Cardiac motion results in image artefacts and quantification errors in many cardiovascular magnetic resonance (CMR) techniques, including microstructural assessment using diffusion tensor ...cardiovascular magnetic resonance (DT‐CMR). Here, we develop a CMR‐compatible isolated perfused porcine heart model that allows comparison of data obtained in beating and arrested states. Ten porcine hearts (8/10 for protocol optimisation) were harvested using a donor heart retrieval protocol and transported to the remote CMR facility. Langendorff perfusion in a 3D‐printed chamber and perfusion circuit re‐established contraction. Hearts were imaged using cine, parametric mapping and STEAM DT‐CMR at cardiac phases with the minimum and maximum wall thickness. High potassium and lithium perfusates were then used to arrest the heart in a slack and contracted state, respectively. Imaging was repeated in both arrested states. After imaging, tissue was removed for subsequent histology in a location matched to the DT‐CMR data using fiducial markers. Regular sustained contraction was successfully established in six out of 10 hearts, including the final five hearts. Imaging was performed in four hearts and one underwent the full protocol, including colocalised histology. The image quality was good and there was good agreement between DT‐CMR data in equivalent beating and arrested states. Despite the use of autologous blood and dextran within the perfusate, T2 mapping results, DT‐CMR measures and an increase in mass were consistent with development of myocardial oedema, resulting in failure to achieve a true diastolic‐like state. A contiguous stack of 313 5‐μm histological sections at and a 100‐μm thick section showing cell morphology on 3D fluorescent confocal microscopy colocalised to DT‐CMR data were obtained. A CMR‐compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent colocalised histology, without the need for onsite preclinical facilities.
A cardiovascular magnetic resonance (CMR)‐compatible isolated perfused beating porcine heart model was developed that allows direct comparison of data acquired in multiple states of contraction between the beating and arrested heart. We describe the development of this model, its successes and failures, including the presence of oedema in the hearts. In this study, microstructural measures were obtained from the porcine hearts using diffusion tensor CMR in the most and least contracted states with subsequent colocalised histology.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The time of arrival of people in Australia is an unresolved question. It is relevant to debates about when modern humans first dispersed out of Africa and when their descendants incorporated genetic ...material from Neanderthals, Denisovans and possibly other hominins. Humans have also been implicated in the extinction of Australia's megafauna. Here we report the results of new excavations conducted at Madjedbebe, a rock shelter in northern Australia. Artefacts in primary depositional context are concentrated in three dense bands, with the stratigraphic integrity of the deposit demonstrated by artefact refits and by optical dating and other analyses of the sediments. Human occupation began around 65,000 years ago, with a distinctive stone tool assemblage including grinding stones, ground ochres, reflective additives and ground-edge hatchet heads. This evidence sets a new minimum age for the arrival of humans in Australia, the dispersal of modern humans out of Africa, and the subsequent interactions of modern humans with Neanderthals and Denisovans.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
This practice-based paper explores the methods of answering the question: what is our collective body? This article offers a case study of collaborative research and seeks to enact a collective body ...as a means of transgressing and occupying individuated neoliberal spaces of higher education. Understanding the processes through which knowledge is collectively built highlights the in-becoming nature of practice-based research and the enabling forces of this inquiry. The methods enacted access a particular rendering of how we understand ourselves as a collective; we answer the question through doing together. The ways we encounter the collective enable understanding around the shifting boundaries of the individual–collective connection, made palpable by a string. Through playful forms of dissent, such as embodied, remembered, and writing encounters, enable connections with others and inspire a refocusing of our individual practices.
Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD) than in healthy controls on postmortem neuropathological evaluation but are more variably observed on ...visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC). Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE) open-access database, were analyzed to compare groups on (1) blinded review of high-resolution T1-weighted research sequences; and (2) quantitative measurement of white matter hypointensity (WMH) volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC), also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A GPR survey was carried out in advance of archaeological excavations at Madjedbebe (formerly known as Malakunanja II), a sandstone rock shelter in western Arnhem Land (Australia) containing numerous ...Aboriginal burials. GPR revealed subsurface patterning of rocks in the shelter deposits and archaeological excavation demonstrated that these were related to burials. Post-excavation, GIS and statistical analysis further elucidated the relationship between the rocks and human burials. This integration of detailed mapping, GPR and excavation afforded the opportunity to test a way to identify unmarked burials using GPR in sandstone rock shelters and to document a marker for burial identification in this region. Application of the methodology developed through this case study provides a useful management tool for Indigenous communities and other heritage practitioners.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Virtual screening of the corporate compound collection yielded compound 1 as a subtype selective muscarinic M1 receptor agonist hit. Initial optimization of the N-capping group of the central ...piperidine ring resulted in compounds 2 and 3 with significantly improved potency and selectivity. Subsequent optimization of substituents on the phenyl ring of the benzimidazolone moiety led to the discovery of novel muscarinic M1 receptor agonists 4 and 5 with excellent potency, general and subtype selectivity, and pharmacokinetic (PK) properties including good central nervous system (CNS) penetration and oral bioavailability. Compound 5 showed robust in vivo activities in animal models of cognition enhancement. The combination of high potency, excellent selectivity, and good PK properties makes compounds 4 and 5 valuable tool compounds for investigating and validating potential therapeutic benefits resulting from selective M1 activation.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Abstract
A
GPR
survey was carried out in advance of archaeological excavations at
M
adjedbebe (formerly known as
M
alakunanja
II
), a sandstone rock shelter in western
A
rnhem
L
and (
A
ustralia) ...containing numerous
A
boriginal burials.
GPR
revealed subsurface patterning of rocks in the shelter deposits and archaeological excavation demonstrated that these were related to burials. Post‐excavation,
GIS
and statistical analysis further elucidated the relationship between the rocks and human burials. This integration of detailed mapping,
GPR
and excavation afforded the opportunity to test a way to identify unmarked burials using
GPR
in sandstone rock shelters and to document a marker for burial identification in this region. Application of the methodology developed through this case study provides a useful management tool for Indigenous communities and other heritage practitioners.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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