A cross-cultural study of language and cognition: Numeral classifiers and solid object categorization.

One of the central issues in cognition is identifying universal and culturally specific patterns of thought. In this study, we examined how one aspect of culture, a linguistic part of speech known asclassifiers, are related to categorization of solid objects. In Experiment 1, we used a numeral classifier elicitation task to examine the classifiers used by speakers of Hmong, Japanese, and Mandarin Chinese (N = 34) with 135 nouns that referred to solid objects. In Experiment 2, adult speakers of English, Japanese, Mandarin Chinese, and Hmong (N = 64) rated the similarity of 39 pictured objects that depicted a subset of the nouns. All groups classified the objects into natural kinds and artifacts, with the category of humans anchoring both divisions. The main difference that emerged from the study was that speakers of Japanese and English rated humans and animals as more similar to each other than Hmong speakers; Mandarin speakers' ratings of the similarity between humans and animals fell in between those of Hmong and English speakers. However, the pattern of categorization of humans and animals found among speakers of the classifier languages contradicted their patterns of classifier use. The findings help to tease apart the effects of language from other cultural factors that impact cognition.

Multiplex Detection of Antibody Landscapes to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Influenza/Common Human Coronaviruses Following Vaccination or Infection With SARS-CoV-2 and Influenza.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses continue to co-circulate, representing 2 major public health threats from respiratory infections with similar clinical presentations. SARS-CoV-2 and influenza vaccines can also now be co-administered. However, data on antibody responses to SARS-CoV-2 and influenza coinfection and vaccine co-administration remain limited. METHODS: We developed a 41-plex antibody immunity assay that can simultaneously characterize antibody landscapes to SARS-CoV-2/influenza/common human coronaviruses. We analyzed sera from 840 individuals (11-93 years), including sera from reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2-positive (n = 218) and -negative (n = 120) cases, paired sera from SARS-CoV-2 vaccination (n = 29) and infection (n = 11), and paired sera from influenza vaccination (n = 56) and RT-PCR-confirmed influenza infection (n = 158) cases. Last, we analyzed sera collected from 377 individuals who exhibited acute respiratory illness (ARI) in 2020. RESULTS: This 41-plex assay has high sensitivity and specificity in detecting SARS-CoV-2 infections. It differentiated SARS-CoV-2 vaccination (antibody responses only to spike protein) from infection (antibody responses to both spike and nucleoprotein). No cross-reactive antibodies were induced to SARS-CoV-2 from influenza vaccination and infection, and vice versa, suggesting no interaction between SARS-CoV-2 and influenza antibody responses. However, cross-reactive antibodies were detected between spike proteins of SARS-CoV-2 and common human coronaviruses that were removed by serum adsorption. Among 377 individuals who exhibited ARI in 2020, 129 were influenza positive; none had serological evidence of SARS-CoV-2/influenza coinfections. CONCLUSIONS: Multiplex detection of antibody landscapes can provide in-depth analysis of the antibody protective immunity to SARS-CoV-2 in the context of other respiratory viruses, including influenza.

Portal vein complications and outcomes following pediatric liver transplantation: Data from the Society of Pediatric Liver Transplantation.

Children who undergo liver transplantation are at risk for portal vein complications (PVCs) including thrombosis (PVT) and stenosis (PVS). Using multicenter data from the Society of Pediatric Liver Transplantation, we analyzed the prevalence, timing, and risk factors for PVC following a first liver transplantation, and assessed the potential impact of PVC on patient outcomes. Our cohort included 4278 patients, of whom 327 (7.6%) developed PVC. Multivariate analysis discovered several factors independently associated with PVC: younger recipient age, lower weight at time of transplantation, diagnosis of biliary atresia (BA), receiving a technical variant graft (TVG), warm ischemia time over 3 h, PVT in the recipient's pretransplantation native liver, and concurrent hepatic artery thrombosis (all p < 0.05). Subgroup analysis of those with BA found higher prevalence in patients transplanted at less than 2 years of age and those with TVGs. There was no difference in PVC prevalence among patients with BA with vs. without prior Kasai portoenterostomy. Most PVT (77.7%) presented within 90 days after transplantation. Patients with PVC had a higher risk of graft failure (23.9% vs. 8.3%; adjusted hazard ratio [HR], 3.08; p < 0.001) and a higher risk of death (16.4% vs. 8.9%; adjusted HR, 1.96; p = 0.01). Recurrence after retransplantation was similar to the overall prevalence in the cohort (8.2%). Our results recognize the common occurrence of PVC following pediatric liver transplantation, describe independently associated risk factors, and determine that patients with PVC have worse outcomes. Further studies are needed to improve PVC prevention, detection, and management strategies.

Education and Psychosocial Factors Predict Odds of Death After Transfer to Adult health Care in Pediatric Liver Transplant Patients.

OBJECTIVES: To analyze demographic, psychosocial, and clinical factors in pediatric liver transplant recipients for their association with death or loss to follow up in adulthood. We aimed to better understand known health disparities in transplant outcomes and identify potentially modifiable risk factors prior to transfer. METHODS: A retrospective cohort study of children who underwent liver transplantation at a large tertiary transplant center and were transferred to adult care between 2000 and 2015. RESULTS: During the study period, 101 qualifying patients were transferred. Ninety-three individuals followed with an adult provider, while 8 were lost to follow up. In total 23 of 93 patients died after transfer (24.7%). Several childhood factors were associated with adult death: Black race [odds ratio (OR) 6.59, P < 0.001]; psychiatric illness or substance use (OR 2.81, P = 0.04); failure to graduate high school before transfer (OR 9.59, P < 0.001); posttransplant tacrolimus medication-level variability index >2.5 (OR 5.36, P = 0.04); provider documentation of medication nonadherence (OR 4.72, P = 0.02); acute cellular rejection (OR 4.44, P = 0.03); the presence of diabetes mellitus (OR 5.71, P = 0.001), and chronic kidney disease (OR 2.82, P = 0.04). Failure to graduate HS was associated with loss to follow up ( P < 0.001). On multivariate analysis, Black race, substance use, diabetes, and failure to graduate HS retained association with adult death (each P < 0.05). CONCLUSIONS: Complex, intertwined patient characteristics are associated with increased odds of death in pediatric liver transplant recipients transferred to adult care. Early recognition of high-risk patients and intervention for modifiable factors, such as improved HS graduation and substance use prevention, may improve long-term outcomes.

Recognition and Outcomes of Pneumococcal Meningitis in 2 Tertiary Pediatric Hospitals Since the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine.

OBJECTIVES: The aims of the study were to analyze the demographics, presentation, laboratory findings, and complications of pediatric Streptococcus pneumoniae meningitis since the introduction of the 13-valent pneumococcal conjugate vaccine, to improve recognition, and to minimize patient morbidity and mortality. METHODS: This study used a retrospective analysis of pediatric pneumococcal meningitis cases at 2 tertiary healthcare systems in the Southeastern United States from 2010 to 2018. RESULTS: We describe 21 cases of pneumococcal meningitis. All patients presented with fever, 95% had altered mental status by history or examination, and 48% had meningeal signs. Forty-three percent had seen another provider within 48 hours of admission. Forty-eight percent had delay in lumbar puncture (LP) of more than 6 hours after antibiotic administration, decreasing rates of positive cerebrospinal fluid cultures from 100% to 40% (P < 0.001). Decision to delay LP was due to either low suspicion for meningitis (n = 4) or clinical instability (n = 6) and was associated with lower rates of meningeal signs (P = 0.014) and higher rates of altered mental status on examination (P = 0.031). Fourteen patients (67%) were up-to-date on pneumococcal immunization. Serotypes were determined in 16 cases, with 2 patients (13%) immunized against the strain that infected them. Primary outcomes included seizures (48%), hearing loss (48%), cranial nerve palsy (33%), and death (5%). Delay in LP with low suspicion for meningitis was associated with longer hospital length of stay approaching statistical significance (P = 0.053). CONCLUSIONS: Pneumococcal meningitis remains a relevant and potentially fatal disease despite widespread use of 13-valent pneumococcal conjugate vaccine. Its diagnosis is often delayed during interactions with physicians, which may put patients at increased risk for poor clinical outcomes.

Genetically and Antigenically Divergent Influenza A(H9N2) Viruses Exhibit Differential Replication and Transmission Phenotypes in Mammalian Models.

Low-pathogenicity avian influenza A(H9N2) viruses, enzootic in poultry populations in Asia, are associated with fewer confirmed human infections but higher rates of seropositivity compared to A(H5) or A(H7) subtype viruses. Cocirculation of A(H5) and A(H7) viruses leads to the generation of reassortant viruses bearing A(H9N2) internal genes with markers of mammalian adaptation, warranting continued surveillance in both avian and human populations. Here, we describe active surveillance efforts in live poultry markets in Vietnam in 2018 and compare representative viruses to G1 and Y280 lineage viruses that have infected humans. Receptor binding properties, pH thresholds for HA activation, in vitro replication in human respiratory tract cells, and in vivo mammalian pathogenicity and transmissibility were investigated. While A(H9N2) viruses from both poultry and humans exhibited features associated with mammalian adaptation, one human isolate from 2018, A/Anhui-Lujiang/39/2018, exhibited increased capacity for replication and transmission, demonstrating the pandemic potential of A(H9N2) viruses.IMPORTANCE A(H9N2) influenza viruses are widespread in poultry in many parts of the world and for over 20 years have sporadically jumped species barriers to cause human infection. As these viruses continue to diversify genetically and antigenically, it is critical to closely monitor viruses responsible for human infections, to ascertain if A(H9N2) viruses are acquiring properties that make them better suited to infect and spread among humans. In this study, we describe an active poultry surveillance system established in Vietnam to identify the scope of influenza viruses present in live bird markets and the threat they pose to human health. Assessment of a recent A(H9N2) virus isolated from an individual in China in 2018 is also reported, and it was found to exhibit properties of adaptation to humans and, importantly, it shows similarities to strains isolated from the live bird markets of Vietnam.

African American Pediatric Liver Transplant Recipients Have an Increased Risk of Death After Transferring to Adult Healthcare.

OBJECTIVE: To analyze the long-term outcomes in pediatric liver transplant recipients after they have transferred to an adult provider and assess for racial disparities in health outcomes. STUDY DESIGN: This is a single-center, retrospective review of pediatric patients who underwent liver transplantation between July 1990 and August 2015 at a tertiary healthcare system with a large transplant center. Patient mortality and retransplantation were assessed after transfer to adult care. RESULTS: There were 120 patients who were transferred, of whom 19 did not meet the inclusion criteria. Of the remaining 101 patients, 64 (63%) transferred care to a nearby affiliated tertiary adult facility, 29 (29%) were followed by other healthcare systems, and 8 (8%) were lost to follow-up. Of the patients followed at our affiliated adult center, 18 of the 64 (28%) died. Of those 18 deaths, 4 (22%) occurred within the first 2 years after transfer, and 10 (55%) within 5 years of transfer. Four patients were retransplanted by an adult provider, of whom 2 eventually received a third transplant. African Americans had higher rates of death after transfer than patients of other races (44% mortality vs 16%, representing 67% of all cases of death; P = .032), with nearly 50% mortality at 20 years from time of transplantation. CONCLUSIONS: Death is common in pediatric liver transplant recipients after transfer to adult care, with African Americans having disproportionately higher mortality. This period of transition of care is a vulnerable time, and measures must be taken to ensure the safe transfer of young adults with chronic health care needs.

Halogen Bonding Heteroditopic Materials for Cooperative Sodium Iodide Binding and Extraction.

A series of novel heteroditopic halogen bonding (XB) receptor functionalised silica based materials, containing mono- and bis-iodotriazole benzo-15-crown-5 groups are investigated for the cooperative binding and extraction of sodium halide ion-pair species from aqueous solution. Characterisation of the XB materials by CHN elemental analysis, 13 C CP/MAS NMR and ATR-FTIR spectroscopies confirms and quantifies the successful incorporation of the ion-pair receptor frameworks to the silica material. ICP-MS solid-liquid extraction studies demonstrate the bidentate XB functionalised material is capable of NaI extraction from water. Importantly, cooperative XB-mediated sodium halide ion-pair binding is determined to be crucial to the material's extraction capabilities, impressively demonstrating a two-fold enhancement in sodium iodide extraction efficiency relative to a heteroditopic hydrogen bonding receptor functionalised silica material analogue.

Resolution of recurrent pediatric acute liver failure with liver transplantation in a patient with NBAS mutation.

BACKGROUND: Pediatric acute liver failure (PALF) remains an enigmatic process of rapid end-organ dysfunction associated with a variety of pathologic conditions though the predominant cause is indeterminate. A growing body of research has identified mutations in the NBAS gene to be associated with recurrent acute liver failure and multi-systemic disease including short stature, skeletal dysplasia, facial dysmorphism, immunologic abnormalities, and Pelger-Huët anomaly. METHODS AND RESULTS: Here, we describe a 4-year-old girl who presented with dehydration in the setting of acute gastroenteritis and fever but went on to develop PALF on day 2 of hospitalization. She clinically recovered with supportive measures, but after discharge, had at least 2 additional episodes of PALF. Ultimately, she underwent liver transplant and her recurrent episodes of PALF did not recur throughout a 6-year follow-up period. Whole-exome sequencing post-liver transplant initially revealed two variants of uncertain significance in the NBAS gene. Parental studies confirmed the c.1549C > T(p.R517C; now likely pathogenic) variant from her mother and a novel c.4646T > C(p.L1549P) variant from her father. In silico analyses predicted these variants to have a deleterious effect on protein function. Consistent with previously characterized NBAS mutation-associated disease (NMAD), our patient demonstrated the following features: progeroid facial features, hypoplasia of the 12th ribs, Pelger-Huët anomaly on peripheral blood smear, and abnormal B and NK cell function. CONCLUSION: Altogether, we describe a novel pathogenic variant in the NBAS gene of a patient with NMAD and report the resolution of recurrent PALF secondary to NMAD following liver transplantation.

TRANSITION of Pediatric Liver Transplant Patients to Adult Care: a Review.

PURPOSE OF REVIEW: Many pediatric liver transplant patients are surviving to adulthood, and providers have come to recognize the importance of effectively transitioning these patients to an adult hepatologist. The review aims to analyze the most recent literature regarding patient outcomes after transition, barriers to successful transition, recommendations from clinicians and medical societies regarding transition programs, and to provide personal insights from our experience in transitioning liver transplant recipients. RECENT FINDINGS: While results were variable between studies, many recent reports show significant morbidity and mortality in patients following transition to adult care. Medical non-adherence is frequently seen in adolescents and young adults both prior to and after transition, and is consistently associated with higher rates of rejection, graft loss, and death. In general, transplant programs with a formal transition process had better patient outcomes though recent findings are mostly-single center and direct comparison between programs is difficult. Societal recommendations for how to create a transition program contain a number of common themes that we have categorized for easier understanding. Successful transition is vital to the continued health of pediatric liver transplant patients. While an effective transition program includes a number of key components, it should be individualized to best function within a given transplant center. Here, we have reviewed a number of recent single-center retrospective studies on transition, but multi-site retrospective or prospective data is lacking, and is a fertile area for future research.

The human hepatocyte TXG-MAPr: gene co-expression network modules to support mechanism-based risk assessment.

Mechanism-based risk assessment is urged to advance and fully permeate into current safety assessment practices, possibly at early phases of drug safety testing. Toxicogenomics is a promising source of mechanisms-revealing data, but interpretative analysis tools specific for the testing systems (e.g. hepatocytes) are lacking. In this study, we present the TXG-MAPr webtool (available at https://txg-mapr.eu/WGCNA_PHH/TGGATEs_PHH/ ), an R-Shiny-based implementation of weighted gene co-expression network analysis (WGCNA) obtained from the Primary Human Hepatocytes (PHH) TG-GATEs dataset. The 398 gene co-expression networks (modules) were annotated with functional information (pathway enrichment, transcription factor) to reveal their mechanistic interpretation. Several well-known stress response pathways were captured in the modules, were perturbed by specific stressors and showed preservation in rat systems (rat primary hepatocytes and rat in vivo liver), with the exception of DNA damage and oxidative stress responses. A subset of 87 well-annotated and preserved modules was used to evaluate mechanisms of toxicity of endoplasmic reticulum (ER) stress and oxidative stress inducers, including cyclosporine A, tunicamycin and acetaminophen. In addition, module responses can be calculated from external datasets obtained with different hepatocyte cells and platforms, including targeted RNA-seq data, therefore, imputing biological responses from a limited gene set. As another application, donors' sensitivity towards tunicamycin was investigated with the TXG-MAPr, identifying higher basal level of intrinsic immune response in donors with pre-existing liver pathology. In conclusion, we demonstrated that gene co-expression analysis coupled to an interactive visualization environment, the TXG-MAPr, is a promising approach to achieve mechanistic relevant, cross-species and cross-platform evaluation of toxicogenomic data.

COVID-19-associated Multisystem Inflammatory Syndrome in Children Presenting as Acute Pancreatitis.

In April 2020, a newly recognized pediatric disorder associated with COVID-19 characterized by significant inflammation with symptoms resembling Kawasaki disease was described by medical teams in the United States, the United Kingdom, and Italy. Before these reports, data from the initial COVID-19 outbreaks in China had not found the virus to cause significant morbidity or mortality in children. To date, pancreatitis has not yet been reported in either acute SARS-CoV-2 infection in children or the subsequent inflammatory syndrome. We describe a patient who presented with acute pancreatitis before rapidly progressing to multisystem organ dysfunction consistent with multisystem inflammatory syndrome in children due to COVID-19. Clinicians should be aware that in the context of the COVID-19 pandemic, pancreatitis can be an early presentation of multisystem inflammatory syndrome in children.

Inflammation-associated suppression of metabolic gene networks in acute and chronic liver disease.

Inflammation has been recognized as essential for restorative regeneration. Here, we analyzed the sequential processes during onset of liver injury and subsequent regeneration based on time-resolved transcriptional regulatory networks (TRNs) to understand the relationship between inflammation, mature organ function, and regeneration. Genome-wide expression and TRN analysis were performed time dependently in mouse liver after acute injury by CCl4 (2 h, 8 h, 1, 2, 4, 6, 8, 16 days), as well as lipopolysaccharide (LPS, 24 h) and compared to publicly available data after tunicamycin exposure (mouse, 6 h), hepatocellular carcinoma (HCC, mouse), and human chronic liver disease (non-alcoholic fatty liver, HBV infection and HCC). Spatiotemporal investigation differentiated lobular zones for signaling and transcription factor expression. Acute CCl4 intoxication induced expression of gene clusters enriched for inflammation and stress signaling that peaked between 2 and 24 h, accompanied by a decrease of mature liver functions, particularly metabolic genes. Metabolism decreased not only in pericentral hepatocytes that underwent CCl4-induced necrosis, but extended to the surviving periportal hepatocytes. Proliferation and tissue restorative TRNs occurred only later reaching a maximum at 48 h. The same upstream regulators (e.g. inhibited RXR function) were implicated in increased inflammation and suppressed metabolism. The concomitant inflammation/metabolism TRN occurred similarly after acute LPS and tunicamycin challenges, in chronic mouse models and also in human liver diseases. Downregulation of metabolic genes occurs concomitantly to induce inflammation-associated genes as an early response and appears to be initiated by similar upstream regulators in acute and chronic liver diseases in humans and mice. In the acute setting, proliferation and restorative regeneration associated TRNs peak only later when metabolism is already suppressed.

Standard-Dose Intradermal Influenza Vaccine Elicits Cellular Immune Responses Similar to Those of Intramuscular Vaccine in Men With and Those Without HIV Infection.

BACKGROUND: Human immunodeficiency virus (HIV)-infected persons are at a higher risk of severe influenza. Although we have shown that a standard-dose intradermal influenza vaccine versus a standard-dose intramuscular influenza vaccine does not result in differences in hemagglutination-inhibition titers in this population, a comprehensive examination of cell-mediated immune responses remains lacking. METHODS: Serological, antigen-specific B-cell, and interleukin 2-, interferon γ-, and tumor necrosis factor α-secreting T-cell responses were assessed in 79 HIV-infected men and 79 HIV-uninfected men. RESULTS: The route of vaccination did not affect the immunoglobulin A and immunoglobulin G (IgG) plasmablast or memory B-cell response, although these were severely impaired in the group with a CD4+ T-cell count of <200 cells/µL. The frequencies of IgG memory B cells measured on day 28 after vaccination were highest in the HIV-uninfected group, followed by the group with a CD4+ T-cell count of ≥200 cells/µL and the group with a CD4+ T-cell count of <200 cells/µL. The route of vaccination did not affect the CD4+ or CD8+ T-cell responses measured at various times after vaccination. CONCLUSIONS: The route of vaccination had no effect on antibody responses, antibody avidity, T-cell responses, or B-cell responses in HIV-infected or HIV-uninfected subjects. With the serological and cellular immune responses to influenza vaccination being impaired in HIV-infected individuals with a CD4+ T-cell count of <200 cells/µL, passive immunization strategies need to be explored to protect this population. CLINICAL TRIALS REGISTRATION: NCT01538940.

Structural and Molecular Characterization of the Hemagglutinin from the Fifth-Epidemic-Wave A(H7N9) Influenza Viruses.

The avian influenza A(H7N9) virus continues to cause human infections in China and is a major ongoing public health concern. Five epidemic waves of A(H7N9) infection have occurred since 2013, and the recent fifth epidemic wave saw the emergence of two distinct lineages with elevated numbers of human infection cases and broader geographic distribution of viral diseases compared to the first four epidemic waves. Moreover, highly pathogenic avian influenza (HPAI) A(H7N9) viruses were also isolated during the fifth epidemic wave. Here, we present a detailed structural and biochemical analysis of the surface hemagglutinin (HA) antigen from viruses isolated during this recent epidemic wave. Results highlight that, compared to the 2013 virus HAs, the fifth-wave virus HAs remained a weak binder to human glycan receptor analogs. We also studied three mutations, V177K-K184T-G219S, that were recently reported to switch a 2013 A(H7N9) HA to human-type receptor specificity. Our results indicate that these mutations could also switch the H7 HA receptor preference to a predominantly human binding specificity for both fifth-wave H7 HAs analyzed in this study.IMPORTANCE The A(H7N9) viruses circulating in China are of great public health concern. Here, we report a molecular and structural study of the major surface proteins from several recent A(H7N9) influenza viruses. Our results improve the understanding of these evolving viruses and provide important information on their receptor preference that is central to ongoing pandemic risk assessment.

Broadly Reactive Human Monoclonal Antibodies Elicited following Pandemic H1N1 Influenza Virus Exposure Protect Mice against Highly Pathogenic H5N1 Challenge.

Broadly cross-reactive antibodies (Abs) that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes, including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (MAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus. The monoclonal antibodies were isolated from individuals shortly following infection with (70-1F02 and 1009-3B05) or vaccination against (05-2G02 and 09-3A01) A(H1N1)pdm09. Three of the MAbs bound HAs from multiple strains of group 1 viruses, and one MAb, 05-2G02, bound to both group 1 and group 2 influenza A virus HAs. All four antibodies prophylactically protected mice against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) strain. Two MAbs, 70-1F02 and 09-3A01, were further tested for their therapeutic efficacy against the same strain and showed good efficacy in this setting as well. One MAb, 70-1F02, cocrystallized with H5 HA and showed heavy-chain-only interactions similar to those seen with the previously described CR6261 anti-stalk antibody. Finally, we show that antibodies that compete with these MAbs are prevalent in serum from an individual recently infected with the A(H1N1)pdm09 virus. The antibodies described here can be developed into broad-spectrum antiviral therapeutics that could be used to combat infections by zoonotic or emerging pandemic influenza viruses.IMPORTANCE The rise in zoonotic infections of humans by emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually worldwide. Currently available antiviral treatment options include only neuraminidase inhibitors, but some influenza viruses are naturally resistant to these drugs, and others quickly develop resistance-conferring mutations. Alternative therapeutics are urgently needed. Broadly protective antibodies that target the conserved "stalk" domain of the hemagglutinin represent potential potent antiviral prophylactic and therapeutic agents that can assist pandemic preparedness. Here, we describe four human monoclonal antibodies that target conserved regions of influenza HA and characterize their binding spectrum as well as their protective capacity in prophylactic and therapeutic settings against a lethal challenge with a zoonotic influenza virus.

Update: Influenza Activity - United States and Worldwide, May 19-September 28, 2019, and Composition of the 2020 Southern Hemisphere Influenza Vaccine.

During May 19-September 28, 2019,* low levels of influenza activity were reported in the United States, with cocirculation of influenza A and influenza B viruses. In the Southern Hemisphere seasonal influenza viruses circulated widely, with influenza A(H3) predominating in many regions; however, influenza A(H1N1)pdm09 and influenza B viruses were predominant in some countries. In late September, the World Health Organization (WHO) recommended components for the 2020 Southern Hemisphere influenza vaccine and included an update to the A(H3N2) and B/Victoria-lineage components. Annual influenza vaccination is the best means for preventing influenza illness and its complications, and vaccination before influenza activity increases is optimal. Health care providers should recommend vaccination for all persons aged ≥6 months who do not have contraindications to vaccination (1).

Update: Influenza Activity in the United States During the 2018-19 Season and Composition of the 2019-20 Influenza Vaccine.

Influenza activity* in the United States during the 2018-19 season (September 30, 2018-May 18, 2019) was of moderate severity (1). Nationally, influenza-like illness (ILI)† activity began increasing in November, peaked during mid-February, and returned to below baseline in mid-April; the season lasted 21 weeks,§ making it the longest season in 10 years. Illness attributed to influenza A viruses predominated, with very little influenza B activity. Two waves of influenza A were notable during this extended season: influenza A(H1N1)pdm09 viruses from October 2018 to mid-February 2019 and influenza A(H3N2) viruses from February through May 2019. Compared with the 2017-18 influenza season, rates of hospitalization this season were lower for adults, but were similar for children. Although influenza activity is currently below surveillance baselines, testing for seasonal influenza viruses and monitoring for novel influenza A virus infections should continue year-round. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.

Performance of Interferon-Gamma Release Assays for Tuberculosis Screening in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: The aim of the study was to analyze the diagnostic accuracy and utility of QuantiFERON-TB Gold In-Tube, an interferon-gamma release assay (IGRA), as a screening tool for latent tuberculosis infection (LTBI) in pediatric patients with inflammatory bowel disease (IBD) undergoing treatment with anti-tumor necrosis factor (anti-TNF) medications. To describe cases of tuberculosis in the pediatric IBD population, TB treatment courses, outcomes, and their effect on IBD management. METHODS: A single-center, retrospective cohort study of pediatric IBD patients who underwent tuberculosis screening. IGRA testing from 2011 to 2017 were analyzed to determine result rates, characteristics, and outcomes. RESULTS: One thousand seven hundred fifty-four (1,754) tests were performed on 859 patients. One thousand six hundred thirty-four (1,634) tests were negative, 9 were positive, and 111 were indeterminate. Eight of 9 positive tests resulted during repeat annual screening while receiving IBD treatment. Five patients were treated for latent tuberculosis infection (LTBI), and 4 were false-positives. IBD therapy was interrupted in 3 patients, with no negative long-term outcomes. We report 1 known false-negative, in a patient who developed disseminated TB on anti-TNF therapy. Indeterminate testing rates were higher at IBD diagnosis than during treatment (10.3% vs 5.3%, P < 0.001). Follow-up testing of indeterminate results was negative in all patients retested, with 14 patients lost to follow-up. No patient with indeterminate testing developed TB. CONCLUSIONS: IGRAs are a useful tool to screen for LTBI, both before anti-TNF therapy and during treatment. Results should be used in concert with detailed history and examination. Positive and indeterminate results should be promptly repeated for timely TB diagnosis and to minimize interruptions in IBD therapy.

Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice.

On 29 March 2013, the Chinese Center for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A(H7N9) virus. The recent human infections with H7N9 virus, totalling over 130 cases with 39 fatalities to date, have been characterized by severe pulmonary disease and acute respiratory distress syndrome (ARDS). This is concerning because H7 viruses have typically been associated with ocular disease in humans, rather than severe respiratory disease. This recent outbreak underscores the need to better understand the pathogenesis and transmission of these viruses in mammals. Here we assess the ability of A/Anhui/1/2013 and A/Shanghai/1/2013 (H7N9) viruses, isolated from fatal human cases, to cause disease in mice and ferrets and to transmit to naive animals. Both H7N9 viruses replicated to higher titre in human airway epithelial cells and in the respiratory tract of ferrets compared to a seasonal H3N2 virus. Moreover, the H7N9 viruses showed greater infectivity and lethality in mice compared to genetically related H7N9 and H9N2 viruses. The H7N9 viruses were readily transmitted to naive ferrets through direct contact but, unlike the seasonal H3N2 virus, did not transmit readily by respiratory droplets. The lack of efficient respiratory droplet transmission was corroborated by low receptor-binding specificity for human-like α2,6-linked sialosides. Our results indicate that H7N9 viruses have the capacity for efficient replication in mammals and human airway cells and highlight the need for continued public health surveillance of this emerging virus.