Biopsy-based optimization and calibration of a signal-intensity-ratio-based MRI method (1.5 Tesla) in a dextran-iron loaded mini-pig model, enabling estimation of very high liver iron concentrations

OBJECTIVE: Magnetic resonance imaging (MRI)-based techniques for non-invasive assessing liver iron concentration (LIC) in patients with iron overload have a limited upper measuring range around 35 mg/g dry weight, caused by signal loss from accelerated T1-, T2-, T2* shortening with increasing LIC. Expansion of this range is necessary to allow evaluation of patients with very high LIC. AIM: To assess measuring range of a gradient-echo R2* method and a T1-weighted spin-echo (SE), signal intensity ratio (SIR)-based method (TE = 25 ms, TR = 560 ms), and to extend the upper measuring range of the SIR method by optimizing echo time (TE) and repetition time (TR) in iron-loaded minipigs. METHODS: Thirteen mini pigs were followed up during dextran-iron loading with repeated percutaneous liver biopsies for chemical LIC measurement and MRIs for parallel non-invasive estimation of LIC (81 examinations) using different TEs and TRs. RESULTS: SIR and R2* method had similar upper measuring range around 34 mg/g and similar method agreement. Using TE = 12 ms and TR = 1200 ms extended the upper measuring range to 115 mg/g and yielded good method of agreement. DISCUSSION: The wider measuring range is likely caused by lesser sensitivity of the SE sequence to iron, due to shorter TE, leading to later signal loss at high LIC, allowing evaluation of most severe hepatic iron overload. Validation in iron-loaded patients is necessary

Self-Rated Health as a Predictor of Death after Two Years:The Importance of Physical and Mental Wellbeing Postintensive Care

Introduction. The objective of this study is, among half-year intensive care survivors, to determine whether self-assessment of health can predict two-year mortality. Methods. The study is a prospective cohort study based on the Procalcitonin and Survival Study trial. Half-year survivors from this 1200-patient multicenter intensive care trial were sent the SF-36 questionnaire. We used both a simple one-item question and multiple questions summarized as a Physical Component Summary (PCS) and a Mental Component Summary (MCS) score. The responders were followed for vital status 730 days after inclusion. Answers were dichotomized into a low-risk and a high-risk group and hazard ratios (HR) with 95% confidence interval (CI) were calculated by Cox proportional hazard analyses. Conclusion. We found that self-rated health measured by a single question was a strong independent predictor of two-year all-cause mortality (HR: 1.8; 95% CI: 1.1–3.0). The multi-item component scores of the SF-36 also predicted two-year mortality (PCS: HR: 2.9; 95% CI 1.7–5.0) (MCS: HR: 1.9; 95% CI 1.1–3.4). These results suggest that self-rated health questions could help in identifying patients at excess risk. Randomized controlled trials are needed to test whether our findings represent causality

Silicon-induced changes in antifungal phenolic acids, flavonoids, and key phenylpropanoid pathway genes during the interaction between miniature roses and the biotrophic pathogen <em>Podosphaera pannosa</em>

Application of 3.6 mm silicon (Si+) to the rose (Rosa hybrida) cultivar Smart increased the concentration of antimicrobial phenolic acids and flavonoids in response to infection by rose powdery mildew (Podosphaera pannosa). Simultaneously, the expression of genes coding for key enzymes in the phenylpropanoid pathway (phenylalanine ammonia lyase, cinnamyl alcohol dehydrogenase, and chalcone synthase) was up-regulated. The increase in phenolic compounds correlated with a 46% reduction in disease severity compared with inoculated leaves without Si application (Si−). Furthermore, Si application without pathogen inoculation induced gene expression and primed the accumulation of several phenolics compared with the uninoculated Si− control. Chlorogenic acid was the phenolic acid detected in the highest concentration, with an increase of more than 80% in Si+ inoculated compared with Si− uninoculated plants. Among the quantified flavonoids, rutin and quercitrin were detected in the highest concentrations, and the rutin concentration increased more than 20-fold in Si+ inoculated compared with Si− uninoculated plants. Both rutin and chlorogenic acid had antimicrobial effects on P. pannosa, evidenced by reduced conidial germination and appressorium formation of the pathogen, both after spray application and infiltration into leaves. The application of rutin and chlorogenic acid reduced powdery mildew severity by 40% to 50%, and observation of an effect after leaf infiltration indicated that these two phenolics can be transported to the epidermal surface. In conclusion, we provide evidence that Si plays an active role in disease reduction in rose by inducing the production of antifungal phenolic metabolites as a response to powdery mildew infection

Development of a Tailored, Complex Intervention for Clinical Reflection and Communication about Suspected Urinary Tract Infections in Nursing Home Residents

Background: Inappropriate antibiotic treatments for urinary tract infections (UTIs) in nursing homes cause the development of resistant bacteria. Nonspecific symptoms and asymptomatic bacteriuria are drivers of overtreatment. Nursing home staff provide general practice with information about ailing residents; therefore, their knowledge and communication skills influence prescribing. This paper describes the development of a tailored, complex intervention for a cluster-randomised trial that targets the knowledge of UTI and communication skills in nursing home staff to reduce antibiotic prescriptions. Methods: A dialogue tool was drafted, drawing on participatory observations in nursing homes, interviews with stakeholders, and a survey in general practice. The tool was tailored through a five-phase process that included stakeholders. Finally, the tool and a case-based educational session were tested in a pilot study. Results: The main barriers were that complex patients were evaluated by healthcare staff with limited knowledge about disease and clinical reasoning; findings reported to general practice were insignificant and included vague descriptions; there was evidence of previous opinion bias; nonspecific symptoms were interpreted as UTI; intuitive reasoning led to the inappropriate suspicion of UTI. Conclusion: Sustainable change in antibiotic-prescribing behaviour in nursing homes requires a change in nursing home staff&rsquo;s beliefs about and management of UTIs

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain

The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30–50% (4–6 mM versus 7–9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced

Planning, implementation and scientific goals of the Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) field mission

The Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) field mission based at Ellington Field, Texas, during August and September 2013 employed the most comprehensive airborne payload to date to investigate atmospheric composition over North America. The NASA ER-2, DC-8, and SPEC Inc. Learjet flew 57 science flights from the surface to 20 km. The ER-2 employed seven remote sensing instruments as a satellite surrogate and eight in situ instruments. The DC-8 employed 23 in situ and five remote sensing instruments for radiation, chemistry, and microphysics. The Learjet used 11 instruments to explore cloud microphysics. SEAC4RS launched numerous balloons, augmented AErosol RObotic NETwork, and collaborated with many existing ground measurement sites. Flights investigating convection included close coordination of all three aircraft. Coordinated DC-8 and ER-2 flights investigated the optical properties of aerosols, the influence of aerosols on clouds, and the performance of new instruments for satellite measurements of clouds and aerosols. ER-2 sorties sampled stratospheric injections of water vapor and other chemicals by local and distant convection. DC-8 flights studied seasonally evolving chemistry in the Southeastern U.S., atmospheric chemistry with lower emissions of NOx and SO2 than in previous decades, isoprene chemistry under high and low NOx conditions at different locations, organic aerosols, air pollution near Houston and in petroleum fields, smoke from wildfires in western forests and from agricultural fires in the Mississippi Valley, and the ways in which the chemistry in the boundary layer and the upper troposphere were influenced by vertical transport in convective clouds

A multidisciplinary approach to landslide monitoring in the Arctic: Case study of the March 2018 ML 1.9 seismic event near the Karrat 2017 landslide

The landslide of 17 June 2017 at Karrat Fjord, central West Greenland, triggered a tsunami that caused four fatalities. The catastrophe highlighted the need for a better understanding of landslides in Greenland and initiated a recent nation-wide landslide screening project led by the Geological Survey of Denmark and Greenland (GEUS; see also&nbsp;Svennevig (2019)&nbsp;this volume). This paper describes an approach for compiling freely available data to improve GEUS’ capability to monitor active landslides in remote areas of the Arctic in near real time. Data include seismological records, space borne Synthetic Aperture Radar (SAR) data and multispectral optical satellite imagery. The workflow was developed in 2018 as part of a collaboration between GEUS and scientists from the Technical University of Denmark (DTU). This methodology provides a model through which GEUS will be able to monitor active landslides and provide relevant knowledge to the public and authorities in the event of future landslides that pose a risk to human life and infrastructure in Greenland. We use a minor event on 26 March 2018, near the site of the Karrat 2017 landslide, as a case study to demonstrate 1) the value of multidisciplinary approaches and 2) that the area around the landslide has continued to be periodically active since the main landslide in 2017

Agents intervening against delirium in the intensive care unit trial-Protocol for a secondary Bayesian analysis

Background Delirium is highly prevalent in the intensive care unit (ICU) and is associated with high morbidity and mortality. The antipsychotic haloperidol is the most frequently used agent to treat delirium although this is not supported by solid evidence. The agents intervening against delirium in the intensive care unit (AID-ICU) trial investigates the effects of haloperidol versus placebo for the treatment of delirium in adult ICU patients. Methods This protocol describes the secondary, pre-planned Bayesian analyses of the primary and secondary outcomes up to day 90 of the AID-ICU trial. We will use Bayesian linear regression models for all count outcomes and Bayesian logistic regression models for all dichotomous outcomes. We will adjust for stratification variables (site and delirium subtype) and use weakly informative priors supplemented with sensitivity analyses using sceptical priors. We will present results as absolute differences (mean differences and risk differences) and relative differences (ratios of means and relative risks). Posteriors will be summarised using median values as point estimates and percentile-based 95% credibility intervals. Probabilities of any benefit/harm, clinically important benefit/harm and clinically unimportant differences will be presented for all outcomes. Discussion The results of this secondary, pre-planned Bayesian analysis will complement the primary frequentist analysis of the AID-ICU trial and facilitate a nuanced and probabilistic interpretation of the trial results.Peer reviewe

Planning, implementation, and scientific goals of the studies of emissions and atmospheric composition, clouds and climate coupling by regional surveys (SEAC\u3csup\u3e4\u3c/sup\u3eRS) field mission

The Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) fieldmission based at Ellington Field, Texas, during August and September 2013 employed the most comprehensive airborne payload to date to investigate atmospheric composition over North America. The NASA ER-2, DC-8, and SPEC Inc. Learjet flew 57 science flights fromthe surface to 20 km. The ER-2 employed seven remote sensing instruments as a satellite surrogate and eight in situ instruments. The DC-8 employed 23 in situ and five remote sensing instruments for radiation, chemistry, and microphysics. The Learjet used 11 instruments to explore cloud microphysics. SEAC4RS launched numerous balloons, augmented AErosol RObotic NETwork, and collaborated with many existing ground measurement sites. Flights investigating convection included close coordination of all three aircraft. Coordinated DC-8 and ER-2 flights investigated the optical properties of aerosols, the influence of aerosols on clouds, and the performance of new instruments for satellite measurements of clouds and aerosols. ER-2 sorties sampled stratospheric injections of water vapor and other chemicals by local and distant convection. DC-8 flights studied seasonally evolving chemistry in the Southeastern U.S., atmospheric chemistry with lower emissions of NOx and SO2 than in previous decades, isoprene chemistry under high and low NOx conditions at different locations, organic aerosols, air pollution near Houston and in petroleum fields, smoke from wildfires in western forests and from agricultural fires in the Mississippi Valley, and the ways in which the chemistry in the boundary layer and the upper troposphere were influenced by vertical transport in convective clouds

Projectile Coulomb excitation with fast radioactive beams

5 pages, 5 figures, 1 table.-- PACS nrs.: 23.20.Ck; 27.20.+n.We report a search for γ rays emanating from Coulomb excitation of fast (30-46 MeV/u) radioactive projectiles He-8, Be-11, Be-12, Be-14 interacting with a lead target. These are clearly identified by their Doppler shift. The 320 keV 1/2(-) --> 1/2(+)γ transition from Be-11 was observed with a cross-section of 191 ± 26 mb which is noticeably less than expected from the known lifetime and in the perturbation limit of pure Coulomb excitation. In the other nuclei rather stringent upper limits of 0.01 to 0.2 Weisskopf units, are placed on the hypothetical transition to 1(-) states.We would like to thank F. Geoffroy, R. Hue and L. Petizon for their technical assistance during the experiment, N. Alamanos, G. Baur aud C. Bertulani for discussions and R. Lombard for drawing our attention to the Bertlmann-Martin bound. This work was partly supported by la Région Basse Normandie. One of us, G. Schrieder, would like to thank for the support by the German Federal Minister for Research and Technology (BMFT) under contract 06DA641.Peer reviewe