Non-invasive Diagnostic Measures of Sensorineural Hearing Loss in Chinchillas

According to the World Health Organization, disabling hearing loss affects nearly 466 million people worldwide. Sensorineural hearing loss (SNHL), which is characterized as damage to the inner ear (e.g., cochlear hair cells) and/or to the neural pathways connecting the inner ear and brain, accounts for 90% of all disabling hearing loss. More concerning is that significant perceptual and physiological aspects of SNHL remain “hidden” from standard clinical diagnostics. Hidden hearing loss (HHL) manifests as the inability to understand speech in loud, noisy environments (e.g., listening in a noisy restaurant) despite a normal audiogram (i.e., normal detection of soft sounds). Recently, HHL has been suggested to result from cochlear synaptopathy, a significant loss of inner-hair-cell/ afferent-nerve synaptic terminals after an acoustic over-exposure causing “only” a temporary threshold shift (TTS), e.g., after a rock concert. In this study, three physiological non-invasive diagnostic measures of HHL will be evaluated in chinchillas: otoacoustic emissions, auditory brainstem responses, and middle-ear-muscle reflex strength. As a first step, the effect of anesthesia will be evaluated. Four animals will be tested twice while awake and then also twice while under anesthesia (xylazine and ketamine). The repeatability, accuracy, and precision of each measure will be examined. Future work will include collecting these measures before and after TTS-inducing noise exposure. The long-term goal of this study is to establish and characterize reliable and efficient HHL measures in the lab using our noise-induced synaptopathy chinchilla model, and then to translate the animal results into a plausible clinical HHL diagnostic for humans

Detecting, distinguishing, and spatiotemporally tracking photogenerated charge and heat at the nanoscale

Since dissipative processes are ubiquitous in semiconductors, characterizing how electronic and thermal energy transduce and transport at the nanoscale is vital for understanding and leveraging their fundamental properties. For example, in low-dimensional transition metal dichalcogenides (TMDCs), excess heat generation upon photoexcitation is difficult to avoid since even with modest injected exciton densities, exciton-exciton annihilation still occurs. Both heat and photoexcited electronic species imprint transient changes in the optical response of a semiconductor, yet the unique signatures of each are difficult to disentangle in typical spectra due to overlapping resonances. In response, we employ stroboscopic optical scattering microscopy (stroboSCAT) to simultaneously map both heat and exciton populations in few-layer \ch{MoS2} on relevant nanometer and picosecond length- and time scales and with 100-mK temperature sensitivity. We discern excitonic contributions to the signal from heat by combining observations close to and far from exciton resonances, characterizing photoinduced dynamics for each. Our approach is general and can be applied to any electronic material, including thermoelectrics, where heat and electronic observables spatially interplay, and lays the groundwork for direct and quantitative discernment of different types of coexisting energy without recourse to complex models or underlying assumptions.Comment: 22 pages, 4 figures, SI included as ancilliary fil

Spectrally Resolved Photodynamics of Individual Emitters in Large-Area Monolayers of Hexagonal Boron Nitride.

Hexagonal boron nitride (h-BN) is a 2D, wide band gap semiconductor that has recently been shown to display bright room-temperature emission in the visible region, sparking immense interest in the material for use in quantum applications. In this work, we study highly crystalline, single atomic layers of chemical vapor deposition grown h-BN and find predominantly one type of emissive state. Using a multidimensional super-resolution fluorescence microscopy technique we simultaneously measure spatial position, intensity, and spectral properties of the emitters, as they are exposed to continuous wave illumination over minutes. As well as low emitter heterogeneity, we observe inhomogeneous broadening of emitter line-widths and power law dependency in fluorescence intermittency; this is strikingly similar to previous work on quantum dots. These results show that high control over h-BN growth and treatment can produce a narrow distribution of emitter type and that surface interactions heavily influence the photodynamics. Furthermore, we highlight the utility of spectrally resolved wide-field microscopy in the study of optically active excitations in atomically thin two-dimensional materials.Junior Research Fellowship, Trinity College. EPSRC Doctoral Training Award (EP/M506485) EPSRC Doctoral Training Centre in Graphene Technology (EP/L016087/1) EPSRC Cambridge NanoDTC (EP/L015978/1) Royal Society University Research Fellowship (UF120277) European Union Horizon 202

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments

Active Adenoviral Vascular Penetration by Targeted Formation of Heterocellular Endothelial–epithelial Syncytia

The endothelium imposes a structural barrier to the extravasation of systemically delivered oncolytic adenovirus (Ad). Here, we introduced a transendothelial route of delivery in order to increase tumor accumulation of virus particles (vp) beyond that resulting from convection-dependent extravasation alone. This was achieved by engineering an Ad encoding a syncytium-forming protein, gibbon ape leukemia virus (GALV) fusogenic membrane glycoprotein (FMG). The expression of GALV was regulated by a hybrid viral enhancer-human promoter construct comprising the human cytomegalovirus (CMV) immediate-early enhancer and the minimal human endothelial receptor tyrosine kinase promoter (“eTie1”). Endothelial cell-selectivity of the resulting Ad-eTie1-GALV vector was demonstrated by measuring GALV mRNA transcript levels. Furthermore, Ad-eTie1-GALV selectively induced fusion between infected endothelial cells and uninfected epithelial cells in vitro and in vivo, allowing transendothelial virus penetration. Heterofusion of infected endothelium to human embryonic kidney 293 (HEK 293) cells, in mixed in vitro cultures or in murine xenograft models, permitted fusion-dependent transactivation of the replication-deficient Ad-eTie1-GALV, due to enabled access to viral E1 proteins derived from the HEK 293 cytoplasm. These data provide evidence to support our proposed use of GALV to promote Ad penetration through tumor-associated vasculature, an approach that may substantially improve the efficiency of systemic delivery of oncolytic viruses to disseminated tumors

The Monument as Ruin: Natality, Spectrality, and the History of the Image in the Tirana Independence Monument

This article examines the Tirana Independence Monument, first inaugurated in November of 2012 on the hundredth anniversary of Albanian independence from the Ottoman Empire. The monument, designed by Visar Obrija and Kai Roman Kiklas, swiftly fell into disrepair until it was recently renovated in November of 2015. The article analyzes the monument’s function in terms of its doubled existence as a sign of perpetual natality (the possibility of the rebirth of national consciousness) and as a ruin with a spectral pseudo-presence (as an object that continually reminds us of the disjunctures that divorce the present from its historicity). It considers the way the monument’s inauguration relates to the politics of monumentality in contemporary Albania, and argues that the monument’s gradual ruination between 2012 and 2015 can be read as a particular manifestation of the history of the image in late capitalist society.Keywords: spectrality, natality, monumentality, Albania, Tirana, independence, national identity, grid, public sculptur

The Alterity of the Image: the Distant Spectator and Films about the Syrian Revolution and War

Images of the Syrian crisis, circulating on the international film festival circuit as well as in mainstream and social media, help to construct narratives about those events, people and places. This article explores how three Syrian documentaries – Silvered Water: Syria Self-Portrait, The War Show and Little Gandhi – appeal to their distant spectators and how the international film festival circuit shapes their aesthetic form. While the use of citizen videos in news reporting has generated a sense of familiarity with the audio-visual style and iconography of Syrian conflict imagery, these films invite us to look at their footage in a different way, foregrounding an experience of cultural distance through an emphasis on the formal qualities of the image. By focusing on the aesthetic rather than merely evidentiary qualities of these documentaries, I draw out a particular kind of transnational cinematic encounter in which, to borrow John Berger’s words, ‘meaning is a response not only to the known, but to the unknown’. Drawing upon the work of Berger and Laura Marks, the article offers a new conceptualization of distant spectatorship in terms of the alterity of the image

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype