Summary Background The American Academy of Pediatrics recommends a permissive hypoxaemic target for an oxygen saturation of 90% for children with bronchiolitis, which is consistent with the WHO ...recommendations for targets in children with lower respiratory tract infections. No evidence exists to support this threshold. We aimed to assess whether the 90% or higher target for management of oxygen supplementation was equivalent to a normoxic 94% or higher target for infants admitted to hospital with viral bronchiolitis. Methods We did a parallel-group, randomised, controlled, equivalence trial of infants aged 6 weeks to 12 months of age with physician-diagnosed bronchiolitis newly admitted into eight paediatric hospital units in the UK (the Bronchiolitis of Infancy Discharge Study BIDS). A central computer randomly allocated (1:1) infants, in varying length blocks of four and six and without stratification, to be clipped to standard oximeters (patients treated with oxygen if pulse oxygen saturation SpO2 <94%) or modified oximeters (displayed a measured value of 90% as 94%, therefore oxygen not given until SpO2 <90%). All parents, clinical staff, and outcome assessors were masked to allocation. The primary outcome was time to resolution of cough (prespecified equivalence limits of plus or minus 2 days) in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN28405428. Findings Between Oct 3, and March 30, 2012, and Oct 1, and March 29, 2013, we randomly assigned 308 infants to standard oximeters and 307 infants to modified oximeters. Cough resolved by 15·0 days (median) in both groups (95% CI for difference −1 to 2) and so oxygen thresholds were equivalent. We recorded 35 serious adverse events in 32 infants in the standard care group and 25 serious adverse events in 24 infants in the modified care group. In the standard care group, eight infants transferred to a high-dependency unit, 23 were readmitted, and one had a prolonged hospital stay. In the modified care group, 12 infants were transferred to a high-dependency unit and 12 were readmitted to hospital. Recorded adverse events did not differ significantly. Interpretation Management of infants with bronchiolitis to an oxygen saturation target of 90% or higher is as safe and clinically effective as one of 94% or higher. Future research should assess the benefits and risks of different oxygen saturation targets in acute respiratory infection in older children, particularly in developing nations where resources are scarce. Funding National Institute for Health Research, Health Technology Assessment programme.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In 1988 the preceding journal of Nature Biotechnology, Bio/Technology, reported a work by Hopp and co-workers about a new tag system for the identification and purification of recombinant proteins: ...the FLAG-tag. Beside the extensively used hexa-his tag system the FLAG-tag has gained broad popularity due to its small size, its high solubility, the presence of an internal Enterokinase cleavage site, and the commercial availability of high-affinity anti-FLAG antibodies. Surprisingly, considering the heavy use of FLAG in numerous laboratories world-wide, we identified in insect cells a post-translational modification (PTM) that abolishes the FLAG-anti-FLAG interaction rendering this tag system ineffectual for secreted proteins. The present publication shows that the tyrosine that is part of the crucial FLAG epitope DYK is highly susceptible to sulfation, a PTM catalysed by the enzyme family of Tyrosylprotein-Sulfo-transferases (TPSTs). We showed that this modification can result in less than 20% of secreted FLAG-tagged protein being accessible for purification questioning the universal applicability of this established tag system.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Accidents or radiological attacks may lead to ingestion of Cs by large numbers of the public. This work models the efficacy of Prussian blue, the medical countermeasure for internal contamination ...with Cs, to prevent acute radiation syndrome as a function of the duration of treatment and the time that treatment starts after uptake. Risk of acute radiation syndrome is modeled using the International Commission on Radiological Protection's acute radiation hazard model. Dose rates to target organs from Cs ingestion were based on the data published by the US Environmental Protection Agency and the retention of Cs in the reference man. Modeling found that treatment is most effective if begun within 15 d of ingestion, and the course length should be at least 75 d to mitigate cancer risk and 290 d to mitigate fatalities due to acute radiation syndrome. Both of these course lengths are much longer than the minimum Prussian blue treatment regimen of 30 d. Extending the treatment time for contaminated individuals would increase demand for Prussian blue following an accident or attack and in turn, would require a larger stockpile of Prussian blue to meet demand. Not enough data is available to determine if this longer treatment time would lead to adverse medical outcomes due to the toxicity of the treatment itself.
Abstract Access to individual-level health data is essential for gaining new insights and advancing science. In particular, modern methods based on artificial intelligence rely on the availability of ...and access to large datasets. In the health sector, access to individual-level data is often challenging due to privacy concerns. A promising alternative is the generation of fully synthetic data, i.e., data generated through a randomised process that have similar statistical properties as the original data, but do not have a one-to-one correspondence with the original individual-level records. In this study, we use a state-of-the-art synthetic data generation method and perform in-depth quality analyses of the generated data for a specific use case in the field of nutrition. We demonstrate the need for careful analyses of synthetic data that go beyond descriptive statistics and provide valuable insights into how to realise the full potential of synthetic datasets. By extending the methods, but also by thoroughly analysing the effects of sampling from a trained model, we are able to largely reproduce significant real-world analysis results in the chosen use case.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Following a radiological terrorist attack or radiation accident, the general public may be exposed to radiation. Historically, modeling efforts have focused on radiation effects on a "reference ...man"-a 70-kg, 180-cm-tall, 20- to 30-y-old male-which does not adequately reflect radiation hazard to special populations, particularly children. This work examines the radiosensitivity of children with respect to reference man to develop a set of parameters for modeling hematopoetic acute radiation syndrome in children. This analysis was performed using animal studies and the results verified using data from medical studies. Overall, the hematopoietic system in children is much more radiosensitive than that in adults, with the LD50 for children being 56% to 91% of the LD50 of adults, depending on age.
Modeling Cutaneous Radiation Injury from Fallout Adams, Tim G; Yeddanapudi, Neelima; Clay, Matthew ...
Disaster medicine and public health preparedness,
06/2019, Volume:
13, Issue:
3
Journal Article
Peer reviewed
Beta radiation from nuclear weapons fallout could pose a risk of cutaneous radiation injury (CRI) to evacuating populations but has been investigated only cursorily. This work examines 2 components ...of CRI necessary for estimating the potential public health consequences of exposure to fallout: dose protraction and depth of dose.
Dose protraction for dry and moist desquamation was examined by adapting the biological effective dose (BED) calculation to a hazard function calculation similar to those recommended by the National Council on Radiation Protection and Measurements for other acute radiation injuries. Depth of burn was examined using Monte Carlo neutral Particle version 5 to model the penetration of beta radiation from fallout to different skin tissues.
Nonlinear least squares analysis of the BED calculation estimated the hazard function parameter θ1 (dose rate effectiveness factors) as 25.5 and 74.5 (Gy-eq)2 h-1 for dry and moist desquamation, respectively. Depth of dose models revealed that beta radiation is primarily absorbed in the dead skin layers and basal layer and that dose to underlying tissues is small (<5% of dose to basal layer).
The low relative dose to tissues below the basal layer suggests that radiation-induced necrosis or deep skin burns are unlikely from direct skin contamination with fallout. These results enable future modeling studies to better examine CRI risk and facilitate effectively managing and treating populations with specialized injuries from a nuclear detonation. (Disaster Med Public Health Preparedness. 2019;13:463-469).
Background
Recent research has shown that photoplethysmography (PPG) based wearable sensors offer a promising potential for chronic disease monitoring. The aim of the present study was to assess the ...performance of an in-ear wearable PPG sensor in acquiring valid and reliable heart rate measurements in a clinical setting, with epileptic patients.
Methods
Patients undergoing video-electroencephalography (EEG) monitoring with concomitant one-lead electrocardiographic (ECG) recordings were equipped with an in-ear sensor developed by cosinuss°.
Results
In total, 2,048 h of recording from 97 patients with simultaneous ECG and in-ear heart rate data were included in the analysis. The comparison of the quality-filtered in-ear heart rate data with the reference ECG resulted in a bias of 0.78 bpm with a standard deviation of ±2.54 bpm; Pearson’s Correlation Coefficient PCC = 0.83; Intraclass Correlation Coefficient ICC = 0.81 and mean absolute percentage error MAPE = 2.57.
Conclusion
These data confirm that the in-ear wearable PPG sensor provides accurate heart rate measurements in comparison with ECG under realistic clinical conditions, especially with a signal quality indicator. Further research is required to investigate whether this technology is helpful in identifying seizure-related cardiovascular changes.
Total synthesis of the anticancer 1,4-dioxane containing natural products silvestrol (1) and episilvestrol (2) is described by an approach based on the proposed biosynthesis of these novel compounds. ...The key steps included an oxidative rearrangement of the protected d-glucose derivative 11 to afford the 1,4-dioxane 12, which could be elaborated to the coupling partner 5 and a photochemical 3 + 2-cycloadditon between the 3-hydroxyflavone 27 and methyl cinnamate followed by base-induced α-ketol rearrangement and reduction to give the cyclopentabenzofuran core 33. The core (−)-6 and 1,4-dioxane fragment 5 were united by a highly stereoselective Mitsunobu coupling with the modified azodicarboxylate DMEAD to afford the axial coupled product 36. Deprotection then gave episilvestrol (2). Silvestrol (1) was synthesized by a coupling between core (−)-6 and the dioxane 44 followed by deprotection. Compound 1 was also synthesized from episilvestrol (2) by a Mitsunobu inversion. In addition, the analogue 4′-desmethoxyepisilvestrol (46) was synthesized via the same route. It was found that 46 and episilvestrol 2 displayed an unexpected concentration-dependent chemical shift variation for the nonexchangeable dioxane protons. Synthetic compounds 1, 2, 38, 46, and 54 were tested against cancer cells lines, and it was found that the stereochemistry of the core was critical for activity. Synthetic analogue 4′-desmethoxyepisilvestrol (46) was also active against lung and colon cancer cell lines.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract
Floods have been occurring with increasing frequency, leading to damage to communities worldwide. These impacts are expected to continue to rise due to increases in the intensity of extreme ...rainfall. Global climate model (GCM) output, while imperfect in reproducing daily rainfall, is the only practical source of future projections of extreme rainfall intensification. This article presents a practical method for translating GCM precipitation output into usable outputs for stormwater and flood management planning at a regional or local level. The method estimates the impact of extreme storm intensification on riverine flooding using available runoff estimates from GCM precipitation and variable infiltration capacity models, focusing on changes in elevation and frequency due to climate change. It allows communities and utilities to obtain a screening-level estimate of climate change impacts to peak discharge rate statistics without conducting hydrologic modeling. This article outlines the method, its implementation for the 48 contiguous states of the United States, and an example calculation for a river in the eastern United States. Changes in extreme storm runoff intensity vary significantly by region, but much of the United States is projected to see increases of 25 and 50% by 2060 and 2090, respectively, for the RCP8.5 scenario.
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