Explainable Deep Learning for Medical Imaging Classification

Machine learning is increasingly being applied to medical imaging tasks. However, the black box\u27\u27 nature of techniques such as deep learning has inhibited the interpretability and trustworthiness of these methods, and therefore their clinical utility. In recent years, explainability methods have been developed to allow better interrogation of these approaches.This thesis presents the novel application of explainable deep learning to several medical imaging tasks, to investigate its potential in patient safety and research. It presents the novel application of explainable deep learning to the detection of aneurysm clips in CT brains for MRI safety. It also presents the novel application of explainable deep learning to the detection of confounding pathology in radiology report texts for dataset curation. Furthermore, it makes novel contributions to Parkinson’s research, using explainable deep learning to identify progressive brain changes in MRI brain scans, and to identify differences in the brains of non-manifesting carriers of Parkinson\u27s genetic risk variants in MRI brain scans. In each case, convolutional neural networks were developed for classification of data, and Shapley Additive exPlanations (SHAP) were used to explain predictions. A novel pipeline was developed to apply SHAP to volumetric medical imaging data.The application of explainable deep learning to various types of data and task demonstrates the flexibility of the combination of convolutional neural networks and SHAP. Additionally, these applications highlight the importance of combining explainability with clinical expertise, to check the viability of the models and to ensure that they meet a clinical need. These novel applications represent useful new tools for safety and research, and potentially for improvement of clinical care

Heat & Social Cooperation: The Effects of Thermal Stress on Altruism

Recent literature has highlighted the effects of temperature on economic outcomes and violence in humans, on both the interpersonal and intergroup levels: as temperatures rise, humans are more likely to exhibit increased aggression and agitation. However, little research has been done on how pro-social behaviors like cooperation and altruism among humans might respond to increased temperatures. As extreme heat events increase in frequency, will humans and communities work together in the face of adverse shocks and crises? Leveraging experimental data collected randomized controlled trails held in 4 locations across the world, this paper seeks to establish a relationship between thermal stress and altruistic behaviors. Additionally, we examine whether a trigger, in this case loss in a competition over a shared resource, has any effect on altruism when interacted with extreme heat. Using a linear probability model, we find that there is little evidence for a link between altruism and thermal stress

'Lost years' : West Indian women writing and publishing in Britain c.1960 to 1979.

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN023189 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The Use of Thermal Techniques for the Characterization and Selection of Natural Biomaterials.

In this paper we explore the ability of thermal analysis to check elastin and collagen integrity in different biomaterial applications. Differential Scanning Calorimetry (DSC) has been used to analyze the first and second order transitions of the biological macromolecules in the hydrated and dehydrated state. First, we report the characterization of control cardiovascular tissues such as pericardium, aortic wall and valvular leaflet. Their thermal properties are compared to pure elastin and pure collagen. Second, we present results obtained on two collagen rich tissues: pericardia with different chemical treatments and collagen with physical treatments. Finally, more complex cardiovascular tissues composed of elastin and collagen are analyzed and the effect of detergent treatment on the physical structure of collagen and elastin is brought to the fore

Protein kinase a-regulated assembly of a MEF2·HDAC4 repressor complex controls c-jun expression in vascular smooth muscle cells

Vascular smooth muscle cells (VSMCs) maintain the ability to modulate their phenotype in response to changing environmental stimuli. This phenotype modulation plays a critical role in the development of most vascular disease states. In these studies, stimulation of cultured vascular smooth muscle cells with platelet-derived growth factor resulted in marked induction of c-jun expression, which was attenuated by protein kinase Cδ and calcium/calmodulin-dependent protein kinase inhibition. Given that these signaling pathways have been shown to relieve the repressive effects of class II histone deacetylases (HDACs) on myocyte enhancer factor (MEF) 2 proteins, we ectopically expressed HDAC4 and observed repression of c-jun expression. Congruently, suppression of HDAC4 by RNA interference resulted in enhanced c-jun expression. Consistent with these findings, mutation of the MEF2 cis-element in the c-jun promoter resulted in promoter activation during quiescent conditions, suggesting that the MEF2 cis-element functions as a repressor in this context. Furthermore, we demonstrate that protein kinase A attenuates c-Jun expression by promoting the formation of a MEF2-HDAC4 repressor complex by inhibiting salt-inducible kinase 1. Finally, we document a physical interaction between c-Jun and myocardin, and we document that forced expression of c-Jun represses the ability of myocardin to activate smooth muscle gene expression. Thus, MEF2 and HDAC4 act to repress c-Jun expression in quiescent VSMCs, protein kinase A enhances this repression, and platelet-derived growth factor derepresses c-Jun expression through calcium/calmodulin-dependent protein kinases and novel protein kinase Cs. Regulation of this molecular "switch" on the c-jun promoter may thus prove critical for toggling between the activated and quiescent VSMC phenotypes

Pediatric anesthesia in Europe:Variations within uniformity

Organization of healthcare strongly differs between European countries and results in country-specific requirements in postgraduate medical training. Within the European Union (EU), the European Board of Anaesthesiology has set recommendations of training for the Specialty of Anaesthesiology including standards for Postgraduate Medical Specialist training including a description for providing service in pediatric anesthesia. However, these standards are advisory and not mandatory. Here we aimed to review the current state and associated challenges of pediatric anesthesia training in Europe. We report an important country-specific variability both in training and regulations of practice of pediatric anesthesia in the EU and in the United Kingdom. The requirements for training in pediatric anesthesia varies between nothing specified (Belgium) or providing anesthesia with direct supervision to a minimum of 50 cases below 5 years of age (Germany) to 3–6 month clinical practice in a specialized pediatric hospital (France). Likewise, the regulations for providing anesthesia to children varies from no regulations at all (Belgium) to age specific requirements and centralization of all children below 4 years of age to specified centers (United Kingdom). Officially recognized pediatric anesthesia fellowship programs are not available in most countries of Europe. It remains unclear if and how country-specific differences in pediatric anesthesia training are associated with clinical outcomes in pediatric perioperative care. There is converging interest and support for the establishment of a European pediatric anesthesia curriculum.</p

Decellularization of pericardial tissue and its impact on tensile viscoelasticity and glycosaminoglycan content

Bovine pericardium is a collagenous tissue commonly used as a natural biomaterial in the fabrication of cardiovascular devices. For tissue engineering purposes, this xenogeneic biomaterial must be decellularized to remove cellular antigens. With this in mind, three decellularization protocols were compared in terms of their effectiveness to extract cellular materials, their effect on glycosaminoglycan (GAG) content and, finally, their effect on tensile biomechanical behavior. The tissue decellularization was achieved by treatment with t-octyl phenoxy polyethoxy ethanol (Triton X-100), tridecyl polyethoxy ethanol (ATE) and alkaline treatment and subsequent treatment with nucleases (DNase/RNase). The quantified residual DNA content (3.0 ± 0.4%, 4.4 ± 0.6% and 5.6 ± 0.7% for Triton X-100, ATE and alkaline treatment, respectively) and the absence of nuclear structures (hematoxylin and eosin staining) were indicators of effective cell removal. In the same way, it was found that the native tissue GAG content decreased to 61.6 ± 0.6%, 62.7 ± 1.1% and 88.6 ± 0.2% for Triton X-100, ATE and alkaline treatment, respectively. In addition, an alteration in the tissue stress relaxation characteristics was observed after alkaline treatment. We can conclude that the three decellularization agents preserved the collagen structural network, anisotropy and the tensile modulus, tensile strength and maximum strain at failure of native tissue