Uncovering the Connection Between Low-Frequency Dynamics and Phase Transformation Phenomena in Molecular Solids.

The low-frequency motions of molecules in the condensed phase have been shown to be vital to a large number of physical properties and processes. However, in the case of disordered systems, it is often difficult to elucidate the atomic-level details surrounding these phenomena. In this work, we have performed an extensive experimental and computational study on the molecular solid camphor, which exhibits a rich and complex structure-dynamics relationship, and undergoes an order-disorder transition near ambient conditions. The combination of x-ray diffraction, variable temperature and pressure terahertz time-domain spectroscopy, ab initio molecular dynamics, and periodic density functional theory calculations enables a complete picture of the phase transition to be obtained, inclusive of mechanistic, structural, and thermodynamic phenomena. Additionally, the low-frequency vibrations of a disordered solid are characterized for the first time with atomic-level precision, uncovering a clear link between such motions and the phase transformation. Overall, this combination of methods allows for significant details to be obtained for disordered solids and the associated transformations, providing a framework that can be directly applied for a wide range of similar systems

Measurement of the Intertablet Coating Uniformity of a Pharmaceutical Pan Coating Process With Combined Terahertz and Optical Coherence Tomography In-Line Sensing.

We present in-line coating thickness measurements acquired simultaneously using two independent sensing modalities: terahertz pulsed imaging (TPI) and optical coherence tomography (OCT). Both techniques are sufficiently fast to resolve the coating thickness of individual pharmaceutical tablets in-situ during the film coating operation and both techniques are direct structural imaging techniques that do not require multivariate calibration. The TPI sensor is suitable to measure coatings greater than 50 μm and can penetrate through thick coatings even in the presence of pigments over a wide range of excipients. Due to the long wavelength, terahertz radiation is not affected by scattering from dust within the coater. In contrast, OCT can resolve coating layers as thin as 20 μm and is capable of measuring the intra-tablet coating uniformity as well as the inter-tablet coating thickness distribution within the coating pan. ¬-However, the OCT technique is less robust when it comes to the compatibility with excipients, dust and potentially the maximum coating thickness that can be resolved. Using a custom built laboratory scale coating unit, the coating thickness measurements were acquired independently by the TPI and OCT sensors throughout a film coating operation. Results of the in-line TPI and OCT measurements were compared against one another and validated with off-line TPI and weight gain measurements. Compared to other process analytical technology (PAT) sensors, such as near-infrared and Raman spectroscopy, the TPI/OCT sensors can resolve the inter-tablet thickness distribution based on sampling a significant fraction of the tablet populations in the process. By combining two complementary sensing modalities it was possible to seamlessly monitor the coating process over the range of film thickness from 20 μm to greater than 250 μm.The authors would like to acknowledge the financial support from UK EPSRC Research Grant EP/L019787/1 and EP/L019922/1. The authors acknowledge BASF for providing the materials used in this study, Colorcon Ltd. (Dartford, UK) for coating process recommendations, Hüttlin GmbH (Bosch Packaging Technology, Schopfheim, Germany) for advice on the coating unit design and the staff of the electronics and mechanical workshops in Department of Chemical Engineering and Biotechnology at University of Cambridge. HL also acknowledges travel support from Joy Welch Educational Charitable Trust

Measurement of the Intertablet Coating Uniformity of a Pharmaceutical Pan Coating Process With Combined Terahertz and Optical Coherence Tomography In-Line Sensing.

We present in-line coating thickness measurements acquired simultaneously using 2 independent sensing modalities: terahertz pulsed imaging (TPI) and optical coherence tomography (OCT). Both techniques are sufficiently fast to resolve the coating thickness of individual pharmaceutical tablets in situ during the film coating operation, and both techniques are direct structural imaging techniques that do not require multivariate calibration. The TPI sensor is suitable to measure coatings greater than 50 μm and can penetrate through thick coatings even in the presence of pigments over a wide range of excipients. Due to the long wavelength, terahertz radiation is not affected by scattering from dust within the coater. In contrast, OCT can resolve coating layers as thin as 20 μm and is capable of measuring the intratablet coating uniformity and the intertablet coating thickness distribution within the coating pan. However, the OCT technique is less robust when it comes to the compatibility with excipients, dust, and potentially the maximum coating thickness that can be resolved. Using a custom-built laboratory scale coating unit, the coating thickness measurements were acquired independently by the TPI and OCT sensors throughout a film coating operation. Results of the in-line TPI and OCT measurements were compared against one another and validated with off-line TPI and weight gain measurements. Compared with other process analytical technology sensors, such as near-infrared and Raman spectroscopy, the TPI and OCT sensors can resolve the intertablet thickness distribution based on sampling a significant fraction of the tablet populations in the process. By combining 2 complementary sensing modalities, it was possible to seamlessly monitor the coating process over the range of film thickness from 20 μm to greater than 250 μm.The authors would like to acknowledge the financial support from UK EPSRC Research Grant EP/L019787/1 and EP/L019922/1. The authors acknowledge BASF for providing the materials used in this study, Colorcon Ltd. (Dartford, UK) for coating process recommendations, Hüttlin GmbH (Bosch Packaging Technology, Schopfheim, Germany) for advice on the coating unit design and the staff of the electronics and mechanical workshops in Department of Chemical Engineering and Biotechnology at University of Cambridge. HL also acknowledges travel support from Joy Welch Educational Charitable Trust

Sex Differences in Left Ventricular Electrical Dyssynchrony and Outcomes with Cardiac Resynchronization Therapy

BACKGROUND: Women seem to derive more benefit from cardiac resynchronization therapy (CRT) than men, even after accounting for the higher burden of risk factors for nonresponse often observed in men. OBJECTIVE: To assess for sex-specific differences in left ventricular (LV) electrical dyssynchrony as a contributing electrophysiological explanation for the greater degree of CRT benefit among women. METHODS: We compared the extent of baseline LV electrical dyssynchrony, as measured by the QRS area (QRSA), among men and women with left bundle branch block (LBBB) undergoing CRT at Duke University (n = 492, 35% women) overall and in relation to baseline QRS characteristics using independent sample t tests and Pearson correlation coefficients. Cox regression analyses were used to relate sex, QRSA, and QRS characteristics to the risk of cardiac transplantation, LV assist device implant, or death. RESULTS: Although the mean QRS duration (QRSd) did not differ by sex, QRSA was greater for women vs men (113.8 μVs vs 98.2 μVs, P < .001), owing to differences in the QRSd <150 ms subgroup (92.3 ± 28.7 μVs vs 67.6 ± 26.2 μVs, P < .001). Among those with nonstrict LBBB, mean QRSd was similar but QRSA was significantly greater among women than men (96.0 ± 25.0 μVs vs 63.6 ± 26.2 μVs, P < .001). QRSA was similar among men and women with strict LBBB (P = .533). Female sex was associated with better long-term outcomes in an unadjusted model (hazard ratio 0.623, confidence interval 0.454–0.857, P = .004) but sex no longer predicted outcomes after accounting for differences in QRSA. CONCLUSIONS: Our study suggests that sex-specific differences in LV dyssynchrony contribute to greater CRT benefit among women. Standard QRSd and morphology assessments seem to underestimate the extent of LV electrical dyssynchrony among women with LBBB

Studying the pharmaceutical film coating process with terahertz sensing, optical coherence tomography and numerical modelling

Terahertz in-line sensing was successfully demonstrated on a production scale setting for measuring the coating thickness of individual pharmaceutical tablets during the film coating process. This paper reports on our recent research progress to combine terahertz in-line sensing, optical coherence tomography and numerical modelling in a lab scale setting to better understand the pharmaceutical film coating process

The significance of the amorphous potential energy landscape for dictating glassy dynamics and driving solid-state crystallisation.

The fundamental origins surrounding the dynamics of disordered solids near their characteristic glass transitions continue to be fiercely debated, even though a vast number of materials can form amorphous solids, including small-molecule organic, inorganic, covalent, metallic, and even large biological systems. The glass-transition temperature, Tg, can be readily detected by a diverse set of techniques, but given that these measurement modalities probe vastly different processes, there has been significant debate regarding the question of why Tg can be detected across all of them. Here we show clear experimental and computational evidence in support of a theory that proposes that the shape and structure of the potential-energy surface (PES) is the fundamental factor underlying the glass-transition processes, regardless of the frequency that experimental methods probe. Whilst this has been proposed previously, we demonstrate, using ab initio molecular-dynamics (AIMD) simulations, that it is of critical importance to carefully consider the complete PES - both the intra-molecular and inter-molecular features - in order to fully understand the entire range of atomic-dynamical processes in disordered solids. Finally, we show that it is possible to utilise this dependence to directly manipulate and harness amorphous dynamics in order to control the behaviour of such solids by using high-powered terahertz pulses to induce crystallisation and preferential crystal-polymorph growth in glasses. Combined, these findings provide compelling evidence that the PES landscape, and the corresponding energy barriers, are the ultimate controlling feature behind the atomic and molecular dynamics of disordered solids, regardless of the frequency at which they occur

Field calibration of sediment flux dependent river incision

Bed erosion and sediment transport are ubiquitous and linked processes in rivers. Erosion can either be modeled as a “detachment limited” function of the shear stress exerted by the flow on the bed, or as a “transport limited” function of the sediment flux capacity of the flow. These two models predict similar channel profiles when erosion rates are constant in space in time, but starkly contrasting behavior in transient settings. Traditionally detachment limited models have been used for bedrock rivers, whereas transport limited models have been used in alluvial settings. In this study we demonstrate that rivers incising into a substrate of loose, but very poorly sorted relict glacial sediment behave in a detachment limited manner. We then develop a methodology by which to both test the appropriate incision model and constrain its form. Specifically we are able to tightly constrain how incision rates vary as a function of the ratio between sediment flux and sediment transport capacity in three rivers responding to deglaciation in the Ladakh Himalaya, northwest India. This represents the first field test of the so-called “tools and cover” effect along individual rivers