Summary
It is recognised that high‐flow nasal therapy can prevent desaturation during airway management. Studies in spontaneously breathing patients show an almost linear relationship between flow ...rate and positive airway pressure in the nasopharynx. Positive airway pressure has been suggested as one of the possible mechanisms explaining how high‐flow nasal therapy works. However, data on pressures generated by high‐flow nasal therapy in apnoeic adults under general anaesthesia are absent. This randomised controlled crossover trial investigated airway pressures generated by different flow rates during high‐flow nasal therapy in anaesthetised and paralysed apnoeic patients, comparing pressures with closed and open mouths. Following induction of anaesthesia and neuromuscular blockade, a continuous jaw thrust was used to enable airway patency. Airway pressure was measured in the right main bronchus, the middle of the trachea and the pharynx, using a fibreoptically‐placed catheter connected to a pressure transducer. Each measurement was randomised with respect to closed or open mouth and different flow rates. Twenty patients undergoing elective surgery were included (mean (SD) age 38 (18) years, BMI 25.0 (3.3) kg.m‐2, nine women, ASA physical status 1 (35%), 2 (55%), 3 (10%). While closed mouths and increasing flow rates demonstrated non‐linear increases in pressure, the pressure increase was negligible with an open mouth. Airway pressures remained below 10 cmH2O even with closed mouths and flow rates up to 80 l.min−1; they were not influenced by catheter position. This study shows an increase in airway pressures with closed mouths that depends on flow rate. The generated pressure is negligible with an open mouth. These data question positive airway pressure as an important mechanism for maintenance of oxygenation during apnoea.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Reference values for radius and tibia strength using multiple-stack high-resolution peripheral quantitative computed tomography (HR-pQCT) with homogenized finite element analysis are ...presented in order to derive critical values improving risk prediction models of osteoporosis. Gender and femoral neck areal bone mineral density (aBMD) were independent predictors of bone strength.
Introduction
The purpose was to obtain reference values for radius and tibia bone strength computed by using the homogenized finite element analysis (hFE) using multiple stacks with a HR-pQCT.
Methods
Male and female healthy participants aged 20–39 years were recruited at the University Hospital of Bern. They underwent interview and clinical examination including hand grip, gait speed and DXA of the hip. The nondominant forearm and tibia were scanned with a double and a triple-stack protocol, respectively, using HR-pQCT (XCT II, SCANCO Medical AG). Bone strength was estimated by using the hFE analysis, and reference values were calculated using quantile regression. Multivariable analyses were performed to identify clinical predictors of bone strength.
Results
Overall, 46 women and 41 men were recruited with mean ages of 25.1 (sd 5.0) and 26.2 (sd 5.2) years. Sex-specific reference values for bone strength were established. Men had significantly higher strength for radius (mean (sd) 6640 (1800) N vs. 4110 (1200) N;
p
< 0.001) and tibia (18,200 (4220) N vs. 11,970 (3150) N;
p
< 0.001) than women. In the two multivariable regression models with and without total hip aBMD, the addition of neck hip aBMD significantly improved the model (
p
< 0.001). No clinical predictors of bone strength other than gender and aBMD were identified.
Conclusion
Reference values for radius and tibia strength using multiple HR-pQCT stacks with hFE analysis are presented and provide the basis to help refining accurate risk prediction models. Femoral neck aBMD and gender were significant predictors of bone strength
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Transnasal humidified rapid insufflation ventilatory exchange prolongs safe apnoeic oxygenation time in children. In adults, transnasal humidified rapid insufflation ventilatory exchange is ...reported to have a ventilatory effect with PaCO2 levels increasing less rapidly than without it. This ventilatory effect has yet to be reproduced in children. In this non‐inferiority study, we tested the hypothesis that children weighing 10–15 kg exhibit no difference in carbon dioxide clearance when comparing two different high‐flow nasal therapy flow rates during a 10‐min apnoea period. Following standardised induction of anaesthesia including neuromuscular blockade, patients were randomly allocated to high‐flow nasal therapy of 100% oxygen at 2 or 4 l.kg−1.min−1. Airway patency was ensured by continuous jaw thrust. The study intervention was terminated for safety reasons when SpO2 values dropped < 95%, or transcutaneous carbon dioxide levels rose > 9.3 kPa, or near‐infrared spectroscopy values dropped > 20% from their baseline values, or after an apnoeic period of 10 min. Fifteen patients were included in each group. In the 2 l.kg−1.min−1 group, mean (SD) transcutaneous carbon dioxide increase was 0.46 (0.11) kPa.min−1, while in the 4 l.kg−1.min−1 group it was 0.46 (0.12) kPa.min−1. The upper limit of a one‐sided 95%CI for the difference between groups was 0.07 kPa.min−1, lower than the predefined non‐inferiority margin of 0.147 kPa.min−1 (p = 0.001). The lower flow rate of 2 l.kg−1.min−1 was non‐inferior to 4 l.kg−1.min−1 relative to the transcutaneous carbon dioxide increase. In conclusion, an additional ventilatory effect of either 2 or 4 l.kg−1.min−1 high‐flow nasal therapy in apnoeic children weighing 10–15 kg appears to be absent.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Against a background of unprecedented climate change, humanity faces the challenge of how to increase global food production without compromising the natural environment. Crop suitability models can ...indicate the best locations to grow different crops and, in doing so, support efficient use of land to leave space for, or share space with, nature. However, challenges in downscaling the climate data needed to drive these models to make predictions for the future has meant that they are often run using national or regional climate projections. At finer spatial scales, variation in climate conditions can have a substantial influence on yield and so the continued use of coarse resolution climate data risks maladaptive agricultural decisions. Opportunities to grow novel crops, for which knowledge of local variation in microclimate may be critical, may be missed.
We demonstrate how microclimate information can be acquired for a region and used to run a mechanistic crop suitability model under present day and possible future climate scenarios.
We use microclimate modelling techniques to generate 100 m spatial resolution climate datasets for the south-west of the UK for present day (2012–2017) and predicted future (2042–2047) time periods. We use these data to run the mechanistic crop model WOrld FOod STudies (WOFOST) for 56 crop varieties, which returns information on maximum crop yields for each planting month.
Over short distances, we find that the highest attainable yields vary substantially and discuss how these differences mean that field-level assessments of climate suitability could support land-use decisions, enabling food production whilst protecting biodiversity.
We provide code for running WOFOST in the WofostR R package, thus enabling integration with microclimate models and meaning that our methodology could be applied anywhere in the world. As such, we make available to anyone the tools to predict climate suitability for crops at high spatial resolution for both present day and possible future climate scenarios.
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•Mechanistic crop models need high resolution data for precise predictions.•We generate 100 m resolution climate data for present and future time periods.•We run the mechanistic crop model WOrld FOod STudies (WOFOST) with these data.•Crop suitability is found to vary substantially over short distances.•Microclimate data could inform agricultural decisions that protect biodiversity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. ...Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low‐back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low‐back pain and on quantitative sensory tests.
Methods
In this double‐blind cross‐over study, 49 patients with chronic low‐back pain received a single oral dose of clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0–10 numeric rating scale and quantitative sensory tests were assessed during 2 h after drug intake.
Results
Pain intensity in the supine position was significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs. 3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005). Pain intensity in the sitting position was not significantly different between groups. No effects on quantitative sensory tests were observed.
Conclusions
This study suggests that clobazam has an analgesic effect in patients with chronic low‐back pain. Muscle relaxation or sedation may have contributed to the effect. Development of substances devoid of these side effects would offer the potential to further investigate the antihyperalgesic action of GABAergic compounds.
Significance
Modulation of GABAergic pain‐inhibitory pathways may be a potential future therapeutic target.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Drugs are prescribed for chronic low back pain without knowing in advance whether a patient will respond to them or not. Quantitative sensory tests (QST) can discriminate patients ...according to sensory phenotype, possibly reflecting underlying mechanisms of pain processing. QST may therefore be a screening tool to identify potential responders to a certain drug. The aim of this study was to investigate whether QST can predict analgesic effects of oxycodone, imipramine and clobazam in chronic low back pain.
Methods
Oxycodone 15 mg (n = 50), imipramine 75 mg (n = 50) and clobazam 20 mg (n = 49) were compared to active placebo tolterodine 1 mg in a randomized, double‐blinded, crossover fashion. Electrical, pressure and thermal QST were performed at baseline and after 1 and 2 h. Pain intensity was assessed on a 0–10 numeric rating scale every 30 min for up to 2 h. The ability of baseline QST to predict pain reduction after 2 h was analysed using linear mixed models. Genetic variants of drug‐metabolizing enzymes and genes affecting pain sensitivity were examined as covariables.
Results
No predictor of analgesic effect was found for oxycodone and clobazam. Thermal QST was associated with analgesic effect of imipramine: patients more sensitive to heat or cold were more likely to experience an effect of imipramine. Pharmacogenetic variants and pain‐related candidate genes were not associated with drug efficacy.
Conclusions
Thermal QST have the potential to predict imipramine effect in chronic low back pain. Oxycodone and clobazam effects could not be predicted by any of the selected QST or genetic variants.
Significance
Predicting drug efficacy in chronic low back pain remains difficult. There is some evidence that patients more sensitive to heat and cold pain respond better to imipramine.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We present an open source slow control system for small and medium scale projects. Thanks to its modular and flexible design, where the various instruments are read and controlled by independent ...plugins, Doberman (Detector OBsERving and Monitoring ApplicatioN) can be quickly adapted for many applications, also making use of existing code or proprietary components. The system uses a SQL database to store the data from the instruments and provides an online application to display and browse through the data. It allows the modification of device settings while the program is running and features a protocol to handle exceptions, including the automated distribution of alarm messages. We present two case studies from astroparticle physics, on which Doberman is successfully deployed: a low-background screening facility installed in a remote underground laboratory and a detector R&D platform using cryogenic liquid xenon.
We report the first dark matter search results from XENON1T, a ∼2000-kg-target-mass dual-phase (liquid-gas) xenon time projection chamber in operation at the Laboratori Nazionali del Gran Sasso in ...Italy and the first ton-scale detector of this kind. The blinded search used 34.2 live days of data acquired between November 2016 and January 2017. Inside the (1042±12)-kg fiducial mass and in the 5,40 keV_{nr} energy range of interest for weakly interacting massive particle (WIMP) dark matter searches, the electronic recoil background was (1.93±0.25)×10^{-4} events/(kg×day×keV_{ee}), the lowest ever achieved in such a dark matter detector. A profile likelihood analysis shows that the data are consistent with the background-only hypothesis. We derive the most stringent exclusion limits on the spin-independent WIMP-nucleon interaction cross section for WIMP masses above 10 GeV/c^{2}, with a minimum of 7.7×10^{-47} cm^{2} for 35-GeV/c^{2} WIMPs at 90% C.L.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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