37 research outputs found

    Quantitative rotating frame relaxometry methods in MRI

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    Macromolecular degeneration and biochemical changes in tissue can be quantified using rotating frame relaxometry in MRI. It has been shown in several studies that the rotating frame longitudinal relaxation rate constant (R1ρ) and the rotating frame transverse relaxation rate constant (R2ρ) are sensitive biomarkers of phenomena at the cellular level. In this comprehensive review, existing MRI methods for probing the biophysical mechanisms that affect the rotating frame relaxation rates of the tissue (i.e. R1ρ and R2ρ) are presented. Long acquisition times and high radiofrequency (RF) energy deposition into tissue during the process of spin-locking in rotating frame relaxometry are the major barriers to the establishment of these relaxation contrasts at high magnetic fields. Therefore, clinical applications of R1ρ and R2ρ MRI using on- or off-resonance RF excitation methods remain challenging. Accordingly, this review describes the theoretical and experimental approaches to the design of hard RF pulse cluster- and adiabatic RF pulse-based excitation schemes for accurate and precise measurements of R1ρ and R2ρ. The merits and drawbacks of different MRI acquisition strategies for quantitative relaxation rate measurement in the rotating frame regime are reviewed. In addition, this review summarizes current clinical applications of rotating frame MRI sequences. © 2016 John Wiley & Sons, Ltd

    Site fertility drives temporal turnover of vegetation at high latitudes

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    Experimental evidence shows that site fertility is a key modulator underlying plant community changes under climate change. Communities on fertile sites, with species having fast dynamics, have been found to react more strongly to climate change than communities on infertile sites with slow dynamics. However, it is still unclear whether this generally applies to high-latitude plant communities in natural environments at broad spatial scales. We tested a hypothesis that vegetation of fertile sites experiences greater changes over several decades and thus would be more responsive under contemporary climate change compared to infertile sites that are expected to show more resistance. We resurveyed understorey communities (vascular plants, bryophytes, and lichens) of four infertile and four fertile forest sites along a latitudinal bioclimatic gradient. Sites had remained outside direct human disturbance. We analyzed the magnitude of temporal community turnover, changes in the abundances of plant morphological groups and strategy classes, and changes in species diversity. In agreement with our hypothesis, temporal turnover of communities was consistently greater on fertile sites compared to infertile sites. However, our results suggest that the larger turnover of fertile communities is not primarily related to the direct effects of climatic warming. Furthermore, community changes in both fertile and infertile sites showed remarkable variation in terms of shares of plant functional groups and strategy classes and measures of species diversity. This further emphasizes the essential role of baseline environmental conditions and nonclimatic drivers underlying vegetation changes. Our results show that site fertility is a key determinant of the overall rate of high-latitude vegetation changes but the composition of plant communities in different ecological contexts is variously impacted by nonclimatic drivers over time.Peer reviewe

    Clinical patterns in asthma based on proximal and distal airway nitric oxide categories

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    <p>Abstract</p> <p>Background</p> <p>The exhaled nitric oxide (eNO) signal is a marker of inflammation, and can be partitioned into proximal [J'aw<sub>NO </sub>(nl/s), maximum airway flux] and distal contributions [CA<sub>NO </sub>(ppb), distal airway/alveolar NO concentration]. We hypothesized that J'aw<sub>NO </sub>and CA<sub>NO </sub>are selectively elevated in asthmatics, permitting identification of four inflammatory categories with distinct clinical features.</p> <p>Methods</p> <p>In 200 consecutive children with asthma, and 21 non-asthmatic, non-atopic controls, we measured baseline spirometry, bronchodilator response, asthma control and morbidity, atopic status, use of inhaled corticosteroids, and eNO at multiple flows (50, 100, and 200 ml/s) in a cross-sectional study design. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J'aw<sub>NO </sub>and CA<sub>NO</sub>.</p> <p>Results</p> <p>J'aw<sub>NO </sub>was not correlated with CA<sub>NO</sub>, and thus asthmatic subjects were grouped into four eNO categories based on upper limit thresholds of non-asthmatics for J'aw<sub>NO </sub>(≄ 1.5 nl/s) and CA<sub>NO </sub>(≄ 2.3 ppb): Type I (normal J'aw<sub>NO </sub>and CA<sub>NO</sub>), Type II (elevated J'aw<sub>NO </sub>and normal CA<sub>NO</sub>), Type III (elevated J'aw<sub>NO </sub>and CA<sub>NO</sub>) and Type IV (normal J'aw<sub>NO </sub>and elevated CA<sub>NO</sub>). The rate of inhaled corticosteroid use (lowest in Type III) and atopy (highest in Type II) varied significantly amongst the categories influencing J'aw<sub>NO</sub>, but was not related to CA<sub>NO</sub>, asthma control or morbidity. All categories demonstrated normal to near-normal baseline spirometry; however, only eNO categories with increased CA<sub>NO </sub>(III and IV) had significantly worse asthma control and morbidity when compared to categories I and II.</p> <p>Conclusions</p> <p>J'aw<sub>NO </sub>and CA<sub>NO </sub>reveal inflammatory categories in children with asthma that have distinct clinical features including sensitivity to inhaled corticosteroids and atopy. Only categories with increase CA<sub>NO </sub>were related to poor asthma control and morbidity independent of baseline spirometry, bronchodilator response, atopic status, or use of inhaled corticosteroids.</p

    Methodologies for Assessing the Acceptability of Oral Formulations among children and older adults: A Systematic Review

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    This is an open access article distributed under the terms and conditions of the Creative Commons Attribution NonCommercial-NoDerivatives 4.0 International CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Acceptability of medicinal products in children and older populations is pivotal in ensuring adherence and therapeutic outcomes. This review systematically identifies studies reporting on formulation aspects of oral medications that affect their acceptability in these patient groups. Particular emphasis is placed on the evaluation of the methodologies employed in the studies. Sixty-eight studies were included for analysis, with 51 (75%) in children and 17 (25%) in older populations. The studies evaluated a range of oral formulations; however, the methodologies used differ considerably in participants’ characteristics, study settings, tools, acceptability definitions and criteria. It is evident that there is a lack of standardisation in study design as well as the assessment methods used in assessing acceptability of medicines in children and older populations. This review presents a systematic analysis on methods employed for assessing acceptability of oral medicines in children and older adults, to provide insights and recommendations regarding the design of reliable instruments in future studies.Peer reviewe
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