Electrophysiological profile and monosynaptic circuitry of efferent vestibular nucleus neurons

As with other sensory modalities, the vestibular system recruits efferent circuitry to transport information from the central nervous system (CNS) to the sensory periphery. This efferent vestibular system (EVS) originates in the brainstem and terminates on vestibular hair cells and afferent fibres in the semicircular canals and otolith organs. Understanding how this central component outputs to the vestibular organs, and mediates motor and vestibular coordination, could potentially impact clinical treatment of vestibular disorders. Previous EVS work has primarily focused on the anatomy, pharmacology, synaptic mechanisms, and peripheral effects of efferent vestibular nucleus (EVN) activation. Although this work is fundamental to understanding this system and its mechanism of action, the behavioural function of the EVS is yet to be ascribed. For this, we need to appreciate the physiology of EVN neurons, and their context of activation within the CNS. In this thesis, I characterise the electrophysiological profile of EVN neurons, and trace their direct monosynaptic circuitry. My methodology includes whole-cell current- and voltage- clamp electrophysiology, and glycoproteindeficient rabies virus tracing techniques. Using these, I enrich understanding of EVN action, and hint at potential functional roles from their CNS partners. The data presented in this thesis provides novel insights into the EVS. EVN neurons are characterised with a homogeneous output, but a heterogeneous synaptic input profile. Inputs to the EVN originate from diverse areas in the brainstem and cortex. These findings suggest that the EVN modulates vestibular end organs in multiple different behavioural contexts. This work forms the basis of subsequent EVS behavioural investigations such as loss of function experiments targeting input regions via optogentic means and subsequent EVS recordings, or silencing of EVN activity and subsequent behavioural testing. Collectively, my results, these future directions, and the existing body of EVS literature, brings us closer than ever to understanding and ascribing a functional role for the EVS

Xenosialitis modulates the function of the Alzheimer’s disease associated SIGLEC3 in human THP1 macrophages

Chronic inflammation is an undisputed feature of late onset Alzheimer’s disease (LOAD). Activated microglia,found around amyloid beta (Aβ) plaques are implicated as the source of inflammation. However they are incapable of efficiently phagocytosing the plaques and therefore lead to Aβ accumulation. The molecular mechanisms responsible for this ambivalent and ultimately neurodestructive behavior of microglia remains elusive. Genome-wide association studies (GWAS) have identified polymorphisms of several genes, including SIGLEC3 and TREM2 found on microglia, which increase LOAD risk. Both proteins are involved either directly or indirectly with maintenance of homeostasis and phagocytosis. Therefore, it is conceivable that dysregulation of these proteins could cause inflammation and faulty phagocytosis as seen in LOAD patients. THP1 human monocyte-derived macrophage cell line was used as a surrogate human model system to study the role of SIGLEC3 signaling. In this regard, the influence of an immunogenic sialic acid - Neu5Gc in comparison to sialic acid - Neu5Ac, serving as a ligand to SIGLEC3, on macrophage functions was analyzed. Furthermore, in order to mimic the environment of an AD brain on a molecular level, macrophages were also chronically treated with nanomolar concentrations of Aβ. The overall hypothesis of this thesis involves the comprehensive idea that chronic inflammation occurs as a result of persistently activated microglia due to improper SIGLEC3 signaling caused by Neu5Gc. The chronically malfunctioning microglia exacerbate neurodegeneration and elicits an inappropriate response to Aβ deposition. Overall, this thesis aims at determining the underlying molecular mechanisms preceding clinically diagnosed LOAD

Abstracts and classification of graduate studies.

Thesis (Ed.M.)--Boston Universit

Development of a quality index tool to assess the completion of J88 forms for rape survivors in South Africa

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in the branch of Public Health Medicine Johannesburg November 2016Background The J88 form is important as a legal document that presents the recorded findings of the healthcare worker during the medical examination after rape has been reported through either the medical or justice system. The quality of how these forms are completed therefore becomes pertinent. There are many anecdotal references to poorly completed J88 forms in South Africa; although assumptions are made by the healthcare sector on what comprises a well completed J88 form, the measure of quality is not completely clear. Aim This study aims to develop and assess a Quality Index Tool for completed J88 forms. Methodology In the first part of the study, a Delphi process used semi-structured telephonic interviews explore the views of eight medical and eight legal experts on what factors they thought contributed to the quality of the completed J88 form. Sixty-three criteria were identified. These were ranked and refined through three rounds where the experts engaged with these issues to come to a level of agreement about what key issues affected the quality of completed J88 forms. These issues were then to be compiled into a tool to assess the quality of J88 forms. In the second part of the study a simple random sample of 160 J88 forms gathered in a larger study from cases reported to the police in 2012 were used. The forms were scored using the Quality Index Tool created in the first part of the study and inter-rater agreement was assessed. These scores were then entered into STATA 13 with province, provider and patient information like sex of the patient, nurse/doctor to determine what the general quality of the J88 forms. T-tests and ANOVAs, were performed to compare the mean score which had been standardised between different groups e.g. child vs. adult patients. A multiple regression model was built to identify patient and provider factors associated with poorer and higher quality of completion of the J88 forms and a logistic regression model was used to assess whether higher quality was associated with writing better conclusions. Results During the first round of the Delphi process, sixty three Quality Statements were identified from the in-depth interviews conducted with the experts. Experts agreed that there was substantial variation in how well the J88 was completed. They identified some factors that were relevant to the completion of the form overall like how legibly the form was completed, and identified specific criteria for different parts of the form like whether an explanation was given if a diagram was not completed. In the subsequent two rounds, consensus on these Quality Statements was sought between the experts. Only two statements achieved perfect consensus (100% agreement). Another twenty two statements achieved a level of agreement above 80%, which was the level of agreement sought in the final round. These twenty four Quality Statements were compiled to form the Quality Index Tool. In the second part of the study, the mean Quality Index Score percentage achieved for the 160 J88 forms scored was 72.1% (range from 65 to 79.2%). Of the 160 J88 forms scored, 6 (3.8%) were completed for male patients and 66 (41.25%) were completed for children (<18 years of age); 36 (22.5%) were completed by nurses. Factors associated with a better score were the patient being an adult, the healthcare worker being a nurse and performing an anal examination. It was also found that a higher score was predictive of a better conclusion in the logistic regression analysis. Conclusion Care of a rape survivor comprises counselling, clinical management and collecting evidence which can be used in the investigation and prosecution of the case. The J88 plays an important role in the latter. Overall, the quality of completion of J88s was variable. Since the Quality Index Tool predicted higher quality in the completion of conclusions it is important to ensure that provider training is intensified. The Quality Index Tool can be used by auditors and researchers who are interested in quality of medico-legal services.MT201

Psychology Case Record

CASE RECORD 1 : Personality Assessment: Undifferentiated Schizophrenia, Schizotypal Disorder, Malingering. CASE RECORD 2 : Diagnostic Clarification: Acute Polymorphic Psychotic Disorder, Adjustment Disorder, Mixed Personality Traits. CASE RECORD 3 : Diagnostic Clarification: Anankastic Personality Disorder, Obsessive Compulsive Disorder. CASE RECORD 4 : IQ Assessment : Attention Deficit Hyperactivity Disorder, Subclinical Seizures, Unspecified Intellectual Disability with Behavioural Problems. CASE RECORD 5 : Neuropsychological Assessment

Comparing visions for CAP reforms post 2015: Farmer intentions and farm bio-economic modelling

This paper illustrates the impacts of two of the potential CAP reform post 2015 scenarios using an optimising farm level model and compares results with farmers’ perception about the policy changes, captured in a farmer intentions survey. The model results suggest that beef farms suffer a loss in farm net margins under fully decoupled (up to -21%) as well as under partially decoupled scenario (up to -19%) compared to current historical single farm payments. The model also shows that farm respond by reducing the number of beef animals on farm by up to 5%. However, under a partial decoupled scenario, beef farms increase calf numbers by 15% to benefit from coupled calf payment. A survey of 1,400 beef producers with respect to their intentions toward 2020 was conducted in the Summer of 2013. A set of hypothetical payment scenarios was used to test self-reported response to a number of scenarios related to expanding and extensifying. These were compared with the modelling results and found a range of responses which could, we argue, be used for future calibration and ‘sense-checking’ of results within future modelling strategies

Augmented Pulmonary Responses to Acute Ozone Exposure in Obese Mice: Roles of TNFR2 and IL-13

Background: Acute ozone (O3) exposure results in greater inflammation and airway hyperresponsiveness (AHR) in obese versus lean mice. Objectives: We examined the hypothesis that these augmented responses to O3 are the result of greater signaling through tumor necrosis factor receptor 2 (TNFR2) and/or interleukin (IL)-13. Methods: We exposed lean wild-type (WT) and TNFR2-deficient (TNFR2–/–) mice, and obese Cpefat and TNFR2-deficient Cpefat mice (Cpefat/TNFR2–/–), to O3 (2 ppm for 3 hr) either with or without treatment with anti–IL-13 or left them unexposed. Results: O3-induced increases in baseline pulmonary mechanics, airway responsiveness, and cellular inflammation were greater in Cpefat than in WT mice. In lean mice, TNFR2 deficiency ablated O3-induced AHR without affecting pulmonary inflammation; whereas in obese mice, TNFR2 deficiency augmented O3-induced AHR but reduced inflammatory cell recruitment. O3 increased pulmonary expression of IL-13 in Cpefat but not WT mice. Flow cytometry analysis of lung cells indicated greater IL-13–expressing CD4+ cells in Cpefat versus WT mice after O3 exposure. In Cpefat mice, anti–IL-13 treatment attenuated O3-induced increases in pulmonary mechanics and inflammatory cell recruitment, but did not affect AHR. These effects of anti–IL-13 treatment were not observed in Cpefat/TNFR2–/– mice. There was no effect of anti–IL-13 treatment in WT mice. Conclusions: Pulmonary responses to O3 are not just greater, but qualitatively different, in obese versus lean mice. In particular, in obese mice, O3 induces IL-13 and IL-13 synergizes with TNF via TNFR2 to exacerbate O3-induced changes in pulmonary mechanics and inflammatory cell recruitment but not AHR

An investigation of genotype-phenotype association in a festulolium forage grass population containing genome-spanning <i>Festuca pratensis</i> chromosome segments in a <i>Lolium perenne</i> background

Alien chromosome introgression is used for the transfer of beneficial traits in plant breeding. For temperate forage grasses, much of the work in this context has focused on species within the ryegrasses (Lolium spp.) and the closely related fescues (Festuca spp.) particularly with a view to combining high forage quality with reliability and enhanced environmental services. We have analysed a L. perenne (perennial ryegrass) population containing the majority of a F. pratensis (meadow fescue) genome as introgressed chromosome segments to identify a) marker-trait associations for nutrient use and abiotic stress response across the family, and b) to assess the effects of introgression of F. pratensis genomic regions on phenotype. Using container-based assays and a system of flowing solution culture, we looked at phenotype responses, including root growth, to nitrogen and phosphorus status in the growing medium and abiotic stresses within this festulolium family. A number of significant marker/trait associations were identified across the family for root biomass on chromosomes 2, 3 and 5 and for heading date on chromosome 2. Of particular interest was a region on chromosome 2 associated with increased root biomass in phosphorus-limited conditions derived from one of the L. perenne parents. A genotype containing F. pratensis chromosome 4 as a monosomic introgression showed increased tiller number, shoot and root growth and genotypes with F. pratensis chromosome segment introgressions at different ends of chromosome 4 exhibited differential phenotypes across a variety of test conditions. There was also a general negative correlation between the extent of the F. pratensis genome that had been introgressed and root-related trait performances. We conclude that 1) the identification of alleles affecting root growth has potential application in forage grass breeding and, 2) F. pratensis introgressions can enhance quantitative traits, however, introgression can also have more general negative effects

A comparison of the retention of pathogenic Escherichia coli O157 by sprouts, leaves and fruits

The retention (binding to or association with the plant) of Escherichia coli by cut leaves and fruits after vigorous water washing was compared with that by sprouts. Retention by fruits and leaves was similar but differed from retention by sprouts in rate, effect of wounding and requirement for poly-β,1-6-N-acetyl-D-glucosamine. Escherichia coli was retained by cut ends of lettuce leaves within 5 min while more than 1 h was required for retention by the intact epidermis of leaves and fruits, and more than 1 day for sprouts. Retention after 5 min at the cut leaf edge was specific for E. coli and was not shown by the plant-associated bacteria Agrobacterium tumefaciens and Sinorhizobium meliloti. Escherichia coli was retained by lettuce, spinach, alfalfa, bean, tomato, Arabidopsis thaliana, cucumber, and pepper leaves and fruits faster than by sprouts. Wounding of leaves and fruits but not sprouts increased bacterial retention. Mutations in the exopolysaccharide synthesis genes yhjN and wcaD reduced the numbers of bacteria retained. PgaC mutants were retained by cut leaves and fruits but not by sprouts. There was no significant difference in the retention of an O157 and a K12 strain by fruits or leaves. However, retention by sprouts of O157 strains was significantly greater than K12 strains. These findings suggest that there are differences in the mechanisms of E coli retention among sprouts, and leaves and fruits