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Abstract The neuromodulator dopamine and excitatory neurotransmitter glutamate have both been implicated in the pathogenesis of psychosis, and dopamine antagonists remain the predominant treatment for psychotic disorders. To date no study has measured the effect of antipsychotics on both of these indices together, in the same population of people with psychosis. Striatal dopamine synthesis capacity (Kicer) and anterior cingulate glutamate were measured using 18F-DOPA positron emission tomography and proton magnetic resonance spectroscopy respectively, before and after at least 5 weeks’ naturalistic antipsychotic treatment in people with first episode psychosis (n = 18) and matched healthy controls (n = 20). The relationship between both measures at baseline and follow-up, and the change in this relationship was analyzed using a mixed linear model. Neither anterior cingulate glutamate concentrations (p = 0.75) nor striatal Kicer (p = 0.79) showed significant change following antipsychotic treatment. The change in relationship between whole striatal Kicer and anterior cingulate glutamate, however, was statistically significant (p = 0.017). This was reflected in a significant difference in relationship between both measures for patients and controls at baseline (t = 2.1, p = 0.04), that was not present at follow-up (t = 0.06, p = 0.96). Although we did not find any effect of antipsychotic treatment on absolute measures of dopamine synthesis capacity and anterior cingulate glutamate, the relationship between anterior cingluate glutamate and striatal dopamine synthesis capacity did change, suggesting that antipsychotic treatment affects the relationship between glutamate and dopamine.

In high-Lundquist-number plasmas, reconnection proceeds via the onset of tearing, followed by a nonlinear phase during which plasmoids continuously form, merge, and are ejected from the current sheet (CS). This process is understood in fully ionized, magnetohydrodynamic plasmas. However, many plasma environments, such as star-forming molecular clouds and the solar chromosphere, are poorly ionized. We use theory and computation to study tearing-mediated reconnection in such poorly ionized systems. In this paper, we focus on the onset and linear evolution of this process. In poorly ionized plasmas, magnetic nulls on scales below v _A,n0 / ν _ni0 , with v _A,n0 the neutral Alfvén speed and ν _ni0 the neutral–ion collision frequency, will self-sharpen via ambipolar diffusion. This sharpening occurs at an increasing rate, inhibiting the onset of reconnection. Once the CS becomes thin enough, however, ions decouple from neutrals and the thinning of the CS slows, allowing the onset of tearing in a time of order ${\nu }_{\mathrm{ni}0}^{-1}$ . We find that the wavelength and growth rate of the mode that first disrupts the forming sheet can be predicted from a poorly ionized tearing dispersion relation; as the plasma recombination rate increases and ionization fraction decreases, the growth rate becomes an increasing multiple of ν _ni0 and the wavelength becomes a decreasing fraction of v _A,n0 / ν _ni0 .

BackgroundContinuous assessment of affective behaviors could improve the diagnosis, assessment and monitoring of chronic mental health and neurological conditions such as depression. However, there are no technologies well suited to this, limiting potential clinical applications.AimTo test if we could replicate previous evidence of hypo reactivity to emotional salient material using an entirely new sensing technique called optomyography which is well suited to remote monitoring.MethodsThirty-eight depressed and 37 controls (≥18, ≤40 years) who met a research diagnosis of depression and an age-matched non-depressed control group. Changes in facial muscle activity over the brow (corrugator supercilli) and cheek (zygomaticus major) were measured whilst volunteers watched videos varying in emotional salience.ResultsAcross all participants, videos rated as subjectively positive were associated with activation of muscles in the cheek relative to videos rated as neutral or negative. Videos rated as subjectively negative were associated with brow activation relative to videos judged as neutral or positive. Self-reported arousal was associated with a step increase in facial muscle activation across the brow and cheek. Group differences were significantly reduced activation in facial muscles during videos considered subjectively negative or rated as high arousal in depressed volunteers compared with controls.ConclusionWe demonstrate for the first time that it is possible to detect facial expression hypo-reactivity in adults with depression in response to emotional content using glasses-based optomyography sensing. It is hoped these results may encourage the use of optomyography-based sensing to track facial expressions in the real-world, outside of a specialized testing environment.

IntroductionPulmonary-resident memory T cells (TRM) and B cells (BRM) orchestrate protective immunity to reinfection with respiratory pathogens. Developing methods for the in situ detection of these populations would benefit both research and clinical settings.MethodsTo address this need, we developed a novel in situ immunolabelling approach combined with clinic-ready fibre-based optical endomicroscopy (OEM) to detect canonical markers of lymphocyte tissue residency in situ in human lungs undergoing ex vivo lung ventilation (EVLV).ResultsInitially, cells from human lung digests (confirmed to contain TRM/BRM populations using flow cytometry) were stained with CD69 and CD103/CD20 fluorescent antibodies and imaged in vitro using KronoScan, demonstrating it’s ability to detect antibody labelled cells. We next instilled these pre-labelled cells into human lungs undergoing EVLV and confirmed they could still be visualised using both fluorescence intensity and lifetime imaging against background lung architecture. Finally, we instilled fluorescent CD69 and CD103/CD20 antibodies directly into the lung and were able to detect TRM/BRM following in situ labelling within seconds of direct intra-alveolar delivery of microdoses of fluorescently labelled antibodies.DiscussionIn situ, no wash, immunolabelling with intra-alveolar OEM imaging is a novel methodology with the potential to expand the experimental utility of EVLV and pre-clinical models.

Zinc transporter 3 (ZnT3) has been implicated in the aetiopathology of schizophrenia. In this pilot study, we tested the hypothesis that the presence of a minor allele of two variants in the gene encoding ZnT3 (SLC30A3) affects brain glutamate and cognitive activity in patients with schizophrenia and bipolar affective disorder. Fifteen patients with schizophrenia (SCZ), 15 with bipolar affective disorder type 2 (BD), and 14 healthy volunteers (HV) were genotyped for two SLC30A3 single nucleotide polymorphisms (rs11126936 and rs11126929). They also underwent structural and functional MRI (n-back) imaging as well as static (PRESS) and functional magnetic resonance spectroscopy (n-back) on a 3 Tesla MRI system. SCZ with at least one copy of the minor allele showed reductions in dorsal anterior cingulate cortex glutamate during the n-back task, whereas SCZ without the minor allele showed an increase in glutamate. BD with the minor allele had reduced glutamate in the anterior cingulate cortex (p < 0.05). There was no effect of SLC30A3 genotype on BOLD activation during n-back or on cortical brain volume. This study supports the further investigation of SLC30A3 and its role in glutamatergic neurotransmission and in the neuropathology of mental illness.

Chemistry plays a key role in many aspects of astrophysical fluids. Atoms and molecules are agents for heating and cooling, determine the ionization fraction, serve as observational tracers, and build the molecular foundation of life. We present the implementation of a chemistry module in the publicly available magnetohydrodynamic code Athena++ . We implement several chemical networks and heating and cooling processes suitable for simulating the interstellar medium (ISM). A general chemical network framework in the KIDA format is also included, allowing users to easily implement their own chemistry. Radiation transfer and cosmic-ray ionization are coupled with chemistry and solved with the simple six-ray approximation. The chemical and thermal processes are evolved as a system of coupled ordinary differential equations with an implicit solver from the CVODE library. We perform and present a series of tests to ensure the numerical accuracy and convergence of the code. Many tests combine chemistry with gas dynamics, including comparisons with analytic solutions, 1D problems of the photodissociation regions and shocks, and realistic 3D simulations of the turbulent ISM. We release the code with the new public version of Athena++ , aiming to provide a robust and flexible code for the astrochemical simulation community.

The inner few parsecs of the Milky Way’s Galactic center contain the central accreting supermassive black hole, over a million stars, and multiple large gaseous structures. In the past, the structures at these length scales have generally been modeled independently of each other. It is consequently not well understood how these complex features interact with each other, nor how gas flows between the outer few parsecs and the inner subarcsecond region (1″ ≈ 0.04 pc). In this work, we present hydrodynamic simulations of the inner few parsecs of the Galactic center that, for the first time, combine a realistic treatment of stellar winds and the circumnuclear disk (CND) as they interact with the gravitational potential of the nuclear star cluster and Sagittarius A*. We observe interactions of the stellar winds with the inner edge of the CND, which leads to the growth of instabilities, induced accretion of cool gas from the inner edge of the disk, and the eventual formation of a small accretion disk of ∼10 ^4 –10 ^5 K within r ∼ 0.1 pc. The formation of an inner disk qualitatively agrees with observations. This disk grows in radial extent and mass with time on ≳10 kyr timescales, with a growth rate of $M\propto {t}_{\mathrm{kyr}}^{3.5}$ . We discuss additional physical mechanisms not yet included in this work that can improve our model.

We extend the general-relativistic magnetohydrodynamics (GRMHD) capabilities of Athena++ to incorporate radiation. The intensity field in each finite-volume cell is discretized in angle, with explicit transport in both space and angle properly accounting for the effects of gravity on null geodesics, and with matter and radiation coupled in a locally implicit fashion. Here we describe the numerical procedure in detail, verifying its correctness with a suite of tests. Motivated in particular by black hole accretion in the high-accretion-rate, thin-disk regime, we demonstrate the application of the method to this problem. With excellent scaling on flagship computing clusters, the port of the algorithm to the GPU-enabled AthenaK code now allows the simulation of many previously intractable radiation-GRMHD systems.

We describe the implementation of multigrid solvers in the Athena++ adaptive mesh refinement (AMR) framework and their application to the solution of the Poisson equation for self-gravity. The new solvers are built on top of the AMR hierarchy and TaskList framework of Athena++ for efficient parallelization. We adopt a conservative formulation for the Laplacian operator that avoids artificial accelerations at level boundaries. Periodic, fixed, and zero-gradient boundary conditions are implemented, as well as open boundary conditions based on a multipole expansion. Hybrid parallelization using both Message Passing Interface and OpenMP is adopted, and we present results of tests demonstrating the accuracy and scaling of the methods. On a uniform grid, we show that multigrid significantly outperforms methods based on fast Fourier transforms, and requires only a small fraction of the computing time required by the (highly optimized) magnetohydrodynamic solver in Athena++. As a demonstration of the capabilities of the methods, we present the results of a test calculation of magnetized protostellar collapse on an adaptive mesh.

We present high-resolution, three-dimensional hydrodynamic simulations of the fueling of supermassive black holes in elliptical galaxies from a turbulent medium on galactic scales, taking M87* as a typical case. The simulations use a new GPU-accelerated version of the Athena++ AMR code, and they span more than six orders of magnitude in radius, reaching scales similar to that of the black hole horizon. The key physical ingredients are radiative cooling and a phenomenological heating model. We find that the accretion flow takes the form of multiphase gas at radii less than about a kpc. The cold gas accretion includes two dynamically distinct stages: the typical disk stage in which the cold gas resides in a rotationally supported disk, and relatively rare chaotic stages (≲10% of the time) in which the cold gas inflows via chaotic streams. Though cold gas accretion dominates the time-averaged accretion rate at intermediate radii, accretion at the smallest radii is dominated by hot virialized gas at most times. The accretion rate scales with radius as $\dot{M}\propto {r}^{1/2}$ when hot gas dominates, and we obtain $\dot{M}\simeq {10}^{-4}\mbox{--}{10}^{-3}\,{M}_{\odot }\,{\mathrm{yr}}^{-1}$ near the event horizon, similar to what is inferred from EHT observations. The orientation of the cold gas disk can differ significantly on different spatial scales. We propose a subgrid model for accretion in lower-resolution simulations in which the hot gas accretion rate is suppressed relative to the Bondi rate by $\sim {({r}_{{\rm{g}}}/{r}_{\mathrm{Bondi}})}^{1/2}$ . Our results can also provide more realistic initial conditions for simulations of black hole accretion at the event horizon scale.

We present global 3D radiation magnetohydrodynamic simulations of accretion onto a 6.62 solar-mass black hole, with quasi-steady-state accretion rates reaching 0.016–0.9 times the critical accretion rate, which is defined as the accretion rate for powering the Eddington luminosity, assuming a 10% radiative efficiency, in three different runs. The simulations show no sign of thermal instability over hundreds of thermal timescales at 10 r _g . The energy dissipation occurs close to the mid-plane in the near-critical runs and near the disk surface in the low–accretion rate run. The total radiative luminosity inside ∼20 r _g is about 1%–30% of the Eddington limit, with radiative efficiencies of about 6% and 3%, respectively, in the sub- and near-critical accretion regimes. In both cases, self-consistent turbulence generated by the magnetorotational instability leads to angular momentum transfer, and the disk is supported by magnetic pressure. Outflows from the central low-density funnel, with a terminal velocity of ∼0.1 c , are seen only in the near-critical runs. We conclude that these magnetic pressure–dominated disks are thermally stable and thicker than the α disk, and that the effective temperature profiles are much flatter than those in the α disks. The magnetic pressures of these disks are comparable within an order of magnitude to the previous analytical magnetic pressure–dominated disk model.

We developed a novel miniature micro-lensed fibre probe for Raman spectroscopy. The fibre probe consists of a single negative-curvature fibre (NCF) and a spliced, cleaved, micro-lensed fibre cap. Using a single NCF, we minimized the Raman background generated from the silica and maintained the diameter of the probe at less than 0.5 mm. In addition, the cap provided fibre closure by blocking the sample from entering the hollow parts of the fibre, enabling the use of the probe in in vivo applications. Moreover, the micro-lensed cap offered an improved collection efficiency (1.5-times increase) compared to a cleaved end-cap. The sensing capabilities of the micro-lensed probe were demonstrated by measuring different concentrations of glucose in aqueous solutions.