Functional and structural organisation of the visual system in human albinism

Albinism is a developmental disorder which involves the misrouting of optic nerve projections, leading to an abnormally organised visual system. Despite the aberrant input, people with albinism have relatively normal vision and experience the world in much the same way as their peers. This thesis explores the functional and structural organisation of visual cortex in human albinism using magnetic resonance imaging (MRI) techniques. This thesis covers four main experiments. Experiment 1 deals with stimulus optimisation for population receptive field (pRF) mapping in healthy adults. pRF mapping is a functional MRI technique for estimating cortical receptive field characteristics non-invasively. In this experiment, a stimulus configuration optimized for short acquisition time requirements is presented and implemented in subsequent experiments. Experiment 2 combines the pRF approach for retinotopic localization with diffusion MRI tractography in healthy adults to show evidence for direct extrastriate connections of the human optic radiation. The optic radiation is the principal white matter pathway for relaying retinal input to visual cortex, and typically considered a projection to primary visual cortex. In this experiment, independent pathways of the optic radiation to visual areas V2 and V3 are identified, and functional-structural methodologies developed for Experiment 4. Experiment 3 investigates the functional organisation of visual cortex in participants with albinism. A pRF mapping approach was implemented, identifying abnormal retinotopic organisation and altered receptive field properties in extrastriate visual cortex. In addition, we explore evidence for and against a dual receptive field model of visual field representation in albinism. Experiment 4 examines the structural and functional connectivity of early visual system in human albinism. In particular, differences in white matter microstructure and inter- hemispheric visual map connectivity are found between participants with albinism and a cohort of healthy controls. This thesis highlights the capacity and limitations of developmental plasticity in human albinism

Aging Effects of Caenorhabditis elegans Ryanodine Receptor Variants Corresponding to Human Myopathic Mutations

Delaying the decline in skeletal muscle function will be critical to better maintenance of an active life-style in old age. The skeletal muscle ryanodine receptor, the major intracellular membrane channel through which calcium ions pass to elicit muscle contraction, is central to calcium ion balance, and is hypothesized to be a significant factor for age-related decline in muscle function. The nematode Caenorhabditis elegans is a key model system for the study of human aging and strains with modified C. elegans ryanodine receptors corresponding to human myopathic variants linked with malignant hyperthermia and related conditions were generated. The altered response of these strains to pharmacological agents reflected results of human diagnostic tests for individuals with these pathogenic variants. Involvement of nerve cells in the C. elegans responses may relate to rare medical symptoms concerning the central nervous system that have been associated with ryanodine receptor variants. These single amino acid modifications in C. elegans also conferred a reduction in lifespan and an accelerated decline in muscle integrity with age, supporting the significance of ryanodine receptor function for human aging

Assessment of Chronic Illness-Related Cognitive Fusion: Preliminary Development and Validation of a New Scale with an IBD Sample

Although research recognizes the advantages of creating specific content measures, no specific measure of chronic illness-related cognitive fusion had been developed to date. The current study presents the development and validation of the Cognitive Fusion Questionnaire-Chronic Illness (CFQ-CI) in a sample of inflammatory bowel disease (IBD) patients and the analysis of the role of this construct in the psychological health of those patients. Results indicated that the 7-item CFQ-CI was a unidimensional measure of cognitive fusion in patients with chronic illnesses, and that scores had adequate/good internal consistency and construct, convergent, and discriminant validity. This study also showed that chronic illness-related cognitive fusion as assessed by the CFQ-CI acted as a mediator in the association between both IBD-related symptoms and shame with quality of life. The development of the CFQ-CI may thus contribute to a better understanding of the mechanisms influencing functional outcomes in chronic illness

Barriers to participation in a placebo-surgical trial for lumbar spinal stenosis

© 2019 Background: Placebo-controlled trials are an important tool when assessing the efficacy of spinal surgical procedures. The most common spinal surgical procedure in older adults is decompression for lumbar spinal stenosis. Before conducting a placebo-surgical trial on decompression surgery, an investigation of patients’ willingness to participate in a placebo-controlled trial of decompression surgery and barriers to participation were explored. Materials: An online survey. Methods: Descriptive analyses of demographic and clinical data, and participants' willingness to participate in a placebo-surgical trial. Logistic regression was used to examine potential predictors of willingness to participate. Two independent researchers performed a coded framework analysis of patients’ barriers to participation. Results: 68 patients were invited and 63 participants completed the survey (91.3% response, mean (SD) age 69.5 (10.9) years, 52% females), 71% suffered from moderate to very severe pain. Ten participants (15.9%) were willing to participate in a placebo-controlled trial. Being married was associated with decreased odds of participating (OR: 0.2; 95% CI, 0.05 to 0.8; P = 0.03), while the main barriers were a lack of information about the procedure, reassurance of a positive outcome with participation, and concerns about the risks and benefits of placebo surgery. Conclusions: A minority of patients with lumbar spinal stenosis were willing to participate in a placebo-controlled trial of surgery. The identified barriers indicate that educating eligible patients about: the need for placebo-surgical trials, the personal risks and benefits of participation, and the importance and potential benefits of placebo trials to others, may be crucial to ensure adequate recruitment into the placebo-controlled surgical trial. Conclusions should be read cautiously however, given the small sample size present in this study

SUcceSS, SUrgery for Spinal Stenosis: Protocol of a randomised, placebo-controlled trial

© Author(s) (or their employer(s)) 2019. Introduction: Central lumbar spinal stenosis (LSS) is a common cause of pain, reduced function and quality of life in older adults. Current management of LSS includes surgery to decompress the spinal canal and alleviate symptoms. However, evidence supporting surgical decompression derives from unblinded randomised trials with high cross-over rates or cohort studies showing modest benefits. This protocol describes the design of the SUrgery for Spinal Stenosis (SUcceSS) trial-the first randomised placebo-controlled trial of decompressive surgery for symptomatic LSS. Methods and analysis: SUcceSS will be a prospectively registered, randomised placebo-controlled trial of decompressive spinal surgery. 160 eligible participants (80 participants/group) with symptomatic LSS will be randomised to either surgical spinal decompression or placebo surgical intervention. The placebo surgical intervention is identical to surgical decompression in all other ways with the exception of the removal of any bone or ligament. All participants and assessors will be blinded to treatment allocation. Outcomes will be assessed at baseline and at 3, 6, 12 and 24 months. The coprimary outcomes will be function measured with the Oswestry Disability Index and the proportion of participants who have meaningfully improved their walking capacity at 3 months postrandomisation. Secondary outcomes include back pain intensity, lower limb pain intensity, disability, quality of life, anxiety and depression, neurogenic claudication score, perceived recovery, treatment satisfaction, adverse events, reoperation rate and rehospitalisation rate. Those who decline to be randomised will be invited to participate in a parallel observational cohort. Data analysis will be blinded and by intention to treat. A trial-based cost-effectiveness analysis will determine the potential incremental cost per quality-adjusted life year gained. Ethics and dissemination: Ethics approval has been granted by the NSW Health (reference:17/247/POWH/601) and the Monash University (reference: 12371) Human Research Ethics Committees. Dissemination of results will be via journal articles and presentations at national and international conferences

The teacher who teaches mathematics as a focus of study in Brazilian professional masters.

Neste artigo analisam-se 96 disserta??es, cujo foco ? o professor que ensina Matem?tica, produzidas nos mestrados profissionais da ?rea de Ensino da Capes, entre 2001 e 2012. Procura-se compreender como o pesquisador, que ? um professor, percebe os participantes de seu estudo e se relaciona com eles. O corpus da pesquisa foi analisado a partir das seguintes categorias: perfil do professor pesquisador e dos participantes; motiva??o e foco das pesquisas; e rela??o pesquisador-participantes. Os resultados evidenciam que, em muitos estudos, o professor (ou futuro professor), participante da pesquisa, ? percebido pelo pesquisador como um aprendiz, mais que como um parceiro ou colaborador. Isso sugere um distanciamento entre ambos que n?o condiz com o fato de pelo menos metade dos estudos mencionar que sua motiva??o adv?m das pr?prias trajet?rias profissionais. Al?m disso, poucas pesquisas analisam a pr?pria pr?tica do pesquisador ou refletem acerca de sua aprendizagem profissional ao realizar sua pesquisa.In this article, we analyzed 96 dissertations produced between 2001 to 2012 focused on the mathematics teacher by Professional Masters in the Teaching area of the Capes. The objective is to understand how a researcher, who is a teacher, perceives and relates to the participants of his studies. The data was analyzed from the following categories: profile of the researcher professor and of the participants; motivation and focus of research; and researcher-participant relationship. The results show how, in many cases, the teacher (or future teacher), who participated in the study it?s perceived as an apprentice rather than as a partner or collaborator. This suggests a gap between the two that does not match the fact that at least half of the studies mention that their motivation comes from their own professional trajectories. In addition, few researches analyze the researcher's own practice or reflect on his professional learning when conducting his research

A Novel Small Molecule 1,2,3,4,6-penta-O-galloyl-α-D-glucopyranose Mimics the Antiplatelet Actions of Insulin

BACKGROUND: We have shown that 1,2,3,4,6-penta-O-galloyl-α-D-glucopyranose (α-PGG), an orally effective hypoglycemic small molecule, binds to insulin receptors and activates insulin-mediated glucose transport. Insulin has been shown to bind to its receptors on platelets and inhibit platelet activation. In this study we tested our hypothesis that if insulin possesses anti-platelet properties then insulin mimetic small molecules should mimic antiplatelet actions of insulin. PRINCIPAL FINDINGS: Incubation of human platelets with insulin or α-PGG induced phosphorylation of insulin receptors and IRS-1 and blocked ADP or collagen induced aggregation. Pre-treatment of platelets with α-PGG inhibited thrombin-induced release of P-selectin, secretion of ATP and aggregation. Addition of ADP or thrombin to platelets significantly decreased the basal cyclic AMP levels. Pre-incubation of platelets with α-PGG blocked ADP or thrombin induced decrease in platelet cyclic AMP levels but did not alter the basal or PGE(1) induced increase in cAMP levels. Addition of α-PGG to platelets blocked agonist induced rise in platelet cytosolic calcium and phosphorylation of Akt. Administration of α-PGG (20 mg kg(-1)) to wild type mice blocked ex vivo platelet aggregation induced by ADP or collagen. CONCLUSIONS: These data suggest that α-PGG inhibits platelet activation, at least in part, by inducing phosphorylation of insulin receptors leading to inhibition of agonist induced: (a) decrease in cyclic AMP; (b) rise in cytosolic calcium; and (c) phosphorylation of Akt. These findings taken together with our earlier reports that α-PGG mimics insulin signaling suggest that inhibition of platelet activation by α-PGG mimics antiplatelet actions of insulin

Quality Control-Driven Image Segmentation Towards Reliable Automatic Image Analysis in Large-Scale Cardiovascular Magnetic Resonance Aortic Cine Imaging

“The final authenticated version is available online at https://doi.org/10.1007/978-3-030-32245-8_83.”© 2019, Springer Nature Switzerland AG. Recent progress in fully-automated image segmentation has enabled efficient extraction of clinical parameters in large-scale clinical imaging studies, reducing laborious manual processing. However, the current state-of-the-art automatic image segmentation may still fail, especially when it comes to atypical cases. Visual inspection of segmentation quality is often required, thus diminishing the improvements in efficiency. This drives an increasing need to enhance the overall data processing pipeline with robust automatic quality scoring, especially for clinical applications. We present a novel quality control-driven (QCD) framework to provide reliable segmentation using a set of different neural networks. In contrast to the prior segmentation and quality scoring methods, the proposed framework automatically selects the optimal segmentation on-the-fly from the multiple candidate segmentations available, directly utilizing the inherent Dice similarity coefficient (DSC) predictions. We trained and evaluated the framework on a large-scale cardiovascular magnetic resonance aortic cine image sequences from the UK Biobank Study. The framework achieved segmentation accuracy of mean DSC at 0.966, mean prediction error of DSC within 0.015, and mean error in estimating lumen area ≤17.6 mm2 for both ascending aorta and proximal descending aorta. This novel QCD framework successfully integrates the automatic image segmentation along with detection of critical errors on a per-case basis, paving the way towards reliable fully-automatic extraction of clinical parameters for large-scale imaging studies