A Novel ISO 26262-Compliant Test Bench to Assess the Diagnostic Coverage of Software Hardening Techniques against Digital Components Random Hardware Failures

This paper describes a novel approach to assess detection mechanisms and their diagnostic coverage, implemented using embedded software, designed to identify random hardware failures affecting digital components. In the literature, many proposals adopting fault injection methods are available, with most of them focusing on transient faults and not considering the functional safety standards requirements. This kind of proposal can benefit developers involved in the automotive market, where strict safety and cost requirements make the adoption of software-only strategies convenient. Hence, we have focused our efforts on compliance with the ISO 26262 automotive functional safety standard. The approach concerns permanent faults affecting microcontrollers and it provides a mapping between the failure mode described in part 11 of the Standard and the chosen fault models. We propose a test bench designed to inject permanent failures into an emulated microcontroller and determine which of them are detected by the embedded software. The main contribution of this paper is a novel fault injection manager integrated with the open-source software GCC, GDB, and QEMU. This test bench manages all the assessment phases, from fault generation to fault injection and the ISA emulation management, up to the classification of the simulation results

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

The neurocognitive gains of diagnostic reasoning training using simulated interactive veterinary cases

The present longitudinal study ascertained training-associated transformations in the neural underpinnings of diagnostic reasoning, using a simulation game named “Equine Virtual Farm” (EVF). Twenty participants underwent structural, EVF/task-based and resting-state MRI and diffusion tensor imaging (DTI) before and after completing their training on diagnosing simulated veterinary cases. Comparing playing veterinarian versus seeing a colorful image across training sessions revealed the transition of brain activity from scientific creativity regions pre-training (left middle frontal and temporal gyrus) to insight problem-solving regions post-training (right cerebellum, middle cingulate and medial superior gyrus and left postcentral gyrus). Further, applying linear mixed-effects modelling on graph centrality metrics revealed the central roles of the creative semantic (inferior frontal, middle frontal and angular gyrus and parahippocampus) and reward systems (orbital gyrus, nucleus accumbens and putamen) in driving pre-training diagnostic reasoning; whereas, regions implicated in inductive reasoning (superior temporal and medial postcentral gyrus and parahippocampus) were the main post-training hubs. Lastly, resting-state and DTI analysis revealed post-training effects within the occipitotemporal semantic processing region. Altogether, these results suggest that simulation-based training transforms diagnostic reasoning in novices from regions implicated in creative semantic processing to regions implicated in improvised rule-based problem-solving

Clinical application of high throughput molecular screening techniques for pharmacogenomics.

Genetic analysis is one of the fastest-growing areas of clinical diagnostics. Fortunately, as our knowledge of clinically relevant genetic variants rapidly expands, so does our ability to detect these variants in patient samples. Increasing demand for genetic information may necessitate the use of high throughput diagnostic methods as part of clinically validated testing. Here we provide a general overview of our current and near-future abilities to perform large-scale genetic testing in the clinical laboratory. First we review in detail molecular methods used for high throughput mutation detection, including techniques able to monitor thousands of genetic variants for a single patient or to genotype a single genetic variant for thousands of patients simultaneously. These methods are analyzed in the context of pharmacogenomic testing in the clinical laboratories, with a focus on tests that are currently validated as well as those that hold strong promise for widespread clinical application in the near future. We further discuss the unique economic and clinical challenges posed by pharmacogenomic markers. Our ability to detect genetic variants frequently outstrips our ability to accurately interpret them in a clinical context, carrying implications both for test development and introduction into patient management algorithms. These complexities must be taken into account prior to the introduction of any pharmacogenomic biomarker into routine clinical testing