Motion-corrected multiparametric renal arterial spin labelling at 3T: Reproducibility and effect of vasodilator challenge

Objectives We investigated the feasibility and reproducibility of free-breathing motion-corrected multiple inversion time (multi-TI) pulsed renal arterial spin labelling (PASL), with general kinetic model parametric mapping, to simultaneously quantify renal perfusion (RBF), bolus arrival time (BAT) and tissue T1. Methods In a study approved by the Health Research Authority, 12 healthy volunteers (mean age, 27.6 ± 18.5 years; 5 male) gave informed consent for renal imaging at 3 T using multi-TI ASL and conventional single-TI ASL. Glyceryl trinitrate (GTN) was used as a vasodilator challenge in six subjects. Flow-sensitive alternating inversion recovery (FAIR) preparation was used with background suppression and 3D-GRASE (gradient and spin echo) read-out, and images were motion-corrected. Parametric maps of RBF, BAT and T1 were derived for both kidneys. Agreement was assessed using Pearson correlation and Bland-Altman plots. Results Inter-study correlation of whole-kidney RBF was good for both single-TI (r2 = 0.90), and multi-TI ASL (r2 = 0.92). Single-TI ASL gave a higher estimate of whole-kidney RBF compared to multi-TI ASL (mean bias, 29.3 ml/min/100 g; p <0.001). Using multi-TI ASL, the median T1 of renal cortex was shorter than that of medulla (799.6 ms vs 807.1 ms, p = 0.01), and mean whole-kidney BAT was 269.7 ± 56.5 ms. GTN had an effect on systolic blood pressure (p < 0.05) but the change in RBF was not significant. Conclusions Free-breathing multi-TI renal ASL is feasible and reproducible at 3 T, providing simultaneous measurement of renal perfusion, haemodynamic parameters and tissue characteristics at baseline and during pharmacological challenge

A Systematic Review of How Multiple Stressors from an Extreme Event Drove Ecosystem-Wide Loss of Resilience in an Iconic Seagrass Community

A central question in contemporary ecology is how climate change will alter ecosystem structure and function across scales of space and time. Climate change has been shown to alter ecological patterns from individuals to ecosystems, often with negative implications for ecosystem functions and services. Furthermore, as climate change fuels more frequent and severe extreme climate events (ECEs) like marine heatwaves (MHWs), such acute events become increasingly important drivers of rapid ecosystem change. However, our understanding of ECE impacts is hampered by limited collection of broad scale in situ data where such events occur. In 2011, a MHW known as the Ningaloo Niño bathed the west coast of Australia in waters up to 4°C warmer than normal summer temperatures for almost 2 months over 1000s of kilometres of coastline. We revisit published and unpublished data on the effects of the Ningaloo Niño in the seagrass ecosystem of Shark Bay, Western Australia (24.6 – 26.6o S), at the transition zone between temperate and tropical seagrasses. Therein we focus on resilience, including resistance to and recovery from disturbance across local, regional and ecosystem-wide spatial scales and over the past 8 yearsThermal effects on temperate seagrass health were severe and exacerbated by simultaneous reduced light conditions associated with sediment inputs from record floods in the south-eastern embayment and from increased detrital loads and sediment destabilisation. Initial extensive defoliation of Amphibolis antarctica, the dominant seagrass, was followed by rhizome death that occurred in 60-80% of the bay’s meadows, equating to decline of over 1000 km2 of meadows. This loss, driven by direct abiotic forcing, has persisted, while indirect biotic effects (e.g. dominant seagrass loss) have allowed colonisation of some areas by small fast-growing tropical species (e.g. Halodule uninervis). Those biotic effects also impacted multiple consumer populations including turtles and dugongs, with implications for species dynamics, food web structure, and ecosystem recovery. We show multiple stressors can combine to evoke extreme ecological responses by pushing ecosystems beyond their tolerance. Finally, both direct abiotic and indirect biotic effects need to be explicitly considered when attempting to understand and predict how ECEs will alter marine ecosystem dynamics

Phenotypic expression and outcomes in individuals with rare genetic variants of hypertrophic cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population. OBJECTIVES: The goal of this study was to compare lifetime outcomes and cardiovascular phenotypes according to the presence of rare variants in sarcomere-encoding genes among middle-aged adults. METHODS: This study analyzed whole exome sequencing and cardiac magnetic resonance imaging in UK Biobank participants stratified according to sarcomere-encoding variant status. RESULTS: The prevalence of rare variants (allele frequency <0.00004) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n = 5,712; 1 in 35), and the prevalence of variants pathogenic or likely pathogenic for HCM (SARC-HCM-P/LP) was 0.25% (n = 493; 1 in 407). SARC-HCM-P/LP variants were associated with an increased risk of death or major adverse cardiac events compared with controls (hazard ratio: 1.69; 95% confidence interval [CI]: 1.38-2.07; P < 0.001), mainly due to heart failure endpoints (hazard ratio: 4.23; 95% CI: 3.07-5.83; P < 0.001). In 21,322 participants with both cardiac magnetic resonance imaging and whole exome sequencing, SARC-HCM-P/LP variants were associated with an asymmetric increase in left ventricular maximum wall thickness (10.9 ± 2.7 mm vs 9.4 ± 1.6 mm; P < 0.001), but hypertrophy (≥13 mm) was only present in 18.4% (n = 9 of 49; 95% CI: 9%-32%). SARC-HCM-P/LP variants were still associated with heart failure after adjustment for wall thickness (hazard ratio: 6.74; 95% CI: 2.43-18.7; P < 0.001). CONCLUSIONS: In this population of middle-aged adults, SARC-HCM-P/LP variants have low aggregate penetrance for overt HCM but are associated with an increased risk of adverse cardiovascular outcomes and an attenuated cardiomyopathic phenotype. Although absolute event rates are low, identification of these variants may enhance risk stratification beyond familial disease

Selected-area small-angle electron diffraction

Selected-area electron diffraction capable of resolving spacings up to 2000 Å from first-order discrete reflections has been achieved using a standard, double-condenser electron microscope. The technique allows photographing of the selected area, at sufficient magnification, that gives rise to the small-angle scattering pattern, in addition to the normal capabilities of obtaining related wide-angle diffraction and wide-angle and small-angle dark-field micrographs. Most, but not all, of the results of discrete and diffuse, small-angle electron diffraction studies from a large variety of specimens including drawn, annealed polyethylene, latex particles, evaporated gold particles, grating replicas, and slit edges have been explained on the basis of the structures observed in the corresponding electron micrographs. Small-angle electron diffraction is found to be more sensitive to defects in the packing of the scattering centres than small-angle X-ray scattering.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44682/1/10853_2004_Article_BF00562952.pd

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Factors influencing family member perspectives on safety in the intensive care unit: a systematic review

Purpose: Patient safety has developed as a strong marker for healthcare quality. Safety matters are important in the intensive care unit (ICU) where complex clinical decisions are made, intensive technology is used, and families hold a unique role. The aim of this review was to identify and describe factors that influence family member's perceptions of safety in the adult ICU. Data sources: Searches were conducted between September and November 2018 and repeated in July 2020 using CINAHL, MEDLINE (EBSCO), PubMed and PsycINFO databases. Study selection: Published primary studies undertaken in adult ICUs and involving adult family member participants exploring safety or feeling safe. No date restrictions were applied. Data extraction: A data extraction form collected information about sample, study design, data collection methods and results from each paper. Methodological quality was assessed using the QualSyst tools for qualitative and quantitative studies. Narrative synthesis was undertaken. Results of data synthesis: Twenty papers were included with 11 papers published since 2010. The majority of papers reported on qualitative studies (n = 16). Four factors were identified that influenced whether family members felt that the patient was safe in ICU: family visiting, information and communication, caring and professional competence. Conclusion: In detailing specific practices that make families feel safe and unsafe in ICU, these review findings provide a structure for clinicians, educators and researchers to inform future work and gives opportunity for the family role in patient safety to be reconsidered.This article is available to RD&E staff via NHS OpenAthens (subject to publisher embargo). Click on the Publisher URL, and log in with NHS OpenAthens if prompted.published version, accepted version (12 month embargo), submitted versio

#Disgusted: Identifying potential sub-factors of Moral Disgust through Reflexive Thematic Analysis of Tweets

Social media provides an untapped resource for exploring Moral Disgust. We therefore drew on ‘tweets’ about Moral Disgust (k=526) to better conceptualise the situations, people, and concepts users found Disgusting. Our Reflexive Thematic Analysis identified two themes and accompanying subthemes: Hierarchical Disgust and Third-Party Disgust. Hierarchical Disgust was constructed from expressions of Disgust directed to power structures, abuses of power, and leaders, whereas Third-Party Disgust comprised expressions directed at negative outcomes for others, often in the form of discrimination or harm. Both themes served as a form of group protection through out-group distancing and normative in-group policing. Importantly, this research extends classic Disgust literature (e.g., Tybur et al., 2013), presenting a novel approach to naturalistic data collection and providing future researchers with an approach to study other emotions, beliefs, and subjects that are expressed online

Short-term Responses of Posidonia australis to Changes in Light Quality

Seagrass meadows are highly productive ecosystems that provide ecosystem services to the coastal zone but are declining globally, particularly due to anthropogenic activities that reduce the quantity of light reaching seagrasses, such as dredging, river discharge and eutrophication. Light quality (the spectral composition of the light) is also altered by these anthropogenic stressors as the differential attenuation of wavelengths of light is caused by materials within the water column. This study addressed the effect of altered light quality on different life-history stages of the seagrass Posidonia australis, a persistent, habitat-forming species in Australia. Aquarium-based experiments were conducted to determine how adult shoots and seedlings respond to blue (peak λ = 451 nm); green (peak λ = 522 nm); yellow (peak λ = 596 nm) and red (peak λ = 673 nm) wavelengths with a control of full-spectrum light (λ = 400 – 700 nm, at 200 μmol photons m-2 s-1). Posidonia australis adults did not respond to changes in light quality relative to full-spectrum light, demonstrating a capacity to obtain enough photons from a range of wavelengths across the visible spectrum to maintain short-term growth at high irradiances. Posidonia australis seedlings (&lt;4 months old) grown in blue light showed a significant increase in xanthophyll concentrations when compared to plants grown in full-spectrum, demonstrating a pigment acclimation response to blue light. These results differed significantly from negative responses to changes in light quality recently described for Halophila ovalis, a colonizing seagrass species. Persistent seagrasses such as P. australis, appear to be better at tolerating short-term changes in light quality compared to colonizing species when sufficient PPFD is present