Latent Transformer Models for out-of-distribution detection

Any clinically-deployed image-processing pipeline must be robust to the full range of inputs it may be presented with. One popular approach to this challenge is to develop predictive models that can provide a measure of their uncertainty. Another approach is to use generative modelling to quantify the likelihood of inputs. Inputs with a low enough likelihood are deemed to be out-of-distribution and are not presented to the downstream predictive model. In this work, we evaluate several approaches to segmentation with uncertainty for the task of segmenting bleeds in 3D CT of the head. We show that these models can fail catastrophically when operating in the far out-of-distribution domain, often providing predictions that are both highly confident and wrong. We propose to instead perform out-of-distribution detection using the Latent Transformer Model: a VQ-GAN is used to provide a highly compressed latent representation of the input volume, and a transformer is then used to estimate the likelihood of this compressed representation of the input. We demonstrate this approach can identify images that are both far- and near- out-of-distribution, as well as provide spatial maps that highlight the regions considered to be out-of-distribution. Furthermore, we find a strong relationship between an image's likelihood and the quality of a model's segmentation on it, demonstrating that this approach is viable for filtering out unsuitable images

Digital LED Pixels: Instructions for use and a characterization of their properties

This article details how to control light emitting diodes (LEDs) using an ordinary desktop computer. By combining digitally addressable LEDs with an off-the-shelf microcontroller (Arduino), multiple LEDs can be controlled independently and with a high degree of temporal, chromatic, and luminance precision. The proposed solution is safe (can be powered by a 5-V battery), tested (has been used in published research), inexpensive (∼ $60 +$2 per LED), highly interoperable (can be controlled by any type of computer/operating system via a USB or Bluetooth connection), requires no prior knowledge of electrical engineering (components simply require plugging together), and uses widely available components for which established help forums already exist. Matlab code is provided, including a ‘minimal working example’ of use suitable for use by beginners. Properties of the recommended LEDs are also characterized, including their response time, luminance profile, and color gamut. Based on these, it is shown that the LEDs are highly stable in terms of both luminance and chromaticity, and do not suffer from issues of warm-up, chromatic shift, and slow response times associated with traditional CRT and LCD monitor technology

Separability of neural responses to standardised mechanical stimulation of limbs

Abstract Considerable scientific and technological efforts are currently being made towards the development of neural prostheses. Understanding how the peripheral nervous system responds to electro-mechanical stimulation of the limb, will help to inform the design of prostheses that can restore function or accelerate recovery from injury to the sensory motor system. However, due to differences in experimental protocols, it is difficult, if not impossible, to make meaningful comparisons between different peripheral nerve interfaces. Therefore, we developed a low-cost electronic system to standardise the mechanical stimulation of a rat’s hindpaw. Three types of mechanical stimulations, namely, proprioception, touch and nociception were delivered to the limb and the electroneurogram signals were recorded simultaneously from the sciatic nerve with a 16-contact cuff electrode. For the first time, results indicate separability of neural responses according to stimulus type as well as intensity. Statistical analysis reveal that cuff contacts placed circumferentially, rather than longitudinally, are more likely to lead to higher classification rates. This flexible setup may be readily adapted for systematic comparison of various electrodes and mechanical stimuli in rodents. Hence, we have made its electro-mechanical design and computer programme available onlin

Exome Sequencing Identifies ZNF644 Mutations in High Myopia

Myopia is the most common ocular disorder worldwide, and high myopia in particular is one of the leading causes of blindness. Genetic factors play a critical role in the development of myopia, especially high myopia. Recently, the exome sequencing approach has been successfully used for the disease gene identification of Mendelian disorders. Here we show a successful application of exome sequencing to identify a gene for an autosomal dominant disorder, and we have identified a gene potentially responsible for high myopia in a monogenic form. We captured exomes of two affected individuals from a Han Chinese family with high myopia and performed sequencing analysis by a second-generation sequencer with a mean coverage of 30× and sufficient depth to call variants at ∼97% of each targeted exome. The shared genetic variants of these two affected individuals in the family being studied were filtered against the 1000 Genomes Project and the dbSNP131 database. A mutation A672G in zinc finger protein 644 isoform 1 (ZNF644) was identified as being related to the phenotype of this family. After we performed sequencing analysis of the exons in the ZNF644 gene in 300 sporadic cases of high myopia, we identified an additional five mutations (I587V, R680G, C699Y, 3′UTR+12 C>G, and 3′UTR+592 G>A) in 11 different patients. All these mutations were absent in 600 normal controls. The ZNF644 gene was expressed in human retinal and retinal pigment epithelium (RPE). Given that ZNF644 is predicted to be a transcription factor that may regulate genes involved in eye development, mutation may cause the axial elongation of eyeball found in high myopia patients. Our results suggest that ZNF644 might be a causal gene for high myopia in a monogenic form

Are we ready for genetic testing for primary open-angle glaucoma?

Following a dramatic reduction in the cost of genotyping technology in recent years, there have been significant advances in the understanding of the genetic basis of glaucoma. Glaucoma patients represent around a quarter of all outpatient activity in the UK hospital eye service and are a huge burden for the National Health Service. A potential benefit of genetic testing is personalised glaucoma management, allowing direction of our limited healthcare resources to the glaucoma patients who most need it. Our review aims to summarise recent discoveries in the field of glaucoma genetics and to discuss their potential clinical utility. While genome-wide association studies have now identified over ten genes associated with primary open-angle glaucoma (POAG), individually, variants in these genes are not predictive of POAG in populations. There are data suggesting some of these POAG variants are associated with conversion from ocular hypertension to POAG and visual field progression among POAG patients. However, these studies have not been replicated yet and such genetic testing is not currently justified in clinical care. In contrast, genetic testing for inherited early-onset disease in relatives of POAG patients with a known genetic mutation is of clear benefit; this can support either regular review to commence early treatment when the disease develops, or discharge from ophthalmology services of relatives who do not carry the mutation. Genetic testing for POAG at a population level is not currently justified

A simplified microwave-based motion detector for home cage activity monitoring in mice

Background: Locomotor activity of rodents is an important readout to assess well-being and physical health, and is pivotal for behavioral phenotyping. Measuring homecage-activity with standard and cost-effective optical methods in mice has become difficult, as modern housing conditions (e.g. individually ventilated cages, cage enrichment) do not allow constant, unobstructed, visual access. Resolving this issue either makes greater investments necessary, especially if several experiments will be run in parallel, or is at the animals' expense. The purpose of this study is to provide an easy, yet satisfying solution for the behavioral biologist at novice makers level. Results: We show the design, construction and validation of a simplified, low-cost, radar-based motion detector for home cage activity monitoring in mice. In addition we demonstrate that mice which have been selectively bred for low levels of anxiety-related behavior (LAB) have deficits in circadian photoentrainment compared to CD1 control animals. Conclusion: In this study we have demonstrated that our proposed low-cost microwave-based motion detector is well-suited for the study of circadian rhythms in mice

The genetics of myopia

Myopia is the most common eye condition worldwide and its prevalence is increasing. While changes in environment, such as time spent outdoors, have driven myopia rates, within populations myopia is highly heritable. Genes are estimated to explain up to 80% of the variance in refractive error. Initial attempts to identify myopia genes relied on family studies using linkage analysis or candidate gene approaches with limited progress. More genome-wide association study (GWAS) approaches have taken over, ultimately resulting in the identification of hundreds of genes for refractive error and myopia, providing new insights into its molecular machinery. These studies showed myopia is a complex trait, with many genetic variants of small effect influencing retinal signaling, eye growth and the normal process of emmetropization. The genetic architecture and its molecular mechanisms are still to be clarified and while genetic risk score prediction models are improving, this knowledge must be expanded to have impact on clinical practice