Comparison of traditional intranasal and aerosol inhalation inoculation of mice with influenza A viruses

AbstractIntranasal instillation of virus in a liquid suspension (IN) is the most frequently employed method to inoculate small mammalian models with influenza virus, but does not reflect a natural route of exposure. In contrast, inoculation via aerosol inhalation (AR) more closely resembles human exposure to influenza virus. Studies in mice have yielded conflicting results regarding virulence induced by virus inoculated by these routes, and have not controlled for potential strain-specific differences, or examined contemporary influenza viruses and avian viruses with pandemic potential. We used a whole-body AR inoculation method to compare infectivity and disease progression of a highly pathogenic H5N1, a low pathogenic H7N9, and a 2009 H1N1 virus with traditional IN inoculation in the mouse model. Generally comparable levels of morbidity and mortality were observed with all viruses examined using either inoculation route, indicating that both IN and AR delivery are appropriate for murine studies investigating influenza virus pathogenicity

Solving the Noether procedure for cubic interactions of higher spins in (A)dS

The Noether procedure represents a perturbative scheme to construct all possible consistent interactions starting from a given free theory. In this note we describe how cubic interactions involving higher spins in any constant-curvature background can be systematically derived within this framework.Comment: 17 pages, LaTex. Invited contribution to the J. Phys. A special volume on "Higher Spin Theories and AdS/CFT" edited by M. Gaberdiel and M. A. Vasiliev. Final version to appear in J. Phys.

Monitoraggio ambientale dell\u2019esposizione a cromo: i risultati dello studio PPTP \u2013 Galvanica

Nell\u2019ambito dello studio PPTP-Galvanica della Regione Lombardia, sono state effettuate indagini di monitoraggio ambientale personali ed in postazione fissa (centro ambiente) al fine di caratterizzare l\u2019esposizione a particolato, ed in particolar modo a cromo esavalente, degli addetti alle attivit\ue0 di galvanica. Dall\u2019esame dei risultati emerge che, in condizione di corretto rispetto delle norme di igiene sul lavoro, le condizioni di processo e di protezione sono tali da assicurare il pi\uf9 ampio rispetto dei limiti previsti. In particolare il campione ha mostrato condizioni ottime nelle grosse realt\ue0 aziendali (dove \ue8 ormai in uso un sistema di lavorazione a \u201cciclo chiuso\u201d), molto buone nelle aziende di medie dimensioni e picchi pi\uf9 problematici di circa 40 \ub5m/m3 in quelle a conduzione famigliare (1 o 2 addetti). Ai fini della valutazione del rischio, non si pu\uf2 quindi escludere che situazioni di lavoro particolari possano portare ad un\u2019esposizione a cromo esavalente meritevole di maggiore attenzione

Transient asymptomatic pulmonary opacities and interstitial lung disease in EGFR-mutated non-small cell lung cancer treated with osimertinib

Introduction: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Some osimertinib-related interstitial lung diseases (ILDs) were shown to be transient, called transient asymptomatic pulmonary opacities (TAPO)—clinically benign pulmonary opacities that resolve despite continued osimertinib treatment—and are not associated with the clinical manifestations of typical TKI-associated ILDs. Methods: In this multicentric study, we retrospectively analyzed 92 patients with EGFR-mutated NSCLC treated with osimertinib. Computed tomography (CT) examinations were reviewed by two radiologists and TAPO were classified according to radiologic pattern. We also analyzed associations between TAPO and patients’ clinical variables and compared clinical outcomes (time to treatment failure and overall survival) for TAPO-positive and TAPO-negative groups. Results: TAPO were found in 18/92 patients (19.6%), with a median follow-up of 114 weeks. Median onset time was 16 weeks (range 6–80) and median duration time 14 weeks (range 8–37). The most common radiologic pattern was focal ground-glass opacity (54.5%). We did not find any individual clinical variable significantly associated with the onset of TAPO or significant difference in clinical outcomes between TAPO-positive and TAPO-negative groups. Conclusions: TAPO are benign pulmonary findings observed in patients treated with osimertinib. TAPO variability in terms of CT features can hinder the differential diagnosis with either osimertinib-related mild ILD or tumor progression. However, because TAPO are asymptomatic, it could be reasonable to continue therapy and verify the resolution of the CT findings at follow-up in selected cases

Personal exposure to airborne ultrafine particles in the urban area of Milan

The relevance of health effects related to ultrafine particles (UFPs; aerodynamic diameter < 100 nm) can be better evaluated using high-resolution strategies for measuring particle number concentrations. In this study, two different portable Condensation Particle Counters (CPCs) were used to measure personal exposure to UFPs in the central area of Milan for one week period during spring, with three sampling sessions per day. Experimental data were continuously collected along an established urban pathway, moving afoot or by different private and public means of transport. Correlation analysis between data measured by two CPCs was performed and general results showed a good agreement, especially at concentrations lower than 2 7105 particles /cm3. UFPs measures were divided on the basis of crossed environments or micro-environments, days of the week and day time (hours). The highest measured mean concentrations and data variability were observed during walking time and moving on motorized vehicles (bus and car), indicating that the highest exposure to UFPs can be reached near motorized traffic. The lowest exposures were observed in green areas and in office microenvironments. An appreciable difference between working and non-working days was observed. Concentration patterns and variation by days of the week and time periods appears related to time trends in traffic intensity

Mammalian Pathogenesis and Transmission of Avian Influenza A(H7N9) Viruses, Tennessee, USA, 2017

Infections with low pathogenicity and highly pathogenic avian influenza A(H7N9) viruses affected poultry in 4 states in the southeastern United States in 2017. We evaluated pathogenicity and transmission of representative viruses in mouse and ferret models and examined replication kinetics in human respiratory tract cells. These viruses can cause respiratory infections in mammalian models

Fine and ultrafine particle levels determined during everyday activities : the PM-CARE project

Exposure to particle number (particles >0.02 \u3bcm in aerodynamic diameter, a.d.) and particle mass levels (PM0.5 , PM1 , PM2.5 and PM10) were determined on 82 non-smoking senior volunteers living in urban and suburban areas of Milan, during the warm and cold seasons of 2005-2006. Measuring devices, comprehending optical counters (6-channel OPC and CPC), a 4-stage cascade impactor, CO and O3 monitors and a NO2 passive sampler, were mounted on trolleys (25kg), especially equipped to provide 24h self-contained air monitoring. Subjects\u2019 activities were individually recorded on timetables, used also for clinical purposes (see Fanetti et al.). When required, outdoor transfers by car or afoot were assisted by project personnel. 24h-average particle number and mass (PM10) concentration means were 19.500 #/cm3 and 41.4 \ub5g/m3 in summer (1913 hours) and 26.600 #/cm3 and 62.0 \ub5g/m3 in winter (1894 hours), with a mean seasonal contribution of PM0.5 to PM10 of 54% and 68%, respectively. Data plots logged by particle counters were apportioned and separately examined according to the most common activities emerging from the timetable. Resulting particle number concentrations are here presented as the mean percent deviation from individual 24h-averaged levels, given as Activity: [a.d. 0.3\u20130.5 \ub5m] and [a.d. >0.02] (total hours monitored; number of subjects). Home at rest: -1% and -20% (1419; 76), Domestic activities: +6% and +7% (307; 75), Flame cooking: +14% and +97% (293; 72), Workplace activities: +18% and -10% (104; 12), Sleep: -7% and -51% (1170; 78), Moving by car: +46% and +141% (103; 81), Promenade: +52% and +27% (66; 32). With the exception of domestic and workplace activities, which could not be better specified, the results reported are indicative of human PM exposure pattern experienced in urban and suburban areas. Substantial increases of overall particle counts are associated with flame cooking and vehicle displacements, whereas PM0.5 levels seem to be mainly associated with outdoor sources

On the cubic interactions of massive and partially-massless higher spins in (A)dS

Cubic interactions of massive and partially-massless totally-symmetric higher-spin fields in any constant-curvature background of dimension greater than three are investigated. Making use of the ambient-space formalism, the consistency condition for the traceless and transverse parts of the parity-invariant interactions is recast into a system of partial differential equations. The latter can be explicitly solved for given s_1-s_2-s_3 couplings and the 2-2-2 and 3-3-2 examples are provided in detail for general choices of the masses. On the other hand, the general solutions for the interactions involving massive and massless fields are expressed in a compact form as generating functions of all the consistent couplings. The St\"uckelberg formulation of the cubic interactions as well as their massless limits are also analyzed.Comment: 42 pages, 2 tables, LaTex. Comments on two-derivative couplings involving partially-massless spin-2 fields added, typos corrected, references added. v2: final version to appear in JHEP. v3: formulae (3.4) and (3.9) correcte

Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice

available in PMC 2010 October 12Recent reports of mild to severe influenza-like illness in humans caused by a novel swine-origin 2009 A(H1N1) influenza virus underscore the need to better understand the pathogenesis and transmission of these viruses in mammals. In this study, selected 2009 A(H1N1) influenza isolates were assessed for their ability to cause disease in mice and ferrets and compared with a contemporary seasonal H1N1 virus for their ability to transmit to naïve ferrets through respiratory droplets. In contrast to seasonal influenza H1N1 virus, 2009 A(H1N1) influenza viruses caused increased morbidity, replicated to higher titers in lung tissue, and were recovered from the intestinal tract of intranasally inoculated ferrets. The 2009 A(H1N1) influenza viruses exhibited less efficient respiratory droplet transmission in ferrets in comparison with the highly transmissible phenotype of a seasonal H1N1 virus. Transmission of the 2009 A(H1N1) influenza viruses was further corroborated by characterizing the binding specificity of the viral hemagglutinin to the sialylated glycan receptors (in the human host) by use of dose-dependent direct receptor-binding and human lung tissue–binding assays

Pathogenesis and transmission of swine origin A(H3N2)v influenza viruses in ferrets

Recent isolation of a novel swine-origin influenza A H3N2 variant virus [A(H3N2)v] from humans in the United States has raised concern over the pandemic potential of these viruses. Here, we analyzed the virulence, transmissibility, and receptor-binding preference of four A(H3N2)v influenza viruses isolated from humans in 2009, 2010, and 2011. High titers of infectious virus were detected in nasal turbinates and nasal wash samples of A(H3N2)v-inoculated ferrets. All four A(H3N2)v viruses possessed the capacity to spread efficiently between cohoused ferrets, and the 2010 and 2011 A(H3N2)v isolates transmitted efficiently to naïve ferrets by respiratory droplets. A dose-dependent glycan array analysis of A(H3N2)v showed a predominant binding to α2-6–sialylated glycans, similar to human-adapted influenza A viruses. We further tested the viral replication efficiency of A(H3N2)v viruses in a relevant cell line, Calu-3, derived from human bronchial epithelium. The A(H3N2)v viruses replicated in Calu-3 cells to significantly higher titers compared with five common seasonal H3N2 influenza viruses. These findings suggest that A(H3N2)v viruses have the capacity for efficient replication and transmission in mammals and underscore the need for continued public health surveillance.National Institutes of Health (U.S.) (GM 57073)Singapore-MIT Alliance for Research and Technolog