Defining molecular initiating events in the adverse outcome pathway framework for risk assessment.

Consumer and environmental safety decisions are based on exposure and hazard data, interpreted using risk assessment approaches. The adverse outcome pathway (AOP) conceptual framework has been presented as a logical sequence of events or processes within biological systems which can be used to understand adverse effects and refine current risk assessment practices in ecotoxicology. This framework can also be applied to human toxicology and is explored on the basis of investigating the molecular initiating events (MIEs) of compounds. The precise definition of the MIE has yet to reach general acceptance. In this work we present a unified MIE definition: an MIE is the initial interaction between a molecule and a biomolecule or biosystem that can be causally linked to an outcome via a pathway. Case studies are presented, and issues with current definitions are addressed. With the development of a unified MIE definition, the field can look toward defining, classifying, and characterizing more MIEs and using knowledge of the chemistry of these processes to aid AOP research and toxicity risk assessment. We also present the role of MIE research in the development of in vitro and in silico toxicology and suggest how, by using a combination of biological and chemical approaches, MIEs can be identified and characterized despite a lack of detailed reports, even for some of the most studied molecules in toxicology.The authors acknowledge the financial support of Unilever.This is the accepted manuscript. The final published version is available from ACS at http://dx.doi.org/10.1021/tx500345

Accurate Parameter Extraction From Liquids Measured Using On-chip Terahertz Spectroscopy

We introduce a method for estimating the permittivity of liquid samples measured using integrated microfluidic/planar Goubau line terahertz waveguides, in which simulation results are incorporated with measurement data to enable accurate frequency-dependent analysis

The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis (vol 10, pg 2437, 2017)

Sofat N, Harrison A, Russell MD, et al. J Pain Res. 2017;10:2437–2449.On page 2443, Table 3, Placebo column, NRS section, the difference was reported as: –0.9 (–0.2 to 0.2). This is incorrect, and it should read as follows: –0.9 (–2.0 to 0.2).Read the original articl

The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis

Osteoarthritis (OA) is the most prevalent arthritis worldwide and is characterized by chronic pain and impaired physical function. We hypothesized that heightened pain in hand OA could be reduced with duloxetine or pregabalin. In this prospective, randomized clinical study, we recruited 65 participants, aged 40–75 years, with a Numerical Rating Scale (NRS) for pain of at least 5. Participants were randomized to one of the following three groups: duloxetine, pregabalin, and placebo. The primary endpoint was the NRS pain score, and the secondary endpoints included the Australian and Canadian Hand Osteoarthritis Index (AUSCAN) pain, stiffness, and function scores and quantitative sensory testing by pain pressure algometry. After 13 weeks, compared to placebo, ANOVA found significant differences between the three groups (P=0.0078). In the intention-to-treat analysis, the pregabalin group showed improvement for NRS pain (P=0.023), AUSCAN pain (P=0.008), and AUSCAN function (P=0.009), but no difference between duloxetine and placebo (P>0.05) was observed. In the per protocol analysis, NRS pain was reduced for pregabalin (P<0.0001) and duloxetine (P=0.029) compared to placebo. We conclude that centrally acting analgesics improve pain outcomes in people with hand arthritis, offering new treatment paradigms for OA pain

Free-space terahertz radiation from a LT-GaAs-on-quartz large-area photoconductive emitter

We report on large-area photoconductive terahertz (THz) emitters with a low-temperature-grown GaAs (LT-GaAs) active layer fabricated on quartz substrates using a lift-off transfer process. These devices are compared to the same LT-GaAs emitters when fabricated on the growth substrate. We find that the transferred devices show higher optical-to-THz conversion efficiencies and significantly larger breakdown fields, which we attribute to reduced parasitic current in the substrate. Through these improvements, we demonstrate a factor of ~8 increase in emitted THz field strength at the maximum operating voltage. In addition we find improved performance when these devices are used for photoconductive detection, which we explain through a combination of reduced parasitic substrate currents and reduced space-charge build-up in the device

Investigation into free-space terahertz radiation from a LT-GaAs-on-quartz photoconductive emitter

We report on large-area photoconductive THz emitters and detectors with an LT-GaAs active region fabricated on quartz substrates using a lift-off transfer process. These devices are compared to the same LT-GaAs emitters when fabricated on the growth substrate. We find that the transferred devices show higher optical-to-THz conversion efficiencies and significantly larger breakdown fields

The conceptual and practical ethical dilemmas of using health discussion board posts as research data.

Increasing numbers of people living with a long-term health condition are putting personal health information online, including on discussion boards. Many discussion boards contain material of potential use to researchers; however, it is unclear how this information can and should be used by researchers. To date there has been no evaluation of the views of those individuals sharing health information online regarding the use of their shared information for research purposes

Spectroscopy of polycrystalline materials using thinned-substrate planar Goubau line at cryogenic temperatures.

We investigate the effect of substrate thickness on the transmission bandwidth of on-chip terahertz-frequency-range planar Goubau lines both experimentally and theoretically. The bandwidth and frequency resolution are improved through substrate thinning and geometry modifications (reducing reflections arising from the THz photoconductive generators and detectors). We demonstrate that the enhanced bandwidth (2 THz) and resolution (3.75 GHz) allows this type of on-chip waveguide to be used for spectroscopic measurements of polycrystalline materials from cryogenic (4 K) to room temperature (292 K) by recording vibrational absorption spectra from overlaid samples of lactose monohydrate

Pinning quantum phase transition for a Luttinger liquid of strongly interacting bosons

One of the most remarkable results of quantum mechanics is the fact that many-body quantum systems may exhibit phase transitions even at zero temperature. Quantum fluctuations, deeply rooted in Heisenberg's uncertainty principle, and not thermal fluctuations, drive the system from one phase to another. Typically, the relative strength of two competing terms in the system's Hamiltonian is changed across a finite critical value. A well-known example is the Mott-Hubbard quantum phase transition from a superfluid to an insulating phase, which has been observed for weakly interacting bosonic atomic gases. However, for strongly interacting quantum systems confined to lower-dimensional geometry a novel type of quantum phase transition may be induced for which an arbitrarily weak perturbation to the Hamiltonian is sufficient to drive the transition. Here, for a one-dimensional (1D) quantum gas of bosonic caesium atoms with tunable interactions, we observe the commensurate-incommensurate quantum phase transition from a superfluid Luttinger liquid to a Mott-insulator. For sufficiently strong interactions, the transition is induced by adding an arbitrarily weak optical lattice commensurate with the atomic granularity, which leads to immediate pinning of the atoms. We map out the phase diagram and find that our measurements in the strongly interacting regime agree well with a quantum field description based on the exactly solvable sine-Gordon model. We trace the phase boundary all the way to the weakly interacting regime where we find good agreement with the predictions of the 1D Bose-Hubbard model. Our results open up the experimental study of quantum phase transitions, criticality, and transport phenomena beyond Hubbard-type models in the context of ultracold gases

Accurate Material Parameter Extraction from Broadband Terahertz Spectroscopy

We demonstrate how a transfer function model based parameter extraction method, combined with total variance analysis, allows the extraction of both the complex refractive index and the thickness of a sample over a bandwidth of > 6 THz from THz time-domain spectroscopy measurements. We discuss how the techniques developed have been applied to absorbent powders measured at variable low temperatures