Tumble Kinematics of Escherichia coli near a Solid Surface.

Bacteria tumble periodically, following environmental cues. Whether they can tumble near a solid surface is a basic issue for the inception of infection or mineral biofouling. Observing freely swimming Escherichia coli near and parallel to a glass surface imaged at high magnification (×100) and high temporal resolution (500 Hz), we identified tumbles as events starting (or finishing, respectively) in abrupt deceleration (or reacceleration, respectively) of the body motion. Selected events show an equiprobable clockwise (CW) or counterclockwise change in direction that is superimposed on a surface CW path because of persistent propulsion. These tumbles follow a common long (about 300 ± 100 ms, N = 52) deceleration-reorientation-acceleration pattern. A wavelet transform multiscale analysis shows these tumbles cause in-plane diffusive reorientations with 1.5 rad2/s rotational diffusivity, a value that compares with that measured in bulk tumbles. In half of the cases, additional few-millisecond bursts of an almost equiprobable CW or counterclockwise change of direction (12 ± 90°, N = 89) occur within the reorientation stage. The highly dispersed absolute values of change of direction (70 ± 66°, N = 89) of only a few bursts destabilize the cell-swimming direction. These first observations of surface tumbles set a foundation for statistical models of run-and-tumble surface motion different from that in bulk and lend support for chemotaxis near solid surface.

Abuse-deterrent properties of REMOXY® ER, a high-viscosity extended-release oxycodone formulation.

OBJECTIVE: These in vitro studies compared abuse-deterrent properties of REMOXY ER (extended-release oxycodone), a novel, high-viscosity gel formulation, versus the two currently marketed ER oxycodone formulations. METHODS: Tampering methods were tailored to each product to maximize oxycodone release with the least complexity, time, and effort, based on the physical/chemical properties of each formulation. Oral abuse was simulated by extracting oxycodone from each manipulated formulation in Common Ingestible Liquids and in Advanced Solvents (not ingestible and requiring additional separation). To simulate injection abuse, oxycodone was extracted from each manipulated formulation in low volumes of injection vehicles, heated or unheated. Inhalation abuse potential was assessed by volatilization. RESULTS: In oral abuse simulations, manipulated REMOXY ER released 2-22 percent of its oxycodone in 20 minutes in five Common Ingestible Liquids, versus 77-85 percent oxycodone released from OxyContin® ER in 5 minutes in four of the five. In six Advanced Solvents, REMOXY ER released 3-37 percent at 20 minutes, versus 55-89 percent released from OxyContin ER at 5 minutes. Minimal oxycodone was extracted from REMOXY ER in five injection vehicles, heated or unheated. In contrast, OxyContin ER released 65-87 percent of its oxycodone within 10 minutes in all vehicles, regardless of heating. Xtampza® ER released 96 percent of its oxycodone in a heated injection vehicle and released 50-60 percent in two unheated injection vehicles. Showing minimal inhalation abuse potential, 9 percent of oxycodone was vaporized from manipulated REMOXY ER at 20 minutes compared to 8.8 percent at 5 minutes for OxyContin ER. CONCLUSIONS: In these studies, REMOXY ER demonstrated robust and meaningful abuse-deterrence relative to OxyContin ER and Xtampza ER. PERSPECTIVE: Abuse-deterrent drugs were intended to help fight opioid abuse. Yet, the persistence of the opioid epidemic indicates that vast improvements in abuse-deterrent technology are sorely needed. A new, high-viscosity, ER oxycodone formulation showed much improved abuse-deterrent properties in simulations of oral, injection, and inhalation abuse, compared to earlier, first-generation formulations.

Autocorrelation analysis for the unbiased determination of power-law exponents in single-quantum-dot blinking.

We present an unbiased and robust analysis method for power-law blinking statistics in the photoluminescence of single nanoemitters, allowing us to extract both the bright- and dark-state power-law exponents from the emitters' intensity autocorrelation functions. As opposed to the widely used threshold method, our technique therefore does not require discriminating the emission levels of bright and dark states in the experimental intensity timetraces. We rely on the simultaneous recording of 450 emission timetraces of single CdSe/CdS core/shell quantum dots at a frame rate of 250 Hz with single photon sensitivity. Under these conditions, our approach can determine ON and OFF power-law exponents with a precision of 3% from a comparison to numerical simulations, even for shot-noise-dominated emission signals with an average intensity below 1 photon per frame and per quantum dot. These capabilities pave the way for the unbiased, threshold-free determination of blinking power-law exponents at the microsecond time scale.