Diagnosis of progressive disseminated histoplasmosis in advanced HIV: A meta-analysis of assay analytical performance

Histoplasmosis is an important cause of mortality in people with advanced HIV, especially in countries with limited access to diagnostic assays. Histoplasmosis can be diagnosed using culture, histopathology, and antibody, antigen, and molecular assays. Several factors may affect the analytical performance of these laboratory assays, including sample type, clinical stage of the disease, and previous use of antifungal treatment, among others. Here we describe the results of a systematic literature review, followed by ameta-analysis of the analytical performances of the diagnostic laboratory assays employed. Our initial search identified 1631 references, of which 1559 references were excluded after title and abstract screening, leaving 72 references identified as studies relevant to the validation of histoplasmosis diagnostic assays. After evaluating the full text, 30 studies were selected for final review, including one paper not identified in the initial search. The meta-analysis for assay analytical performance shows the following results for the overall sensitivity (Sen) and specificity (Spe) of the various methods evaluated: Culture, Sen 77%(no data for specificity calculation); antibody detection assays, Sen 58%/Spe 100%; antigen detection assays, Sen 95%/Spe 97%; and DNA detection assays (molecular), Sen 95%/Spe 99%. Of the 30 studies reviewed, nearly half (n = 13) evaluated Histoplasma antigen assays, which were determined to be the most accurate methodology for diagnosis of progressive disseminated histoplasmosis in advanced HIV (inverse of the negative likelihood ratio was 13.2). Molecular assays appear promising for accurate diagnosis of histoplasmosis, but consensus on exact techniques is needed. Cultures showed variable sensitivity related to sample type and laboratory handling. Finally, antibody assays presented high specificity but low sensitivity. This poor sensitivity is most likely due the highly immunosuppressed state of this patient population. Diagnostic assays are crucial for accurate diagnosis of progressive disseminated histoplasmosis (PDH) with advanced HIV disease. © 2019 by the authors. All rights reserved

Organizational learning and emotion: constructing collective meaning in support of strategic themes

Missing in the organizational learning literature is an integrative framework that reflects the emotional as well as the cognitive dynamics involved. Here, we take a step in this direction by focusing in depth over time (five years) on a selected organization which manufactures electronic equipment for the office industry. Drawing on personal construct theory, we define organizational learning as the collective re-construal of meaning in the direction of strategically significant themes. We suggest that emotions arise as members reflect on progress or lack of progress in achieving organizational learning. Our evidence suggests that invalidation – where organizational learning fails to correspond with expectations – gives rise to anxiety and frustration, while validation – where organizational learning is aligned with or exceeds expectations – evokes comfort or excitement. Our work aims to capture the key emotions involved as organizational learning proceeds

High Humidity Leads to Loss of Infectious Influenza Virus from Simulated Coughs

Background The role of relative humidity in the aerosol transmission of influenza was examined in a simulated examination room containing coughing and breathing manikins. Methods Nebulized influenza was coughed into the examination room and Bioaerosol samplers collected size-fractionated aerosols (\u3c1 µM, 1–4 µM, and \u3e4 µM aerodynamic diameters) adjacent to the breathing manikin’s mouth and also at other locations within the room. At constant temperature, the RH was varied from 7–73% and infectivity was assessed by the viral plaque assay. Results Total virus collected for 60 minutes retained 70.6–77.3% infectivity at relative humidity ≤23% but only 14.6–22.2% at relative humidity ≥43%. Analysis of the individual aerosol fractions showed a similar loss in infectivity among the fractions. Time interval analysis showed that most of the loss in infectivity within each aerosol fraction occurred 0–15 minutes after coughing. Thereafter, losses in infectivity continued up to 5 hours after coughing, however, the rate of decline at 45% relative humidity was not statistically different than that at 20% regardless of the aerosol fraction analyzed. Conclusion At low relative humidity, influenza retains maximal infectivity and inactivation of the virus at higher relative humidity occurs rapidly after coughing. Although virus carried on aerosol particles \u3c4 µM have the potential for remaining suspended in air currents longer and traveling further distances than those on larger particles, their rapid inactivation at high humidity tempers this concern. Maintaining indoor relative humidity \u3e40% will significantly reduce the infectivity of aerosolized virus

Emplacement and high-temperature evolution of gabbros of the 16.5°N oceanic core complexes (Mid-Atlantic Ridge): Insights ito the compositional variability of the lower oceanic crust

This study reports the composition of the oceanic crust from the 16.5°N region of the Mid‐Atlantic Ridge, a spreading ridge segment characterized by a complex detachment fault system and three main oceanic core complexes (southern, central, and northern OCCs). Lithologies recovered from the core complexes include both greenschist facies and weathered pillow basalt, diabase, peridotite, and gabbro, while only weathered and fresh pillow basalt was dredged from the rift valley floor. The gabbros are compositionally bimodal, with the magmatic crust in the region formed by scattered intrusions of chemically primitive plutonic rocks (i.e., dunites and troctolites), associated with evolved oxide‐bearing gabbros. We use thermodynamic models to infer that this distribution is expected in regions where small gabbroic bodies are intruded into mantle peridotites. The occurrence of ephemeral magma chambers located in the lithospheric mantle enables large proportions of the melt to be erupted after relatively low degrees of fractionation. A large proportion of the dredged gabbros reveal evidence for deformation at high‐temperature conditions. In particular, chemical changes in response to deformation and the occurrence of very high‐temperature ultramylonites (>1000 °C) suggest that the deformation related to the oceanic detachment commenced at near‐solidus conditions. This event was likely associated with the expulsion of interstitial, evolved magmas from the crystal mush, a mechanism that enhanced the formation of disconnected oxide‐gabbro seams or layers often associated with crystal‐plastic fabrics in the host gabbros. This granulite‐grade event was soon followed by hydrothermal alteration revealed by the formation of amphibole‐rich veins at high‐temperature conditions (~900 °C)

Isolation of H5N6, H7N9 and H9N2 avian influenza A viruses from air sampled at live poultry markets in China, 2014 and 2015

Zoonotic infections by avian influenza viruses occur at the human-poultry interface, but the modes of transmission have not been fully investigated. We assessed the potential for airborne and fomite transmission at live poultry markets in Guangzhou city and in Hong Kong Special Administrative Region (SAR), China, during 2014 and 2015. Viral genome and infectious avian influenza A viruses of H5N6, H7N9, and H9N2 subtypes were detected predominantly from particles larger or equal to 1 μm in diameter in the air sampled with cyclone-based bioaerosol samplers at the live poultry markets in Guangzhou. Influenza A(H9N2) viruses were ubiquitously isolated every month during the study period from air and environmental swabs, and different lineages of H9N2 virus were isolated from markets where chickens and minor land-based poultry were sold. The use of de-feathering devices increased the quantity of virus-laden airborne particles while market closure reduced the amount of such particles. The results highlight the possibility of airborne transmission of avian influenza viruses among poultry or from poultry to humans within such settings. This may explain epidemiological observations in which some patients with H7N9 infection reported being in markets but no direct contact with live poultry or poultry stalls.published_or_final_versio

Viable Influenza A Virus in Airborne Particles Expelled During Coughs Versus Exhalations

Background To prepare for a possible influenza pandemic, a better understanding of the potential for the airborne transmission of influenza from person to person is needed. Objectives The objective of this study was to directly compare the generation of aerosol particles containing viable influenza virus during coughs and exhalations. Methods Sixty-one adult volunteer outpatients with influenza-like symptoms were asked to cough and exhale three times into a spirometer. Aerosol particles produced during coughing and exhalation were collected into liquid media using aerosol samplers.The samples were tested for the presence of viable influenza virus using a viral replication assay (VRA). Results Fifty-three test subjects tested positive for influenza A virus. Of these, 28 (53%) produced aerosol particles containing viable influenza A virus during coughing, and 22 (42%) produced aerosols with viable virus during exhalation. Thirteen subjects had both cough aerosol and exhalation aerosol samples that contained viable virus, 15 had positive cough aerosol samples but negative exhalation samples, and 9 had positive exhalation samples but negative cough samples. Conclusions Viable influenza A virus was detected more often in cough aerosol particles than in exhalation aerosol particles, but the difference was not large. Because individuals breathe much more often than they cough, these results suggest that breathing may generate more airborne infectious material than coughing over time. However, both respiratory activities could be important in airborne influenza transmission. Our results are also consistent with the theory that much of the aerosol containing viable influenza originates deep in the lung

High Humidity Leads to Loss of Infectious Influenza Virus from Simulated Coughs

Abstract Background: The role of relative humidity in the aerosol transmission of influenza was examined in a simulated examination room containing coughing and breathing manikins

New Alloying Systems for Sintered Steels: Critical Aspects of Sintering Behavior

Oxygen-sensitive alloying elements such as Mn, Si, and Cr have a high potential for improving the properties of low alloyed sintered steels while reducing the alloying cost. However, it is necessary to find a way for avoiding, or at least minimizing, the oxidation of these elements especially during the early stages of the sintering cycle. In this study Mn, Si, and Cr were introduced in the form of a master alloy powder designed to be mixed with the iron base powder and provide the final composition of the steel during the sintering process. The reduction/oxidation phenomena taking place during the heating stage were studied by thermogravimetry, dilatometry, and mass spectroscopy, using either reducing (H2) or inert (Ar) atmospheres. The results show how the difference in chemical activity between base iron powder and master alloy causes the so called "internal-getter" effect, by which the reduction of less stable iron oxides leads to oxidation of the elements with higher affinity for oxygen. This effect can be somehow minimized when sintering in H2, since the iron oxides are reduced at lower temperatures at which the reactivity of the elements in the master alloy is lower. However, H2 concentration in the processing atmosphere needs to be carefully adapted to the specific composition of the materials being processed in order to minimize decarburization by methane formation during sintering.Höganäs AB Sweden, financial support provided through the Höganäs Chair IVPublicad

Dysregulation of the Norepinephrine Transporter Sustains Cortical Hypodopaminergia and Schizophrenia-Like Behaviors in Neuronal Rictor Null Mice

A novel animal model highlights the link between Akt dysfunction, reduced cortical dopamine function, norepinephrine transporters, and schizophrenia-like behaviors

A dominant-negative effect drives selection of TP53 missense mutations in myeloid malignancies

TP53, which encodes the tumor suppressor p53, is the most frequently mutated gene in human cancer. The selective pressures shaping its mutational spectrum, dominated by missense mutations, are enigmatic, and neomorphic gain-of-function (GOF) activities have been implicated. We used CRISPR-Cas9 to generate isogenic human leukemia cell lines of the most common TP53 missense mutations. Functional, DNA-binding, and transcriptional analyses revealed loss of function but no GOF effects. Comprehensive mutational scanning of p53 single-amino acid variants demonstrated that missense variants in the DNA-binding domain exert a dominant-negative effect (DNE). In mice, the DNE of p53 missense variants confers a selective advantage to hematopoietic cells on DNA damage. Analysis of clinical outcomes in patients with acute myeloid leukemia showed no evidence of GOF for TP53 missense mutations. Thus, a DNE is the primary unit of selection for TP53 missense mutations in myeloid malignancies