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This summary on Lassa virus (LASV) infection and Lassa fever disease (LF) was developed from a clinical perspective to provide clinicians with a condensed, accessible understanding of the current literature. The information provided highlights pathogenesis, clinical features, and diagnostics emphasizing therapies and vaccines that have demonstrated potential value for use in clinical or research environments.We conducted an integrative literature review on the clinical and pathological features, vaccines, and treatments for LASV infection, focusing on recent studies and in vivo evidence from humans and/or non-human primates (NHPs), when available.Two antiviral medications with potential benefit for the treatment of LASV infection and 1 for post-exposure prophylaxis were identified, although a larger number of therapeutic candidates are currently being evaluated. Multiple vaccine platforms are in pre-clinical development for LASV prevention, but data from human clinical trials are not yet available.We provide succinct summaries of medical countermeasures against LASV to give the busy clinician a rapid reference. Although there are no approved drugs or vaccines for LF, we provide condensed information from a literature review for measures that can be taken when faced with a suspected infection, including investigational treatment options and hospital engineering controls.

Background Chronic disease is the leading cause of mortality in the United States. Health information technology (HIT) tools show promise for improving disease management. Objectives This study aims to understand the following: (1) how self-perceptions of health compare between those with and without disease; (2) how HIT usage varies between chronic disease profiles (diabetes, hypertension, cardiovascular disease, pulmonary disease, depression, cancer, and comorbidities); (3) how HIT trends have changed in the past 6 years; and (4) the likelihood that a given chronic disease patient uses specific HIT tools. Methods The Health Information National Trends Survey (HINTS) inclusive of 2014 to 2020 served as the primary data source with statistical analysis completed using Stata. Bivariate analyses and two-tailed t-tests were conducted to compare self-perceived health and HIT usage to chronic disease. Logistic regression models were created to examine the odds of a specific patient using various forms of HIT, controlling for demographics and comorbidities. Results Logistic regression models controlling for sociodemographic factors and comorbidities showed that pulmonary disease, depression, and cancer patients had an increased likelihood of using HIT tools, for example, depression patients had an 81.1% increased likelihood of looking up health information (p Conclusion This study demonstrates that certain chronic disease cohorts appear to have greater HIT usage than others. Further analysis should be done to understand what factors influence patients to utilize HIT which may provide additional insights into improving design and user experience for other populations with the goal of improving management of disease. Such analyses could also establish a new baseline to account for differences in HIT usage as a direct consequence of the novel coronavirus disease 2019 (COVID-19) pandemic.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.

Categorization of biopsy specimens into inflammatory reaction patterns is central to dermatopathologic assessment. Mixed inflammatory patterns are poorly characterized and may represent clinicopathologic challenges. The purpose of this study was to identify clinical and histopathologic findings associated with the mixed spongiotic-interface dermatitis (SID) histopathologic pattern.Fifty-one institutional biopsy specimens of SID were identified over a 2-year period by retrospective natural language search. Histopathologic and clinical features were identified.The most common histopathologic features associated with SID were mild spongiosis (51%), focal vacuolar interface change (72%), lymphocytic exocytosis (92%), and superficial-dermal lymphocytic infiltrate (94%) with variable eosinophils (61%). Clinically, 80% of subjects presented with a symmetric morbilliform eruption. Polypharmacy (94%), immunosuppression (47%), and history of malignancy (47%) were common. The most common diagnoses were drug reaction (37%), possible drug reaction (12%), and viral exanthem (12%). Drug reaction with eosinophilia and systemic symptoms represented 25% of all confirmed cutaneous adverse drug reactions (CADR). Average time from drug initiation to symptom initiation was 20 days (SD: 22.3, range: 0-90); median disease duration was 25.5 days. Spongiotic vesicles and Langerhans cells were less common in patients with a strong clinicopathologic diagnosis of drug reaction compared to non-drug eruptions (p = 0.04).The mixed SID pattern is commonly encountered in CADR but may represent a more subacute course, implying consideration for inciting medication(s) started before the typical 7- to 14-day window.

BACKGROUND: Airway mucus plugs in asthma are associated with exacerbation frequency, increased eosinophilia, and reduced lung function. The relationship between mucus plugs and spatially overlapping ventilation abnormalities observed at hyperpolarized gas MRI has not been assessed quantitatively. PURPOSE: To assess regional associations between CT mucus plugs scored by individual bronchopulmonary segment and corresponding measurements of segmental ventilation defect percentage (VDP) at hyperpolarized helium 3 ((3)He) MRI. MATERIALS AND METHODS: In this secondary analysis of a Health Insurance Portability and Accountability Act–compliant prospective observational cohort, participants in the Severe Asthma Research Program (SARP) III (NCT01760915) between December 2012 and August 2015 underwent hyperpolarized (3)He MRI to determine segmental VDP. Segmental mucus plugs at CT were scored by two readers, with segments scored as plugged only if both readers agreed independently. A linear mixed-effects model controlling for interpatient variability was then used to assess differences in VDP in plugged versus plug-free segments. RESULTS: Forty-four participants with asthma were assessed (mean age ± standard deviation, 47 years ± 15; 29 women): 19 with mild-to-moderate asthma and 25 with severe asthma. Mucus plugs were observed in 49 total bronchopulmonary segments across eight of 44 patients. Segments containing mucus plugs had a median segmental VDP of 25.9% (25th–75th percentile, 7.3%–38.3%) versus 1.4% (25th–75th percentile, 0.1%–5.2%; P < .001) in plug-free segments. Similarly, the model estimated a segmental VDP of 18.9% (95% CI: 15.7, 22.2) for mucus-plugged segments versus 5.1% (95% CI: 3.3, 7.0) for plug-free segments (P < .001). Participants with one or more mucus plugs had a median whole-lung VDP of 11.1% (25th–75th percentile, 7.1%–18.9%) versus 3.1% (25th–75th percentile, 1.1%–4.4%) in those without plugs (P < .001). CONCLUSION: Airway mucus plugging at CT was associated with reduced ventilation in the same bronchopulmonary segment at hyperpolarized helium 3 MRI, suggesting that mucus plugging may be an important cause of ventilation defects in asthma. © RSNA, 2021 Online supplemental material is available for this article.

The following paper presents case examples of one research team's use of social network analysis (SNA) with three different collaboratives in South Florida: (a) a Collective Impact initiative seeking to end youth homelessness, (b) a university collaborative of campus organizations working towards Black students' concerns, and (c) a movement network of local social justice organizations. The research team used SNA to assess the level of connectivity of three different community coalitions. While research questions were slightly different for each collaborative, each project asked about the frequency of communication between organizations to determine connectivity. Results vary between case examples. Both the Youth Homeless Collaboration and the Black Student Association used Gephi to analyze results, while The Community Partnership used R to measure network centrality. The paper concludes with a general discussion of challenges related to using SNA as an action research tool, as well as the role of power in organizational networks.

Many injured patients are transported directly to trauma centers, found to be minimally injured, and discharged directly home from the emergency department (ED). Our objectives were to characterize the short-term outcomes in this discharged patient population and to identify patient factors predictive of ED return visits.We conducted a retrospective population-based cohort study using linked administrative data sets involving patients assessed at trauma centers in Ontario, Canada between April 1, 2009, and March 31, 2020. Patients who were assessed by a trauma team and discharged directly home from ED were included. The primary outcome was the percentage of patients with an ED return visit within 14 days. We used multivariate logistic regression analyses to identify patient characteristics predictive of at least one ED return visit.There were 5,550 patients included in the study. A total of 1,004 (18.1%) of patients had at least one ED return visit, but only 100 patients (1.8%) were admitted to hospital following initial discharge. Common reasons for ED return visits included wound care concerns (17.2%), head injury complaints (15.6%), and substance misuse (6.8%). Rural residence (odds ratio [OR], 1.83; 95% CI, 1.45-2.29), history of anxiety disorder (OR, 2.05; 95% CI, 1.54-2.73), high baseline ED usage (OR, 2.58; 95% CI, 2.03-3.28), penetrating injury (OR, 1.42; 95% CI, 1.20-1.68), and extremity fracture (OR, 1.52; 95% CI, 1.24-1.88) predicted return visits.Patients discharged directly have high rates of ED return visits but low rates of hospital admission or delayed surgical intervention. Trauma services should expand quality assurance initiatives to capture return visits, understand any gaps in clinical service provision, and aim to minimize unnecessary ED return visits.Prognostic/Epidemiological; Level IV.

BackgroundAutologous fat grafting is commonly used for soft-tissue repair (approximately 90,000 cases per year in the United States), but outcomes are limited by volume loss (20% to 80%) over time. Human allograft adipose matrix (AAM) stimulates de novo adipogenesis in vivo, but retention requires optimization. The extracellular matrix derived from superficial fascia, interstitial within the adipose layer, is typically removed during AAM processing. Thus, fascia, which contains numerous important proteins, might cooperate with AAM to stimulate de novo adipogenesis, improving long-term retention compared to AAM alone.MethodsHuman AAM and fascia matrix proteins (back and upper leg regions) were identified by mass spectrometry and annotated by gene ontology. A three-dimensional in vitro angiogenesis assay was performed. Finally, AAM and/or fascia (1 mL) was implanted into 6- to 8-week-old male Fischer rats. After 8 weeks, the authors assessed graft retention by gas pycnometry and angiogenesis (CD31) and adipocyte counts (hematoxylin and eosin) histologically.ResultsGene ontology annotation revealed an angiogenic enrichment pattern unique to the fascia, including lactadherin, collagen alpha-3(V) chain, and tenascin-C. In vitro, AAM stimulated 1.0 ± 0.17 angiogenic sprouts per bead. The addition of fascia matrix increased sprouting by 88% (2.0 ± 0.12; P < 0.001). A similar angiogenic response (CD31) was observed in vivo. Graft retention volume was 25% (0.25 ± 0.13) for AAM, significantly increasing to 60% (0.60 ± 0.14) for AAM/fascia ( P < 0.05). De novo adipogenesis was 12% (12.4 ± 7.4) for AAM, significantly increasing to 51% (51.2 ± 8.0) for AAM/fascia ( P < 0.001) by means of adipocyte quantification.ConclusionsCombining fascia matrix with AAM improves angiogenesis and adipogenesis compared to AAM alone in rats. These preliminary in vitro and pilot animal studies should be further validated before definitive clinical adoption.Clinical relevance statementWhen producing an off-the-shelf adipose inducing product by adding a connective tissue fascial component (that is normally discarded) to the mix of adipose matrix, vasculogenesis is increased and, thus, adipogenesis and graft survival is improved. This is a significant advance in this line of product.

OBJECTIVE: To determine the costs and catastrophic costs incurred by drug-susceptible (DS) pulmonary TB patients in The Gambia.METHODS: This observational study collected cost and socio-economic data using a micro-costing approach from the household perspective from 244 adult DS-TB patients with pulmonary TB receiving treatment through the national treatment programme in The Gambia. We used data collected between 2017 and 2020 using an adapted version of the WHO generic patient cost survey instrument to estimate costs and the proportion of patients experiencing catastrophic costs (≥20% of household income).RESULTS: The mean total cost of the TB episode was $104.11 (2018 USD). Direct costs were highest before treatment ($22.93). Indirect costs accounted for over 50% of the entire episode costs. Using different income estimation approaches and catastrophic cost thresholds, 0.4–75% of participants encountered catastrophic costs, showing the variability of results given the different assumptions we utilised.CONCLUSIONS: We show that despite the benefits of free TB care and treatment, DS-TB patients still incur substantial direct and indirect costs, and cases of impoverishing expenditure varied vastly depending on the income estimation approaches used.

Skin cancer is highly curable under most circumstances; however, locally advanced or metastatic disease historically has poor outcomes and limited treatment options. Treatment has recently been advanced by the discovery of pertinent genes influencing pathogenesis and further revolutionized by the advent of specific gene expression profiles (GEPs). GEPs have been developed to help refine current diagnostic and prognostic strategies used in skin cancer with the goal to ultimately help guide management and treatment modalities to improve patient care. This article provides a high-level review of diagnostic and prognostic GEPs that have been developed specifically for squamous cell carcinoma and melanoma.

The burden of nosocomial respiratory infections in rural southern Africa is poorly understood. We established a surveillance program at a rural Zambian hospital to detect influenza-like illness (ILI) and respiratory infections among hospitalized patients and a cohort of healthcare workers (HCWs). Nasopharyngeal specimens from symptomatic patients and HCWs underwent broadly multiplexed molecular testing to detect viruses and atypical bacteria. During 1 year of surveillance, 15 patients (1.7% of admissions) developed ILI more than 48 hours after admission. Among 44 HCWs, 19 (43%) experienced at least one ILI episode, with a total of 31 ILI episodes detected. Respiratory viruses were detected in 45% of patient and 55% of HCW specimens. The cumulative incidence of influenza infection among HCWs over 1 year was 9%. Overall, respiratory viruses were commonly found among patients and HCWs in a rural Zambian hospital with limited infection control infrastructure.

X-linked hypophosphatemic rickets (XLH) is a rare condition affecting bone metabolism. It has characteristic dental features such as poorly mineralised dentine, spontaneous abscess formation in the absence of caries and taurodontism. There are limited published data about patients with this condition undergoing orthodontic treatment, and there is no clear guideline on the suitability of orthodontic treatment in this cohort. We present a case report of a patient with XLH with a confirmed PHEX gene mutation undergoing orthodontic treatment and clinical recommendations to support treatment.

The optimal order of vasopressor discontinuation during shock resolution remains unclear. We evaluated the incidence of hypotension in patients receiving concomitant vasopressin (VP) and norepinephrine (NE) based on the order of their discontinuation. In this retrospective cohort study, consecutive patients receiving concomitant VP and NE infusions for shock admitted to intensive care units were evaluated. The primary outcome was hypotension incidence following discontinuation of VP or NE (VP1 and NE1 groups, respectively). Secondary outcomes included the incidence of acute kidney injury (AKI) and arrhythmias. Subgroup analysis was conducted by examining outcomes based on the type of shock. Of the 2,035 included patients, 952 (46.8%) were VP1 and 1,083 (53.2%) were NE1. VP1 had a higher incidence of hypotension than NE1 (42.1% vs. 14.2%; P P = .009), higher hospital [29% (278/952) vs. 24% (258/1083); P = .006], and 28-day mortality [37% (348/952) vs. 29% (317/1,083); P p-value p-value p-value

Introduction: SHORT syndrome is a rare autosomal dominant condition described by its acronym of short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger abnormality, and teething delay. Individuals have a distinct progeroid craniofacial appearance with a triangular face, frontal bossing, hypoplastic or thin alae nasi, large low-set ears, and mandibular retrognathia. Objectives: To systematically appraise the literature and update the clinical phenotype with emphasis on the dental condition. Design: A systematic literature search was carried out to update the clinical phenotype, identifying reports of individuals with SHORT syndrome published after August 2015. The same search strategy but not limited to publication date was carried out to identify reports of the dental phenotype. Two independent reviewers screened 1937 articles with 55 articles identified for full-text review. Results: Nineteen individuals from 11 families were identified. Facial dysmorphism including ocular depression, triangular shaped face, frontal bossing, large low-set ears, and micrognathia were the most consistent features followed by lipodystrophy, insulin resistance, and intrauterine growth restriction. Teething delay, microdontia, hypodontia, and enamel hypoplasia have all been reported. Conclusion: Features that comprise the SHORT acronym do not accurately or completely describe the clinical phenotype. The craniofacial appearance is one of the most consistent features. Lipodystrophy and insulin resistance may also be considered cardinal features. After teething delay, enamel hypoplasia and microdontia are the most common dental manifestations. We present recommendations for the dental and orthodontic/orthognathic management of individuals with SHORT syndrome.

Importanceβ-amyloid plaques and neurofibrillary tau deposits biologically define Alzheimer disease.ObjectiveTo perform post hoc analyses of amyloid reduction after donanemab treatment and assess its association with tau pathology and clinical measures.Design, Setting, and ParticipantsThe Study of LY3002813 in Participants With Early Symptomatic Alzheimer’s Disease (TRAILBLAZER-ALZ) was a phase 2, placebo-controlled, randomized clinical trial conducted from December 18, 2017, to December 4, 2020, with a double-blind period of up to 76 weeks and a 48-week follow-up period. The study was conducted at 56 centers in the US and Canada. Enrolled were participants from 60 to 85 years of age with gradual and progressive change in memory function for 6 months or more, early symptomatic Alzheimer disease, elevated amyloid, and intermediate tau levels.InterventionsDonanemab (an antibody specific for the N-terminal pyroglutamate β-amyloid epitope) dosing was every 4 weeks: 700 mg for the first 3 doses, then 1400 mg for up to 72 weeks. Blinded dose-reduction evaluations occurred at 24 and 52 weeks based on amyloid clearance.Main Outcomes and MeasuresChange in amyloid, tau, and clinical decline after donanemab treatment.ResultsThe primary study randomized 272 participants (mean [SD] age, 75.2 [5.5] years; 145 female participants [53.3%]). The trial excluded 1683 of 1955 individuals screened. The rate of donanemab-induced amyloid reduction at 24 weeks was moderately correlated with the amount of baseline amyloid (Spearman correlation coefficient r, −0.54; 95% CI, −0.66 to −0.39; P APOE) ε4 carriers (95% CI, 24%-59%; P Conclusions and RelevanceResults of post hoc analyses for donanemab-treated participants suggest that baseline amyloid levels were directly associated with the magnitude of amyloid reduction and inversely associated with the probability of achieving complete amyloid clearance. The donanemab-induced slowing of tau was more pronounced in those with complete amyloid clearance and in brain regions identified later in the pathologic sequence. Data from other trials will be important to confirm aforementioned observations, particularly treatment response by APOE ε4 status.Trial RegistrationClinicalTrials.gov Identifier: NCT03367403

Researchers studying children’s reports of sexual abuse have focused on how questioners overtly assess coaching and truthfulness (e.g., “Did someone tell you what to say?”). Yet attorneys, and defense attorneys, in particular, may be motivated to ask about suggestive influence and truthfulness in subtle ways, such as with implied meaning (e.g., “Did your mom help you remember?”). Such questions may be particularly challenging for children, who may interpret statements literally, misunderstanding the suggested meaning. The purpose of this study was to examine and categorize how attorneys’ ask about suggestive influence and truthfulness. We wanted to learn how attorneys subtly accuse suggestive influence, and how frequently this occurred. We hypothesized that questions indirectly accusing suggestive influence would be common, and that defense attorneys would ask more subtle questions, and fewer overt questions, than prosecutors. We examined 7,103 lines of questioning asked by prosecutors and defense attorneys to 64 children testifying about alleged child sexual abuse. We found that 9% of all attorneys’ lines of questioning asked about suggestive influence or truthfulness. The majority (66%) of these were indirect accusations. Indirect accusations of suggestive influence spanned a range of subtleties and topics, including addressing conversational influences (e.g., coaching), incidental influences (e.g., witnessing abuse), and others. We also found defense attorneys were less likely than prosecutors to ask about suggestive influence and truthfulness overtly. We conclude that attorneys commonly ask about suggestive influence and truthfulness in subtle ways that developing children may struggle to understand, and which may result in affirmations of influence, even when allegations are true.

With age, children become increasingly likely to make initial disclosures of transgressions, such as maltreatment, to peers. The present study examined adults’ credibility evaluations of children’s disclosures to peers across two studies. Study 1 examined credibility evaluations when children disclosed (or concealed) to a peer compared to an adult. Study 2 examined credibility ratings when children disclosed consistently or inconsistently across peer and adult interviews. Children were interviewed by a same-age peer and an adult regarding an event where an adult confederate spilled water on a laptop and broke it. In Study 1, participants heard a child interviewed by either a same-age peer or adult. In Study 2, participants heard a child interviewed by both the same-age peer and adult. In both studies, participants evaluated the child’s credibility. Children who disclosed the transgression were rated as significantly less credible than those who concealed the transgression; however, credibility ratings did not differ by whether the child was interviewed by a peer or adult (Study 1). Furthermore, children who concealed the transgression across both interviews were rated as significantly more credible than children who disclosed in both interviews or disclosed to the peer, but not the adult, interviewer (Study 2). The current study provides the first evidence that peer disclosures may hinder children’s credibility and that adults may be hesitant to believe children’s disclosures of an adult’s transgression.

Synthetic clays are promising biomaterials for delivery of therapeutic molecules in regenerative medicine. However, before their use can be translated into clinical applications, their safety must be assessed in human volunteers. The aim of this study was to test the hypothesis that a synthetic nanoclay (LAPONITE) does not cause irritation to the human skin. To achieve this, a nanoclay gel at two different concentrations (1.5 and 3% w/v) was applied on the forearm of healthy volunteers for 24 h. 1% sodium lauryl sulfate (SLS) and 3% (w/v) polyacrylic acid were used as the positive and negative controls, respectively. The compromise in the skin barrier function was measured by trans-epidermal water loss (TEWL), erythema by spectroscopic measurements, and skin inflammatory biomarkers (IL-1α and IL-1RA) by the enzyme-linked immunosorbent assay. We found that the nanoclay caused no prolonged increase in TEWL, erythema, or induction of inflammatory cytokines. This was in contrast to 1% SLS, a known irritant, which induced significant increases in both skin erythema and TEWL. We conclude that the nanoclay is not an irritant and is thus suitable for therapeutic interventions at the skin surface.

Background Antenatal titration testing is traditionally performed using a manual tube test. Tube testing has limitations; it is a manual, time-consuming method with wide interobserver variability. Gel-based testing is an attractive alternative because it is more precise and can be automated. This study's objective was to summarize the published literature that assessed the relationship between titrations performed by tube and gel for anti-D alloimmunized pregnancies. Study design and methods A comprehensive literature search was performed. Articles were selected if research was original and compared at least five pairs of anti-D titration tests performed by gel and tube. Differences in the number of dilutions between gel and tube methods were compared overall by study and cell type using linear models. Results A total of 512 articles were identified; eight were included, and titer data from 384 tube and gel pairs were abstracted. The median anti-D titer in tube was 8 (range 0-2048) and by gel was 64 (range 0-4096). Anti-D gel titration results were 2.1 (95% CI; 1-3.3) additional dilutions greater than in tube. Most studies utilized double-dose reagent cells for testing. At a tube titer of 16, the sensitivity and specificity of gel titrations is maximal (91% and 94% respectively) at a gel titer of 64. Conclusion Overall, titrations performed by gel were two dilutions higher than the corresponding tube titer. For titrations, double-dose reagent cells should be considered to standardize practice. A rigorous prospective study is needed to compare tube titrations with gel titrations using a standardized process.

Objectives This article is one of a series on acute, severe diseases of humans caused by emerging viruses for which there are no or limited licensed medical countermeasures. We approached this summary on South American Hemorrhagic Fevers from a clinical perspective, focusing on pathogenesis, clinical features, and diagnostics, with an emphasis on therapies and vaccines that have demonstrated potential for use in an emergency situation through their evaluation in nonhuman primates (NHPs) and/or in humans. Methods A standardized literature review was conducted on the clinical, pathological, vaccine, and treatment factors for South American Hemorrhagic Fevers as a group and for each individual virus/disease. Results We identified two treatments and one vaccine platform that have demonstrated potential benefit for treating or preventing infection in humans and four other potential treatments currently under investigation. Conclusion We provide succinct summaries of these countermeasures to give the busy clinician a head start in reviewing the literature if faced with a patient with a South American Hemorrhagic Fever. We also provide links to other authoritative sources of information.

Wnt signaling regulates cell proliferation and cell differentiation as well as migration and polarity during development. However, it is still unclear how the Wnt ligand distribution is precisely controlled to fulfil these functions. Here, we show that the planar cell polarity protein Vangl2 regulates the distribution of Wnt by cytonemes. In zebrafish epiblast cells, mouse intestinal telocytes and human gastric cancer cells, Vangl2 activation generates extremely long cytonemes, which branch and deliver Wnt protein to multiple cells. The Vangl2-activated cytonemes increase Wnt/β-catenin signaling in the surrounding cells. Concordantly, Vangl2 inhibition causes fewer and shorter cytonemes to be formed and reduces paracrine Wnt/β-catenin signaling. A mathematical model simulating these Vangl2 functions on cytonemes in zebrafish gastrulation predicts a shift of the signaling gradient, altered tissue patterning, and a loss of tissue domain sharpness. We confirmed these predictions during anteroposterior patterning in the zebrafish neural plate. In summary, we demonstrate that Vangl2 is fundamental to paracrine Wnt/β-catenin signaling by controlling cytoneme behaviour., Cytonemes are cellular projections known to transfer Wnt ligands between cells, but their regulation remains unclear. Here, the authors show that activation of the planar cell polarity protein Vangl2 generates long and branched cytonemes increasing paracrine Wnt/β-catenin signaling.

Introduction Children with Apert syndrome have hypertelorism and midfacial hypoplasia, which can be treated with facial bipartition (FB), often aided by rigid external distraction. The technique involves a midline osteotomy that lateralizes the maxillary segments, resulting in posterior cross-bites and midline diastema. Varying degrees of spontaneous realignment of the dental arches occurs postoperatively. This study aims to quantify these movements and assess whether they occur as part of a wider skeletal relapse or as dental compensation. Methods Patients who underwent FB and had high quality computed tomography scans at the preoperative stage, immediately postsurgery, and later postoperatively were reviewed. DICOM files were converted to three-dimensional bone meshes and anatomical point-to-point displacements were quantified using nonrigid iterative closest point registration. Displacements were visualized using arrow maps, thereby providing an overview of the movements of the facial skeleton and dentition. Results Five patients with Apert syndrome were included. In all cases, the arrow maps demonstrated initial significant anterior movement of the frontofacial segment coupled with medial rotation of the orbits and transverse divergence of the maxillary arches. The bony position following initial surgery was shown to be largely stable, with primary dentoalveolar relapse correcting the dental alignment. Conclusions This study showed that spontaneous dental compensation occurs following FB without compromising the surgical result. It may be appropriate to delay active orthodontic for 6-months postoperatively until completion of this early compensatory phase.

Background Symptom intensity during a common cold is highly variable, particularly after the illness peaks, contributing to delay in recovery. Rhinoviruses frequently cause colds and, during acute infections, generate leukotriene B4 and prostaglandin E2 (PGE2). PGE2 is known to initiate oxylipin class switching and resolution of acute inflammation. Thus, we hypothesized that during acute rhinovirus colds, oxylipins with pro-resolving capabilities reduce symptom severity and speed recovery. Methods Four groups of healthy volunteers were inoculated with placebo or 3 different doses of rhinovirus A16. Participants kept daily records of symptoms and contributed serial nasal lavage fluid samples. We collected semi-quantitative mass spectrometry data for 71 oxylipins in these acute samples from all participants. An ensemble analysis approach was used to further reduce this dataset. Results Levels of 15-keto-PGE2 at day 3 of the cold were consistently among the top candidates in these models of recovery symptoms. 15-keto-PGE2 was the only oxylipin with an interaction between inoculum dose and time. Acute 15-keto-PGE2 levels were inversely associated with symptoms during cold recovery in a multivariable analysis (P = .0043). Conclusions These findings show that high 15-keto-PGE2 levels during the acute cold are associated with fewer symptoms during recovery.

Kidneys donated after circulatory death (DCD) are increasingly being used for transplantation in adults to alleviate organ shortage. Pediatric data on survival benefits of DCD transplantation compared with remaining on the waitlist for a kidney donated after brain death (DBD) offer are lacking.We used Scientific Registry of Transplant Recipients to identify 285 pediatric (18 y) DCD kidney transplants performed between 1987 and 2017. Propensity score matching was used to create a comparison group of 1132 DBD transplants. We used sequential Cox analysis to evaluate survival benefit of DCD transplantation versus remaining on the waitlist and Cox regression to evaluate patient and graft survival.DCD transplantation was associated with a higher incidence of delayed graft function (adjusted odds ratio: 3.0; P 0.001). The risks of graft failure (adjusted hazard ratio [aHR], 0.89; P = 0.46) and death (aHR, 1.2; P = 0.67) were similar between DCD and DBD recipients. We found a significant survival benefit of DCD transplantation compared with remaining on the waitlist awaiting a DBD kidney (aHR, 0.44; P = 0.03).Despite a higher incidence of delayed graft function, long-term patient and graft survival are similar between pediatric DCD and DBD kidney transplant recipients. DCD transplantation in children is associated with a survival benefit, despite pediatric priority for organ allocation, compared with remaining on the waitlist.

Pediatric kidney transplant outcomes associated with expanded-criteria donors (ECD) and high Kidney Donor Profile Index (KDPI) kidneys are unknown. We reviewed the Scientific Registry of Transplant Recipients data from 1987-2017 to identify 96 ECD and 92 > 85 KDPI kidney recipients ( 85 KDPI transplants, respectively. We used Cox regression for patient/graft survival and sequential Cox approach for survival benefit of ECD and > 85 KDPI transplantationvs remaining on the waitlist. After adjustment, ECD recipients were at significantly increased risk of graft failure (adjusted hazard ratio [aHR] = 1.6; P = .001) but not of mortality (aHR = 1.33; P = .15) compared with non-ECD recipients. We observed no survival benefit of ECD transplants vs remaining on the waitlist (aHR = 1.05; P = .83). We found no significant difference in graft failure (aHR = 1.27; P = .12) and mortality (aHR = 1.41; P = .13) risks between > 85 KDPI and ≤ 85 KDPI recipients. However, > 85 KDPI transplants were associated with a survival benefit vs remaining on the waitlist (aHR = 0.41; P = .01). ECD transplantation in children is associated with a high graft loss risk and no survival benefit, whereas > 85 KDPI transplantation is associated with a survival benefit for children vs remaining on the waitlist.

It is generally believed that the phosphenes induced by transcranial electric current stimulation (tECS) are a product of retinal activation, even when electrode placement is directly over the primary visual cortex. However, the origins of these tECS-induced phosphenes have not yet been conclusively determined. In this study, phosphene detection thresholds using an FPz-Oz montage were compared with those from (i) an Oz-Cz montage to determine whether prefrontal regions, such as the retina, contribute to phosphenes and (ii) an FPz-Cz montage to determine whether the visual cortex in the occipital lobe contributes to phosphenes. Twenty-two participants received transcranial current stimulation with each of these montages (as well as a T3-T4 montage included for exploratory purposes) at 6, 10, 16, 20, 24, 28, and 32 Hz. To estimate differences in current density at the retina and occipital lobe across montages, modeling of current density at phosphene thresholds was measured across 20 head models. Consistent with the proposal that tECS-induced phosphenes are generated in the retina, increasing current density near the retina (FPz-Oz relative to Oz-Cz montage) reduced phosphene thresholds. However, increasing current density near the occipital cortex (FPz-Oz relative to FPz-Cz montage) also reduced phosphene thresholds while also requiring less current density at the retina according to the modeling estimates. This suggests that tECS of this occipital cortex also contributed to phosphene perception. © 2020 Bioelectromagnetics Society.

BACKGROUND Preoperative thrombocytopenia is associated with inferior outcomes in surgical patients, though concurrent anemia may obfuscate these relationships. This investigation assesses the prevalence and clinical significance of preoperative thrombocytopenia with thorough consideration of preoperative anemia status. METHODS This is an observational cohort study of adults undergoing elective surgery with planned postoperative hospitalization from January 1, 2009 to May 3, 2018. Patients were designated into 4 groups: normal platelet and hemoglobin concentrations, isolated thrombocytopenia (ie, platelet count

Summary Background Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of these patients is generally intensive, because local regrowth (with the potential for salvage) occurs in 25% of patients, and distant metastases occur in 10% of patients. It is unclear for how long these patients should be followed up. To address this issue, we did conditional survival modelling using the International Watch & Wait Database (IWWD), which is a large-scale registry of patients with a clinical complete response after neoadjuvant chemotherapy who have been managed by a watch-and-wait strategy. Methods We did a retrospective, multicentre registry study using a dataset from the IWWD, which includes data from 47 clinics across 15 countries. We selected patients (aged ≥18 years) with rectal cancer who had a clinical complete response after neoadjuvant chemotherapy, and who were subsequently managed by a watch-and-wait strategy between Nov 25, 1991, and Dec 31, 2015. Patients who had not achieved a clinical complete response or who had undergone any surgical procedure were excluded. The criteria used for defining a clinical complete response and the specific surveillance strategies were at the discretion of each participating centre. We used conditional survival modelling to estimate the probability of patients remaining free of local regrowth or distant metastasis for an additional 2 years after sustaining a clinical complete response or being distant metastasis-free for 1, 3, and 5 years from the date of the decision to commence watch and wait. The primary outcomes were conditional local regrowth-free survival at 3 years, and conditional distant metastasis-free survival at 5 years. Findings We identified 793 patients in the IWWD with clinical complete response who had been managed by a watch-and-wait strategy. Median follow-up was 55·2 months (IQR 36·0–75·6). The probability of remaining free from local regrowth for an additional 2 years if a patient had a sustained clinical complete response for 1 year was 88·1% (95% CI 85·8–90·9), for 3 years was 97·3% (95·2–98·6), and for 5 years was 98·6% (97·6–100·0). The probably of remaining free from distant metastasis for a further 2 years in patients who had a clinical complete response without distant metastasis for 1 year was 93·8% (92·3–95·9), for 3 years was 97·8% (96·6–99·3), and for 5 years was 96·6% (94·0–98·9). Interpretation These results suggest that the intensity of active surveillance in patients with rectal cancer managed by a watch-and-wait approach could be reduced if they achieve and maintain a clinical complete response within the first 3 years of starting this approach. Funding European Registration of Cancer Care, financed by the European Society of Surgical Oncology, the Champalimaud Foundation Lisbon, the Bas Mulder Award, granted by the Alpe d’HuZes Foundation and the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre.

LAPONITE® clay nanoparticles are known to exert osteogenic effects on human bone marrow stromal cells (HBMSCs), most characteristically, an upregulation in alkaline phosphatase activity and increased calcium deposition. The specific properties of LAPONITE® that impart its bioactivity are not known. In this study the role of lithium, a LAPONITE® degradation product, was investigated through the use of lithium salts and lithium modified LAPONITE® formulations. In contrast to intact particles, lithium ions applied at concentrations equivalent to that present in LAPONITE®, failed to induce any significant increase in alkaline phosphatase (ALP) activity. Furthermore, no significant differences were observed in ALP activity with modified clay structures and the positive effect on osteogenic gene expression did not correlate with the lithium content of modified clays. These results suggest that other properties of LAPONITE® nanoparticles, and not their lithium content, are responsible for their bioactivity.

Rectal cancer patients frequently receive pre-operative radiotherapy (RT), prior to surgical resection. However, colorectal cancer is heterogeneous and the degree of tumour response to pre-operative RT is highly variable. There are currently no clinically approved methods of predicting response to RT, and a significant proportion of patients will show no clinical benefit, despite enduring the side-effects. We evaluated the use of Raman spectroscopy (RS), a non-destructive technique able to provide the unique chemical fingerprint of tissues, as a potential tool to stratify patient response to pre-operative RT. Raman measurements were obtained from the formalin-fixed, paraffin-embedded (FFPE) pre-treatment biopsy specimens of 20 rectal cancer patients who received pre-operative RT. A principal component analysis and linear discriminant analysis algorithm was able to classify patient response to pre-operative RT as good or poor, with an accuracy of 86.04 ± 0.14% (standard error). Patients with a good response to RT showed greater contributions from protein-associated peaks, whereas patients who responded poorly showed greater lipid contributions. These results demonstrate that RS is able to reliably classify tumour response to pre-operative RT from FFPE biopsies and highlights its potential to guide personalised cancer patient treatment.

International research has explored lawyer-child interactions in court; however, little focus has been spent examining other aspects of lawyers' interactions with children (e.g., interview preparation; building rapport).The present study investigated lawyer's self-reported interactions with child witnesses.Participants included 96 lawyers (MA survey was used to gather self-reported data on how lawyers prepare for, question, and respond to children as witnesses in court. We then explored whether these strategies differed depending on the role of the Canadian lawyer (i.e., prosecution or defence), experience, or gender.Results indicate that lawyers report and demonstrate knowledge consistent with current best practices in questioning children. While gender and experience did not appear to play a strong role in lawyer-child interactions, prosecutors reported behavior more consistent with best practices compared to defence lawyers.These findings provide important insight into strengths and weaknesses of lawyer-child interactions in court as well as highlight a strong need for future research to examine the link between self-reported behavior (i.e., perceived behavior) with observable behavior (i.e., actual behavior) in lawyer-child interactions.

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values-8 as genome-wide significant, and p-values-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values5. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.

Characterizing complex microbial communities with single-cell resolution has been a long-standing goal of microbiology. We present Microbe-seq, a high-throughput method that yields the genomes of individual microbes from complex microbial communities. We encapsulate individual microbes in droplets with microfluidics and liberate their DNA, which we then amplify, tag with droplet-specific barcodes, and sequence. We explore the human gut microbiome, sequencing more than 20,000 microbial single-amplified genomes (SAGs) from a single human donor and coassembling genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe microbial interactions, reconstructing the horizontal gene transfer (HGT) network and observing HGT between 92 species pairs; we also identify a significant in vivo host-phage association between crAssphage and one strain of Bacteroides vulgatus . Microbe-seq contributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution.

open access article Cells are continually exposed to agents arising from the internal and external environments, which may damage DNA. This damage can cause aberrant cell function, and therefore DNA damage may play a critical role in the development of, conceivably, all major human diseases, e.g., cancer, neurodegenerative and cardiovascular disease, and aging. Single-cell gel electrophoresis (i.e., the comet assay) is one of the most common and sensitive methods to study the formation and repair of a wide range of types of DNA damage (e.g., single- and double-strand breaks, alkali-labile sites, DNA-DNA crosslinks, and, in combination with certain repair enzymes, oxidized purines, and pyrimidines), in both in vitro and in vivo systems. However, the low sample throughput of the conventional assay and laborious sample workup are limiting factors to its widest possible application. With the "scoring" of comets increasingly automated, the limitation is now the ability to process significant numbers of comet slides. Here, a high-throughput (HTP) variant of the comet assay (HTP comet assay) has been developed, which significantly increases the number of samples analyzed, decreases assay run time, the number of individual slide manipulations, reagent requirements, and risk of physical damage to the gels. Furthermore, the footprint of the electrophoresis tank is significantly decreased due to the vertical orientation of the slides and integral cooling. Also reported here is a novel approach to chilling comet assay slides, which conveniently and efficiently facilitates the solidification of the comet gels. Here, the application of these devices to representative comet assay methods has been described. These simple innovations greatly support the use of the comet assay and its application to areas of study such as exposure biology, ecotoxicology, biomonitoring, toxicity screening/testing, together with understanding pathogenesis.

Trypanosomatid gut parasites are common in pollinators and costly for social bees. The recently described honey bee trypanosomatid Lotmaria passim is widespread, abundant, and correlated with colony losses in some studies. The potential for amelioration of infection by antimicrobial plant compounds has been thoroughly studied for closely related trypanosomatids of humans and is an area of active research in bumble bees, but remains relatively unexplored in honey bees. We recently identified several floral volatiles that inhibited growth of L. passim in vitro. Here, we tested the dose-dependent effects of four such compounds on infection, mortality, and food consumption in parasite-inoculated honey bees. We found that diets containing the monoterpenoid carvacrol and the phenylpropanoids cinnamaldehyde and eugenol at gt; 10-fold the inhibitory concentrations for cell cultures reduced infection, with parasite numbers decreased by gt; 90 % for carvacrol and cinnamaldehyde and gt; 99 % for eugenol; effects of the carvacrol isomer thymol were non-significant. However, both carvacrol and eugenol also reduced bee survival, whereas parasite inoculation did not, indicating costs of phytochemical exposure that could exceed those of infection itself. To our knowledge, this is the first controlled screening of phytochemicals for effects on honey bee trypanosomatid infection, identifying potential treatments for managed bees afflicted with a newly characterized, cosmopolitan intestinal parasite.

BackgroundResponses of the metabolome to acute aerobic exercise may predict maximum oxygen consumption (VO2max) and longer-term outcomes, including the development of diabetes and its complications.MethodsSerum samples were collected from overweight/obese trained (OWT) and normal-weight trained (NWT) runners prior to and immediately after a supervised 90-minute treadmill run at 60% VO2max (NWT = 14, OWT = 11) in a cross-sectional study. We applied a liquid chromatography high-resolution-mass spectrometry-based untargeted metabolomics platform to evaluate the effect of acute aerobic exercise on the serum metabolome.ResultsNWT and OWT metabolic profiles shared increased circulating acylcarnitines and free fatty acids (FFAs) with exercise, while intermediates of adenine metabolism, inosine, and hypoxanthine were strongly correlated with body fat percentage and VO2max. Untargeted metabolomics-guided follow-up quantitative lipidomic analysis revealed that baseline levels of fatty acid esters of hydroxy fatty acids (FAHFAs) were generally diminished in the OWT group. FAHFAs negatively correlated with visceral fat mass and HOMA-IR. Strikingly, a 4-fold decrease in FAHFAs was provoked by acute aerobic running in NWT participants, an effect that negatively correlated with circulating IL-6; these effects were not observed in the OWT group. Machine learning models based on a preexercise metabolite profile that included FAHFAs, FFAs, and adenine intermediates predicted VO2max.ConclusionThese findings in overweight human participants and healthy controls indicate that exercise-provoked changes in FAHFAs distinguish normal-weight from overweight participants and could predict VO2max. These results support the notion that FAHFAs could modulate the inflammatory response, fuel utilization, and insulin resistance.Trial registrationClinicalTrials.gov, NCT02150889.FundingNIH DK091538, AG069781, DK098203, TR000114, UL1TR002494.

Drug penetration into solid tumours remains a major challenge in the effective treatment of cancer. Microbubble (MB) mediated sonoporation offers a potential solution to this by enhancing the uptake of drugs into cells. Additionally, in using an ultrasound (US) trigger, drug delivery can be localised to the tumour, thus reducing the off-site toxicity associated with systemic delivery. The majority of in vitro studies involving the observation of MB-enhanced drug efficacy have been conducted on 2D monolayer cell cultures, which are known to be poor models for in vivo tumours. 3D spheroid cultures allow for the production of multicellular cultures complete with extracellular matrix (ECM) components. These cultures effectively recreate many of the physiological features of the tumour microenvironment and have been shown to be far superior to previous 2D monolayer models. However, spheroids are typically handled in well-plates in which the fluid environment is static, limiting the physiological relevance of the model. The combination of 3D cultures and microfluidics would allow for the production of a dynamic system in which spheroids are subjected to in vivo like fluid flow and shear stresses. This study presents a microfluidic device containing an array of spheroid traps, into which multiple pre-grown colorectal cancer (CRC) spheroids were loaded. Reservoirs interfaced with the chip use hydrostatic pressure to passively drive flow through the system and subject spheroids to capillary like flow velocities. The use of reservoirs also enabled multiple chips to be run in parallel, allowing for the screening of multiple therapeutic treatments (n = 690 total spheroids analysed). This microfluidic platform was used to investigate MB enhanced drug delivery and showed that co-delivery of 3 μM doxorubicin (DOX) + MB + US reduced spheroid viability to 48 ± 2%, compared to 75 ± 5% observed with 3 μM DOX alone. Delivery of drug loaded MBs (DLMBs), in which DOX-loaded liposomes (DOX-LS) were conjugated to MBs, reduced spheroid viability to 62 ± 3%, a decrease compared to the 75 ± 3% viability observed with DOX-LS in the absence of MBs + US.

Background Microtia is an inherited condition that results in varying degrees of external ear deformities; the most extreme form is anotia. Effective surgical reconstruction techniques have been developed. However, these usually require multistage procedures and have other inherent disadvantages. Tissue engineering technologies offer new approaches in the field of external ear reconstruction. In this setting, chondrocytes are cultured in the laboratory with the aim of creating bioengineered cartilage matrices. However, cartilage engineering has many challenges, including difficulty in culturing sufficient chondrocytes. To overcome these hurdles, the authors propose a novel model of cartilage engineering that involves co-culturing chondrocytes and adipose-derived stem cells on an allograft adipose-derived extracellular matrix scaffold. Methods Auricular chondrocytes from porcine ear were characterized. Adipose-derived stem cells were isolated and expanded from human lipoaspirate. Then, the auricular chondrocytes were cultured on the allograft adipose matrix either alone or with the adipose-derived stem cells at different ratios and examined histologically. Results Cartilage induction was most prominent when the cells were co-cultured on the allograft adipose matrix at a ratio of 1:9 (auricular chondrocyte-to-adipose-derived stem cell ratio). Furthermore, because of the xenogeneic nature of the experiment, the authors were able to determine that the adipose-derived stem cells contributed to chondrogenesis by means of a paracrine stimulation of the chondrocytes. Conclusions In this situation, adipose-derived stem cells provide sufficient support to induce the formation of cartilage when the number of auricular chondrocytes available is limited. This novel model of cartilage engineering provides a setting for using the patient's own chondrocytes and adipose tissue to create a customized ear framework that could be further used for surgical reconstruction.

Introduction Lie-telling appears to peak during adolescence; however, previous research has not yet examined lie-telling frequency in adolescents' friendships. Increased lie-telling may be problematic given that honesty is crucial for trust within positive relationships, and more positive relationships lead to more positive well-being. The present study examined adolescents’ lies to friends and longitudinal associations between lying, friendship quality, and depressive symptoms. Methods Canadian adolescents (Time 1: N = 1313, Mage = 11.65, SD = 11.75, 50% male) reported how often they lied to their friends about their mental health/mood, possessions, romantic relationships, school, and to avoid spending time with them. Participants also completed measures of friendship quality and depressive symptoms. Participants completed these measures at two time points one year apart. Results Poorer friendship quality predicted more frequent lie-telling over time. Greater depressive symptoms predicted more frequent lie-telling over time, and more frequent lie-telling predicted greater depressive symptoms over time. Lies about mental health in particular were bidirectionally associated with both friendship quality and depressive symptoms over time. Conclusions These findings highlight the developmental importance of lie-telling during adolescence. More negative friendships lead to greater lie-telling over time. Additionally, increased lie-telling predicted and is predicted by depressive symptoms, suggesting that lie-telling may be an important indicator of poor mental health.

Honest disclosures of COVID-19 behaviors and symptoms is critical. A sample of adults on MTurk ( N = 451, 20–82 years of age) were asked if they have concealed social distancing practices, COVID-19 symptoms, and quarantine instructions, as well as how they evaluated others’ COVID-19 concealment. Those who believed they had contracted COVID-19 engaged in greater rates of concealment and evaluated concealment more positively compared to those without the virus. As age and communal orientation increased, COVID-19 concealment behaviors decreased, and evaluations of this concealment were rated more negatively. Implications for public health initiatives and psychological theory on concealing health information is discussed.

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p

Analysis of modern animals and Ediacaran trace fossils predicts that the oldest bilaterians were simple and small. Such organisms would be difficult to recognize in the fossil record, but should have been part of the Ediacara Biota, the earliest preserved macroscopic, complex animal communities. Here, we describe Ikaria wariootia gen. et sp. nov. from the Ediacara Member, South Australia, a small, simple organism with anterior/posterior differentiation. We find that the size and morphology of Ikaria match predictions for the progenitor of the trace fossil Helminthoidichnites—indicative of mobility and sediment displacement. In the Ediacara Member, Helminthoidichnites occurs stratigraphically below classic Ediacara body fossils. Together, these suggest that Ikaria represents one of the oldest total group bilaterians identified from South Australia, with little deviation from the characters predicted for their last common ancestor. Further, these trace fossils persist into the Phanerozoic, providing a critical link between Ediacaran and Cambrian animals.

BACKGROUND: Hyperpolarized helium 3 magnetic resonance imaging ((3)He MRI) is useful for investigating pulmonary physiology of pediatric asthma, but a detailed assessment of the safety profile of this agent has not been performed in children. OBJECTIVE: To evaluate the safety of (3)He MRI in children and adolescents with asthma. MATERIALS AND METHODS: This was a retrospective observational study. (3)He MRI was performed in 66 pediatric patients (mean age 12.9 years, range 8–18 years, 38 male, 28 female) between 2007 and 2017. Fifty-five patients received a single repeated examination and five received two repeated examinations. We assessed a total of 127 (3)He MRI exams. Heart rate, respiratory rate and pulse oximetry measured oxygen saturation (SpO(2)) were recorded before, during (2 min and 5 min after gas inhalation) and 1 h after MRI. Blood pressure was obtained before and after MRI. Any subjective symptoms were also noted. Changes in vital signs were tested for significance during the exam and divided into three subject age groups (8–12 years, 13–15 years, 16–18 years) using linear mixed-effects models. RESULTS: There were no serious adverse events, but three minor adverse events (2.3%; headache, dizziness and mild hypoxia) were reported. We found statistically significant increases in heart rate and SpO(2) after (3)He MRI. The youngest age group (8–12 years) had an increased heart rate and a decreased respiratory rate at 2 min and 5 min after (3)H inhalation, and an increased SpO(2) post MRI. CONCLUSION: The use of (3)He MRI is safe in children and adolescents with asthma.

Objective:To identify patient and provider characteristics associated with high-volume antibiotic prescribing for children in Tennessee, a state with high antibiotic utilization.Design:Cross-sectional, retrospective analysis of pediatric (aged Methods:Patient and provider characteristics, including county of prescription fill, rural versus urban county classification, patient age group, provider type (nurse practitioner, physician assistant, physician, or dentist), physician specialty, and physician years of practice were analyzed.Results:Tennessee providers wrote 1,940,011 pediatric outpatient antibiotic prescriptions yielding an antibiotic prescribing rate of 1,165 per 1,000 population, 50% higher than the national pediatric antibiotic prescribing rate. Mean antibiotic prescribing rates varied greatly by county (range, 39–2,482 prescriptions per 1,000 population). Physicians wrote the greatest number of antibiotic prescriptions (1,043,030 prescriptions, 54%) of which 56% were written by general pediatricians. Pediatricians graduating from medical school prior to 2000 were significantly more likely than those graduating after 2000 to be high antibiotic prescribers. Overall, 360 providers (1.7% of the 21,798 total providers in this dataset) were responsible for nearly 25% of both overall and broad-spectrum antibiotic prescriptions; 20% of these providers practiced in a single county.Conclusions:Fewer than 2% of providers account for 25% of pediatric antibiotic prescriptions. High antibiotic prescribing for children in Tennessee is associated with specific patient and provider characteristics that can be used to design stewardship interventions targeted to the highest prescribing providers in specific counties and specialties.

Lie-telling and secret-keeping are common behaviors during adolescence. Given the importance of honesty for building trust in positive relationships, the present study examined relations between lie-telling, secret-keeping, and relationship quality over time. Additionally, given the protective role of positive relationships in developing depression, the present study examined how lying to and keeping secrets from parents related to depressive symptoms over time. Children and adolescents (N = 1313; 8 to 15 years old at Time 1, Mage= 11.65, SD = 11.75; 50.04% male) reported on lying to parents, secret-keeping from parents, relationship quality with parents, and depressive symptoms at two time points one year apart. The results indicated that greater secret-keeping was bidirectionally associated with poorer parent-child relationship quality and greater depressive symptoms over time. Thus, keeping secrets from parents appears to be an important behavior to examine in the context of development between late childhood and adolescence.

When deep convolutional neural networks (CNNs) are trained “end-to-end” on raw data, some of the feature detectors they develop in their early layers resemble the representations found in early visual cortex. This result has been used to draw parallels between deep learning systems and human visual perception. In this study, we show that when CNNs are trained end-to-end they learn to classify images based on whatever feature is predictive of a category within the dataset. This can lead to bizarre results where CNNs learn idiosyncratic features such as high-frequency noise-like masks. In the extreme case, our results demonstrate image categorisation on the basis of a single pixel. Such features are extremely unlikely to play any role in human object recognition, where experiments have repeatedly shown a strong preference for shape. Through a series of empirical studies with standard high-performance CNNs, we show that these networks do not develop a shape-bias merely through regularisation methods or more ecologically plausible training regimes. These results raise doubts over the assumption that simply learning end-to-end in standard CNNs leads to the emergence of similar representations to the human visual system. In the second part of the paper, we show that CNNs are less reliant on these idiosyncratic features when we forgo end-to-end learning and introduce hard-wired Gabor filters designed to mimic early visual processing in V1.

The verbs ask and tell can be used both epistemically, referring to the flow of information, and deontically, referring to obligations through polite requests or commands. Some researchers suggest that children’s understanding of deontic modals emerges earlier than their understanding of epistemic modals, possibly because theory of mind is required to understand epistemic modals. In the current study, 184 children aged 3–6 years were presented with vignettes depicting epistemic and deontic asking and telling and were asked whether the speaker asked or told, followed by first-order theory-of-mind tasks. An emergence of both epistemic and deontic understanding was found at 5 years of age, and both were correlated with children’s theory-of-mind understanding. These findings are consistent with arguments that both epistemic and deontic understanding implicate theory-of-mind awareness and provide insight into the developmental trajectory of children’s understanding.

Background Physical activity plays an important role in maintaining good health and wellbeing, non-communicable disease prevention and can improve healthcare outcomes. Some progress is being made on incorporating physical activity into routine care, but less on engaging health system leaders in the ‘whole systems’ approaches which are increasingly recognised as important for addressing complex public health challenges such as physical inactivity. This commentary builds upon the findings of a recent study and aims to identify opportunities for engaging National Health Service (NHS) systems leaders in whole systems approaches to physical activity. Opportunities for action in England Pockets of good practice exist from which lessons can be learned, but there are systemic issues that discourage and create barriers, and a need for meaningful engagement, leadership and action at national, regional and local levels. National and regional actors like Sport England, NHS England, health professional bodies, Active Partnerships, the Local Government Association and the Office for Health Improvement and Disparities can encourage and support government and the NHS to change policy drivers, culture and practices. Emerging opportunities include the 2021 White Paper Integration and Innovation, development of local integrated care systems, leadership from health charities and investment in non-clinical interventions (‘social prescribing’). At local level, public health and physical activity specialists and other organisations have a key role as champions and facilitators of local whole systems approaches and engagement of local NHS leaderships. Finally, although whole systems action is about collaborative leadership, individual champions of physical activity can make a difference in influencing NHS leaders at every level towards whole systems working.

Registry data from Europe has shown an increase in age at end-stage kidney disease for patients with Alport syndrome in recent years. Whether a similar delay in transplant age has occurred in the United States for Alport patients across all racial/ethnic groups is unknown.We used data from the Scientific Registry of Transplant Recipients (SRTR) to identify 3,794 Alport patients transplanted between 12/1987 and 12/2017. We divided the study period into five equal eras to assess temporal trends in age at transplant, graft survival, and patient survival across racial groups using linear regression and Cox regression models.The mean age at transplant for Blacks (28.3 years; difference (Black vs. White): 8.9 years; p0.0001) and Hispanics (28.7 years; difference (Hispanics vs. White): 8.7 years; p 0.0001) was significantly younger compared with that of Whites. We observed a temporal increase in age at transplant for Whites but not for Blacks and Hispanics (p-value for interaction: 0.001). Black recipients were at a higher risk of graft loss (aHR: 1.78; 95% CI: 1.47, 2.15; p 0.0001) and death (aHR: 1.73; 95% CI: 1.11, 2.69; p = 0.02) compared with White recipients. We observed significant improvements in graft survival with each successive era (p 0.01). Temporal trends in graft survival (interaction p = 0.46) were not modified by race.We found racial disparities in age at transplant and long-term graft survival for patients with Alport syndrome in the United States. The age at transplant increased over time for Whites but not Black and Hispanic patients.