Integrated silicon carbide electro-optic modulator.

Owing to its attractive optical and electronic properties, silicon carbide is an emerging platform for integrated photonics. However an integral component of the platform is missing-an electro-optic modulator, a device which encodes electrical signals onto light. As a non-centrosymmetric crystal, silicon carbide exhibits the Pockels effect, yet a modulator has not been realized since the discovery of this effect more than three decades ago. Here we design, fabricate, and demonstrate a Pockels modulator in silicon carbide. Specifically, we realize a waveguide-integrated, small form-factor, gigahertz-bandwidth modulator that operates using complementary metal-oxide-semiconductor (CMOS)-level voltages on a thin film of silicon carbide on insulator. Our device is fabricated using a CMOS foundry compatible fabrication process and features no signal degradation, no presence of photorefractive effects, and stable operation at high optical intensities (913 kW/mm2), allowing for high optical signal-to-noise ratios for modern communications. Our work unites Pockels electro-optics with a CMOS foundry compatible platform in silicon carbide.

Big conductance calcium-activated potassium channel openers control spasticity without sedation.

BACKGROUND AND PURPOSE: Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drugs that target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R. Toxicological and safety studies were performed in animals and humans. KEY RESULTS: VSN16R had nanomolar activity in tissue-based, functional assays and dose-dependently inhibited spasticity in a mouse experimental encephalomyelitis model of MS. This effect occurred with over 1000-fold therapeutic window, without affecting normal muscle tone. Efficacy was achieved at plasma levels that are feasible and safe in humans. VSN16R did not bind to known CB1 /CB2 /GPPR55 cannabinoid-related receptors in receptor-based assays but acted on a vascular cannabinoid target. This was identified as the major neuronal form of the big conductance, calcium-activated potassium (BKCa ) channel. Drug-induced opening of neuronal BKCa channels induced membrane hyperpolarization, limiting excessive neural-excitability and controlling spasticity. CONCLUSIONS AND IMPLICATIONS: We identified the neuronal form of the BKCa channel as the target for VSN16R and demonstrated that its activation alleviates neuronal excitability and spasticity in an experimental model of MS, revealing a novel mechanism to control spasticity. VSN16R is a potential, safe and selective ligand for controlling neural hyper-excitability in spasticity.

Factors affecting missed appointment rates for pediatric patients insured by medicaid in a traditional hospital-based resident clinic and hospital-owned practice settings.

Missed appointment rates (MAR) of pediatric patients insured by Medicaid and seen in a traditional hospital-based continuity (teaching) clinic were compared to the rates for the same patients after their care had been transitioned to a community practice. The hypothesis is that when rewarded with shorter waiting times, a less chaotic environment, and more pediatrician continuity, the MAR for patients insured by Medicaid would be lower in the practice setting than it had been in continuity clinic. The MAR decreased from 33% in the continuity clinic in 1999 to 18% in the community practice in 2001 (p<0.01). It was also hypothesized that the MAR for patients insured by Medicaid would be higher in practices with a higher percentage of Medicaid appointments. Among 15 hospital-owned pediatric practices, the MAR for patients insured by Medicaid was positively correlated with the percentage of total appointments that were made by patients insured by Medicaid (correlation coefficient 0.706 [p<0.01]).