Right Temporoparietal Gray Matter Predicts Accuracy of Social Perception in the Autism Spectrum

Individuals with an autism spectrum disorder (ASD) show hallmark deficits in social perception. These difficulties might also reflect fundamental deficits in integrating visual signals. We contrasted predictions of a social perception and a spatial–temporal integration deficit account. Participants with ASD and matched controls performed two tasks: the first required spatiotemporal integration of global motion signals without social meaning, the second required processing of socially relevant local motion. The ASD group only showed differences to controls in social motion evaluation. In addition, gray matter volume in the temporal–parietal junction correlated positively with accuracy in social motion perception in the ASD group. Our findings suggest that social–perceptual difficulties in ASD cannot be reduced to deficits in spatial–temporal integration

Stronger Neural Modulation by Visual Motion Intensity in Autism Spectrum Disorders

Theories of autism spectrum disorders (ASD) have focused on altered perceptual integration of sensory features as a possible core deficit. Yet, there is little understanding of the neuronal processing of elementary sensory features in ASD. For typically developed individuals, we previously established a direct link between frequency-specific neural activity and the intensity of a specific sensory feature: Gamma-band activity in the visual cortex increased approximately linearly with the strength of visual motion. Using magnetoencephalography (MEG), we investigated whether in individuals with ASD neural activity reflect the coherence, and thus intensity, of visual motion in a similar fashion. Thirteen adult participants with ASD and 14 control participants performed a motion direction discrimination task with increasing levels of motion coherence. A polynomial regression analysis revealed that gamma-band power increased significantly stronger with motion coherence in ASD compared to controls, suggesting excessive visual activation with increasing stimulus intensity originating from motion-responsive visual areas V3, V6 and hMT/V5. Enhanced neural responses with increasing stimulus intensity suggest an enhanced response gain in ASD. Response gain is controlled by excitatory-inhibitory interactions, which also drive high-frequency oscillations in the gamma-band. Thus, our data suggest that a disturbed excitatoryinhibitory balance underlies enhanced neural responses to coherent motion in ASD

Density of conjugated antibody determines the extent of Fc receptor dependent capture of nanoparticles by liver sinusoidal endothelial cells

Despite considerable progress in the design of multifunctionalized nanoparticles (NPs) that selectively target specific cell types, their systemic application often results in unwanted liver accumulation. The exact mechanisms for this general observation are still unclear. Here we asked whether the number of cell-targeting antibodies per NP determines the extent of NP liver accumulation and also addressed the mechanisms by which antibody-coated NPs are retained in the liver. We used polysarcosine-based peptobrushes (PBs), which in an unmodified form remain in the circulation for >24 h due to the absence of a protein corona formation and low unspecific cell binding, and conjugated them with specific average numbers (2, 6, and 12) of antibodies specific for the dendritic cell (DC) surface receptor, DEC205. We assessed the time-dependent biodistribution of PB-antibody conjugates by in vivo imaging and flow cytometry. We observed that PB-antibody conjugates were trapped in the liver and that the extent of liver accumulation strongly increased with the number of attached antibodies. PB-antibody conjugates were selectively captured in the liver via Fc receptors (FcR) on liver sinusoidal endothelial cells, since systemic administration of FcR-blocking agents or the use of F(ab')2 fragments prevented liver accumulation. Cumulatively, our study demonstrates that liver endothelial cells play a yet scarcely acknowledged role in liver entrapment of antibody-coated NPs and that low antibody numbers on NPs and the use of F(ab')2 antibody fragments are both sufficient for cell type-specific targeting of secondary lymphoid organs and necessary to minimize unwanted liver accumulation.Drug Delivery Technolog

Bulk ion heating with ICRH in JET DT plasmas

Reactor relevant ICRH scenarios have been assessed during DT experiments on the JET tokamak using H mode divertor discharges with ITER-like shapes and safety factors. Deuterium minority heating in tritium plasmas was demonstrated for the first time. For 9% deuterium, an ICRH power of 6 MW gave 1.66 MW of fusion power from reactions between suprathermal deuterons and thermal tritons. The Q value of the steady state discharge reached 0.22 for the length of the RF flat-top (2.7 s), corresponding to three plasma energy replacement times. The Doppler broadened neutron spectrum showed a deuteron energy of 125 keV, which was optimum for fusion and close to the critical energy. Thus, strong bulk ion heating was obtained at the same time as high fusion efficiency. Deuterium fractions around 20% produced the strongest ion heating together with a strong reduction of the suprathermal deuteron tail. The ELMs had low amplitude and high frequency and each ELM transported less plasma energy content than the 1% required by ITER. The energy confinement time, on the ITERH97-P scale, was 0.90, which is sufficient for ignition in ITER. 3He minority heating, in approximately 50:50 D:T plasmas with up to 10% 3He, also demonstrated strong bulk ion heating. Central ion temperatures up to 13 keV were achieved, together with central electron temperatures up to 12 keV. The normalized H mode confinement time was 0.95. Second harmonic tritium heating produced energetic tritons above the critical energy. This scheme heats the electrons in JET, unlike in ITER where the lower power density will allow mainly ion heating. The inverted scenario of tritium minority ICRH in a deuterium plasma was demonstrated as a successful heating method producing both suprathermal neutrons and bulk ion heating. Theoretical calculations of the DT reactivity mostly give excellent agreement with the measured reaction rates

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome