15 research outputs found
Rapid-scan electron paramagnetic resonance using an EPR-on-a-Chip sensor
Electron paramagnetic resonance (EPR) spectroscopy is the method of choice to investigate and quantify paramagnetic species in many scientific fields, including materials science and the life sciences. Common EPR spectrometers use electromagnets and microwave (MW) resonators, limiting their application to dedicated lab environments. Here, we present an improved design of a miniaturized EPR spectrometer implemented on a silicon microchip (EPR-on-a-chip, EPRoC). In place of a microwave resonator, EPRoC uses an array of injection-locked voltage-controlled oscillators (VCOs), each incorporating a 200 μm diameter coil, as a combined microwave source and detector. The individual miniaturized VCO elements provide an excellent spin sensitivity reported to be about 4 × 109spins/√Hz, which is extended by the array over a larger area for improved concentration sensitivity. A striking advantage of this design is the possibility to sweep the MW frequency instead of the magnetic field, which allows the use of smaller, permanent magnets instead of the bulky and powerhungry electromagnets required for field-swept EPR. Here, we report rapid scan EPR (RS-EPRoC) experiments performed by sweeping the frequency of the EPRoC VCO array. RS-EPRoC spectra demonstrate an improved SNR by approximately two orders of magnitude for similar signal acquisition times compared to continuous wave (CW-EPRoC) methods, which may improve the absolute spin and concentration sensitivity of EPR-on-a-Chip at 14 GHz to about 6 × 107 spins/√Hz and 3.6 nM⁄√Hz, respectively
BTS guideline for oxygen use in adults in healthcare and emergency settings
The full Guideline for oxygen use in adults in healthcare and emergency settings, published in Thorax1 provides an update to the 2008 BTS Emergency oxygen guideline.2 The following is a summary of the recommendations and good practice points. The sections noted to within this summary refer to the full guideline sections
Development of a non-invasive method to detect pericellular spatial oxygen gradients using FLIM
PhDExtracellular oxygen concentrations affect cellular metabolism and influence tissue
function. Detection methods for these extracellular oxygen concentrations currently have
poor spatial resolution and are frequently invasive. Fluorescence Lifetime Imaging
Microscopy (FLIM) offers a non-invasive method for quantifying local oxygen
concentrations. However, existing FLIM methods also show limited spatial resolution >1
μm and low time-resolved accuracy and precision, due to widefield time-gate.
This study describes a new optimised approach using FLIM to quantity
extracellular oxygen concentration with high accuracy (±7 μmol/kg) and spatial resolution
( ≅ 0.3 μm). An oxygen sensitive fluorescent dye, tris(2,2′-bipyridyl)ruthenium(II) chloride
hexahydrate [Ru(bipy)3]+2, was excited with a multi-photon laser and fluorescence lifetime
was measured using time-correlated single photon counting (TCSPC). The system was fully
calibrated with optimised techniques developed for avoiding artefacts associated with
photon pile-up and phototoxicity, whilst maximising spatial and temporal resolution. An
extended imaging protocol (1800 sec) showed no phototoxic effects on cells at dye
concentrations of <0.4 mM. Extracellular spatial oxygen gradients were identified around
isolated chondrocytes, seeded in three-dimensional agarose gel. The technique was
validated by regulating oxygen cellular consumption and thus confirming that the oxygen
gradient was governed by cellular consumption. The technique identified a subpopulation
of cells exhibiting statistically significant spatial oxygen gradients at the cell perihery. The
subpopulation was shown to be significantly larger in cell diameter correlating with what
that expected from chondrocytes in the deep zone. This technique provides an exciting
opportunity to non-invasively quantify pericellular spatial oxygen gradients from within
three-dimensional cellular constructs without prior manipulation of the cells. Thus by
examining cellular metabolisms it will advance our understanding of the optimal cellular
environment for tissue engineering and regenerative medicine
The development of a near infrared spectroscopy system and its application for non invasive monitoring of cerebral blood and tissue oxygenation in the newborn infants
This project had two main objectives. The first of these was to design and construct
a spectroscopic instrument to monitor small changes in optical transmission across an infant's
head at several near infrared wavelengths resulting from changes in the cerebral oxygenation
status. The overall attenuation of light by brain tissue is very high and is dominated by the
scattering properties of the tissue. Hence a major requirement of the instrument was the ability
to measure spectral changes at very low light levels. Once the instrument was available, the
second objective was to convert the measured changes in optical transmission into changes
in the concentration of the naturally occurring chromophores oxyhaemoglobin,
deoxyhaemoglobin and oxidised and reduced cytochrome c oxidase. An important aspect of
the work was that the chromophore concentration measurements should be quantified in non-arbitrary
units.
Medical Physics is, by its nature, highly interdisciplinary and this is reflected in the
introductory chapter which briefly covers the clinical problems, the medical science
background and the technical aspects of monitoring the cerebral oxygenation status of
newborn infants. The second and third chapters examine those constituents of brain tissue
which absorb and scatter light and how the complication of multiple scattering can be dealt
with in performing quantitative spectroscopy.
The fourth and fifth chapters describe the technical details of the instrument design
and construction from the initial step of setting its design specifications to the final testing of
its performance.
The sixth chapter examines the absorption characteristics of the main chromophores
of interest namely oxyhaemoglobin, deoxyhaemoglobin and the cytochrome enzymes of the
respiratory chain within the brain cells. A discussion on the interpretation of the redox state
of the respiratory enzymes in terms of the metabolic state of the brain is also included.
The final chapter describes the data analysis methods, the measurement of optical
pathlengths in scattering media and introduces a non-linear modification to the Beer-Lambert
law which improves the accuracy of the spectroscopic measurements in highly scattering
media
Preclinical MRI of the Kidney
This Open Access volume provides readers with an open access protocol collection and wide-ranging recommendations for preclinical renal MRI used in translational research. The chapters in this book are interdisciplinary in nature and bridge the gaps between physics, physiology, and medicine. They are designed to enhance training in renal MRI sciences and improve the reproducibility of renal imaging research. Chapters provide guidance for exploring, using and developing small animal renal MRI in your laboratory as a unique tool for advanced in vivo phenotyping, diagnostic imaging, and research into potential new therapies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Preclinical MRI of the Kidney: Methods and Protocols is a valuable resource and will be of importance to anyone interested in the preclinical aspect of renal and cardiorenal diseases in the fields of physiology, nephrology, radiology, and cardiology. This publication is based upon work from COST Action PARENCHIMA, supported by European Cooperation in Science and Technology (COST). COST (www.cost.eu) is a funding agency for research and innovation networks. COST Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation. PARENCHIMA (renalmri.org) is a community-driven Action in the COST program of the European Union, which unites more than 200 experts in renal MRI from 30 countries with the aim to improve the reproducibility and standardization of renal MRI biomarkers
Preclinical MRI of the kidney : methods and protocols
This Open Access volume provides readers with an open access protocol collection and wide-ranging recommendations for preclinical renal MRI used in translational research. The chapters in this book are interdisciplinary in nature and bridge the gaps between physics, physiology, and medicine. They are designed to enhance training in renal MRI sciences and improve the reproducibility of renal imaging research. Chapters provide guidance for exploring, using and developing small animal renal MRI in your laboratory as a unique tool for advanced in vivo phenotyping, diagnostic imaging, and research into potential new therapies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Preclinical MRI of the Kidney: Methods and Protocols is a valuable resource and will be of importance to anyone interested in the preclinical aspect of renal and cardiorenal diseases in the fields of physiology, nephrology, radiology, and cardiology. This publication is based upon work from COST Action PARENCHIMA, supported by European Cooperation in Science and Technology (COST). COST (www.cost.eu) is a funding agency for research and innovation networks. COST Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation. PARENCHIMA (renalmri.org) is a community-driven Action in the COST program of the European Union, which unites more than 200 experts in renal MRI from 30 countries with the aim to improve the reproducibility and standardization of renal MRI biomarkers
Separator fluid volume requirements in multi-infusion settings
INTRODUCTION. Intravenous (IV) therapy is a widely used method for the administration of medication in hospitals worldwide. ICU and surgical patients in particular often require multiple IV catheters due to incompatibility of certain drugs and the high complexity of medical therapy. This increases discomfort by painful invasive procedures, the risk of infections and costs of medication and disposable considerably. When different drugs are administered through the same lumen, it is common ICU practice to flush with a neutral fluid between the administration of two incompatible drugs in order to optimally use infusion lumens. An important constraint for delivering multiple incompatible drugs is the volume of separator fluid that is sufficient to safely separate them. OBJECTIVES. In this pilot study we investigated whether the choice of separator fluid, solvent, or administration rate affects the separator volume required in a typical ICU infusion setting. METHODS. A standard ICU IV line (2m, 2ml, 1mm internal diameter) was filled with methylene blue (40 mg/l) solution and flushed using an infusion pump with separator fluid. Independent variables were solvent for methylene blue (NaCl 0.9% vs. glucose 5%), separator fluid (NaCl 0.9% vs. glucose 5%), and administration rate (50, 100, or 200 ml/h). Samples were collected using a fraction collector until <2% of the original drug concentration remained and were analyzed using spectrophotometry. RESULTS. We did not find a significant effect of administration rate on separator fluid volume. However, NaCl/G5% (solvent/separator fluid) required significantly less separator fluid than NaCl/NaCl (3.6 ± 0.1 ml vs. 3.9 ± 0.1 ml, p <0.05). Also, G5%/G5% required significantly less separator fluid than NaCl/NaCl (3.6 ± 0.1 ml vs. 3.9 ± 0.1 ml, p <0.05). The significant decrease in required flushing volume might be due to differences in the viscosity of the solutions. However, mean differences were small and were most likely caused by human interactions with the fluid collection setup. The average required flushing volume is 3.7 ml. CONCLUSIONS. The choice of separator fluid, solvent or administration rate had no impact on the required flushing volume in the experiment. Future research should take IV line length, diameter, volume and also drug solution volumes into account in order to provide a full account of variables affecting the required separator fluid volume
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ESICM LIVES 2017 : 30th ESICM Annual Congress. September 23-27, 2017.
INTRODUCTION. Unplanned readmission to intensive care is highly
undesirable in that it contributes to increased variance in care,
disruption, difficulty in resource allocation and may increase length
of stay and mortality particularly if subject to delays. Unlike the ICU
admission from the ward, readmission prediction has received
relatively little attention, perhaps in part because at the point of ICU
discharge, full physiological information is systematically available to
the clinician and so it is expected that readmission should be largely
due to unpredictable factors. However it may be that there are
multidimensional trends that are difficult for the clinician to perceive
that may nevertheless be predictive of readmission.
OBJECTIVES. We investigated whether machine learning (ML)
techniques could be used to improve on the simple published SWIFT
score [1] for the prediction of unplanned readmission to ICU within
48 hours.
METHODS. We extracted systolic BP, pulse pressure, heart and
respiration rate, temperature, SpO2, bilirubin, creatinine, INR, lactate,
white cell count, platelet count, pH, FiO2, and total Glasgow Coma
Score from ICU stays of over 2000 adult patients from our hospital
electronic patient record system. We trained our own custom
multidimensional / time-sensitive algorithmic ML system to predict
failed discharges defined as either readmission or unexpected death
within 48 hours of discharge. We used 10-fold cross validation to assess performance. We also assessed the effect of augmenting our
system by transfer learning (TL) with 44,000 additional cases from
the MIMIC III database.
RESULTS. The SWIFT score performed relatively poorly with an
AUROC of around 0.6 which our ML system trained on local data was
also able to match. However when augmented with an additional
dataset by TL, the AUROC for the ML system improved statistically
and clinically significantly to over 0.7.
CONCLUSIONS. Machine learning is able to improve on predictors
based on simple multiple logistic regression. Thus there is likely to
be information in the trends and in combinations of variables. A
disadvantage with this technique is that ML approaches require large
amounts of data for training. However, ML approaches can be
improved by TL. Basing prediction models on locally derived data
augmented by TL is a potentially novel approach to generating tools
that customised to the institution yet can exploit the potential power
of ML algorithms.
REFERENCES
[1] Gajic O, Malinchoc M, Comfere TB, et al. The Stability and
Workload Index for Transfer score predicts unplanned intensive care
unit patient readmission: initial development and validation. Crit Care
Med. 2008;36(3):676–82.
Grant Acknowledgement
This work was internally funded