Individuals with Williams Syndrome (WS) or Downs Syndrome (DS) are often described as hypersociable, friendly and overly trusting of others. This hypersociability is a major concern for parents/caregivers due to the associated increased risk of exploitation and victimisation. Two brain regions - the amygdala and the orbitofrontal cortex (OFC) - have been implicated in driving this hypersociability in WS, and in the general population and have associations with emotional evaluation, threat detection and social motivation. However, there has been little neuroimaging research on this topic, especially in DS, to date. The aim of the present study was to investigate the potential neuroanatomical and neuropsychological correlates of hypersociability in WS and DS. Twelve individuals with WS (M = 22 years of age) and eleven individuals with DS (M = 26 years of age) completed a neuropsychological battery of executive functioning and social measures, including informant ratings on an ecologically measure of social approach. Clinical groups and twelve typically developing controls (M = 23 years) underwent a magnetic resonance imaging scan to investigate volumetric differences in the OFC and the amygdala. As expected, WS individuals displayed the highest overall social approach, especially in relation to need to approach strangers and drive to interact with strangers, as well as inappropriate/overfriendly behaviours. Both groups rated similarly in terms of social trust and unconditional positive regard. Emotion recognition abilities were similar across groups, with the DS group displaying some difficulties with negative emotions (especially anger). Inhibition and flexibility were similarly impaired across WS and DS. Compared to neurotypical controls, the DS group showed increased amygdala volumes bilaterally, while the WS group showed an enlarged right medial OFC. Approach ratings were significantly correlated with left amygdala and medial and left lateral OFC volumes in WS, and with these same regions bilaterally in DS. Results provide potential biological explanations for the hypersociability seen in WS and DS. Future research should focus on other potential neural correlates, as well as potential genetic and hormonal contributions to approach.

Research must be well designed, properly conducted and clearly and transparently reported. Our independent medical research institute wanted a simple, generic tool to assess the quality of the research conducted by its researchers, with the goal of identifying areas that could be improved through targeted educational activities. Unfortunately, none was available, thus we devised our own. Here, we report development of the Quality Output Checklist and Content Assessment (QuOCCA), and its application to publications from our institute’s scientists. Following consensus meetings and external review by statistical and methodological experts, 11 items were selected for the final version of the QuOCCA: research transparency (items 1–3), research design and analysis (items 4–6) and research reporting practices (items 7–11). Five pairs of raters assessed all 231 articles published in 2017 and 221 in 2018 by researchers at our institute. Overall, the results were similar between years and revealed limited engagement with several recommended practices highlighted in the QuOCCA. These results will be useful to guide educational initiatives and their effectiveness. The QuOCCA is brief and focuses on broadly applicable and relevant concepts to open, high-quality, reproducible and well-reported science. Thus, the QuOCCA could be used by other biomedical institutions and individual researchers to evaluate research publications, assess changes in research practice over time and guide the discussion about high-quality, open science. Given its generic nature, the QuOCCA may also be useful in other research disciplines.

It is challenging to determine which patients with obstructive sleep apnea (OSA) have impaired driving ability. Vulnerability to this neurobehavioral impairment may be explained by lower brain metabolites levels involved in mitochondrial metabolism. This study compared markers of brain energy metabolism in OSA patients identified as vulnerable vs resistant to driving impairment following extended wakefulness. 44 patients with moderate‐severe OSA underwent 28hr extended wakefulness with three 90min driving simulation assessments. Using a two‐step cluster analysis, objective driving data (steering deviation and crashes) from the 2nd driving assessment (22.5 h awake) was used to categorise patients into vulnerable (poor driving, n = 21) or resistant groups (good driving, n = 23). 1H magnetic resonance spectra were acquired at baseline using two scan sequences (short echo PRESS and longer echo‐time asymmetric PRESS), focusing on key metabolites, creatine, glutamate, N‐acetylaspartate (NAA) in the hippocampus, anterior cingulate cortex and left orbito‐frontal cortex. Based on cluster analysis, the vulnerable group had impaired driving performance compared with the resistant group and had lower levels of creatine (PRESS p = ns, APRESS p = 0.039), glutamate, (PRESS p < 0.01, APRESS p < 0.01), NAA (PRESS p = 0.038, APRESS p = 0.035) exclusively in the left orbito‐frontal cortex. Adjusted analysis, higher glutamate was associated with a 21% (PRESS) and 36% (APRESS) reduced risk of vulnerable classification. Brain mitochondrial bioenergetics in the frontal brain regions are impaired in OSA patients who are vulnerable to driving impairment following sleep loss. These findings provide a potential way to identify at risk OSA phenotype when assessing fitness to drive, but this requires confirmation in larger future studies.

Abstract The most aggressive B-cell lymphomas frequently manifest extranodal distribution and carry somatic mutations in the poorly characterized gene TBL1XR1. Here, we show that TBL1XR1 mutations skew the humoral immune response towards generating abnormal immature memory B-cells (MB), while impairing plasma cell differentiation. At the molecular level, TBL1XR1 mutants co-opt SMRT/HDAC3 repressor complexes towards binding the MB cell transcription factor (TF) BACH2, at the expense of the germinal center (GC) TF BCL6, leading to pre-memory transcriptional reprogramming and cell-fate bias. Upon antigen recall, TBL1XR1 mutant MB cells fail to differentiate into plasma cells and instead preferentially reenter new GC reactions, providing evidence for a cyclic re-entry lymphomagenesis mechanism. Ultimately, TBL1XR1 alterations lead to a striking extranodal immunoblastic lymphoma phenotype that mimics the human disease. Both human and murine lymphomas feature expanded MB-like cell populations, consistent with a MB-cell origin and delineating an unforeseen pathway for malignant transformation of the immune system. Citation Format: Leandro Venturutti, Matt Teater, Andrew Zhai, Amy Chadburn, Leena Babiker, Daleum Kim, Louis Staudt, Michael Green, Pedro Farinha, Andrew Weng, Christian Steidl, Ryan Morin, David Scott, Gil Privé, Ari Melnick. TBL1XR1 mutations drive extranodal lymphomagenesis by inducing a protumorigenic memory B-cell fate [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-42.

Objectives:To evaluate brain metabolites in objective insomnia subtypes defined from polysomnography (PSG): insomnia with short sleep duration (I-SSD) and insomnia with normal sleep duration (I-NSD), relative to good sleeping controls (GSCs).Methods:PSG empirically grouped insomnia patients into I-SSD (n = 12: mean [SD] total sleep time [TST] = 294.7 minutes [30.5]) or I-NSD (n = 19: TST = 394.4 minutes [34.9]). 1H magnetic resonance spectroscopy (MRS) acquired in the left occipital cortex (LOCC), left prefrontal cortex, and anterior cingulate cortex was used to determine levels of creatine, aspartate, glutamate, and glutamine (referenced to water). Glutathione, glycerophosphocholine, lactate, myoinositol, and N-acetylaspartate measurements were also obtained. Sixteen GSCs were included for comparison. Multivariate analysis of variance was used to evaluate differences in creatine, aspartate, glutamate, and glutamine.Results:Aspartate and glutamine concentrations were reduced in the LOCC in I-SSD compared with I-NSD (both p < .05, d = .80-.99). Creatine displayed a nonsignificant mean reduction in I-SSD compared with I-NSD (p = .05, d = .58). Glutamine was reduced in I-SSD compared with controls (p < .05, d = .93). There were no differences in metabolites between all (I-SSD and I-NSD) insomnia patients and controls. In patients with insomnia, LOCC glutamine concentrations were found to be positively correlated with TST (r = .43, p < .05) and negatively correlated with wake-time after sleep onset (r = -.40, p < .05).Conclusions:Results indicate that I-SSD is associated with reduced brain metabolites in the LOCC compared with I-NSD and control concentrations of aspartate, glutamine, and creatine.Clinical Trial Registration:Insomnia MRS imaging sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000050853.Trial Identification Number:12612000050853.

The objective of the current study was to quantify the degree of white matter (WM) abnormalities in chronic and virally suppressed HIV-infected (HIV+) persons while carefully taking into account demographic and disease factors. Diffusion tensor imaging (DTI) was conducted in 40 HIV− and 82 HIV+ men with comparable demographics and life style factors. The HIV+ sample was clinically stable with successful viral control. Diffusion was measured across 32 non-colinear directions with a b -value of 1000 s/mm 2 ; fractional anisotropy (FA) and mean diffusivity (MD) maps were quantified with Itrack IDL. Using the ENIGMA DTI protocol, FA and MD values were extracted for each participant and in 11 skeleton regions of interest (SROI) from standard labels in the JHU ICBM-81 atlas covering major striato-frontal and parietal tracks. We found no major differences in FA and MD values across the 11 SROI between study groups. Within the HIV+ sample, we found that a higher CNS penetrating antiretroviral treatment, higher current CD4+ T cell count, and immune recovery from the nadir CD4+ T cell count were associated with increased FA and decreased MD ( p < 0.05–0.006), while HIV duration, symptomatic, and asymptomatic cognitive impairment were associated with decreased FA and increased MD ( p < 0.01–0.004). Stability of HIV treatment and antiretroviral CNS penetration efficiency in addition to current and historical immune recovery were related to higher FA and lower MD ( p = 0.04– p < 0.01). In conclusion, WM DTI measures are near normal except for patients with neurocognitive impairment and longer HIV disease duration.

Introduction The report, “A Mixed Bag”, published by NCEPOD in 2010 was a review of Parenteral Nutrition (PN) in hospitalised patients. It demonstrated that only 19% of adults received care deemed to represent good clinical practice. Particular attention was drawn to poor documentation of nutritional issues. Aims/Background To audit the administration of Parenteral Nutrition within the RVH, Belfast in direct comparison with NCEPOD report and to identify where discrepancies existed. Method Consecutive patients started on PN at the time of the NCEPOD report were identified using pharmacy records. Each patient's medical, dietetic and nutrition nursing notes were independently reviewed using the NCEPOD PN Questionnaire. Results 27 patients were identified with patients excluded due to missing casenotes. No treatment goal was documented for 89% of patients. Twelve percent of patients had PN started at a weekend, refeeding risk was not documented for these patients but was for all others. The initial bag was inappropriate for patient needs in 17%, the majority of these started at the weekend. While combining records revealed good clinical monitoring, this was poor in medical notes compared with dietetic/nursing records. Metabolic complications occurred in 39%, similar to NCEPOD. There was a universal lack of documentation regarding central venous catheter insertion. Figure 1 Figure 2 Conclusion Our audit reiterates the findings of the NCEPOD report, with particular regard to documentation and complications. Patients started at the weekend appeared to have poorer documentation. The development of a PN proforma or clinical check list may be useful to identify and reduce risks/complications.

Physiological and pathological changes to the anisotropic mechanical properties of skeletal muscle are still largely unknown, with only a few studies quantifying changes in vivo. This study used the noninvasive MR elastography (MRE) technique, in combination with diffusion tensor imaging (DTI), to measure shear modulus anisotropy in the human skeletal muscle in the lower leg. Shear modulus measurements parallel and perpendicular to the fibre direction were made in 10 healthy subjects in the medial gastrocnemius, soleus and tibialis anterior muscles. The results showed significant differences in the medial gastrocnemius (μ‖ =0.86 ± 0.15 kPa; μ⊥ = 0.66 ± 0.19 kPa, P < 0.001), soleus (μ‖ = 0.83 ± 0.22 kPa; μ⊥ = 0.65 ± 0.13 kPa, P < 0.001) and the tibialis anterior (μ‖ = 0.78 ± 0.24 kPa; μ⊥ = 0.66 ± 0.16 kPa, P = 0.03) muscles, where the shear modulus measured in the direction parallel is greater than that measured in the direction perpendicular to the muscle fibres. No significant differences were measured across muscle groups. This study provides the first direct estimates of the anisotropic shear modulus in the triceps surae muscle group, and shows that the technique may be useful for the probing of mechanical anisotropy changes caused by disease, aging and injury. Copyright © 2013 John Wiley & Sons, Ltd.

Muscle stiffness has been reported to increase following eccentric muscle exercise, but to date only indirect methods have been used to measure it. This study aimed to use Magnetic Resonance Elastography (MRE), a noninvasive imaging technique, to assess the time‐course of passive elasticity changes in the medial gastrocnemius and soleus muscles before and after a bout of eccentric exercise. Shear storage modulus ( G ′) and loss modulus ( G ′′) measurements were made in eight healthy subjects for both muscles in vivo before, one hour after, 48 hours after and 1 week after eccentric exercise. The results show a 21% increase in medial gastrocnemius storage modulus following eccentric exercise with a peak occurring ~48 hours after exercise (before exercise 1.15 ± 0.23 kPa, 48 hours after 1.38 ± 0.27 kPa). No significant changes in soleus muscle storage modulus were measured for the exercise protocol used in this study, and no significant changes in loss modulus were observed. This study provides the first direct measurements in skeletal muscle before and after eccentric exercise damage and suggests that MRE can be used to detect the time course of changes to muscle properties. Copyright © 2012 John Wiley & Sons, Ltd.

Purpose: To investigate the anisotropic elasticity of soft tissues using MR elastography (MRE) combined with diffusion tensor imaging (DTI). Materials and Methods: The storage moduli parallel (mu?) and perpendicular (mu?) to the local fiber orientation were calculated assuming a transversely isotropic model. The local fiber orientation was provided by DTI. The proposed technique was validated against rheometry using anisotropic viscoelastic phantoms with various fiber volume fractions (Vf = 0%, 15%, and 35%) and bovine skeletal muscle samples. Results: The anisotropic ratio (mu?/mu?) as measured by MRE correlated well with rheometry for all samples (R2 = 0.809). The combined MRE/DTI technique was also able to differentiate different levels of mechanical anisotropy with the mechanical anisotropy (mu?/mu?) of the Vf = 35% phantoms being significantly higher than the Vf = 15% and the isotropic (Vf = 0%) phantoms. The bovine muscle samples showed significantly higher mechanical anisotropy than all phantoms. Conclusion: This study has demonstrated the feasibility of the proposed imaging technique for characterizing mechanical anisotropy of anisotropic materials and biological tissues, and validated the mechanical anisotropy results. J. Magn. Reson. Imaging 2013;37:217226. (c) 2012 Wiley Periodicals, Inc.

Accurate mechanical properties of tissues are essential for inclusion in computational models of impact injury. High quality large deformation (i.e. nonlinearly viscoelastic) tissue properties at high strain rates relevant to injury are limited in literature and this is mostly due to the complexities characterizing nonlinear viscoelastic properties past the linear viscoelastic limit, and experimental challenges at high loading rates. The authors suggest a method of combining static compressive preload and high frequency shear strain to understand large deformation tissue properties in vivo. The authors investigated this method in stages, combining ex vivo rheometry and Magnetic Resonance Elastography (MRE) tests under static preload, and also demonstrated proof of principle in in vivo MRE data.

Traditional magnetic resonance elastography (MRE) applies small amplitude vibration to tissues. Thus currently MRE measures only the small deformation behaviour of tissues. MRE has the potential to estimate the strain-varying shear modulus of soft tissues, if applied at different static strains, which may allow prediction of the large-strain behaviour of tissues. This study uses MRE of bovine liver specimens under various levels of static compressive pre-strain up to 30%. Storage and loss moduli measured using MRE increased non-linearly with static compressive pre-strain, and exponential models fit well to these data to describe this relationship (R(2)>0.93). Based on these models, a 10% linear compression of liver would result in a 47% overestimate of the 'true' storage modulus of the uncompressed tissue. The results of this study have implications for MRE transducer design and interpretation of results from in vivo MRE studies.

Background: The cerebellum has never been mechanically characterised, despite its physiological importance in the control of motion and the clinical prevalence of cerebellar pathologies. The aim of this study was to measure the linear viscoelastic properties of the cerebellum in human volunteers using Magnetic Resonance Elastography (MRE).Methods: Coronal plane brain 3D MRE data was performed on eight healthy adult volunteers, at 80 Hz, to compare the properties of cerebral and cerebellar tissues. The linear viscoelastic storage (G') and loss moduli (G '') were estimated from the MRE wave images by solving the wave equation for propagation through an isotropic linear viscoelastic solid. Contributions of the compressional wave were removed via application of the curl-operator.Results: The storage modulus for the cerebellum was found to be significantly lower than that for the cerebrum, for both white and grey matter. Cerebrum: white matter (mean +/- SD) G'=2.41 +/- 0.23 kPa, grey matter G'=2.34 +/- 0.22 kPa; cerebellum: white matter, G'=1.85 +/- 0.18 kPa, grey matter G'=1.77 +/- 0.24 kPa; cerebrum vs cerebellum, p<0.001. For the viscous behaviour, there were differences in between regions and also by tissue type, with the white matter being more viscous than grey matter and the cerebrum more viscous than the cerebellum. Cerebrum: white matter G ''=1.21 +/- 0.21 kPa, grey matter G ''=1.11 +/- 0.03 kPa; cerebellum: white matter G ''=1.1 +/- 0.23 kPa, grey matter G ''=0.94 +/- 0.17 kPa.Discussion: These data represent the first available data on the viscoelastic properties of cerebellum, which suggest that the cerebellum is less physically stiff than the cerebrum, possibly leading to a different response to mechanical loading. These data will be useful for modelling of the cerebellum for a range of purposes. (C) 2011 Elsevier Ltd. All rights reserved.

Biomechanical properties of the human tongue are needed for finite element models of the upper airway and may be important to elucidate the pathophysiology of obstructive sleep apneoa. Tongue viscoelastic properties have not been characterized previously. Magnetic resonance elastography (MRE) is an emerging imaging technique that can measure the viscoelastic properties of soft tissues in-vivo. In this study, MRE was used to measure the viscoelastic properties of the tongue and soft palate in 7 healthy volunteers during quiet breathing. Results show that the storage shear modulus of the tongue and soft palate is 2.67±0.29 and 2.53±0.31 kPa (mean ± SD), respectively. This is the first study to investigate the mechanical properties of the tongue using MRE, and it provides necessary data for future studies of patient groups with altered upper airway function.

A 1.5T full-body MRI scanner acquires high resolution T2 and MRE images. A transducer consisting of two coaxial coils is driven by a signal generator, mounted onto a standard head-coil and triggered by the MR spectrometer (Philips Medical Systems). The vibrations are transmitted to the brain using a bite-bar and personalised, moulded mouthguard for coupling. An excitation of 80Hz was used to optimise wave penetration while maintaining attenuation at a reasonable level. An optimised motion-sensitized, spin-echo sequence, including double motion encoding gradients is phase-locked to the mechanical excitation to image 3D steady-state displacements fields. A full 3D reconstruction of the viscoelastic parameters (complex-valued shear modulus) was applied with optimised filtering and application of the curl operator [9] to remove longitudinal wave contributions. Results High resolution brain images were obtained in the coronal plane to include both cerebral hemispheres and the cerebellum as shown in an example T2weighted slice image in Fig 1a. An excitation frequency of 80 Hz transmitted waves to the brain tissue. Fig 1b shows an example displacement image in the s-direction at an arbitrary time point. Total mechanical wave amplitudes were in the range of 2 – 25 µm (Fig 1c) and resulted in wavelengths of 6 – 20 mm (Fig 1d). Storage (Gd) and loss (Gl) moduli maps (Fig 1e, f) were reconstructed and average storage moduli across all volunteers for grey (1.42 kPa) and white (1.34 kPa) matter in the cerebrum were measured. Storage moduli were also measured in the cerebellum for grey and white matter (1.10 kPa and 1.14 kPa) and were observed to be lower than in the cerebrum with only grey matter showing a significant difference (P=0.001). Discussion MR Elastography images acquired in the coronal plane enabled measurements to be made in the left and right cerebral hemispheres and compare directly with measurements in the cerebellum. Viscoelastic properties of the cerebellum appear slightly lower than in the cerebrum with a significant difference appearing in grey matter. The latest high resolution brain MR-elastography images have resulted in lower viscoelastic measurements than previously reported possibly due to a different imaging plane compared to published data in the transverse orientation. The latest measurements also have a significant increase in phase stability of mechanical excitation due to individualized, moulded mouthguards. This, along with increased spatial resolution has revealed more structural details which may decrease measured values due to higher reflections. References

Magnetic resonance elastography (MRE) is a non-invasive imaging technique used to visualise and quantify mechanical properties of tissue, providing information beyond what can be currently achieved with standard MR sequences and could, for instance, provide new insight into pathological processes in the brain. This study uses the MRE technique at 3 T to extract the complex shear modulus for in vivo brain tissue utilizing a full three-dimensional approach to reconstruction, removing contributions of the dilatational wave by application of the curl operator. A calibrated phantom is used to benchmark the MRE measurements, and in vivo results are presented for healthy volunteers. The results provide data for in vivo brain storage modulus (G'), finding grey matter (3.1 kPa) to be significantly stiffer than white matter (2.7 kPa). The first in vivo loss modulus (G'') measurements show no significant difference between grey matter (2.5 kPa) and white matter (2.5 kPa).