Evaluation of uncomplicated acute respiratory tract infection management in veterans: A national utilization review.

BackgroundAntibiotics are overprescribed for acute respiratory tract infections (ARIs). Guidelines provide criteria to determine which patients should receive antibiotics. We assessed congruence between documentation of ARI diagnostic and treatment practices with guideline recommendations, treatment appropriateness, and outcomes.MethodsA multicenter quality improvement evaluation was conducted in 28 Veterans Affairs facilities. We included visits for pharyngitis, rhinosinusitis, bronchitis, and upper respiratory tract infections (URI-NOS) that occurred during the 2015-2016 winter season. A manual record review identified complicated cases, which were excluded. Data were extracted for visits meeting criteria, followed by analysis of practice patterns, guideline congruence, and outcomes.ResultsOf 5,740 visits, 4,305 met our inclusion criteria: pharyngitis (n = 558), rhinosinusitis (n = 715), bronchitis (n = 1,155), URI-NOS (n = 1,475), or mixed diagnoses (>1 ARI diagnosis) (n = 402). Antibiotics were prescribed in 68% of visits: pharyngitis (69%), rhinosinusitis (89%), bronchitis (86%), URI-NOS (37%), and mixed diagnosis (86%). Streptococcal diagnostic testing was performed in 33% of pharyngitis visits; group A Streptococcus was identified in 3% of visits. Streptococcal tests were ordered less frequently for patients who received antibiotics (28%) than those who did not receive antibiotics 44%; P < .01). Although 68% of visits for rhinosinusitis had documentation of symptoms, only 32% met diagnostic criteria for antibiotics. Overall, 39% of patients with uncomplicated ARIs received appropriate antibiotic management. The proportion of 30-day return visits for ARI care was similar for appropriate (11%) or inappropriate (10%) antibiotic management (P = .22).ConclusionsAntibiotics were prescribed in most uncomplicated ARI visits, indicating substantial overuse. Practice was frequently discordant with guideline diagnostic and treatment recommendations

Assessment of herbaceous vegetation classification using orthophotos produced from the image acquired with unmanned aerial systems

Arguably the most popular remote-sensing products are classified images. However, there are no definitive procedures to assess classification accuracy that simultaneously consider resources available and field efforts. The explosive usage of unmanned aerial systems (UAS) in land surveys adds new challenges to classification assessment, as orthorectified images usually contain significant artifacts. This study aims to identify the optimal ratio between training and validation sample size within a supervised classification approach applied to UAS orthophotos. As a case study, we used a wetland area west of Portland, OR, USA, treated with various glyphosate formulations to control Phalaris arundinacea, commonly known as reed canary grass. A completely randomized design with five replications and six glyphosate formulations was used to assess P. arundinacea vigor following repeated herbicide applications. The change in P. arundinacea vitality was monitored with high-resolution four-band imagery acquired with a SlantRange 3PX camera installed on a DJI Matrice 210. The orthophotos created from images were produced with Pix4D, which was subsequently preprocessed with ERDAS Imagine 2020 to reduce the noise, shadows, and artifacts. All images were classified with the maximum likelihood classification algorithm. Simple random and stratified random sampling methods were applied to collect training and validation samples, evaluating eight ratios of training to validation samples to assess their classification accuracy. We found that increasing the training-to-validation sample size ratio enhances accuracy, with the 3:1 ratio being the most reliable in classifying P. arundinacea vigor. Our study provides evidence that image preprocessing and enhancement are essential for UAS-based imagery

Novel Mouse Model for Analysis of Macrophage Function in Neuroblastoma

Background: Neuroblastoma is the third most common childhood cancer and accounts for 12% of cancer-associated deaths in children under the age of 15. Patients with high risk neuroblastoma have a poor 5-year survival rate of less than 50%. Neuroblastoma tumors treated with the histone deacetylase inhibitor (HDACi) vorinostat have increased infiltration of macrophages with upregulated immune cell-surface receptors. Neuroblastoma cells release VEGF and M-CSF, which may alter intratumoral macrophage populations. VEGF has also been implicated in alteration of amyloid precursor protein family processing. Our lab demonstrated that amyloid precursor protein 2 (APLP2), a member of the amyloid precursor protein family, plays an important role in the migration of tumor cells. APLP2 is known to be expressed by macrophages, but no studies have previously examined macrophage functions that are impacted by APLP2 in the context of neuroblastoma disease and its treatment by HDACi drugs. Significance of Problem: Because of the high morbidity and mortality associated with neuroblastoma, studies such as this one that are designed to comprehend the interaction of immunity and treatment in neuroblastoma are clinically significant. The results from this study are also expected to expand our comprehension of macrophage function and regulation, and thus will be of broad value in the immunology and oncology fields. Experimental Design and Results: We have treated neuroblastoma tumor cells in vitro with M344, an HDACi with structural similarity to vorinostat, and showed that M344 decreases neuroblastoma cell growth. In addition, we have generated mice that lack APLP2 expression in cells expressing the Csf-1 receptor (a protein characteristically expressed by macrophages and dendritic cells). We discovered that following polarization, macrophages collected from the bone marrow of these mice have an altered distribution of M1 and M2 sub-populations, which are macrophage sub-populations known to differ in their migratory capabilities. Furthermore, we have shown that M1 and M2 subpopulations of bone marrow-derived macrophages from normal mice differ in their expression of APLP2. Thus, APLP2 is influential in macrophage biology, and we have created a novel mouse model for defining its specific contributions in mice treated with HDACi that influence macrophage biology. Conclusions: Based on the data that we have acquired, we are well positioned to fully explore both the impact of HDACi drugs on macrophage/dendritic cell populations in a syngeneic neuroblastoma mouse model, and to define the role of APLP2 in the function of these cell populations in the context of neuroblastoma.https://digitalcommons.unmc.edu/chri_forum/1000/thumbnail.jp

Optimizing the bioenergy water footprint by selecting SRC willow canopy phenotypes: regional scenario simulations

© The Author(s) 2019. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Background and Aims: Bioenergy is central for the future energy mix to mitigate climate change impacts; however, its intricate link with the water cycle calls for an evaluation of the carbon–water nexus in biomass production. The great challenge is to optimize trade-offs between carbon harvest and water use by choosing cultivars that combine low water use with high productivity. Methods: Regional scenarios were simulated over a range of willow genotype × environment interactions for the major UK soil × climate variations with the process-based model LUCASS. Soil available water capacity (SAWC) ranged from 51 to 251 mm and weather represented the north-west (wet, cool), north-east (dry, cool), south-west (wet, warm) and south-east (dry, warm) of the UK. Scenario simulations were evaluated for small/open narrow-leaf (NL) versus large/closed broad-leaf (BL) willow canopy phenotypes using baseline (1965–89) and warmer recent (1990–2014) weather data. Key Results: The low productivity under baseline climate in the north could be compensated by choosing BL cultivars (e.g. ‘Endurance’). Recent warmer climate increased average productivity by 0.5–2.5 t ha−1, especially in the north. The modern NL cultivar ‘Resolution’ had the smallest and most efficient water use. On marginal soils (SAWC <100 mm), yields remained below an economic threshold of 9 t ha−1 more frequently under baseline than recent climate. In the drought-prone south-east, ‘Endurance’ yielded less than ‘Resolution’, which consumed on average 17 mm year−1 less water. Assuming a planting area of 10 000 ha, in droughty years between 1.3 and 4.5 × 106 m3 of water could be saved, with a small yield penalty, for ‘Resolution’. Conclusions: With an increase in air temperature and occasional water scarcities expected with climate change, high-yielding NL cultivars should be the preferred choice for sustainable use of marginal lands and reduced competition with agricultural food crops.Peer reviewedFinal Published versio

Functional Evolution of cis-Regulatory Modules at a Homeotic Gene in Drosophila

It is a long-held belief in evolutionary biology that the rate of molecular evolution for a given DNA sequence is inversely related to the level of functional constraint. This belief holds true for the protein-coding homeotic (Hox) genes originally discovered in Drosophila melanogaster. Expression of the Hox genes in Drosophila embryos is essential for body patterning and is controlled by an extensive array of cis-regulatory modules (CRMs). How the regulatory modules functionally evolve in different species is not clear. A comparison of the CRMs for the Abdominal-B gene from different Drosophila species reveals relatively low levels of overall sequence conservation. However, embryonic enhancer CRMs from other Drosophila species direct transgenic reporter gene expression in the same spatial and temporal patterns during development as their D. melanogaster orthologs. Bioinformatic analysis reveals the presence of short conserved sequences within defined CRMs, representing gap and pair-rule transcription factor binding sites. One predicted binding site for the gap transcription factor KRUPPEL in the IAB5 CRM was found to be altered in Superabdominal (Sab) mutations. In Sab mutant flies, the third abdominal segment is transformed into a copy of the fifth abdominal segment. A model for KRUPPEL-mediated repression at this binding site is presented. These findings challenge our current understanding of the relationship between sequence evolution at the molecular level and functional activity of a CRM. While the overall sequence conservation at Drosophila CRMs is not distinctive from neighboring genomic regions, functionally critical transcription factor binding sites within embryonic enhancer CRMs are highly conserved. These results have implications for understanding mechanisms of gene expression during embryonic development, enhancer function, and the molecular evolution of eukaryotic regulatory modules

Consilient Discrepancy: Porosity and Atmosphere in Cinema and Architecture

Cinema constitutes a way of looking at the world, at a world – its aspect, its appearance; but it also presents how that world looks, its prospect – by the prospective glance it throws back toward us. The “look” of a film – its mood, ambiance or atmosphere – eclipses formal and aesthetics registers. It is fundamentally world-forming, and therefore both cosmogonic and ethical: cosmogonic because it produces a world in the midst of, and as, the temporality that devolves through its passage; and ethical because the world it brings about is an inhabited world, a conjugation of people and place that constructs particular ways of being-there-together. The premise here is that atmosphere, ambiance and mood have never been vague categories for cinema and need not be for architecture: rather, that they are in fact producible through deliberate organizational strategies – kinematic and narrative in film, tectonic and material in architecture – according to what might be called “consilient discrepancy” – the coexistence of disseveral systems in unaligned multiplicity that, while never fusing, resonate to produce emergent conditions. Cinema offers architecture an accessible and instructive instance of such consilient discrepancy, because, in it, atmosphere is more fully captured and the conditions that create it more evidently analyzable. To that extent, cinema provides architecture with comparative grounds for engaging with atmosphere through a properly tectonic practice that can potentially enrich the design and experience of architecture. Consilient discrepancy is evident across multiple registers in film. It can function at the level of narrative, space and time and thus puts into question verisimilitude, causality, situational and durational veracity. An example of this is the constitutive disjunctions of Jean-Luc Godard’s jump cut montage where sampled film sequences, film and photographic stills, texts and citations, ambient sound, spoken word and music, build into complex assemblages of sense (Histoire(s) du Cinema, 1998). It is evident in Nicholas Roeg’s multiple, simultaneous temporalities where past and future events interpenetrate and mutually condition the narrative present (Bad Timing, 1980). Similarly, we can find it in Michelangelo Antonioni’s sequence shots that traverse multiple timeframes across the same space – a technique that enables past and present to communicate and amplify the affective, foundational value of the unseen and off-frame (The Passenger, 1975). Another example would be David Lynch’s labyrinthine existential settings, constituted of interminable slippages between indeterminable and infinitely potentialized spaces of dreams, imagination, memory and reality (Mulholland Drive, 2001). Likewise, we could cite Michael Hanake’s persistent displacement of causality and verisimilitude through ambiguous narrative viewpoints (Caché, 2005), and Roy Andersson’s radically liminal settings and characters whose lives constitute larval pre- and/or posthuman states of existence (A Pigeon Sat on a Branch Reflecting on Existence, 2014). This paper will foreground two foundational characteristics of atmosphere in cinema, as evident in the works just cited, and explore their applicability to architecture. The first characteristic is the consilient discrepancy outlined here by way of introduction, and the second, related characteristic, is a spatiality of porosity and occlusion. The provisional aim of comparing cinema and architecture according to this tectonic logic is to go beyond typical ways of understanding cinema’s formal engagement with architecture. For this purpose, a detailed analysis of Béla Tarr’s film Werckmeister Harmonies (2000) will serve as a case study for how the medium of cinema generates atmosphere, ambiance and mood through visual language. This will be followed by a similarly detailed consideration of concomitant qualities created in two recent works by the architects Flores Prats, the Mills Museum and Casal Balaguer. Functioning as exemplars of how cinematic qualities can be made manifest in architecture, these precedents will further substantiate the cinematic–architectonic proposition ventured in this paper

Cartilage Repair Surgery: Outcome Evaluation by Using Noninvasive Cartilage Biomarkers Based on Quantitative MRI Techniques?

Background. New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair

The anti-bacterial iron-restriction defence mechanisms of egg white; the potential role of three lipocalin-like proteins in resistance against Salmonella

Salmonella enterica serovar Enteritidis (SE) is the most frequently-detected Salmonella in foodborne outbreaks in the European Union. Among such outbreaks, egg and egg products were identified as the most common vehicles of infection. Possibly, the major antibacterial property of egg white is iron restriction, which results from the presence of the iron-binding protein, ovotransferrin. To circumvent iron restriction, SE synthesise catecholate siderophores (i.e. enterobactin and salmochelin) that can chelate iron from host iron-binding proteins. Here, we highlight the role of lipocalin-like proteins found in egg white that could enhance egg-white iron restriction through sequestration of certain siderophores, including enterobactin. Indeed, it is now apparent that the egg-white lipocalin, Ex-FABP, can inhibit bacterial growth via its siderophore-binding capacity in vitro. However, it remains unclear whether ex-FABP performs such a function in egg white or during bird infection. Regarding the two other lipocalins of egg white (Cal-γ and α-1-glycoprotein), there is currently no evidence to indicate that they sequester siderophores

A Role for the Juxtamembrane Cytoplasm in the Molecular Dynamics of Focal Adhesions

Focal adhesions (FAs) are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRAP studies in live cells, with in silico simulations and mathematical modeling, we show that the FA plaque proteins paxillin and vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA-associated fraction undergoing exchange, a juxtamembrane fraction experiencing attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs displays a gradient of FA plaque proteins with respect to both concentration and dynamics. Based on these findings, we propose a new model for the regulation of FA dynamics in which this juxtamembrane domain acts as an intermediary layer, enabling an efficient regulation of FA formation and reorganization