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A woman in her 30s was referred to an otolaryngologist with an acute onset of aural fullness, noise sensitivity, unilateral sudden onset hearing loss, vertigo and tinnitus. She had a confirmed COVID-19 infection 5 weeks prior. A pure tone audiogram confirmed sensorineural hearing loss. MRI identified an empty sella of the pituitary gland and without an obvious cause for hearing loss. Oral prednisolone and betahistine were prescribed, and her audiovestibular symptoms slowly improved over the subsequent months. The patient continues to experience intermittent tinnitus. Refereed/Peer-reviewed

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease in urgent need of disease biomarkers for the assessment of promising therapeutic candidates in clinical trials. Raman spectroscopy is an attractive technique for identifying disease related molecular changes due to its simplicity. Here, we describe a fibre optic fluid cell for undertaking spontaneous Raman spectroscopy studies of human biofluids that is suitable for use away from a standard laboratory setting. Using this system, we examined serum obtained from patients with ALS at their first presentation to our centre ( n = 66) and 4 months later ( n = 27). We analysed Raman spectra using bounded simplex-structured matrix factorization (BSSMF), a generalisation of non-negative matrix factorisation which uses the distribution of the original data to limit the factorisation modes (spectral patterns). Biomarkers associated with ALS disease such as measures of symptom severity, respiratory function and inflammatory/immune pathways (C3/C-reactive protein) correlated with baseline Raman modes. Between visit spectral changes were highly significant ( p = 0.0002) and were related to protein structure. Comparison of Raman data with established ALS biomarkers as a trial outcome measure demonstrated a reduction in required sample size with BSSMF Raman. Our portable, simple to use fibre optic system allied to BSSMF shows promise in the quantification of disease-related changes in ALS over short timescales.

The diagnosis of muscle disorders ("myopathies") can be challenging and new biomarkers of disease are required to enhance clinical practice and research. Despite advances in areas such as imaging and genomic medicine, muscle biopsy remains an important but time-consuming investigation. Raman spectroscopy is a vibrational spectroscopy application that could provide a rapid analysis of muscle tissue, as it requires no sample preparation and is simple to perform. Here, we investigated the feasibility of using a miniaturised, portable fibre optic Raman system for the rapid identification of muscle disease. Samples were assessed from 27 patients with a final clinico-pathological diagnosis of a myopathy and 17 patients in whom investigations and clinical follow-up excluded myopathy. Multivariate classification techniques achieved accuracies ranging between 71-77%. To explore the potential of Raman spectroscopy to identify different myopathies, patients were subdivided into mitochondrial and non-mitochondrial myopathy groups. Classification accuracies were between 74-89%. Observed spectral changes were related to changes in protein structure. These data indicate fibre optic Raman spectroscopy is a promising technique for the rapid identification of muscle disease that could provide real time diagnostic information. The application of fibre optic Raman technology raises the prospect of in vivo bedside testing for muscle diseases which would significantly streamline the diagnostic pathway of these disorders.

Recent technological advances have led to the development of small wearable microelectronic sensors (accelerometers) that detect motion, gravitational acceleration, and velocity with six degrees of freedom (forward-backward, updown, and side-to-side plus rotational vectors). We have used these motion sensors to create new analytical tools called biokinetographs (BKGs). BKGs allow for more precise screening, diagnosing, monitoring, assessment and predicting of function of elderly people as they ambulate using sophisticated analysis of the unique electronic motion signature of each person. Remarkable visual differences in “functional walking signatures” are evident on the BKGs between fallers and non-fallers. This presentation will summarize our current efforts to translate this new technology into novel clinical and research tools for improving function, reducing injurious falls, and diagnosing orthopedic and neurological conditions for elderly people.

DNA origami is one of the most effective tools for bottom-up construction of novel objects and devices at the nanometer-scale. However, many applications require larger structures than can be obtained with the conventional single-stranded scaffold, typically 7249 nucleotides. Here, we address this limitation by developing custom-made single-stranded scaffolds that bind pre-assembled origami tiles and induce their one-dimensional organization in high yields. Our synthetic method allows the conversion of multiple repetitive and unique sequences into correctly assembled, large backbones, and to finely tune the position and frequency of each building block. Granted with these regions, three and five origami tiles were successfully arranged in 1-D with the aid of one or two scaffolds, forming a nano-"railroad track". This new method increases length scale in DNA origami without increasing cost and complexity, and is anticipated to increase the yield of other approaches aiming to assemble large origami structures.

Elastic transient deformation of a half space due to a point of hot fluid injection at constant rate is studied in this paper. The half space ground surface is modelled as a thermostatic pervious boundary. Biot’s three-dimensional consolidation theory with thermal effect is introduced to derive the analytical solutions of the transient consolidation deformation due to a point of hot fluid injection. The stratum is modelled as a saturated isotropic poroelastic half space. Using Laplace and Hankel integral transforms, closed-form solutions of the horizontal and vertical displacements are obtained. The maximum ground surface horizontal displacement can be exactly derived, and it is around 30% of the maximum ground surface vertical displacement. Moreover, the golden ratio appears in the maximum ground surface horizontal displacement and corresponding vertical displacement of a half space. The study concludes that golden ratio emerges in this phenomenon, and the horizontal displacement should be properly considered in the prediction of vertical displacement induced by a hot fluid injection. The study can provide better understanding of the hot fluid injection induced responses of an isotropic porous elastic half space.

Highly monodisperse sequence-defined spherical nucleic acids (HE12–SNAs) for delivery of small-molecule anticancer drugs., We report a spherical nucleic acid (SNA) system for the delivery of BKM120, an anticancer drug for treatment of chronic lymphocytic leukemia (CLL). While promising for cancer treatment, this drug crosses the blood–brain barrier causing significant side-effects in patients. The DNA nanoparticle encapsulates BKM120 in high efficiency, and is unparalleled in its monodispersity, ease of synthesis and stability in different biological media and in serum. These DNA nanostructures demonstrate efficient uptake in human cervical cancer (HeLa) cells, and increased internalization of cargo. In vitro studies show that BKM120-loaded nanoparticles promote apoptosis in primary patient CLL lymphocytes, and act as sensitizers of other antitumor drugs, without causing non-specific inflammation. Evaluation of this drug delivery system in vivo shows long circulation times up to 24 hours, full body distribution, accumulation at tumor sites and minimal leakage through the blood–brain barrier. Our results demonstrate the great potential of these delivery vehicles as a general platform for chemotherapeutic drug delivery.

This work presents the closed-form solutions of the long-term thermal stresses, displacements and temperature increment of the cross-anisotropic strata subjected to a point heat source at great depth. The medium is initially modeled with cross-anisotropic mechanical and thermal properties. Under this assumption, the properties of the materials are different between the planes on and normal to the isotropic plane. Using Hankel and Fourier transforms, this paper presents the analytic solutions to soils or rocks affected by the point heat source, such as the repositories of nuclear wastes. The general solutions are further simplified to cases of materials with isotropic mechanical properties, and they are finally extended to fully isotropic in each property of the strata. Based on numerical results, the thermal stresses, displacements and temperature change of the thermoelastic half space are significantly affected by the anisotropy of mechanical and thermal properties of the strata.

Thermoelastic response due to a line heat source is analog to poroelastic reaction caused by a fluid line sink. In this study, the strata are modeled as a thermoelastic or poroelastic half space bounded by horizontal surface in the mathematical model. Thermomechanics and poromechanics are applied on the formulation of basic governing equations, and an analogy is drawn to show the similarity. Using Hankel transform technique and approaching symbolic integral through Mathematica, the closed-form solutions of the horizontal and vertical displacements due to a fluid line sink are obtained. The displacements produced by the line heat source are described through analog quantities between thermoelasticity and poroelasticity. The solutions can be applied to dewater operations and build waste repository.