To investigate the incidence of bacterial and fungal coinfection of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this retrospective ...observational study across two London hospitals during the first UK wave of coronavirus disease 2019 (COVID-19).
A retrospective case series of hospitalized patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (20 February–20 April 2020; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza-positive patients admitted during the 2019–2020 flu season. Patient demographics, microbiology and clinical outcomes were analysed.
A total of 836 patients with confirmed SARS-CoV-2 were included; 27 (3.2%) of 836 had early confirmed bacterial isolates identified (0–5 days after admission), rising to 51 (6.1%) of 836 throughout admission. Blood cultures, respiratory samples, pneumococcal or Legionella urinary antigens and respiratory viral PCR panels were obtained from 643 (77%), 110 (13%), 249 (30%), 246 (29%) and 250 (30%) COVID-19 patients, respectively. A positive blood culture was identified in 60 patients (7.1%), of which 39 were classified as contaminants. Bacteraemia resulting from respiratory infection was confirmed in two cases (one each community-acquired Klebsiella pneumoniae and ventilator-associated Enterobacter cloacae). Line-related bacteraemia was identified in six patients (three Candida, two Enterococcus spp. and one Pseudomonas aeruginosa). All other community-acquired bacteraemias (n = 16) were attributed to nonrespiratory infection. Zero concomitant pneumococcal, Legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; Staphylococcus aureus was the most common respiratory pathogen isolated in community-acquired coinfection (4/24; 16.7%), with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n = 3) were attributed to line-related infections. Comparable rates of positive coinfection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141; 1.4%), respiratory cultures (10/38; 26.3%) and pneumococcal-positive antigens (1/19; 5.3%) were low.
We found a low frequency of bacterial coinfection in early COVID-19 hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.
Purpose:
To demonstrate knowledge‐based 3D dose prediction for external beam radiotherapy.
Methods:
Using previously treated plans as training data, an artificial neural network (ANN) was trained to ...predict a dose matrix based on patient‐specific geometric and planning parameters, such as the closest distance (r) to planning target volume (PTV) and organ‐at‐risks (OARs). Twenty‐three prostate and 43 stereotactic radiosurgery/radiotherapy (SRS/SRT) cases with at least one nearby OAR were studied. All were planned with volumetric‐modulated arc therapy to prescription doses of 81 Gy for prostate and 12–30 Gy for SRS. Using these clinically approved plans, ANNs were trained to predict dose matrix and the predictive accuracy was evaluated using the dose difference between the clinical plan and prediction, δD = Dclin − Dpred. The mean (〈δDr〉), standard deviation (σδDr), and their interquartile range (IQR) for the training plans were evaluated at a 2–3 mm interval from the PTV boundary (rPTV) to assess prediction bias and precision. Initially, unfiltered models which were trained using all plans in the cohorts were created for each treatment site. The models predict approximately the average quality of OAR sparing. Emphasizing a subset of plans that exhibited superior to the average OAR sparing during training, refined models were created to predict high‐quality rectum sparing for prostate and brainstem sparing for SRS. Using the refined model, potentially suboptimal plans were identified where the model predicted further sparing of the OARs was achievable. Replans were performed to test if the OAR sparing could be improved as predicted by the model.
Results:
The refined models demonstrated highly accurate dose distribution prediction. For prostate cases, the average prediction bias for all voxels irrespective of organ delineation ranged from −1% to 0% with maximum IQR of 3% over rPTV ∈ − 6, 30 mm. The average prediction error was less than 10% for the same rPTV range. For SRS cases, the average prediction bias ranged from −0.7% to 1.5% with maximum IQR of 5% over rPTV ∈ − 4, 32 mm. The average prediction error was less than 8%. Four potentially suboptimal plans were identified for each site and subsequent replanning demonstrated improved sparing of rectum and brainstem.
Conclusions:
The study demonstrates highly accurate knowledge‐based 3D dose predictions for radiotherapy plans.
This review is a comprehensive description of the past decade of research into understanding how the geometry and size of nanoparticles affect their interaction with biological systems: from single ...cells to whole organisms. Recently, there has been a great deal of effort to use both the shape and the size of nanoparticles to target specific cellular uptake mechanisms, biodistribution patterns, and pharmacokinetics. While the successes of spherical lipid-based nanoparticles have heralded marked changes in chemotherapy worldwide, the history of asbestos-induced lung disease casts a long shadow over fibrous materials to date. The impact of particle morphology is known to be intertwined with many physicochemical parameters, namely, size, elasticity, surface chemistry, and biopersistence. In this review, we first highlight some of the morphologies observed in nature as well as shapes available to us through synthetic strategies. Following this we discuss attempts to understand the cellular uptake of nanoparticles through various theoretical models before comparing this with observations from in vitro and in vivo experiments. In addition, we consider the impact of nanoparticle shape at different size regimes on targeting, cytotoxicity, and cellular mechanics.
The Parker Solar Probe (PSP) has observed copious rapid magnetic field direction changes in the near-Sun solar wind. These features have been called "switchbacks," and their origin is a mystery. But ...their widespread nature suggests that they may be generated by a frequently occurring process in the Sun's atmosphere. We examine the possibility that the switchbacks originate from coronal jets. Recent work suggests that many coronal jets result when photospheric magnetic flux cancels, and forms a small-scale "minifilament" flux rope that erupts and reconnects with coronal field. We argue that the reconnected erupting-minifilament flux rope can manifest as an outward propagating Alfvénic fluctuation that steepens into an increasingly compact disturbance as it moves through the solar wind. Using previous observed properties of coronal jets that connect to coronagraph-observed white-light jets (a.k.a. "narrow CMEs"), along with typical solar wind speed values, we expect the coronal-jet-produced disturbances to traverse near-perihelion PSP in 25 minutes, with a velocity of ∼400 km s−1. To consider further the plausibility of this idea, we show that a previously studied series of equatorial latitude coronal jets, originating from the periphery of an active region, generate white-light jets in the outer corona (seen in STEREO/COR2 coronagraph images; 2.5-15 R ), and into the inner heliosphere (seen in Solar-Terrestrial Relations Observatory (STEREO)/Hi1 heliospheric imager images; 15-84 R ). Thus it is tenable that disturbances put onto open coronal magnetic field lines by coronal-jet-producing erupting-minifilament flux ropes can propagate out to PSP space and appear as switchbacks.
Slab2, a comprehensive subduction zone geometry model Hayes, Gavin P; Moore, Ginevra L; Portner, Daniel E ...
Science (American Association for the Advancement of Science),
10/2018, Letnik:
362, Številka:
6410
Journal Article
Recenzirano
Subduction zones are home to the most seismically active faults on the planet. The shallow megathrust interfaces of subduction zones host Earth's largest earthquakes and are likely the only faults ...capable of magnitude 9+ ruptures. Despite these facts, our knowledge of subduction zone geometry-which likely plays a key role in determining the spatial extent and ultimately the size of subduction zone earthquakes-is incomplete. We calculated the three-dimensional geometries of all seismically active global subduction zones. The resulting model, called Slab2, provides a uniform geometrical analysis of all currently subducting slabs.
The Hippo pathway plays an important role in regulating tissue homeostasis, and its effectors, the transcriptional co-activators Yes-associated protein (YAP) and WW domain–containing transcription ...regulator 1 (WWTR1 or TAZ), are responsible for mediating the vast majority of its physiological functions. Although YAP and TAZ are thought to be largely redundant and similarly regulated by Hippo signaling, they have developmental, structural, and physiological differences that suggest they may differ in their regulation and downstream functions. To better understand the functions of YAP and TAZ in the Hippo pathway, using CRISPR/Cas9, we generated YAP KO, TAZ KO, and YAP/TAZ KO cell lines in HEK293A cells. We evaluated them in response to many environmental conditions and stimuli and used RNA-Seq to compare their transcriptional profiles. We found that YAP inactivation has a greater effect on cellular physiology (namely, cell spreading, volume, granularity, glucose uptake, proliferation, and migration) than TAZ inactivation. However, functional redundancy between YAP and TAZ was also observed. In summary, our findings confirm that the Hippo pathway effectors YAP and TAZ are master regulators for multiple cellular processes but also reveal that YAP has a stronger influence than TAZ.
Neurons in the central nervous system (CNS) lose their ability to regenerate early in development, but the underlying mechanisms are unknown. By screening genes developmentally regulated in retinal ...ganglion cells (RGCs), we identified Krüppel-like factor-4 (KLF4) as a transcriptional repressor of axon growth in RGCs and other CNS neurons. RGCs lacking KLF4 showed increased axon growth both in vitro and after optic nerve injury in vivo. Related KLF family members suppressed or enhanced axon growth to differing extents, and several growth-suppressive KLFs were up-regulated postnatally, whereas growth-enhancing KLFs were down-regulated. Thus, coordinated activities of different KLFs regulate the regenerative capacity of CNS neurons.
Broadly neutralizing antibodies (bNAbs), able to prevent viral entry by diverse global viruses, are a major focus of HIV vaccine design, with data from animal studies confirming their ability to ...prevent HIV infection. However, traditional vaccine approaches have failed to elicit these types of antibodies. During chronic HIV infection, a subset of individuals develops bNAbs, some of which are extremely broad and potent. This review describes the immunological and virological factors leading to the development of bNAbs in such "elite neutralizers". The features, targets and developmental pathways of bNAbs from their precursors have been defined through extraordinarily detailed within-donor studies. These have enabled the identification of epitope-specific commonalities in bNAb precursors, their intermediates and Env escape patterns, providing a template for vaccine discovery. The unusual features of bNAbs, such as high levels of somatic hypermutation, and precursors with unusually short or long antigen-binding loops, present significant challenges in vaccine design. However, the use of new technologies has led to the isolation of more than 200 bNAbs, including some with genetic profiles more representative of the normal immunoglobulin repertoire, suggesting alternate and shorter pathways to breadth. The insights from these studies have been harnessed for the development of optimized immunogens, novel vaccine regimens and improved delivery schedules, which are providing encouraging data that an HIV vaccine may soon be a realistic possibility.
Increased understanding of photosynthetic energy conversion and advances in chemical synthesis and instrumentation have made it possible to create artificial nanoscale devices and semibiological ...hybrids that carry out many of the functions of the natural process. Artificial light-harvesting antennas can be synthesized and linked to artificial reaction centers that convert excitation energy to chemical potential in the form of long-lived charge separation. Artificial reaction centers can form the basis for molecular-level optoelectronic devices. In addition, they may be incorporated into the lipid bilayer membranes of artificial vesicles, where they function as components of light-driven proton pumps that generate transmembrane proton motive force. The proton gradient may be used to synthesize adenosine triphosphate via an ATP synthase enzyme. The overall energy transduction process in the liposomal system mimics the solar energy conversion system of a photosynthetic bacterium. The results of this research illustrate the advantages of designing functional nanoscale devices based on biological paradigms.
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