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We investigate two-phase free-surface turbulence (FST) associated with an underlying shear flow under the condition of strong turbulence (SFST) characterized by large Froude (
) and Weber (
) numbers. We perform direct numerical simulations of three-dimensional viscous flows with air and water phases. In contrast to weak FST (WFST) with small free-surface distortions and anisotropic underlying turbulence with distinct inner/outer surface layers, we find SFST to be characterized by large surface deformation and breaking accompanied by substantial air entrainment. The interface inner/outer surface layers disappear under SFST, resulting in nearly isotropic turbulence with
scaling of turbulence kinetic energy near the interface (where
is wavenumber). The SFST air entrainment is observed to occur over a range of scales following a power law of slope
. We derive this using a simple energy argument. The bubble size spectrum in the volume follows this power law (and slope) initially, but deviates from this in time due to a combination of ongoing broad-scale entrainment and bubble fragmentation by turbulence. For varying
, we find that air entrainment is suppressed below critical values
, the entrainment rate scales as
when gravity dominates surface tension in the bubble formation process, while the entrainment rate scales linearly with
when surface tension dominates.
We investigate the entropy for a class of upper semi-continuous set-valued functions, called Markov set-valued functions, that are a generalization of single-valued Markov interval functions. It is known that the entropy of a Markov interval function can be found by calculating the entropy of an associated shift of finite type. In this paper, we construct a similar shift of finite type for Markov set-valued functions and use this shift space to find upper and lower bounds on the entropy of the set-valued function.
Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease.
A literature search was performed using the keywords ‘nasopharyngeal neoplasm’, ‘cetuximab’ and ‘Erbitux’.
Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting.
There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.
We analyse the turbulence characteristics and consider the closure modelling of the air entraining flow in the wake of three-dimensional, rectangular dry transom sterns obtained using high-resolution implicit large eddy simulations (iLES) (Hendrickson et al., J. Fluid Mech., vol. 875, 2019, pp. 854–883). Our focus is the incompressible highly variable density turbulence (IHVDT) in the near surface mixed-phase region
behind the stern. We characterize the turbulence statistics in
and determine it to be highly anisotropic due to quasi-steady wave breaking. Using unconditioned Reynolds decomposition for our analysis, we show that the turbulent mass flux (TMF) is important in IHVDT for the production of turbulent kinetic energy and is as relevant to the mean momentum equations as the Reynolds stresses. We develop a simple, regional explicit algebraic closure model for the TMF based on a functional relationship between the fluxes and tensor flow quantities. A priori tests of the model show mean density gradients and buoyancy effects are the main driving parameters for predicting the turbulent mass flux and the model is capable of capturing the highly localized nature of the TMF in
We present high-resolution implicit large eddy simulation (iLES) of the turbulent air-entraining flow in the wake of three-dimensional rectangular dry transom sterns with varying speeds and half-beam-to-draft ratios
. We employ two-phase (air/water), time-dependent simulations utilizing conservative volume-of-fluid (cVOF) and boundary data immersion (BDIM) methods to obtain the flow structure and large-scale air entrainment in the wake. We confirm that the convergent-corner-wave region that forms immediately aft of the stern wake is ballistic, thus predictable only by the speed and (rectangular) geometry of the ship. We show that the flow structure in the air–water mixed region contains a shear layer with a streamwise jet and secondary vortex structures due to the presence of the quasi-steady, three-dimensional breaking waves. We apply a Lagrangian cavity identification technique to quantify the air entrainment in the wake and show that the strongest entrainment is where wave breaking occurs. We identify an inverse dependence of the maximum average void fraction and total volume entrained with
. We determine that the average surface entrainment rate initially peaks at a location that scales with draft Froude number and that the normalized average air cavity density spectrum has a consistent value providing there is active air entrainment. A small parametric study of the rectangular geometry and stern speed establishes and confirms the scaling of the interface characteristics with draft Froude number and geometry. In Part 2 (Hendrikson & Yue, J. Fluid Mech., vol. 875, 2019, pp. 884–913) we examine the incompressible highly variable density turbulence characteristics and turbulence closure modelling.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
OBJECTIVES/SPECIFIC AIMS: To examine rural-urban disparities in prevalence of diagnosed diabetes in veterans receiving care at the VA and to determine the extent to which demographic factors and obesity levels contribute to identified disparities. METHODS/STUDY POPULATION: A retrospective serial cross-sectional analysis was employed. A stratified weighted random sample of veterans who received care at a VA facility was selected each year for 2007 through 2012. Rural Urban Commuting Area (RUCA) codes were based on resident zip code. Diabetes was defined by two or more primary or secondary ICD-9 codes for diabetes (250.xx) within a 12 month period. Data were analyzed using complex survey-specific procedures. RESULTS/ANTICIPATED RESULTS: Diabetes prevalence 2007-2012 was lowest in urban (20.5%-21.0%), followed by highly rural (21.1%-22.1%) and rural (22.3%-23.0%) areas with the prevalence being significantly higher on the insular islands (31.0%-32.4%). In 2012, 41% of urban, 43% of rural and highly rural and 30% of insular island veterans were obese. Relative to urban areas, the odds ratio for prevalent diabetes was 1.10 (95% CI: 1.08, 1.12) for rural veterans, 1.19 (95% CI: 1.16, 1.23) for insular island veterans, and 1.00 (95% CI: 0.98, 1.02) for highly rural veterans. DISCUSSION/SIGNIFICANCE OF IMPACT: Prevalence of diagnosed diabetes is high in veterans residing in rural, highly rural and urban areas, but markedly higher on the insular islands. Understanding the burden of disease and factors driving disparities provides information required to develop targeted interventions.
For more than four decades after the introduction of cv. Italia (Vitis vinifera L.) in Brazil, several somatic mutations in the genome of cv. Italia and its somatic mutants gave rise to phenotypes which generated at least five new cultivars of fine table grapes. Since no molecular marker proved to be effective in discriminating cv. Italia (V. vinifera L.) and its coloured mutants (Rubi, Benitaka, Brasil, Black Star), primers for the long terminal repeat (LTR) sequences were developed to analyse Inter Retrotransposon Amplified Polymorphism (IRAP) and Retrotransposon-Microsatellite Amplified Polymorphism (REMAP), and investigate how the coloured cultivars derived from clonal propagations of somatic mutations are genetically structured. Primers for LTR sequences of IRAP and REMAP markers were edited from grape sequence databases available at a GenBank. Twenty-four primers, denominated DKS001–DKS024, were edited. Three hundred and forty-nine DNA segments were amplified by individual DKS primers and DKS/ISSR (Inter Simple Sequence Repeats) primer combinations, at an average of 13.96 amplicons per primer pair. High genetic divergence between the five cultivars was inferred from polymorphism in retrotransposons IRAP and REMAP. The analysis of polymorphism of IRAP and REMAP retrotransposons was crucial to show that clonal propagation of somatic mutations may lead towards the formation of genetically divergent cultivars by the formation of genetically structured vineyards and show the mixture of genomes within each cultivar.
In experimental and clinical studies, green or black tea consumption has been shown to reduce oxidative stress. However, these studies involved high levels of tea consumption and may not reflect patterns in the general population. Here, we examined the association between black or green tea consumption and oxidative stress in a cross-sectional study of 889 premenopausal US women aged 35–54 years. Tea consumption was measured using the Block-98 FFQ. Urinary 8-iso-PGF2α (F2-IsoP) and 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (15-F2t-IsoP-M) were used as biomarkers of oxidative stress. These compounds were measured by MS and normalised to creatinine. Linear regression was used to calculate the geometric mean differences (GMD) and 95% CI for log-transformed urinary F2-IsoP or 15-F2t-IsoP-M in relation to black or green tea consumption. We further examined whether adjusting for caffeine impacted associations between tea and oxidative stress. Geometric means of urinary F2-IsoP and 15-F2t-IsoP-M were 1·44 (95% CI 1·39, 1·49) and 0·71 (95% CI 0·69, 0·73) ng/mg creatinine, respectively. Overall, green tea consumption was not associated with urinary F2-IsoP or 15-F2t-IsoP-M. High-level black tea consumption (≥5 cups/week compared with 0) was associated with higher 15-F2t-IsoP-M concentrations (adjusted GMD=0·10, 95 % CI 0·02–0.19) but not F2-IsoP. Adjusting for caffeine nullified the association between black tea and 15-F2t-IsoP-M. Our findings do not support the hypothesis that dietary tea consumption is inversely associated with oxidative stress.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
Life span bias potentially alters species abundance in death assemblages through the overrepresentation of short-lived organisms compared with their long-lived counterparts. Although previous work found that life span bias did not contribute significantly to live–dead discordance in bivalve assemblages, life span bias better explained discordance in two groups: longer-lived bivalve species and species with known life spans. More studies using local, rather than global, species-wide life spans and mortality rates would help to determine the prevalence of life span bias, especially for long-lived species with known life spans. Here, we conducted a field study at two sites in North Carolina to assess potential life span bias between Mercenaria mercenaria and Chione elevata, two long-lived bivalve species that can be aged directly. We compared the ability of directly measured local life spans with that of regional and global life spans to predict live–dead discordance between these two species. The shorter-lived species (C. elevata) was overrepresented in the death assemblage compared with its live abundance, and local life span data largely predicted the amount of live–dead discordance; local life spans predicted 43% to 88% of discordance. Furthermore, the global maximum life span for M. mercenaria resulted in substantial overpredictions of discordance (1.4 to 1.6 times the observed live–dead discordance). The results of this study suggest that life span bias should be considered as a factor affecting proportional abundances of species in death assemblages and that using life span estimates appropriate to the study locality improves predictions of discordance based on life span compared with using global life span estimates.
Individuals with schizophrenia have deficits in social cognition that are associated with poor functional outcome. Unfortunately, current treatments result in only modest improvement in social cognition. Oxytocin, a neuropeptide with pro-social effects, has significant benefits for social cognition in the general population. However, studies examining the efficacy of oxytocin in schizophrenia have yielded inconsistent results. One reason for inconsistency may be that oxytocin has typically not been combined with psychosocial interventions. It may be necessary for individuals with schizophrenia to receive concurrent psychosocial treatment while taking oxytocin to have the context needed to make gains in social cognitive skills.
The current study tested this hypothesis in a 24-week (48 session) double-blind, placebo-controlled trial that combined oxytocin and Cognitive-Behavioral Social Skills Training (CBSST), which included elements from Social Cognition and Interaction Training (SCIT). Participants included 62 outpatients diagnosed with schizophrenia (placebo n = 31; oxytocin n = 31) who received 36 IU BID, with supervised administration 45 min prior to sessions on CBSST group therapy days. Participants completed a battery of measures administered at 0, 12, and 24 weeks that assessed social cognition.
CBSST generally failed to enhance social cognition from baseline to end of study, and there was no additive benefit of oxytocin beyond the effects of CBSST alone.
Findings suggest that combined CBSST and oxytocin had minimal benefit for social cognition, adding to the growing literature indicating null effects of oxytocin in multi-dose trials. Methodological and biological factors may contribute to inconsistent results across studies.
Foodborne non-typhoidal salmonellosis causes approximately 1 million illnesses annually in the USA. In April 2015, we investigated a multistate outbreak of 65 Salmonella Paratyphi B variant L(+) tartrate(+) infections associated with frozen raw tuna imported from Indonesia, which was consumed raw in sushi. Forty-six (92%) of 50 case-patients interviewed ate sushi during the week before illness onset, and 44 (98%) of 45 who specified ate sushi containing raw tuna. Two outbreak strains were isolated from the samples of frozen raw tuna. Traceback identified a single importer as a common source of tuna consumed by case-patients; this importer issued three voluntary recalls of tuna sourced from one Indonesian processor. Four Salmonella Weltevreden infections were also linked to this outbreak. Whole-genome sequencing was useful in establishing a link between Salmonella isolated from ill people and tuna. This outbreak highlights the continuing foodborne illness risk associated with raw seafood consumption, the importance of processing seafood in a manner that minimises contamination with pathogenic microorganisms and the continuing need to ensure imported foods are safe to eat. People at higher risk for foodborne illness should not consume undercooked animal products, such as raw seafood.
Bovine herpes virus 1 (BHV-1) manifests as a latent viral infection putatively affecting bovines. Understanding its effect on cattle herds is critical to maintaining sustainable beef and dairy production systems, as well as aiding in the development of herd health policies. The primary objective of the current study was, therefore, to use a whole-farm bio-economic model to evaluate the effect of herd seroprevalence to BHV-1 on the productive and economic performance of a spring calving beef cow herd. As part of a wider epidemiological study of herd pathogen status, a total of 4240 cows from 134 spring calving beef cow herds across the Republic of Ireland were blood sampled to measure the seroprevalence to BHV-1. Using data from a national breeding database, productive and reproductive performance indicators were used to parameterize a single year, static and deterministic whole-farm bio-economic model. A spring-calving, pasture-based suckler beef cow production system with an emphasis on calf-to-weanling production was simulated. The impact of BHV-1 seropositivity on whole-farm technical and economic performance was relatively small, with a marginal drop in the net margin of 4% relative to a baseline seronegative herd. Subsequent risk factors for increased pathogenicity were considered such as total herd size, percentage of intra-herd movements and vaccination status for BHV-1. In contrast to all others, scenarios representing herds that were either small in size or those which indicated an active vaccination policy for BHV-1 had no reduction in net margin against the baseline as a result of seropositivity to BHV-1.
Early postnatal intestinal development involves the preparation of the intestinal epithelium for extrauterine life when maternal secretions provide the sole nutrient source. A further shift in the digestive capability of the epithelium occurs later in development with the introduction of complex solid foods. Ontogenesis involves extensive epithelial cell proliferation and cytodifferentiation including changes in the expression of enzymes, receptors and transport systems and is regulated through the interaction of endogenous and exogenous factors. The mucosal epithelium plays a key rôle in the reception and transmisson of these trophic signals. In particular, the interplay between dietary constituents and microvillar membranes exerts profound influence on intestinal development and adaptation during the postnatal period.