New approaches to the analysis of eye movement behaviour across expertise while viewing brain MRIs

Abstract Brain tumour detection and diagnosis requires clinicians to inspect and analyse brain magnetic resonance images. Eye-tracking is commonly used to examine observers’ gaze behaviour during such medical image interpretation tasks, but analysis of eye movement sequences is limited. We therefore used ScanMatch, a novel technique that compares saccadic eye movement sequences, to examine the effect of expertise and diagnosis on the similarity of scanning patterns. Diagnostic accuracy was also recorded. Thirty-five participants were classified as Novices, Medics and Experts based on their level of expertise. Participants completed two brain tumour detection tasks. The first was a whole-brain task, which consisted of 60 consecutively presented slices from one patient; the second was an independent-slice detection task, which consisted of 32 independent slices from five different patients. Experts displayed the highest accuracy and sensitivity followed by Medics and then Novices in the independent-slice task. Experts showed the highest level of scanning pattern similarity, with medics engaging in the least similar scanning patterns, for both the whole-brain and independent-slice task. In the independent-slice task, scanning patterns were the least similar for false negatives across all expertise levels and most similar for experts when they responded correctly. These results demonstrate the value of using ScanMatch in the medical image perception literature. Future research adopting this tool could, for example, identify cases that yield low scanning similarity and so provide insight into why diagnostic errors occur and ultimately help in training radiologists

Compact spectrometer based on disordered multi-mode interferometer

We demonstrate a compact (40 ${\mu}$m $\times$ 260 ${\mu}$m) spectrometer based on multimode interference aided by scattering of light from random SiO$_2$-filled hole arrays on a silicon-on-insulator platform. We characterize the performance of the spectrometer for wavelengths around 1310 nm, and report that the spectrometer can reconstruct a broadband $\sim$ 67 nm source, as well as Lorentzian probes of $\sim$ 1 nm bandwidth. This compact nanometer level resolution spectrometer can be fabricated at a low cost for lab-on-a-chip sensing and imaging applications.Comment: 11 pages, 6 figure

Targeting danger molecules in tendinopathy: the HMGB1/TLR4 axis

Objectives: To seek evidence of the danger molecule, high-mobility group protein B1 (HMGB1) expression in human tendinopathy and thereafter, to explore mechanisms where HMGB1 may regulate inflammatory mediators and matrix regulation in human tendinopathy. Methods: Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from patients undergoing arthroscopic stabilisation surgery. Markers of inflammation and HMGB1 were quantified by reverse transcriptase PCR (RT-PCR) and immunohistochemistry. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction and used through passage 3. In vitro effects of recombinant HMGB1 on tenocyte matrix and inflammatory potential were measured using quantitative RT-PCR, ELISA and immunohistochemistry staining. Results: Tendinopathic tissues demonstrated significantly increased levels of the danger molecule HMGB1 compared with control tissues with early tendinopathy tissue showing the greatest expression. The addition of recombinant human HMGB1 to tenocytes led to significant increase in expression of a number of inflammatory mediators, including interleukin 1 beta (IL-1β), IL-6, IL-33, CCL2 and CXCL12, in vitro. Further analysis demonstrated rhHMGB1 treatment resulted in increased expression of genes involved in matrix remodelling. Significant increases were observed in Col3, Tenascin-C and Decorin. Moreover, blocking HMGB1 signalling via toll-like receptor 4 (TLR4) silencing reversed these key inflammatory and matrix changes. Conclusion: HMGB1 is present in human tendinopathy and can regulate inflammatory cytokines and matrix changes. We propose HMGB1 as a mediator driving the inflammatory/matrix crosstalk and manipulation of the HMGB1/TLR4 axis may offer novel therapeutic approaches targeting inflammatory mechanisms in the management of human tendon disorders

Non-diffracting beam generated from a photonic integrated circuit based axicon-like lens

We demonstrate an on-chip silicon-on-insulator (SOI) device to generate a non-diffracting beam of ≈850 µm length from a diffractive axicon-like lens etched using a low resolution (200 nm feature size, 250 nm gap) deep-ultraviolet lithographic fabrication. The device consists of circular gratings with seven stages of 1x2 multimode interferometers. We present a technique to apodize the gratings azimuthally by breaking up the circles into arcs which successfully increased the penetration depth in the gratings from ≈5 µm to ≈60 µm. We characterize the device’s performance by coupling 1300±50 nm swept source laser in to the chip from the axicon and measuring the out-coupled light from a grating coupler. Further, we also present the implementation of balanced homodyne detection method for the spectral characterization of the device and show that the position of the output lobe of the axicon does not change significantly with wavelength

Fibroblast activation and inflammation in frozen shoulder

Introduction: Frozen shoulder is a common, fibro-proliferative disease characterised by the insidious onset of pain and progressively restricted range of shoulder movement. Despite the prevalence of this disease, there is limited understanding of the molecular mechanisms underpinning the pathogenesis of this debilitating disease. Previous studies have identified increased myofibroblast differentiation and proliferation, immune cell influx and dysregulated cytokine production. We hypothesised that subpopulations within the fibroblast compartment may take on an activated phenotype, thus initiating the inflammatory processes observed in frozen shoulder. Therefore, we sought to evaluate the presence and possible pathogenic role of known stromal activation proteins in Frozen shoulder, Methods: Shoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients undergoing shoulder stabilisation surgery. Fibroblast activation marker expression (CD248, CD146, VCAM and PDPN, FAP) was quantified using immunohistochemistry. Control and diseased fibroblasts were cultured for in vitro studies from capsule biopsies from instability and frozen shoulder surgeries, respectively. The inflammatory profile and effects of IL-1β upon diseased and control fibroblasts was assessed using ELISA, immunohistochemistry and qPCR. Results: Immunohistochemistry demonstrated increased expression of fibroblast activation markers CD248, CD146, VCAM and PDPN in the frozen shoulder group compared with control (p < 0.05). Fibroblasts cultured from diseased capsule produced elevated levels of inflammatory protein (IL-6, IL-8 & CCL-20) in comparison to control fibroblasts. Exposing control fibroblasts to an inflammatory stimuli, (IL-1ß) significantly increased stromal activation marker transcript and protein expression (CD248, PDPN and VCAM). Conclusions: These results show that fibroblasts have an activated phenotype in frozen shoulder and this is associated with inflammatory cytokine dysregulation. Furthermore, it supports the hypothesis that activated fibroblasts may be involved in regulating the inflammatory and fibrotic processes involved in this disease

Exploring the intersections between Novel Psychoactive Substances (NPS) and other substance use in a police custody suite setting in the North East of England

Aims: Novel psychoactive substances (NPS), a range of plant-based/synthetic substances that mimic effects of other illicit substances (e.g. cannabis), are now illegal in the United Kingdom (May 2016) to produce/supply. Negative behavioural consequences of NPS use mean that users frequently transgress the law are arrested and detained in police custody suites. Evidence shows a link between traditional substance use and offending behaviour, with significant police time spent on alcohol-related incidents. We explore the intersections between NPS and other substances with police staff and users in custody; specifically the similarities and differences in treatment, management and policing of these substances. Methods: A qualitative study using semistructured interviews and thematic analysis. We recruited 15 police staff (4 women/11 men) and 25 NPS users (9 women/16 men). Results: Police staff perceived NPS users to be extremely volatile in custody and reported feeling less knowledgeable about how to manage and respond to their needs compared to other substance users (e.g. alcohol, heroin). Users rarely took NPS in isolation and often compared them to other illicit substances, balancing effects versus costs. Conclusion: NPS use has a striking effect on custody work, primarily because of unpredictable user behaviour, adding further pressure to already overstretched police staff

Stromal ‘activation’ markers do not confer pathogenic activity in tendinopathy

Tendinopathy is a highly prevalent musculoskeletal pathology associated with incremental injury as result of repetitive microtrauma. We sought to explore the physiological significance of stromal “activation” signatures in a human model of tendinopathy. Torn supraspinatus tendon and matched intact subscapularis tendon biopsies were collected from patients undergoing shoulder surgery while healthy tendon was collected from patients undergoing anterior cruciate ligament (ACL) reconstruction. Expression of stromal activation markers was analyzed at transcript/protein level using qRT‐PCR and immunohistochemistry. Gene expression of stromal activation markers was silenced by siRNA‐mediated knockdown or induced by IL‐1β stimulation. Expression of “activation” markers podoplanin, VCAM‐1 and CD248 was identified in human tendon tissue. Podoplanin and VCAM‐1 expression were significantly increased in tendinopathic tissue. Knockdown of podoplanin and VCAM‐1 in normal and tendinopathic tenocytes did not have any significant effect on expression of matrix genes COL1A1, COL3A1, TNC, or DCN. Similarly, no changes in release of inflammatory mediators IL‐6, IL‐8, and CCL2 were observed in podoplanin/VCAM‐1 knockdown cultures. Our data suggest that silencing expression of stromal “activation” markers does not affect the intrinsic inflammatory profile or matrix regulatory behavior of tenocytes. We propose that the term “activation” is more appropriately reflected by alterations in tenocyte behavior that induce changes in the stromal microenvironment and overall tissue architecture rather than identification through potentially arbitrary phenotypic traits

A Cannabinoid CB 1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects

Peer reviewedPostprin

Graphene oxide integrated silicon photonics for detection of vapour phase volatile organic compounds

From Springer Nature via Jisc Publications RouterHistory: received 2020-01-07, accepted 2020-05-17, registration 2020-05-20, pub-electronic 2020-06-12, online 2020-06-12, collection 2020-12Publication status: PublishedAbstract: The optical response of a graphene oxide integrated silicon micro-ring resonator (GOMRR) to a range of vapour phase Volatile Organic Compounds (VOCs) is reported. The response of the GOMRR to all but one (hexane) of the VOCs tested is significantly higher than that of the uncoated (control) silicon MRR, for the same vapour flow rate. An iterative Finite Difference Eigenmode (FDE) simulation reveals that the sensitivity of the GO integrated device (in terms of RIU/nm) is enhanced by a factor of ~2, which is coupled with a lower limit of detection. Critically, the simulations reveal that the strength of the optical response is determined by molecular specific changes in the local refractive index probed by the evanescent field of the guided optical mode in the device. Analytical modelling of the experimental data, based on Hill-Langmuir adsorption characteristics, suggests that these changes in the local refractive index are determined by the degree of molecular cooperativity, which is enhanced for molecules with a polarity that is high, relative to their kinetic diameter. We believe this reflects a molecular dependent capillary condensation within the graphene oxide interlayers, which, when combined with highly sensitive optical detection, provides a potential route for discriminating between different vapour phase VOCs