abilities, children were presented with both a Copula Elicitation Task and a Discourse Production Task. Analyses revealed an association between children’s discourse integration skills and their use ofestarwith adjectives to express transitory properties, a finding that indicates that children’s acquisition ofestaris mastered late – at least in part because of their late development of discourse integration skills more generally. Most studies on the acquisition ofestarwith adjectival complements have focused primarily on comprehension. Experimental studies on children’sproductionofestarare rare. As such, this experimental study is one of the few that examines children’s use ofestarin production and the first, as far as we know, that provides empirical support for the link between discourse integration skills in children and their use ofestarwith adjectival predicates.

This article presents a developmental pathway for the acquisition of morphosyntactic variation. Although there is abundant evidence that morphosyntactic variation is pervasive among adults, much le...

Industrial symbiosis (IS) is a business model that proposes symbiotic exchanges, allowing the flow of resources, wastes, and utilities between companies. In recent years, IS initiatives have been exponentially growing around the world. This can be attributed to the increasing awareness on the possibility of obtaining economic, environmental, and social benefits through the implementation of this model. Despite the exponential growth of IS initiatives, the companies are still facing problems in the achievement of reliable and permanent synergies. Over the years the literature has identified several factors in the IS emerging process. Incentives are among these factors, being defined as unlocking tools or mechanisms related to diverse dimensions such as economic, political, social, intermediaries, process, and technology. Authors believe that the large-scale implementation of IS incentives has not been properly addressed. In order to promote facilitated IS implementation and achieve a replicator effect, incentives should be fully addressed. In many case studies, it has been observed that the incentives for IS can be threatened by risks, compromising the implementation, and hindering the emerging process. This study developed a dedicated framework that is composed of incentive identification from best practices of IS and expert consultation; a risk assessment model based on risk factors identification and clustering; and finally, the mitigation actions based on the assessment outputs. The main result of this study is one set of mitigations actions that correlate the implementation levels (clusters) and the potential stakeholders involved.

The COVID‐19 pandemic has provided an opportunity to rethink the way the majority of patient consultations are conducted, with a move from face‐to‐face visits to remote consultations. This article, which is applicable to all primary care clinicians undertaking medication review, outlines the main principles of optimising remote consultations, with a focus on older people living with frailty during COVID‐19.

Introduction Chronic caloric deprivation and obesity are complicated by elevations of serum total cortisol levels. The effects of acute overfeeding and fasting on circulating free cortisol levels and interconversion of cortisone to free cortisol are unknown. We hypothesized that serum free cortisol and free cortisol-to-cortisone ratio (a surrogate measure of 11β-hydroxysteroid dehydrogenase [11β-HSD] activity) would increase after both overfeeding and fasting. Methods We prospectively studied 22 healthy volunteers who underwent a 10-day high-calorie protocol followed by a 10-day fast, separated by a 2-week wash-out period, in a Clinical Research Center. Fasting morning free and total cortisol and free cortisone levels (liquid chromatography-tandem mass spectrometry, Mayo Labs) and percent body fat (dual-energy x-ray absorptiometry) were performed at baseline before and after 10 days of each intervention. Results High-calorie feeding increased total and free cortisol and the free cortisol-to-free cortisone ratio (p Conclusion Overfeeding and fasting both increase circulating free cortisol levels and appear to alter 11β-HSD activity. The effect of fasting, but not overfeeding, on free cortisol levels is modified by sex. Greater percent fat mass may be relatively protective against starvation-induced hypercortisolemia in women. Further study is warranted to determine whether elevated cortisol levels contribute to complications of starvation and obesity, such as bone fragility. Presentation: No date and time listed

Need to track the progress of a tribal treaty? Examine correspondence between territorial officials and Washington? Research accounts of battles and troop movements? Review records of agricultural and industrial production? Examine shipping records? Explore firsthand accounts of frontier life via letters and financial documents? Trace family histories using passenger lists? View petitions for statehood? All this and more can be done using Territorial Papers of the United States, 1764-1953. Documents come from National Archives and Records Administration and the official records of the Departments of State and the Interior. This is an excellent source for primary documents regarding this period of history, though it should be noted these documents largely come from a white, male, governmental, non-native perspective, as might be expected for the time period. Strong in advanced search options, it could use some improvement in the finer points (see under Searching and Critical Evaluation).

Understanding the distribution, abundance and habitat preferences of species in the Southern Ocean provides a foundation for assessing the impacts of environmental change and anthropogenic disturbance on Antarctic ecosystems. In near-shore waters at Casey and Davis Stations, photoquadrat surveys were used to determine sea anemone distribution and abundance, habitat preferences, associations with other species and the impact of human disturbance on sea anemone distribution. Two distinct sea anemone morphotypes were found in this study: large sea anemones that require hard substrate for attachment and small, burrowing sea anemones found in muddy sediment. The large sea anemones were found in rocky habitats, with the exception of some sedimentary habitats where other biota were used as substrate. The large sea anemones were associated with a diverse community of epibenthic species found in rocky habitats. The burrowing sea anemones were associated with a less diverse assemblage of sediment-dwelling epibenthos. At Casey Station, sea anemones were more abundant in habitats adjacent to a former waste disposal site than at control sites. The reason for this is not yet known, but may be due to high organic matter inputs or, alternatively, a longer sea ice duration providing protection from ice scour.

An understanding of larval dispersal and connectivity in corals provides valuable insight into the processes of population maintenance and replenishment and is vital for effective management. Here, we used a genotyping by sequencing approach to explore patterns of genetic connectivity in two species of coral with different reproductive modes (brooding and broadcast spawning) at the Rowley Shoals in northwest Australia. Our data revealed strikingly different patterns of genetic structure in the two species. High levels of genetic subdivision in the brooding coral I. brueggemanni was consistent with extensive self-recruitment and restricted connectivity. In contrast, the broadcast spawning coral A. digitifera formed a single panmictic population with extensive gene flow. Our results highlight the wide variation in metapopulation connectivity that exists among corals and support the well-established link between reproductive mode and population genetic structure in the marine environment.

Background: Global Longitudinal Strain (GLS) is a sensitive indicator of cardiac function in children. However, GLS analysis is limited by time-consuming manual tracing and interobserver variability. This study aims to assess clinical feasibility of AutoStrain, a “hands-off” method of GLS analysis in children. Hypothesis: AutoStrain will quickly and accurately calculate GLS in children. Methods: We prospectively enrolled 168 patients, who underwent clinically indicated echocardiograms (mean age:12±4 years). Strain parameters were measured using three methods: 1) Fully automated (AutoStrain, Phillips Medical Systems), 2) Semiautomated (manual correction of automated measurements), 3) Conventional manual measurements (2D-CPA, TomTec), from apical 4-, 3- and 2-chamber views. Automated analyses were timed with a stopwatch. Results: Fully automated measurements were feasible in all cases. The results are depicted in Table 1 and Figure 1. Fully automated AutoStrain showed a strong correlation with manual GLS (R=0.71, p Conclusions: AutoStrain is a rapid, clinically feasible method for quantifying GLS in children. We speculate that accuracy of AutoStrain may improve in the future with inclusion of pediatric training datasets, as the anatomical intelligence program currently relies on adult datasets. Automated analysis may save time in busy laboratories, with the ultimate aim for a “hands off” future in functional assessment.