210 research outputs found
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Summary of second annual MCBK public meeting: Mobilizing Computable Biomedical Knowledge—A movement to accelerate translation of knowledge into action
The volume of biomedical knowledge is growing exponentially and much of this knowledge is represented in computer executable formats, such as models, algorithms and programmatic code. There is a growing need to apply this knowledge to improve health in Learning Health Systems, health delivery organizations, and other settings. However, most organizations do not yet have the infrastructure required to consume and apply computable knowledge, and national policies and standards adoption are not sufficient to ensure that it is discoverable and used safely and fairly, nor is there widespread experience in the process of knowledge implementation as clinical decision support. The Mobilizing Computable Biomedical Knowledge (MCBK) community formed in 2016 to address these needs. This report summarizes the main outputs of the Second Annual MCBK public meeting, which was held at the National Institutes of Health on July 18‐19, 2019 and brought together over 150 participants from various domains to frame and address important dimensions for mobilizing CBK.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154970/1/lrh2-sup-0001-supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154970/2/lrh210222.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154970/3/lrh210222_am.pd
An observational study of patient characteristics associated with the mode of admission to acute stroke services in North East, England
Objective
Effective provision of urgent stroke care relies upon admission to hospital by emergency ambulance and may involve pre-hospital redirection. The proportion and characteristics of patients who do not arrive by emergency ambulance and their impact on service efficiency is unclear. To assist in the planning of regional stroke services we examined the volume, characteristics and prognosis of patients according to the mode of presentation to local services.
Study design and setting
A prospective regional database of consecutive acute stroke admissions was conducted in North East, England between 01/09/10-30/09/11. Case ascertainment and transport mode were checked against hospital coding and ambulance dispatch databases.
Results
Twelve acute stroke units contributed data for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by private transport or non-emergency ambulance; 252 unknown mode. Emergency ambulance patients were older (76 vs 69 years), more likely to be from institutional care (10% vs 1%) and experiencing total anterior circulation symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency admission (11% vs 4%). However patients attending without emergency ambulance had lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1% vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly dependent patients were admitted by emergency ambulance, but none received thrombolysis.
Conclusion
Presentations of new stroke without emergency ambulance involvement were not unusual but were associated with a better outcome due to younger age, milder neurological impairment and lower levels of pre-stroke dependency. Most patients with a high level of pre-stroke dependency arrived by emergency ambulance but did not receive thrombolysis. It is important to be aware of easily identifiable demographic groups that differ in their potential to gain from different service configurations
A Minimal Model of Metabolism Based Chemotaxis
Since the pioneering work by Julius Adler in the 1960's, bacterial chemotaxis has been predominantly studied as metabolism-independent. All available simulation models of bacterial chemotaxis endorse this assumption. Recent studies have shown, however, that many metabolism-dependent chemotactic patterns occur in bacteria. We hereby present the simplest artificial protocell model capable of performing metabolism-based chemotaxis. The model serves as a proof of concept to show how even the simplest metabolism can sustain chemotactic patterns of varying sophistication. It also reproduces a set of phenomena that have recently attracted attention on bacterial chemotaxis and provides insights about alternative mechanisms that could instantiate them. We conclude that relaxing the metabolism-independent assumption provides important theoretical advances, forces us to rethink some established pre-conceptions and may help us better understand unexplored and poorly understood aspects of bacterial chemotaxis
FIREBall-2: advancing TRL while doing proof-of-concept astrophysics on a suborbital platform
Here we discuss advances in UV technology over the last decade, with an
emphasis on photon counting, low noise, high efficiency detectors in
sub-orbital programs. We focus on the use of innovative UV detectors in a NASA
astrophysics balloon telescope, FIREBall-2, which successfully flew in the Fall
of 2018. The FIREBall-2 telescope is designed to make observations of distant
galaxies to understand more about how they evolve by looking for diffuse
hydrogen in the galactic halo. The payload utilizes a 1.0-meter class telescope
with an ultraviolet multi-object spectrograph and is a joint collaboration
between Caltech, JPL, LAM, CNES, Columbia, the University of Arizona, and NASA.
The improved detector technology that was tested on FIREBall-2 can be applied
to any UV mission. We discuss the results of the flight and detector
performance. We will also discuss the utility of sub-orbital platforms (both
balloon payloads and rockets) for testing new technologies and proof-of-concept
scientific ideasComment: Submitted to the Proceedings of SPIE, Defense + Commercial Sensing
(SI19
Chemotactic response and adaptation dynamics in Escherichia coli
Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia
coli is integral for detecting chemicals over a wide range of background
concentrations, ultimately allowing cells to swim towards sources of attractant
and away from repellents. Its biochemical mechanism based on methylation and
demethylation of chemoreceptors has long been known. Despite the importance of
adaptation for cell memory and behavior, the dynamics of adaptation are
difficult to reconcile with current models of precise adaptation. Here, we
follow time courses of signaling in response to concentration step changes of
attractant using in vivo fluorescence resonance energy transfer measurements.
Specifically, we use a condensed representation of adaptation time courses for
efficient evaluation of different adaptation models. To quantitatively explain
the data, we finally develop a dynamic model for signaling and adaptation based
on the attractant flow in the experiment, signaling by cooperative receptor
complexes, and multiple layers of feedback regulation for adaptation. We
experimentally confirm the predicted effects of changing the enzyme-expression
level and bypassing the negative feedback for demethylation. Our data analysis
suggests significant imprecision in adaptation for large additions.
Furthermore, our model predicts highly regulated, ultrafast adaptation in
response to removal of attractant, which may be useful for fast reorientation
of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript
(19 pages, 5 figures) and supplementary information; added additional
clarification on alternative adaptation models in supplementary informatio
Accelerating Haplotype-Based Genome-Wide Association Study Using Perfect Phylogeny and Phase-Known Reference Data
The genome-wide association study (GWAS) has become a routine approach for mapping disease risk loci with the advent of large-scale genotyping technologies. Multi-allelic haplotype markers can provide superior power compared with single-SNP markers in mapping disease loci. However, the application of haplotype-based analysis to GWAS is usually bottlenecked by prohibitive time cost for haplotype inference, also known as phasing. In this study, we developed an efficient approach to haplotype-based analysis in GWAS. By using a reference panel, our method accelerated the phasing process and reduced the potential bias generated by unrealistic assumptions in phasing process. The haplotype-based approach delivers great power and no type I error inflation for association studies. With only a medium-size reference panel, phasing error in our method is comparable to the genotyping error afforded by commercial genotyping solutions
FIREBall-2: flight preparation of a proven balloon payload to image the intermediate redshift circumgalactic medium
FIREBall-2 is a stratospheric balloon-borne 1-m telescope coupled to a UV
multi-object slit spectrograph designed to map the faint UV emission
surrounding z~0.7 galaxies and quasars through their Lyman-alpha line emission.
This spectro-imager had its first launch on September 22nd 2018 out of Ft.
Sumner, NM, USA. Because the balloon was punctured, the flight was abruptly
interrupted. Instead of the nominal 8 hours above 32 km altitude, the
instrument could only perform science acquisition for 45 minutes at this
altitude. In addition, the shape of the deflated balloon, combined with a full
Moon, revealed a severe off-axis scattered light path, directly into the UV
science detector and about 100 times larger than expected. In preparation for
the next flight, and in addition to describing FIREBall-2's upgrade, this paper
discusses the exposure time calculator (ETC) that has been designed to analyze
the instrument's optimal performance (explore the instrument's limitations and
subtle trade-offs)
Dependence of Bacterial Chemotaxis on Gradient Shape and Adaptation Rate
Simulation of cellular behavior on multiple scales requires models that are sufficiently detailed to capture central intracellular processes but at the same time enable the simulation of entire cell populations in a computationally cheap way. In this paper we present RapidCell, a hybrid model of chemotactic Escherichia coli that combines the Monod-Wyman-Changeux signal processing by mixed chemoreceptor clusters, the adaptation dynamics described by ordinary differential equations, and a detailed model of cell tumbling. Our model dramatically reduces computational costs and allows the highly efficient simulation of E. coli chemotaxis. We use the model to investigate chemotaxis in different gradients, and suggest a new, constant-activity type of gradient to systematically study chemotactic behavior of virtual bacteria. Using the unique properties of this gradient, we show that optimal chemotaxis is observed in a narrow range of CheA kinase activity, where concentration of the response regulator CheY-P falls into the operating range of flagellar motors. Our simulations also confirm that the CheB phosphorylation feedback improves chemotactic efficiency by shifting the average CheY-P concentration to fit the motor operating range. Our results suggest that in liquid media the variability in adaptation times among cells may be evolutionary favorable to ensure coexistence of subpopulations that will be optimally tactic in different gradients. However, in a porous medium (agar) such variability appears to be less important, because agar structure poses mainly negative selection against subpopulations with low levels of adaptation enzymes. RapidCell is available from the authors upon request
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