A Neuroimaging Preparation Protocol Tailored for Autism.

This paper describes the key basic elements required for a successful multi-parametric MRI data acquisition in awake children with autism. The procedure was designed by taking into account methodological challenges arising from the acquisition of Resting State fMRI (RS fMRI) data, and factors such as cost, time, and staff availability. The ultimate aim was to prepare an imaging preparation protocol with high transferability to the whole autism spectrum, adaptable for use in a multi-site research with multiple time points. As part of a randomized pharmaco-intervention study, 31 children aged 4-10 years with Neurofibromatosis 1 and autism underwent MR imaging at baseline and end of intervention. The protocol consisted of tailored habituation instructions including gradual exposure to scanner noise, a social stories booklet, positive incentive strategies, and Play Therapy support. Success rate for initial acquisition was 71% for GABA+ MR spectroscopy at either location, 87% for perfusion, and 67% for diffusion assessment, and 71% for RS fMRI. Qualitative data indicated that 84% parents found the habituation protocol helpful. LAY SUMMARY: Here we describe a protocol for brain Magnetic Resonance Imaging (MRI) tailored for children with ASD to help reduce stress and avoid sedation during scanning. This procedure can make advanced medical imaging more accessible and promote a better MRI experience for families of children with ASD.

Use of Laser Speckle Contrast Analysis during pelvic surgery in a uterine transplantation model.

AIM: Uterine transplantation (UTx) is proposed for treatment of uterine factor infertility. Our aim was to assess whether Endoscopic Laser Speckle Contrast Analysis (eLASCA) could evaluate pelvic blood flow at anastomotic sites required for sheep and rabbit UTx. RESULTS/METHODOLOGY: eLASCA detected blood flow in rabbit UTx #7 and #9. In sheep UTx #2, #3 and #5, the results allowed us to conclude that blood flow was present in the uterine graft following transplantation; and post-UTx, the animal had heart and respiratory rates, and oxygen saturation compatible with a normal hemodynamic status. CONCLUSION: These preliminary results establish the potential of Laser Speckle Contrast Analysis as noncontact and real-time tool for observation of spatially-resolved blood flow from which other parameters can be derived.

Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA).

Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = - 2.12, p = .055), GABA/Glx ratio (t(12) = - 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration: EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu).

The attentive homunculus: ERP evidence for somatotopic allocation of attention in tactile search.

Our brain constantly receives tactile information from the body's surface. We often only become aware of this information when directing our attention towards the body. Here, we report a study investigating the behavioural and neural response when selecting a target amongst distractor vibrations presented simultaneously to several locations either across the hands or body. Comparable visual search studies have revealed the N2pc as the neural correlate of visual selective attention. Analogously, we describe an enhanced negativity contralateral to the tactile target side. This effect is strongest over somatosensory areas and lasts approximately 200ms from the onset of the somatosensory N140 ERP component. Based on these characteristics we named this electrophysiological signature of attentional tactile target selection during tactile search the N140-central-contralateral (N140cc). Furthermore, we present supporting evince that the N140cc reflects attentional enhancement of target rather than suppression of distractor locations; the component was not reliably altered by distractor but rather by target location changes. Taken together, our findings present a novel electrophysiological marker of tactile search and show how attentional selection of touch operates by mainly enhancing task relevant locations within the somatosensory homunculus.

Comparative evaluation of tigecycline susceptibility testing methods for expanded-spectrum cephalosporin- and carbapenem-resistant gram-negative pathogens.

We evaluated the Vitek2, Etest, and MIC Test Strip (MTS) methods of tigecycline susceptibility testing with 241 expanded-spectrum cephalosporin-resistant and/or carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii clinical isolates by using dry-form broth microdilution (BMD) as the reference method. The MIC(50/90)s were as follows: BMD, 1/4 µg/ml; Vitek2, 4/≥8 µg/ml; Etest, 2/4 µg/ml; MTS, 0.5/2 µg/ml. Vitek2 produced 9.1/21.2% major errors, Etest produced 0.4/0.8% major errors, and MTS produced no major errors but 0.4/3.3% very major errors (FDA/EUCAST breakpoints). Vitek2 tigecycline results require confirmation by BMD or Etest for multidrug-resistant pathogens.