133 research outputs found
Staphylococcus aureus in cystic fibrosis: pivotal role or bit part actor?
Purpose of review: describe why this review is timely and relevant. The cystic fibrosis lung has long been appreciated as a competitive niche for complex interactions between bacterial species. The individual relationships between effects on the host, and thereafter clinical outcomes, has been poorly understood. We aim to describe the role of Staphyloccus aureus, one of the most commonly encountered bacteria cultured from the respiratory tracts of people with CF, and itâs complex interplay with other organisms, with particular attention to Pseudomonas aeruginosa. Recent findings: describe the main themes in the literature covered by the article. We describe the challenges posed in understanding the role that S. aureus plays in the CF lung, including the difficulties in interpreting culture results depending upon sampling technique, relationships with P. aeruginosa and the rest of the microbiome, as well as discussing the relative merits and potential harms of antibiotic prophylaxis. Finally, we describe the particular challenge of methicillin-resistant S. aureus. Summary: describe the implications of the findings for clinical practice or research. We describe research underway that will address the long-held contentious issues of antibiotic prophylaxis. We also describe the emerging research interest in determining whether, at differences phases in the evolution of CF airways infection, S. aureus infection can have both harmful and protective effects for the host
An ex vivocystic fibrosis model recapitulates key clinical aspects of chronic Staphylococcus aureus infection
Staphylococcus aureus is one of the most prevalent organisms isolated from the airways of people with cystic fibrosis (CF), predominantly early in life. Yet its role in the pathology of lung disease is poorly understood. Clinical studies are limited in scope by age and health of participants and in vitro studies are not always able to accurately recapitulate chronic disease characteristics such as the development of small colony variants. Further, animal models also do not fully represent features of clinical disease: in particular, mice are not readily colonized by S. aureus and when infection is established it leads to the formation of abscesses, a phenomenon almost never observed in the human CF lung. Here, we present details of the development of an existing ex vivo pig lung model of CF infection to investigate the growth of S. aureus. We show that S. aureus is able to establish infection and demonstrates clinically significant characteristics including small colony variant phenotype, increased antibiotic tolerance and preferential localisation in mucus. Tissue invasion and the formation of abscesses were not observed, in line with clinical data
Robust Single-view Cone-beam X-ray Pose Estimation with Neural Tuned Tomography (NeTT) and Masked Neural Radiance Fields (mNeRF)
Many tasks performed in image-guided, mini-invasive, medical procedures can
be cast as pose estimation problems, where an X-ray projection is utilized to
reach a target in 3D space. Expanding on recent advances in the differentiable
rendering of optically reflective materials, we introduce new methods for pose
estimation of radiolucent objects using X-ray projections, and we demonstrate
the critical role of optimal view synthesis in performing this task. We first
develop an algorithm (DiffDRR) that efficiently computes Digitally
Reconstructed Radiographs (DRRs) and leverages automatic differentiation within
TensorFlow. Pose estimation is performed by iterative gradient descent using a
loss function that quantifies the similarity of the DRR synthesized from a
randomly initialized pose and the true fluoroscopic image at the target pose.
We propose two novel methods for high-fidelity view synthesis, Neural Tuned
Tomography (NeTT) and masked Neural Radiance Fields (mNeRF). Both methods rely
on classic Cone-Beam Computerized Tomography (CBCT); NeTT directly optimizes
the CBCT densities, while the non-zero values of mNeRF are constrained by a 3D
mask of the anatomic region segmented from CBCT. We demonstrate that both NeTT
and mNeRF distinctly improve pose estimation within our framework. By defining
a successful pose estimate to be a 3D angle error of less than 3 deg, we find
that NeTT and mNeRF can achieve similar results, both with overall success
rates more than 93%. However, the computational cost of NeTT is significantly
lower than mNeRF in both training and pose estimation. Furthermore, we show
that a NeTT trained for a single subject can generalize to synthesize
high-fidelity DRRs and ensure robust pose estimations for all other subjects.
Therefore, we suggest that NeTT is an attractive option for robust pose
estimation using fluoroscopic projections
Genetic Disruption of System xc-Mediated Glutamate Release from Astrocytes Increases Negative-Outcome Behaviors While Preserving Basic Brain Function in Rat
The importance of neuronal glutamate to synaptic transmission throughout the brain illustrates the immense therapeutic potential and safety risks of targeting this system. Astrocytes also release glutamate, the clinical relevance of which is unknown as the range of brain functions reliant on signaling from these cells hasn\u27t been fully established. Here, we investigated system xc- (Sxc), which is a glutamate release mechanism with an in vivo rodent expression pattern that is restricted to astrocytes. As most animals do not express Sxc, we first compared the expression and sequence of the obligatory Sxc subunit xCT among major classes of vertebrate species. We found xCT to be ubiquitously expressed and under significant negative selective pressure. Hence, Sxc likely confers important advantages to vertebrate brain function that may promote biological fitness. Next, we assessed brain function in male genetically modified rats (MSxc) created to eliminate Sxc activity. Unlike other glutamatergic mechanisms, eliminating Sxc activity was not lethal and didn\u27t alter growth patterns, telemetry measures of basic health, locomotor activity, or behaviors reliant on simple learning. However, MSxc rats exhibited deficits in tasks used to assess cognitive behavioral control. In a pavlovian conditioned approach, MSxc rats approached a food-predicted cue more frequently than WT rats, even when this response was punished. In attentional set shifting, MSxc rats displayed cognitive inflexibility because of an increased frequency of perseverative errors. MSxc rats also displayed heightened cocaine-primed drug seeking. Hence, a loss of Sxc-activity appears to weaken control over nonreinforced or negative-outcome behaviors without altering basic brain function
Sunyaev-Zel'dovich observations of galaxy clusters out to the virial radius with the Arcminute Microkelvin Imager
We present observations using the Small Array of the Arcminute Microkelvin
Imager (AMI; 14-18 GHz) of four Abell and three MACS clusters spanning
0.171-0.686 in redshift. We detect Sunyaev-Zel'dovich (SZ) signals in five of
these without any attempt at source subtraction, although strong source
contamination is present. With radio-source measurements from high-resolution
observations, and under the assumptions of spherical -model,
isothermality and hydrostatic equilibrium, a Bayesian analysis of the data in
the visibility plane detects extended SZ decrements in all seven clusters over
and above receiver noise, radio sources and primary CMB imprints. Bayesian
evidence ratios range from 10^{11}:1 to 10^{43}:1 for six of the clusters and
3000:1 for one with substantially less data than the others. We present
posterior probability distributions for, e.g., total mass and gas fraction
averaged over radii internal to which the mean overdensity is 1000, 500 and
200, r_200 being the virial radius. Reaching r_200 involves some extrapolation
for the nearer clusters but not for the more-distant ones. We find that our
estimates of gas fraction are low (compared with most in the literature) and
decrease with increasing radius. These results appear to be consistent with the
notion that gas temperature in fact falls with distance (away from near the
cluster centre) out to the virial radius.Comment: 18 pages, 10 figures, submitted to MNRAS (updated authors and fixed
Figure 1
AMI observations of Lynds Dark Nebulae: further evidence for anomalous cm-wave emission
Observations at 14.2 to 17.9 GHz made with the AMI Small Array towards
fourteen Lynds Dark Nebulae with a resolution of 2' are reported. These sources
are selected from the SCUBA observations of Visser et al. (2001) as small
angular diameter clouds well matched to the synthesized beam of the AMI Small
Array. Comparison of the AMI observations with radio observations at lower
frequencies with matched uv-plane coverage is made, in order to search for any
anomalous excess emission which can be attributed to spinning dust. Possible
emission from spinning dust is identified as a source within a 2' radius of the
Scuba position of the Lynds dark nebula, exhibiting an excess with respect to
lower frequency radio emission. We find five sources which show a possible
spinning dust component in their spectra. These sources have rising spectral
indices in the frequency range 14.2--17.9 GHz. Of these five one has already
been reported, L1111, we report one new definite detection, L675, and three new
probable detections (L944, L1103 and L1246). The relative certainty of these
detections is assessed on the basis of three criteria: the extent of the
emission, the coincidence of the emission with the Scuba position and the
likelihood of alternative explanations for the excess. Extended microwave
emission makes the likelihood of the anomalous emission arising as a
consequence of a radio counterpart to a protostar or a proto-planetary disk
unlikely. We use a 2' radius in order to be consistent with the IRAS
identifications of dark nebulae (Parker 1988), and our third criterion is used
in the case of L1103 where a high flux density at 850 microns relative to the
FIR data suggests a more complicated emission spectrum.Comment: submitted MNRA
Radio continuum observations of Class I protostellar disks in Taurus: constraining the greybody tail at centimetre wavelengths
We present deep 1.8 cm (16 GHz) radio continuum imaging of seven young
stellar objects in the Taurus molecular cloud. These objects have previously
been extensively studied in the sub-mm to NIR range and their SEDs modelled to
provide reliable physical and geometrical parametres.We use this new data to
constrain the properties of the long-wavelength tail of the greybody spectrum,
which is expected to be dominated by emission from large dust grains in the
protostellar disk. We find spectra consistent with the opacity indices expected
for such a population, with an average opacity index of beta = 0.26+/-0.22
indicating grain growth within the disks. We use spectra fitted jointly to
radio and sub-mm data to separate the contributions from thermal dust and radio
emission at 1.8 cm and derive disk masses directly from the cm-wave dust
contribution. We find that disk masses derived from these flux densities under
assumptions consistent with the literature are systematically higher than those
calculated from sub-mm data, and meet the criteria for giant planet formation
in a number of cases.Comment: submitted MNRA
High resolution AMI Large Array imaging of spinning dust sources: spatially correlated 8 micron emission and evidence of a stellar wind in L675
We present 25 arcsecond resolution radio images of five Lynds Dark Nebulae
(L675, L944, L1103, L1111 & L1246) at 16 GHz made with the Arcminute
Microkelvin Imager (AMI) Large Array. These objects were previously observed
with the AMI Small Array to have an excess of emission at microwave frequencies
relative to lower frequency radio data. In L675 we find a flat spectrum compact
radio counterpart to the 850 micron emission seen with SCUBA and suggest that
it is cm-wave emission from a previously unknown deeply embedded young
protostar. In the case of L1246 the cm-wave emission is spatially correlated
with 8 micron emission seen with Spitzer. Since the MIR emission is present
only in Spitzer band 4 we suggest that it arises from a population of PAH
molecules, which also give rise to the cm-wave emission through spinning dust
emission.Comment: accepted MNRA
AMI-LA radio continuum observations of Spitzer c2d small clouds and cores: Perseus region
We present deep radio continuum observations of the cores identified as
deeply embedded young stellar objects in the Perseus molecular cloud by the
Spitzer c2d programme at a wavelength of 1.8 cm with the Arcminute Microkelvin
Imager Large Array (AMI-LA). We detect 72% of Class 0 objects from this sample
and 31% of Class I objects. No starless cores are detected. We use the flux
densities measured from these data to improve constraints on the correlations
between radio luminosity and bolometric luminosity, infrared luminosity and,
where measured, outflow force. We discuss the differing behaviour of these
objects as a function of protostellar class and investigate the differences in
radio emission as a function of core mass. Two of four possible very low
luminosity objects (VeLLOs) are detected at 1.8 cm.Comment: 18 pages, 9 figures, accepted MNRA
- âŠ