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Wet markets have been implicated in multiple zoonotic outbreaks, including COVID-19. They are also a conduit for legal and illegal trade in wildlife, which threatens thousands of species. Yet wet markets supply food to millions of people around the world, and differ drastically in their physical composition, the goods they sell, and the subsequent risks they pose. As such, policy makers need to know how to target their actions to efficiently safeguard human health and biodiversity without depriving people of ready access to food. Here, we propose a taxonomy of wet markets, oriented around the presence of live or dead animals, and whether those animals are domesticated or wild (either captive-reared or wild-caught). We assess the dimensions and levels of risk that different types of wet markets pose to people and to biodiversity. We identify six key risk factors of wet markets that can affect human health: (1) presence of high disease-risk animal taxa, (2) presence of live animals, (3) hygiene conditions, (4) market size, (5) animal density and interspecies mixing, and (6) the length and breadth of animal supply chains. We also identify key factors informing risk to biodiversity. Finally, we recommend targeted, risk-adjusted policies to more efficiently and humanely address the dangers posed by wet markets.

Aircraft can hold large numbers of persons in close proximity for long periods, which can increase the risk for transmission of infectious disease.* Current CDC guidelines recommend against travel for persons who have not been vaccinated against COVID-19, and a January 2021 CDC order requires masking for all persons while on airplanes.†,§ Research suggests that seating proximity on aircraft is associated with increased risk for infection with SARS-CoV-2, the virus that causes COVID-19 (1,2). However, studies quantifying the benefit of specific distancing strategies to prevent transmission, such as keeping aircraft cabin middle seats vacant, are limited. Using bacteriophage MS2 virus as a surrogate for airborne SARS-CoV-2, CDC and Kansas State University (KSU) modeled the relationship between SARS-CoV-2 exposure and aircraft seating proximity, including full occupancy and vacant middle seat occupancy scenarios. Compared with exposures in full occupancy scenarios, relative exposure in vacant middle seat scenarios was reduced by 23% to 57% depending upon the modeling approach. A 23% exposure reduction was observed for a single passenger who was in the same row and two seats away from the SARS-COV-2 source, rather than in an adjacent middle seat. When quantifying exposure reduction to a full 120-passenger cabin rather than to a single person, exposure reductions ranging from 35.0% to 39.4% were predicted. A 57% exposure reduction was observed under the vacant middle seat condition in a scenario involving a three-row section that contained a mix of SARS-CoV-2 sources and other passengers. Based on this laboratory model, a vacant middle seat reduces risk for exposure to SARS-CoV-2 from nearby passengers. These data suggest that increasing physical distance between passengers and lowering passenger density could help reduce potential COVID-19 exposures during air travel. Physical distancing of airplane passengers, including through policies such as middle seat vacancy, could provide additional reductions in SARS-CoV-2 exposure risk.

Low-density polyethylene (LDPE) is a commodity polymer widely used in a variety of applications. Due to the complexity of its molecular structure, which includes molecular weight distribution and randomly distributed long-chain branching, its rheological behavior is varied. In the present work, a mathematical model is used to predict molecular and rheological properties of LDPE produced in a high-pressure tubular reactor under different operating conditions. The agreement between flow curve predictions and experimental data is very good, demonstrating the potential of this model as a predictive tool for industrial producers.

The first combustion experiments aboard the Japanese Experiment Module “Kibo” on the International Space Station, titled “Elucidation of Flame Spread and Group Combustion Excitation Mechanism of Randomly Distributed Droplet Clouds (Group Combustion)” were conducted in 2017 in order to bridge the gap between droplet combustion and spray combustion through flame spread over droplet arrays, droplet-cloud elements and randomly distributed droplet clouds. n-Decane droplets were distributed randomly on a SiC-fiber lattice, and the flame spread and group-combustion excitation were observed. During the flame spread near the group-combustion-excitation limit, two types of anomalous behavior appeared: large-scale ignition and re-burning by a slow flame propagation in a burned area. We successfully simulated similar phenomena by a flame-spread experiment using droplet-cluster arrays. The large-scale ignition phenomenon is caused by the ignition of a flammable mixture generated by heating multiple droplets existing outside the local flame-spread limit. The re-burning phenomenon by the slow flame propagation in a burned area is caused by the ignition of a flammable mixture diluted by the combustion products after the radiative extinction of the group flame. There is the possibility of a cool-flame appearance in both phenomena.

Experimental observations of two-stage autoignition dynamics of fiber-supported normal dodecane droplets in air under normal gravity are presented for a range of pressures and temperatures. High-sp...

Aircraft cabins have high-performance ventilation systems, yet typically hold large numbers of people in close proximity for long periods. The current study estimated airborne virus exposure and infection reductions for vacant middle seats and masking in aircraft. Tracer particle data reported by U.S. Transportation Command (TRANSCOM) and CFD simulations reported by Boeing were used, along with NIOSH data, to build nonlinear regression models with particle exposure and distance from particle source as variables. These models that estimate exposure at given distances from the viral source were applied to evaluate exposure reductions when middle seats are vacant compared to full occupancy. Reductions averaged 54% for the seat row where an infectious passenger is located and 36% for a 24-row cabin containing one infectious passenger, with middle seats vacant. Analysis of the TRANSCOM data showed that universal masking (surgical masks) reduced exposures by 62% and showed masking and physical distancing provide further reductions when practiced together. For a notional scenario involving 10 infectious passengers, compared with no intervention, masking, distancing, and both would prevent 6.2, 3.8 and 7.6 secondary infections, respectively, using the Wells-Riley equation. These results suggest distancing and masking reduce SARS CoV-2 exposure risk when an infectious passenger is present.

SUMMARYSARS-CoV-2 infection causes a spectrum of clinical outcomes and diverse memory responses. Population studies indicate that viral neutralizing antibody responses are protective, but do not always develop post-infection. Other antiviral antibody effector functions, T-cell responses, or immunity to seasonal coronaviruses (OC43, 229E) have been implicated but not defined in all ages. Here, we identify that children and adult subjects generate polyfunctional antibodies to the spike protein after asymptomatic infection or mild disease, with some subjects developing cellular responses without seroconversion. Diversity in immunity was explained by two clusters distinguished by CD4+ T-cell cytokines, age, and antibodies to seasonal coronaviruses. Post-vaccination neutralizing responses were predicted by specific post-infection immune measures, including IL-2, spike-IgA, OC43-IgG1, 229E-IgM. We confirm a key role for CD4+ T cell cytokines in functionality of anti-spike antibodies, and show that antibody diversity is impacted by age, Th/Th2 cytokine biases, and antibody isotypes to SARS-CoV-2 and seasonal coronaviruses.

Pneumocystis jirovecii is the most common cause of fungal pneumonia in children under the age of 2 years. However, the inability to culture and propagate this organism has hampered the acquisition of a fungal genome as well as the development of recombinant antigens to conduct seroprevalence studies. In this study, we performed proteomics on Pneumocystis-infected mice and used the recent P. murina and P. jirovecii genomes to prioritize antigens for recombinant protein expression. We focused on a fungal glucanase due to its conservation among fungal species. We found evidence of maternal IgG to this antigen, followed by a nadir in pediatric samples between 1 and 3 months of age, followed by an increase in prevalence over time consistent with the known epidemiology of Pneumocystis exposure. Moreover, there was a strong concordance of anti-glucanase responses and IgG against another Pneumocystis antigen, PNEG_01454. Taken together, these antigens may be useful tools for Pneumocystis seroprevalence and seroconversion studies.

Within the scope of this work, an optimization approach of existing investigations on electroplated hard gold contacts is to be developed, which have an initial Vickers hardness of 103 HV. These investigations envisage the height-controlled bonding of structures in the multichip integration of optical components. The investigations relate to the influence of material hardness and roughness on the plastic deformation behaviour during bond formation by thermocompression bonding (TCB). Furthermore, pre-treatments such as mechanical surface planarization and chemical surface activation using atmospheric pressure plasma are employed prior to the bonding process to enable the reduction of the bonding parameters pressure and temperature and consequently contribute to control the plastic deformation during thermocompression and reduce the typical plastic deformation range of 30 % to a deformation range below 5 %. The previous investigations were performed on gold contacts, which have been thermally annealed prior to the bonding process and resulted in a plastic deformation range up to 30 %. With the new approach, i.e. throughout the material hardening and altering the surface condition, a plastic deformation range below 3 % was successfully obtained. The attainable bonding temperatures and bonding pressures were between 190 °C–250 °C and 145 MPa–230 MPa, respectively. The bonding time varied between 30 s and 60 s.

The objective of this study is to develop and validate a specific screening instrument for assessing the quality of life (QoL) of patients with orofacial clefts. The Cleft-Screen-Questionnaire (CSQ) aims at identifying the main problematic areas and is intended for the routine use in everyday clinical practice to constantly evaluate the conditions' and treatments' effects on patients' well-being.First, a pool of 58 questions is created by collecting items from validated questionnaires previously used for assessing the QoL in cleft populations. After the removal of duplicate questions, the questionnaires are answered by 152 patients from a tertiary care center. A factor analysis followed by the calculation of Cronbach's alpha as a reliability measurement led to the final CSQ presented here.The applied factor analysis resulted in five factors. Items showing low factor loadings (seen as0.5) were excluded initially. Accordingly, factor analysis led to a preliminary number of 43 items. A reliability analysis using Cronbach's alpha and corrected alpha if item deleted showed an overall moderate to high reliability (seen as: 0.6-0.9). After excluding questions with increasing alphas if item deleted, analyses yielded in a final number of 38 questions.The final 38-item CSQ is a reliable instrument for evaluating the health-related QoL of cleft patients.

Balanced fusion and fission are key for the proper function and physiology of mitochondria1,2. Remodelling of the mitochondrial inner membrane is mediated by the dynamin-like protein mitochondrial genome maintenance 1 (Mgm1) in fungi or the related protein optic atrophy 1 (OPA1) in animals3–5. Mgm1 is required for the preservation of mitochondrial DNA in yeast6, whereas mutations in the OPA1 gene in humans are a common cause of autosomal dominant optic atrophy—a genetic disorder that affects the optic nerve7,8. Mgm1 and OPA1 are present in mitochondria as a membrane-integral long form and a short form that is soluble in the intermembrane space. Yeast strains that express temperature-sensitive mutants of Mgm19,10 or mammalian cells that lack OPA1 display fragmented mitochondria11,12, which suggests that Mgm1 and OPA1 have an important role in inner-membrane fusion. Consistently, only the mitochondrial outer membrane—not the inner membrane—fuses in the absence of functional Mgm113. Mgm1 and OPA1 have also been shown to maintain proper cristae architecture10,14; for example, OPA1 prevents the release of pro-apoptotic factors by tightening crista junctions15. Finally, the short form of OPA1 localizes to mitochondrial constriction sites, where it presumably promotes mitochondrial fission16. How Mgm1 and OPA1 perform their diverse functions in membrane fusion, scission and cristae organization is at present unknown. Here we present crystal and electron cryo-tomography structures of Mgm1 from Chaetomium thermophilum. Mgm1 consists of a GTPase (G) domain, a bundle signalling element domain, a stalk, and a paddle domain that contains a membrane-binding site. Biochemical and cell-based experiments demonstrate that the Mgm1 stalk mediates the assembly of bent tetramers into helical filaments. Electron cryo-tomography studies of Mgm1-decorated lipid tubes and fluorescence microscopy experiments on reconstituted membrane tubes indicate how the tetramers assemble on positively or negatively curved membranes. Our findings convey how Mgm1 and OPA1 filaments dynamically remodel the mitochondrial inner membrane. Crystal and electron cryo-tomography structures of Mgm1 from Chaetomium thermophilum reveal that Mgm1 forms bent tetramers, which further assemble into helical filaments on both positively and negatively curved membranes.

BACKGROUND: The current neuroblastoma (NBL) staging system employs image-defined risk factors (IDRFs) to assess numerous anatomic features, but the impact of IDRFs on surgical and oncologic outcomes is unclear. METHODS: The Vanderbilt Cancer Registry identified children treated for NBL from 2002 to 2017. Tumor volume (TV) and IDRFs were measured radiographically at diagnosis and before resection. Perioperative and oncologic outcomes were evaluated. RESULTS: At diagnosis of 106 NBL, 61% were IDRF positive. MYCN-amplified and undifferentiated NBL had more IDRFs than nonamplified and more differentiated tumors (p = 0.001 and p = 0.01). Of 86 NBLs resected, 43% were IDRF positive, which associated with higher stage, risk, and TV (each p < 0.001). The presence of IDRF at resection was also associated with increased blood loss (p < 0.001), longer operating times (p < 0.001), greater incidence of intraoperative complications (p = 0.03), more frequent ICU admissions postoperatively (p < 0.001), and longer hospital stays (p < 0.001). IDRF negative and positive tumors did not have significantly different rates of gross total resection (p = 0.2). Five-year relapse-free and overall survival was similar for IDRF negative and positive NBL (p = 0.9 and p = 0.8). CONCLUSIONS: IDRFs at diagnosis were associated with larger, less differentiated, advanced stage, and higher risk NBL and at resection with increased operative difficulty and perioperative morbidity. However, the frequency of gross total resection and patient survival after resection were not associated with the presence of IDRFs. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: Level III.

Serologic testing of residual blood samples from 812 children from a hospital in New Orleans, LA, between March and May 2020, demonstrated a SARS-CoV-2 seroprevalence of 6.8% based on S and N protein IgG; Black and Hispanic children, and children living in zip codes with lower household incomes were over-represented.

BACKGROUND: Circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA may represent a more reliable indicator of infection than nasal RNA, but quantitative reverse transcription PCR (RT-qPCR) lacks diagnostic sensitivity for blood samples. METHODS: A CRISPR-augmented RT-PCR assay that sensitively detects SARS-CoV-2 RNA was employed to analyze viral RNA kinetics in longitudinal plasma samples from nonhuman primates (NHPs) after virus exposure; to evaluate the utility of blood SARS-CoV-2 RNA detection for coronavirus disease 2019 (COVID-19) diagnosis in adults cases confirmed by nasal/nasopharyngeal swab RT-PCR results; and to identify suspected COVID-19 cases in pediatric and at-risk adult populations with negative nasal swab RT-qPCR results. All blood samples were analyzed by RT-qPCR to allow direct comparisons. RESULTS: CRISPR-augmented RT-PCR consistently detected SARS-CoV-2 RNA in the plasma of experimentally infected NHPs from 1 to 28 days after infection, and these increases preceded and correlated with rectal swab viral RNA increases. In a patient cohort (n = 159), this blood-based assay demonstrated 91.2% diagnostic sensitivity and 99.2% diagnostic specificity versus a comparator RT-qPCR nasal/nasopharyngeal test, whereas RT-qPCR exhibited 44.1% diagnostic sensitivity and 100% specificity for the same blood samples. This CRISPR-augmented RT-PCR assay also accurately identified patients with COVID-19 using one or more negative nasal swab RT-qPCR results. CONCLUSION: Results of this study indicate that sensitive detection of SARS-CoV-2 RNA in blood by CRISPR-augmented RT-PCR permits accurate COVID-19 diagnosis, and can detect COVID-19 cases with transient or negative nasal swab RT-qPCR results, suggesting that this approach could improve COVID-19 diagnosis and the evaluation of SARS-CoV-2 infection clearance, and predict the severity of infection. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04358211. FUNDING: Department of Defense, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the National Center for Research Resources.

Nitrate is an abundant nutrient and electron acceptor throughout Earth’s biosphere. Virtually all nitrate in nature is produced by the oxidation of nitrite by the nitrite oxidoreductase (NXR) multiprotein complex. NXR is a crucial enzyme in the global biological nitrogen cycle, and is found in nitrite-oxidizing bacteria (including comammox organisms), which generate the bulk of the nitrate in the environment, and in anaerobic ammonium-oxidizing (anammox) bacteria which produce half of the dinitrogen gas in our atmosphere. However, despite its central role in biology and decades of intense study, no structural information on NXR is available. Here, we present a structural and biochemical analysis of the NXR from the anammox bacterium Kuenenia stuttgartiensis, integrating X-ray crystallography, cryo-electron tomography, helical reconstruction cryo-electron microscopy, interaction and reconstitution studies and enzyme kinetics. We find that NXR catalyses both nitrite oxidation and nitrate reduction, and show that in the cell, NXR is arranged in tubules several hundred nanometres long. We reveal the tubule architecture and show that tubule formation is induced by a previously unidentified, haem-containing subunit, NXR-T. The results also reveal unexpected features in the active site of the enzyme, an unusual cofactor coordination in the protein’s electron transport chain, and elucidate the electron transfer pathways within the complex., The oxidoreductase (NXR) multiprotein complex is a key enzyme in the nitrogen cycle. A detailed structural and biochemical characterization of NXR from the anammox bacterium Kuenenia stuttgartiensis shows that this complex is a filament-forming protein that catalysers both nitrite oxidation and nitrate reduction, and elucidates the mechanisms governing complex assembly and function.

Cryo-electron tomography combined with subtomogram averaging (StA) has yielded high-resolution structures of macromolecules in their native context. However, high-resolution StA is not commonplace due to beam-induced sample drift, images with poor signal-to-noise ratios (SNR), challenges in CTF correction, and limited particle number. Here we address these issues by collecting tilt series with a higher electron dose at the zero-degree tilt. Particles of interest are then located within reconstructed tomograms, processed by conventional StA, and then re-extracted from the high-dose images in 2D. Single particle analysis tools are then applied to refine the 2D particle alignment and generate a reconstruction. Use of our hybrid StA (hStA) workflow improved the resolution for tobacco mosaic virus from 7.2 to 4.4 Å and for the ion channel RyR1 in crowded native membranes from 12.9 to 9.1 Å. These resolution gains make hStA a promising approach for other StA projects aimed at achieving subnanometer resolution., Combining cryo-electron tomography with subtomogram averaging (StA) allows the in situ structure determination of proteins and protein complexes. Here, the authors present the hybrid StA (hStA) workflow that combines the advantages of single particle cryo-EM and StA and consists of a tomographic data collection scheme and a data processing workflow and they demonstrate how hStA can improve the resolution using two examples: the ion channel RyR1 and tobacco mosaic virus.

BACKGROUNDChildren (≤18 years) account for ∼20% of the US population but currently represent METHODSDuring the March 18th-May 15th 2020 Louisiana Stay At Home Order, 1690 blood samples from 812 individuals from a Children’s Hospital were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Demographics, COVID-19 testing, and clinical presentation abstracted from medical records were compared with local COVID-19 cases.RESULTSIn total, 62 subjects (7.6%) were found to be seropositive. The median age was 11 years with 50.4% female. The presenting complaint of seropositive patients was chronic illness (43.5%). Only 18.2% had a previous positive COVID-19 PCR or antibody test. Seropositivity was significantly associated with parish (counties), race, and residence in a low-income area. Importantly, seropositivity was linearly correlated with cumulative COVID-19 case number for all ages by parish.CONCLUSIONIn a large retrospective study, the seropositivity prevalence for SARS-CoV-2 in children in Louisiana during the mandated Stay At Home Order was 7.6%. Residence location, race, and lower socioeconomic factors were linked to more frequent seropositivity in children and correlated to regional COVID-19 case rates. Thus, a significant number of children in Louisiana had SARS-CoV-2 infections that went undetected and unreported and may have contributed to virus transmission.

Transient, isolated n-alkane droplet combustion is simulated at elevated pressure for helium-diluent substituted-air mixtures. We report the presence of unique quasi-steady, three-stage burning behavior of large sphero-symmetric n-alkane droplets at these elevated pressures and helium substituted ambient fractions. Upon initiation of reaction, hot-flame diffusive burning of large droplets is initiated that radiatively extinguishes to establish cool flame burning conditions in nitrogen/oxygen “air” at atmospheric and elevated pressures. However, at elevated pressure and moderate helium substitution for nitrogen (XHe > 20%), the initiated cool flame burning proceeds through two distinct, quasi-steady-state, cool flame burning conditions. The classical “Hot flame” (∼1500 K) radiatively extinguishes into a “Warm flame” burning mode at a moderate maximum reaction zone temperature (∼ 970 K), followed by a transition to a lower temperature (∼765 K), quasi-steady “Cool flame” burning condition. The reaction zone (“flame”) temperatures are associated with distinctly different yields in intermediate reaction products within the reaction zones and surrounding near-field, and the flame-standoff ratios characterizing each burning mode progressively decrease. The presence of all three stages first appears with helium substitution near 20%, and the duration of each stage is observed to be strongly dependent on helium substitutions level between 20–60%. For helium substitution greater than 60%, the hot flame extinction is followed by only the lower temperature cool flame burning mode. In addition to the strong coupling between the diffusive loss of both energy and species and the slowly evolving degenerate branching in the low and negative temperature coefficient (NTC) kinetic regimes, the competition between the low-temperature chain branching and intermediate-temperature chain termination reactions control the “Warm” and “Cool” flame quasi-steady conditions and transitioning dynamics. Experiments onboard the International Space Station with n-dodecane droplets confirm the existence of these combustion characteristics and predictions agree favorably with these observations.

Cryo electron tomography (cryo-ET) combined with subtomogram averaging (StA) enables structural determination of macromolecules in their native context. A few structures were reported by StA at resolution higher than 4.5 Å, however all of these are from viral structural proteins or vesicle coats. Reaching high resolution for a broader range of samples is uncommon due to beam-induced sample drift, poor signal-to-noise ratio (SNR) of images, challenges in CTF correction, limited number of particles. Here we propose a strategy to address these issues, which consists of a tomographic data collection scheme and a processing workflow. Tilt series are collected with higher electron dose at zero-degree tilt in order to increase SNR. Next, after performing StA conventionally, we extract 2D projections of the particles of interest from the higher SNR images and use the single particle analysis tools to refine the particle alignment and generate a reconstruction. We benchmarked our proposedhybrid StA (hStA)workflow and improved the resolution for tobacco mosaic virus from 7.2 to 5.2 Å and the resolution for the ion channel RyR1 in crowded native membranes from 12.9 to 9.1 Å. We demonstrate thathStAcan improve the resolution obtained by conventional StA and promises to be a useful tool for StA projects aiming at subnanometer resolution or higher.

Droplet-combustion experiments with normal-alkane fuels, carried out onboard the International Space Station, have shown that, after radiative extinction of a droplet burning with an ordinary hot flame, often quasi-steady burning is initiated and sustained by a chemical-kinetic mechanism associated with cool flames. This second, cool-flame combustion stage occurs in a partial-burning regime in which both fuel and oxygen leak through a reaction zone that is controlled by the low-temperature chemistry of cool flames. This second stage persists for an appreciable period of time, after which it is terminated by cool-flame extinction, often at a measurable non-zero droplet diameter. This extinction diameter depends on the fuel and on the composition of the ambient atmosphere. Experiments involving large fuel droplets of different initial diameters indicate that the value of this cool-flame extinction diameter may vary with the initial droplet diameter and with the ignition energy imparted by the hot-wire igniters, even though the cool flame lies well within the region described as the inner quasi-steady zone, where flame structures are independent of initial conditions. These observations imply that the effective ambient atmosphere during the second stage likely depends on the previous combustion history. In the present contribution, evaluations are reported concerning possible influences of the ignition process, of the first-stage hot-flame combustion, and of prior cool-flame combustion on the effective atmosphere in which the second-stage combustion and extinction occur. It is concluded that analysis of influences of fuel leakage and condensation may be needed.

Background: Despite the paucity of evidence supporting chemotherapy in the treatment of node-negative, HER2-positive breast cancer measuring

Millimeter-size fuel droplets burning in microgravity show substantial thermal expansion at earlier times in their burning history. Here, we develop a simple model that accounts for thermal expansion of the liquid fuel and compare it against experimental measurements. The results show that excellent agreement with measured droplet-diameter histories throughout the hot-flame period of combustion is obtained when the effect of thermal expansion is included.

Experimental observations are presented concerning radiative extinction of large n-alkane droplets in diluent-substituted environments at moderately varied pressures in microgravity onboard the International Space Station. The fuels considered are n-heptane, n-octane, and n-decane with carbon dioxide, helium, and xenon used as inerts, replacing nitrogen as diluents at varying amounts. It is shown that a simple scaling analysis, based on the assumptions that radiative extinction occurs when the flame temperature drops to a critical value and that the radiative heat loss rate is a fraction of the heat-release rate at the flame, is able to correlate the measured droplet diameter at extinction as a function of its initial diameter and of the ambient gas-mixture properties.

1. Monika L. Dietrich, MD* 2. Russell W. Steele, MD†,‡ 1. *Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 2. †Department of Pediatrics, Ochsner Health Center for Children, New Orleans, LA 3. ‡University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA * Abbreviations: ANF: : acute necrotizing fasciitis ARF: : acute rheumatic fever GAS: : group A Streptococcus IVIG: : intravenous immunoglobulin MRSA: : methicillin-resistant Staphylococcus aureus MSSA: : methicillin-susceptible S aureus PANDAS: : pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections PSGN: : poststreptococcal glomerulonephritis STSS: : streptococcal toxic shock syndrome 1. Clinical prediction rules for group A Streptococcus pharyngitis are unreliable in children, and unless viral etiology is strongly suspected, throat swab with a rapid antigen detection test should be performed. 2. Avoid “proof of cure” cultures when treating pharyngitis. 3. Clindamycin is important in invasive group A Streptococcus infection for toxin mediation but should not be used alone secondary to possible resistance. After completing this article, readers should be able to: 1. Understand the epidemiology, transmission, and major virulence factors of group A Streptococcus (GAS) infections. 2. Plan the appropriate diagnostic evaluation of suspected GAS infection. 3. Recognize the clinical features of, and major complications associated with, invasive and noninvasive GAS infections. 4. Plan appropriate management for a patient with a GAS infection. In 1933, Rebecca Lancefield changed our understanding of β-hemolytic streptococci by developing a system of serologic classification based on the carbohydrate composition of cell wall antigens. Of these organisms, the most significant in human pathogenicity is group A Streptococcus (GAS), otherwise known as Streptococcus pyogenes . (1) GAS is responsible for an impressively wide variety of clinical manifestations, from noninvasive infections, such as pharyngitis, scarlet fever, erysipelas, and cellulitis, to invasive disease, including sepsis, streptococcal toxic shock syndrome (STSS), and necrotizing fasciitis (Table 1). It has also been linked to multiple nonsuppurative complications including acute rheumatic fever (ARF), poststreptococcal glomerulonephritis (PSGN), and the controversial pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Globally, an estimated 18 million people are suffering from a serious GAS-related illness, with about 1.78 million new cases annually. Hundreds of millions of people develop less serious GAS infection every year, placing a massive burden on healthcare systems. The …

BACKGROUND: Embryonal tumors arise typically in infants and young children and are often massive at presentation. Operative resection is a cornerstone in the multimodal treatment of embryonal tumors but potentially disrupts therapeutic timelines. When used appropriately, minimally invasive surgery can minimize treatment delays. The oncologic integrity and safety attainable with minimally invasive resection of embryonal tumors, however, remains controversial. METHODS: Query of the Vanderbilt Cancer Registry identified all children treated for intracavitary, embryonal tumors during a 15-year period. Tumors were assessed radiographically to measure volume (mL) and image-defined risk factors (neuroblastic tumors only) at time of diagnosis, and at preresection and postresection. Patient and tumor characteristics, perioperative details, and oncologic outcomes were compared between minimally invasive surgery and open resection of tumors of comparable size. RESULTS: A total of 202 patients were treated for 206 intracavitary embryonal tumors, of which 178 were resected either open (n = 152, 85%) or with minimally invasive surgery (n = 26, 15%). The 5-year, relapse-free, and overall survival were not significantly different after minimally invasive surgery or open resection of tumors having a volume less than 100 mL, corresponding to the largest resected with minimally invasive surgery (P = .249 and P = .124, respectively). No difference in margin status or lymph node sampling between the 2 operative approaches was detected (p = .333 and p = .070, respectively). Advantages associated with minimally invasive surgery were decreased blood loss (P < .001), decreased operating time (P = .002), and shorter hospital stay (P < .001). Characteristically, minimally invasive surgery was used for smaller volume and earlier stage neuroblastic tumors without image-defined risk factors. CONCLUSION: When selected appropriately, minimally invasive resection of pediatric embryonal tumors, particularly neuroblastic tumors, provides acceptable oncologic integrity. Large tumor volume, small patient size, and image-defined risk factors may limit the broader applicability of minimally invasive surgery.

Droplet combustion experiments carried out onboard the International Space Station, using pure fuels and fuel mixtures, have shown that quasi-steady burning can be sustained by a non-traditional flame configuration, namely a “cool flame” burning in the “partial-burning” regime where both fuel and oxygen leak through the low-temperature-controlled flame-sheet. Recent experiments involving large, bi-component fuel ( n -decane and hexanol, 50/50 by volume) droplets at elevated pressures show that the visible, hot flame becomes extremely weak while the burning rate remains relatively high, suggesting the possible simultaneous presence of “cool” and “hot” flames of roughly equal importance. The radiant output from these bi-component droplets is relatively high and cannot be accounted for only by the presence of a visible hot flame. In this analysis we explore the theoretical possibility of a dual-flame structure, where one flame lies close to the droplet surface, called the “cool flame”, and the other farther away from the droplet surface, termed the “hot flame”. A Burke-Schumann analysis of this dual structure seems to indicate that such flame structures are possible over a limited range of initial conditions. These theoretical results can be compared against available experimental data for pure and bi-component fuel droplet combustion to test how realistic the model may be.

Objectives To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. Study design The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. Results Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200 cells/μL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. Conclusions Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.