Brain-Wide Analysis of the Supraspinal Connectome Reveals Anatomical Correlates to Functional Recovery After Spinal Injury

The supraspinal connectome is essential for normal behavior and homeostasis and consists of numerous sensory, motor, and autonomic projections from brain to spinal cord. Study of supraspinal control and its restoration after damage has focused mostly on a handful of major populations that carry motor commands, with only limited consideration of dozens more that provide autonomic or crucial motor modulation. Here, we assemble an experimental workflow to rapidly profile the entire supraspinal mesoconnectome in adult mice and disseminate the output in a web-based resource. Optimized viral labeling, 3D imaging, and registration to a mouse digital neuroanatomical atlas assigned tens of thousands of supraspinal neurons to 69 identified regions. We demonstrate the ability of this approach to clarify essential points of topographic mapping between spinal levels, measure population-specific sensitivity to spinal injury, and test the relationships between region-specific neuronal sparing and variability in functional recovery. This work will spur progress by broadening understanding of essential but understudied supraspinal populations

Improving spatially resolved MSI analysis of tissue sections for DMPK and toxicity studies

The aim of the work presented herein was to re-evaluate the sample preparation pipeline for mass spectrometry imaging (MSI) experiments focusing on metabolite distributions and drug disposition. The work evaluated the steps from sample collection to quantitative interpretation of the results. A major focus of the work was set on the integration of the evaluated and newly developed workflows with orthogonal tissue imaging techniques. The work evaluated the effects of sample collection in formalin and subsequent preparation into formalin-fixed, paraffin embedded tissues. Overall, these treatments were found to substantially alter the tissue metabolome and distort metabolite and drug distributions, validating the current ‘gold standard’ of fresh-frozen tissues for metabolite and drug disposition focused MSI studies. These high-quality tissues require commonly cryo-sectioning to enable MSI analysis. Sample embedding strategies were explored to allow simultaneous preparation and analysis of several tissue specimens at once to increase technical reproducibility. To achieve highest preservation of the specimens, a novel embedding medium based on a hydroxypropyl-methylcellulose and polyvinylpyrrolidone hydrogel was developed. Within the frame of this work, strategies to decontaminate prepared tissue sections prior to MSI analysis will be reviewed, to minimize the infection risk when handling human tissues or specimen from infection models. Irradiation with UV-C light was found to be a suited decontamination as it enables accurate elucidation of endogenous biodistributions whilst only inflicting minor alterations to the tissue metabolome. The utility of a novel DESI setup based on a triple-quadrupole mass spectrometer was described and its application to elucidate drug disposition within tissues. The quantitative relationship of DESI- and MALDI-MSI were explored and some of the newly developed and established workflows were utilized in a multi-omics approach to elucidate the toxicokinetic effects of polymyxin B1 in a model of drug induced nephrotoxicity.Open Acces

Science handbook

2003 handbook for the faculty of Scienc

Science handbook

2003 handbook for the faculty of Scienc

Education and Social Work handbook

2004 handbook for the faculty of Education and Social Wor

Science handbook

2004 handbook for the faculty of Scienc

Automatic Population of Structured Reports from Narrative Pathology Reports

There are a number of advantages for the use of structured pathology reports: they can ensure the accuracy and completeness of pathology reporting; it is easier for the referring doctors to glean pertinent information from them. The goal of this thesis is to extract pertinent information from free-text pathology reports and automatically populate structured reports for cancer diseases and identify the commonalities and differences in processing principles to obtain maximum accuracy. Three pathology corpora were annotated with entities and relationships between the entities in this study, namely the melanoma corpus, the colorectal cancer corpus and the lymphoma corpus. A supervised machine-learning based-approach, utilising conditional random fields learners, was developed to recognise medical entities from the corpora. By feature engineering, the best feature configurations were attained, which boosted the F-scores significantly from 4.2% to 6.8% on the training sets. Without proper negation and uncertainty detection, the quality of the structured reports will be diminished. The negation and uncertainty detection modules were built to handle this problem. The modules obtained overall F-scores ranging from 76.6% to 91.0% on the test sets. A relation extraction system was presented to extract four relations from the lymphoma corpus. The system achieved very good performance on the training set, with 100% F-score obtained by the rule-based module and 97.2% F-score attained by the support vector machines classifier. Rule-based approaches were used to generate the structured outputs and populate them to predefined templates. The rule-based system attained over 97% F-scores on the training sets. A pipeline system was implemented with an assembly of all the components described above. It achieved promising results in the end-to-end evaluations, with 86.5%, 84.2% and 78.9% F-scores on the melanoma, colorectal cancer and lymphoma test sets respectively

Neurological and Mental Disorders

Mental disorders can result from disruption of neuronal circuitry, damage to the neuronal and non-neuronal cells, altered circuitry in the different regions of the brain and any changes in the permeability of the blood brain barrier. Early identification of these impairments through investigative means could help to improve the outcome for many brain and behaviour disease states.The chapters in this book describe how these abnormalities can lead to neurological and mental diseases such as ADHD (Attention Deficit Hyperactivity Disorder), anxiety disorders, Alzheimer’s disease and personality and eating disorders. Psycho-social traumas, especially during childhood, increase the incidence of amnesia and transient global amnesia, leading to the temporary inability to create new memories.Early detection of these disorders could benefit many complex diseases such as schizophrenia and depression

Science handbook

2004 handbook for the faculty of Scienc