Intravenous ketamine for treatment-resistant depression patients who have failed to respond to transcranial magnetic stimulation: A case series.

BACKGROUND: For individuals with treatment-resistant depression (TRD), transcranial magnetic stimulation (TMS) has become a well-established approach. In the past decade, intravenous (IV) racemic ketamine has also emerged as a potential treatment for TRD. Currently, little data is available on the clinical effects of IV racemic ketamine in TRD patients who experienced TMS-failure. METHODS: Twenty-one (21) TRD patients who had failed to respond to a standard course of high-frequency left-dorsolateral prefrontal cortex TMS were subsequently scheduled to received IV racemic ketamine infusions. The IV racemic ketamine protocol consisted of 0,5 mg/kg infusions over 60 min, 3 times a week over 2 weeks. RESULTS: Treatment was safe with minimal side-effects. Mean baseline MADRS score was 27.6 ± 6.4 (moderate depression), decreasing down to 18.6 ± 8.9 (mild depression) post-treatment. Mean percent improvement was 34.5 % ± 21.1 from baseline to post-treatment. Paired sample t-test showed significant MADRS score decrease pre- to post-treatment [t(20) = 7.212, p < .001]. Overall, four (4) patients (19.0 %) responded and two (2) of those achieved remission (9.5 %). LIMITATIONS: Limitations of this case series include its retrospective and uncontrolled open-label nature, the lack of self-rating and standardized adverse events questionnaires, as well as follow-ups beyond the immediate treatment period. CONCLUSIONS: Novel ways to increase the clinical effects of ketamine are being explored. We discuss potential combination approaches of ketamine with other modalities to augment its effects. Given the global burden of TRD, novel approaches are needed to curb the current mental health epidemic around the world.

Transcranial magnetic stimulation and intravenous ketamine combination therapy for treatment-resistant bipolar depression: A case report.

About a third of patients suffering from major depression develop treatment-resistant depression (TRD). Although repetitive transcranial magnetic stimulation (rTMS) and intravenous ketamine have proven effective for the management of TRD, many patients remain refractory to treatment. We present the case of a patient suffering from bipolar TRD. The patient was referred to us after failure to respond to first-and second-line pharmacotherapy and psychotherapy. After minimal response to both rTMS and ketamine alone, we attempted a combination rTMS and ketamine protocol, which led to complete and sustained remission. Various comparable and complimentary mechanisms of antidepressant action of ketamine and rTMS are discussed, which support further study of this combination therapy. Future research should focus on the feasibility, tolerability, and efficacy of this novel approach.

Kardar-Parisi-Zhang universality in a one-dimensional polariton condensate.

Revealing universal behaviours is a hallmark of statistical physics. Phenomena such as the stochastic growth of crystalline surfaces1 and of interfaces in bacterial colonies2, and spin transport in quantum magnets3-6 all belong to the same universality class, despite the great plurality of physical mechanisms they involve at the microscopic level. More specifically, in all these systems, space-time correlations show power-law scalings characterized by universal critical exponents. This universality stems from a common underlying effective dynamics governed by the nonlinear stochastic Kardar-Parisi-Zhang (KPZ) equation7. Recent theoretical works have suggested that this dynamics also emerges in the phase of out-of-equilibrium systems showing macroscopic spontaneous coherence8-17. Here we experimentally demonstrate that the evolution of the phase in a driven-dissipative one-dimensional polariton condensate falls in the KPZ universality class. Our demonstration relies on a direct measurement of KPZ space-time scaling laws18,19, combined with a theoretical analysis that reveals other key signatures of this universality class. Our results highlight fundamental physical differences between out-of-equilibrium condensates and their equilibrium counterparts, and open a paradigm for exploring universal behaviours in driven open quantum systems.

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series.

Intermittent theta burst stimulation (iTBS) using 600 pulses is an effective and FDA-cleared transcranial magnetic stimulation (TMS) protocol for major depressive disorder (MDD). Prolonged iTBS (piTBS) using 1,800 pulses could increase the effectiveness of TMS for MDD, but its real-world effectiveness is still debated. We assessed the safety, tolerability, and preliminary effectiveness of a 3x daily piTBS 1,800 pulses protocol delivered over 2 weeks in 27 participants. Only four participants (18.2%) achieved response, two of them achieving remission (9.1%). Five participants (18.5%) experienced tolerability issues. Future studies should focus on the neurophysiological effects of TBS protocols to determine optimal parameters.

Drone-Mountable Gas Sensing Platform Using Graphene Chemiresistors for Remote In-Field Monitoring.

We present the design, fabrication, and testing of a drone-mountable gas sensing platform for environmental monitoring applications. An array of graphene-based field-effect transistors in combination with commercial humidity and temperature sensors are used to relay information by wireless communication about the presence of airborne chemicals. We show that the design, based on an ESP32 microcontroller combined with a 32-bit analog-to-digital converter, can be used to achieve an electronic response similar, within a factor of two, to state-of-the-art laboratory monitoring equipment. The sensing platform is then mounted on a drone to conduct field tests, on the ground and in flight. During these tests, we demonstrate a one order of magnitude reduction in environmental noise by reducing contributions from humidity and temperature fluctuations, which are monitored in real-time with a commercial sensor integrated to the sensing platform. The sensing device is controlled by a mobile application and uses LoRaWAN, a low-power, wide-area networking protocol, for real-time data transmission to the cloud, compatible with Internet of Things (IoT) applications.

Temperature and Photoperiod Affect the Sensitivity of Biofilms to Nickel and its Accumulation.

Whereas metal impacts on fluvial communities have been extensively investigated, effects of abiotic parameters on community responses to contaminants are poorly documented. Variations in photoperiod and temperature commonly occur over the course of a season and could affect aquatic biofilm communities and their responses to contaminants. Our objective was to characterize the influence of environmental conditions (photoperiod and temperature) on nickel (Ni) bioaccumulation and toxicity using a laboratory-grown biofilm. Environmental parameters were chosen to represent variations that can occur over the summer season. Biofilms were exposed for 7 days to six dissolved Ni treatments (ranging from 6 to 115 µM) at two temperatures (14 and 20 °C) using two photoperiods (16:8 and 12:12-h light:dark cycle). Under these different scenarios, structural (dry weight biomass and chlorophyll-a) and functional biomarkers (photosynthetic yield and Ni content) were analyzed at four sampling dates, allowing us to evaluate Ni sensitivity of biofilms over time. The results highlight the effects of temperature on Ni accumulation and tolerance of biofilms. Indeed, biofilms exposed at 20 °C accumulated 1.6-4.2-fold higher concentrations of Ni and were characterized by a lower median effect concentration value using photosynthetic yield compared with those exposed at 14 °C. In terms of photoperiod, significantly greater rates of Ni accumulation were observed at the highest tested Ni concentration for biofilms exposed to a 12:12-h compared with a 16:8-h light:dark cycle. Our study demonstrates the influence of temperature on biofilm metabolism and illustrates that environmental factors may influence Ni accumulation response and thus Ni responses of phototrophic biofilms. Environ Toxicol Chem 2022;41:1649-1662. © 2022 SETAC.

Mutations Accounting for Congenital Fibrinogen Disorders: An Update.

Fibrinogen is a complex protein that plays a key role in the blood clotting process. It is a hexamer composed of two copies of three distinct chains: Aα, Bß, and γ encoded by three genes, FGA, FGB, and FGG, clustered on the long arm of chromosome 4. Congenital fibrinogen disorders (CFDs) are divided into qualitative deficiencies (dysfibrinogenemia, hypodysfibrinogenemia) in which the mutant fibrinogen molecule is present in the circulation and quantitative deficiencies (afibrinogenemia, hypofibrinogenemia) with no mutant molecule present in the bloodstream. Phenotypic manifestations are variable, patients may be asymptomatic, or suffer from bleeding or thrombosis. Causative mutations can occur in any of the three fibrinogen genes and can affect one or both alleles. Given the large number of studies reporting on novel causative mutations for CFDs since the review on the same topic published in 2016, we performed an extensive search of the literature and list here 120 additional mutations described in both quantitative and qualitative disorders. The visualization of causative single nucleotide variations placed on the coding sequences of FGA, FGB, and FGG reveals important structure function insight for several domains of the fibrinogen molecule.

Exciton-Exciton Interaction beyond the Hydrogenic Picture in a MoSe_{2} Monolayer in the Strong Light-Matter Coupling Regime.

In transition metal dichalcogenides' layers of atomic-scale thickness, the electron-hole Coulomb interaction potential is strongly influenced by the sharp discontinuity of the dielectric function across the layer plane. This feature results in peculiar nonhydrogenic excitonic states in which exciton-mediated optical nonlinearities are predicted to be enhanced compared to their hydrogenic counterparts. To demonstrate this enhancement, we perform optical transmission spectroscopy of a MoSe_{2} monolayer placed in the strong coupling regime with the mode of an optical microcavity and analyze the results quantitatively with a nonlinear input-output theory. We find an enhancement of both the exciton-exciton interaction and of the excitonic fermionic saturation with respect to realistic values expected in the hydrogenic picture. Such results demonstrate that unconventional excitons in MoSe_{2} are highly favorable for the implementation of large exciton-mediated optical nonlinearities, potentially working up to room temperature.

Inducing micromechanical motion by optical excitation of a single quantum dot.

Hybrid quantum optomechanical systems1 interface a macroscopic mechanical degree of freedom with a single two-level system such as a single spin2-4, a superconducting qubit5-7 or a single optical emitter8-12. Recently, hybrid systems operating in the microwave domain have witnessed impressive progress13,14. Concurrently, only a few experimental approaches have successfully addressed hybrid systems in the optical domain, demonstrating that macroscopic motion can modulate the two-level system transition energy9,10,15. However, the reciprocal effect, corresponding to the backaction of a single quantum system on a macroscopic mechanical resonator, has remained elusive. In contrast to an optical cavity, a two-level system operates with no more than a single energy quantum. Hence, it requires a much stronger hybrid coupling rate compared to cavity optomechanical systems1,16. Here, we build on the large strain coupling between an oscillating microwire and a single embedded quantum dot9. We resonantly drive the quantum dot's exciton using a laser modulated at the mechanical frequency. State-dependent strain then results in a time-dependent mechanical force that actuates microwire motion. This force is almost three orders of magnitude larger than the radiation pressure produced by the photon flux interacting with the quantum dot. In principle, the state-dependent force could constitute a strategy to coherently encode the quantum dot quantum state onto a mechanical degree of freedom1.

Dispersion relation of the collective excitations in a resonantly driven polariton fluid.

Exciton-polaritons in semiconductor microcavities constitute the archetypal realization of a quantum fluid of light. Under coherent optical drive, remarkable effects such as superfluidity, dark solitons or the nucleation of vortices have been observed, and can be all understood as specific manifestations of the condensate collective excitations. In this work, we perform a Brillouin scattering experiment to measure their dispersion relation [Formula: see text] directly. The results, such as a speed of sound which is apparently twice too low, cannot be explained upon considering the polariton condensate alone. In a combined theoretical and experimental analysis, we demonstrate that the presence of an excitonic reservoir alongside the polariton condensate has a dramatic influence on the characteristics of the quantum fluid, and explains our measurement quantitatively. This work clarifies the role of such a reservoir in polariton quantum hydrodynamics. It also provides an unambiguous tool to determine the condensate-to-reservoir fraction in the quantum fluid, and sets an accurate framework to approach ideas for polariton-based quantum-optical applications.

Optical valley Hall effect for highly valley-coherent exciton-polaritons in an atomically thin semiconductor.

Spin-orbit coupling is a fundamental mechanism that connects the spin of a charge carrier with its momentum. In the optical domain, an analogous synthetic spin-orbit coupling is accessible by engineering optical anisotropies in photonic materials. Both yield the possibility of creating devices that directly harness spin and polarization as information carriers. Atomically thin transition metal dichalcogenides promise intrinsic spin-valley Hall features for free carriers, excitons and photons. Here we demonstrate spin- and valley-selective propagation of exciton-polaritons in a monolayer of MoSe2 that is strongly coupled to a microcavity photon mode. In a wire-like device we trace the flow and helicity of exciton-polaritons expanding along its channel. By exciting a coherent superposition of K and K' tagged polaritons, we observe valley-selective expansion of the polariton cloud without either an external magnetic field or coherent Rayleigh scattering. The observed optical valley Hall effect occurs on a macroscopic scale, offering the potential for applications in spin-valley-locked photonic devices.

Emergence of quantum correlations from interacting fibre-cavity polaritons.

Over the past decade, exciton-polaritons in semiconductor microcavities have revealed themselves as one of the richest realizations of a light-based quantum fluid1, subject to fascinating new physics and potential applications2-6. For instance, in the regime of large two-body interactions, polaritons can be used to manipulate the quantum properties of a light field7-9. In this work, we report on the emergence of quantum correlations in laser light transmitted through a fibre-cavity polariton system. We observe a dispersive shape of the autocorrelation function around the polariton resonance that indicates the onset of this regime. The weak amplitude of these correlations indicates a state that still remains far from a low-photon-number state. Nonetheless, given the underlying physical mechanism7, our work opens up the prospect of eventually using polaritons to turn laser light into single photons.

Thermal Decoherence of a Nonequilibrium Polariton Fluid.

Exciton polaritons constitute a unique realization of a quantum fluid interacting with its environment. Using selenide-based microcavities, we exploit this feature to warm up a polariton condensate in a controlled way and monitor its spatial coherence. We determine directly the amount of heat picked up by the condensate by measuring the phonon-polariton scattering rate and comparing it with the loss rate. We find that, upon increasing the heating rate, the spatial coherence length decreases markedly, while localized phase structures vanish, in good agreement with a stochastic mean-field theory. From the thermodynamical point of view, this regime is unique, as it involves a nonequilibrium quantum fluid with no well-defined temperature but which is nevertheless able to pick up heat with dramatic effects on the order parameter.

Enhanced Second-Order Nonlinearity for THz Generation by Resonant Interaction of Exciton-Polariton Rabi Oscillations with Optical Phonons.

Semiconductor microcavities in the strong-coupling regime exhibit an energy scale in the terahertz (THz) frequency range, which is fixed by the Rabi splitting between the upper and lower exciton-polariton states. While this range can be tuned by several orders of magnitude using different excitonic media, the transition between both polaritonic states is dipole forbidden. In this work, we show that, in cadmium telluride microcavities, the Rabi-oscillation-driven THz radiation is actually active without the need for any change in the microcavity design. This feature results from the unique resonance condition which is achieved between the Rabi splitting and the phonon-polariton states and leads to a giant enhancement of the second-order nonlinearity.

The Impact of a Cognitive-Behavioral Therapy on Event-Related Potentials in Patients with Tic Disorders or Body-Focused Repetitive Behaviors.

CONTEXT: Tic disorders (TD) are characterized by the presence of non-voluntary contractions of functionally related groups of skeletal muscles in one or multiple body parts. Patients with body-focused repetitive behaviors (BFRB) present frequent and repetitive behaviors, such as nail biting or hair pulling. TD and BFRB can be treated with a cognitive-behavioral therapy (CBT) that regulates the excessive amount of sensorimotor activation and muscular tension. Our CBT, which is called the cognitive-psychophysiological (CoPs) model, targets motor execution and inhibition, and it was reported to modify brain activity in TD. However, psychophysiological effects of therapy are still poorly understood in TD and BFRB patients. Our goals were to compare the event-related potentials (ERP) of TD and BFRB patients to control participants and to investigate the effects of the CoPs therapy on the P200, N200, and P300 components during a motor and a non-motor oddball task. METHOD: Event-related potential components were compared in 26 TD patients, 27 BFRB patients, and 27 control participants. ERP were obtained from 63 EEG electrodes during two oddball tasks. In the non-motor task, participants had to count rare stimuli. In the motor task, participants had to respond with a left and right button press for rare and frequent stimuli, respectively. ERP measures were recorded before and after therapy in both patient groups. RESULTS: CoPs therapy improved symptoms similarly in both clinical groups. Before therapy, TD and BFRB patients had reduced P300 oddball effect during the non-motor task, in comparison with controls participants. An increase in the P300 oddball effect was observed posttherapy. This increase was distributed over the whole cortex in BFRB patients, but localized in the parietal area in TD patients. DISCUSSION: These results suggest a modification of neural processes following CoPs therapy in TD and BFRB patients. CoPs therapy seems to impact patients' attentional processes and context updating capacities in working memory (i.e., P300 component). Our results are consistent with a possible role of the prefrontal cortex and corpus callosum in mediating interhemispheric interference in TD.

Exciton-polariton gas as a nonequilibrium coolant.

Using angle-resolved Raman spectroscopy, we show that a resonantly excited ground-state exciton-polariton fluid behaves like a nonequilibrium coolant for its host solid-state semiconductor microcavity. With this optical technique, we obtain a detailed measurement of the thermal fluxes generated by the pumped polaritons. We thus find a maximum cooling power for a cryostat temperature of 50 K and below where optical cooling is usually suppressed, and we identify the participation of an ultrafast cooling mechanism. We also show that the nonequilibrium character of polaritons constitutes an unexpected resource: each scattering event can remove more heat from the solid than would be normally allowed using a thermal fluid with normal internal equilibration.

Spontaneous coherent phase transition of polaritons in CdTe microcavities.

We report on evidence for polariton condensation out of a reservoir of incoherent polaritons. Polariton population and first-order coherence are investigated by spectroscopic imaging of the far-field emission of a CdTe-based microcavity under nonresonant pumping. With increasing pumping power, stimulated emission with thresholdlike behavior and spectral narrowing is observed in the strong exciton-photon coupling regime. We show that it comes from a narrow ring in k space, exhibiting enhanced spatial and angular coherence at the stimulation onset.