Seasonal human influenza viruses continually change antigenically to escape from neutralizing antibodies. It remains unclear how genetic variation in the intrahost virus population and selection at the level of individual hosts translates to the fast-paced evolution observed at the global level because emerging intrahost antigenic variants are rarely detected. We tracked intrahost variants in the hemagglutinin and neuraminidase surface proteins using longitudinally collected samples from 52 patients infected by A/H3N2 influenza virus, mostly young children, who received oseltamivir treatment. We identified emerging putative antigenic variants and oseltamivir resistant variants, most of which remained detectable in samples collected at subsequent days, and identified variants that emerged intrahost immediately prior to increases in global rates. In contrast to most putative antigenic variants, oseltamivir resistant variants rapidly increased to high frequencies in the virus population. Importantly, the majority of putative antigenic variants and oseltamivir resistant variants were first detectable four or more days after onset of symptoms or start of treatment, respectively. Our observations demonstrate that de novo variants emerge, and may be positively selected, during the course of infection. Additionally, based on the 4-7 day post-treatment delay in emergence of oseltamivir resistant variants in six out of the eight individuals with such variants, we find that limiting sample collection for routine surveillance and diagnostic testing to early timepoints after onset of symptoms can potentially preclude detection of emerging, positively selected variants.
The separation is much more sensitive for laminar flow than for turbulent flow. These remarks have been attested for both subsonic and supersonic flows. However, they are not applicable to transonic flows when there are interactions between boundary layer and shock wave. Along with the Reynolds number, the Mach number is a necessary dimensionless parameter for the condition and the mechanism of separations. The report presents one part of studies on laminar separation with Mach number of incompressible flow. The laminar regimes correspond to flows through wind turbine blades. Our experimental work for laminar separation phenomenon was carried out in a subsonic open circuit wind tunnel by taking photographs. The accuracy of experimental results basically depends on the accuracy of wind tunnel and the quality of smoke on density and constitutive materials. Experimental results permit to determine the position of separation and the form of turbulent region followed from the separation point. Numerical studies were simultaneously realized. Based on obtained experimental and numerical results, the report presents also the comparison between the laminar separation and the turbulent separation.
Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole resistant Candida spp. isolates in low-and-middle-income -countries (LMICs) compared to high-income-countries (HIC). We describe the epidemiology, Candida spp. distribution, treatment and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalised infants < 60 days postnatal age with sepsis (August 2018-February 2021). 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34) and median birth weight was 1270 g (IQR: 990–1692). Only a minority had high risk criteria, such as being born < 28 weeks, 19% (24/127), or birth weight < 1000 g, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%) and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrolment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.
Background: Chyluria is a rare condition where chyle is excreted into the urine. Clinically, most patients manifest with intermittent passage of milky urine. Patients may also present with dysuria, urinary frequency, urgency, retention, or with the sequelae of chronic malnutrition. Case Report: We present a 55-year-old African American man who presented to the emergency department complaining of milky white urine, dysuria, decreased urine output, and suprapubic abdominal pain once a day. Why Should an Emergency Physician Be Aware of This?: Patients may present to the emergency department complaining of milk-colored urine, hematuria, urinary retention, or the sequelae of malnutrition. Initial evaluations should include laboratory investigations of common causes of chyluria and the severity of the potential malnutrition. If the patient presents with urinary retention, after relieving the obstruction in the emergency department, assessment for clot/chyle burden and likelihood of recurrence of urinary retention should be performed by urology. Arrangements for proper outpatient follow-up should be made if the disease manifestations are not severe enough to warrant admission.
The evolution of influenza viruses is fundamentally shaped by within-host processes. However, the within-host evolutionary dynamics of influenza viruses remain incompletely understood, in part because most studies have focused on within-host virus diversity of infections in otherwise healthy adults based on single timepoint data. Here, we analysed the within-host evolution of 82 longitudinally sampled individuals, mostly young children, infected with A/H3N2 or A/H1N1pdm09 viruses between 2007 and 2009. For A/H1N1pdm09 infections during the 2009 pandemic, nonsynonymous changes were common early in infection but decreased or remained constant throughout infection. For A/H3N2 viruses, early infection was dominated by purifying selection. However, as the A/H3N2 infections progressed for longer-than-average duration (up to 2 weeks) in relatively young or influenza naive individuals, nonsynonymous variants increased in frequencies even though within-host virus titres decreased, leading to the maintenance of virus diversity via mutation-selection balance and provide important opportunities for within-host virus evolution.
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