Quantitative neostriatal neuroanatomy as a basis of frontostriatal circuit dysfunction in neuropsychiatric disease

Background and Purpose: Neuropsychiatric diseases are protean, affecting cognition, emotion and behaviour, including such diseases as reactions to traumatic stress (post-traumatic stress disorder), cerebrovascular disease and the neurodegenerative dementias. There has been much interest in understanding the neural basis of neuropsychiatric disease. A model that has been employed to investigate such disease has been the endophenotype, a restricted set of phenotypic or clinical features that may have a more specific structural and hence, genetic basis. An example of an endophenotype is frontal-executive neuropsychological function, localised to the neural substrate of dorsolateral prefrontal cortex frontostriatal circuit. Consequently, it is possible to explore the structural basis of an endophenotype by studying the components of neural circuits carrying such functions. Thus, frontostriatal circuits may be useful as a structural basis for endophenotypes related to frontal cognitive function. These circuits extensively mediate cognition, emotion and behaviour within humans. The caudate nucleus and putamen, comprising the human neostriatum, serve crucial roles within frontostriatal circuits. The caudate and putamen may thus serve as a potential, quantifiable component of the structural basis for endophenotypes. It was hypothesized that functional change may be reflected in structural changes in the neostriatum due to neuroplasticity. Thus functional activation or disconnection might impact upon the structure of the caudate or putamen. Other corticostriatal circuits in addition to frontostriatal circuits may thus be affected. These studies were designed to measure the volume of the neostriatum as a quantified neuroanatomical basis of the endophenotype of frontostriatal dysfunction within specific neuropsychiatric diseases. <...

Exploring the affordances of a worked example offloaded from a textbook

In designing a set of instructional materials to use in his classroom, a teacher heavily offloaded items (e.g., worked examples, practice questions, exercises) from school-based materials and textbooks. At a cursory level, one may easily dismiss this as a thoughtless lifting of curricular materials. But upon careful analysis – as is detailed in this paper – a different picture emerges. In this paper, we describe and analyse how this teacher adapted one of many worked examples, beyond its typical use, during instruction to develop students’ conceptual understanding of proportionality. We argue that he noticed and harnessed multiple affordances in a single item that most teachers may overlook, without the need to modify the example, and propose a notion of “affordance space” as a lens to view teachers’ design of instructional materials.The study reported in this paper is part of a larger research project known as “Big Ideas in School Mathematics Curriculum” (Grant number: OER 31/19 BK) funded by the Office of Educational Research, National Institute of Education, Nanyang Technological University, Singapore

Saccadic Eye Movement Characteristics in Adult Niemann-Pick Type C Disease: Relationships with Disease Severity and Brain Structural Measures

Niemann-Pick Type C disease (NPC) is a rare genetic disorder of lipid metabolism. A parameter related to horizontal saccadic peak velocity was one of the primary outcome measures in the clinical trial assessing miglustat as a treatment for NPC. Neuropathology is widespread in NPC, however, and could be expected to affect other saccadic parameters. We compared horizontal saccadic velocity, latency, gain, antisaccade error percentage and self-paced saccade generation in 9 adult NPC patients to data from 10 age-matched controls. These saccadic measures were correlated with appropriate MRI-derived brain structural measures (e.g., dorsolateral prefrontal cortex, frontal eye fields, supplemental eye fields, parietal eye fields, pons, midbrain and cerebellar vermis) and with measures of disease severity and duration. The best discriminators between groups were reflexive saccade gain and the two volitional saccade measures. Gain was also the strongest correlate with disease severity and duration. Most of the saccadic measures showed strongly significant correlations with neurophysiologically appropriate brain regions. While our patient sample is small, the apparent specificity of these relationships suggests that as new diagnostic methods and treatments become available for NPC, a broader range of saccadic measures may be useful tools for the assessment of disease progression and treatment efficacy.No external funding was received for this study. JCLL self-funded computational, travel and accommodation costs to conduct his component of this research in Melbourne

Shape alterations in the striatum in chorea-acanthocytosis

Chorea-acanthocytosis (ChAc) is an uncommon autosomal recessive disorder due to mutations of the VPS13A gene, which encodes for the membrane protein chorein. ChAc presents with progressive limb and orobuccal chorea, but there is often a marked dysexecutive syndrome. ChAc may first present with neuropsychiatric disturbance such as obsessive-compulsive disorder (OCD), suggesting a particular role for disruption to striatal structures involved in non-motor frontostriatal loops, such as the head of the caudate nucleus. Two previous studies have suggested a marked reduction in volume in the caudate nucleus and putamen, but did not examine morphometric change

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Striatal morphology, frontostriatal circuits and functional correlates in neurodegenerative disease

© 2017 Dr. Jeffrey Chee Leong LooiThis thesis comprises five major sections, based on research work that I have led via an international network of collaborators that I established. The studies in this thesis are targeted at characterising quantitative measures of the structural integrity of recurrent fronto-striato-pallido-thalamo-cortical neural circuits and the relationship of such measures to clinical manifestations of neurodegenerative disease. Section 1 presents the foundational basis of my conceptualisation of quantitative measurement of human brain neuroanatomical structures (shape and volume – morphology), specifically, the striatum, as a means of developing in vivo biomarkers that correlate to clinical intermediate phenotypic manifestations (endophenotypes) of neurodegenerative disease. I describe here the international collaborative research network I established to conduct the research program embodied in this thesis. Section 2 involves the results of studies of the in vivo morphology of the striatum in neurodegenerative diseases in which neuropathology of the striatum has been implicated, comparing relative differences in striatal morphology between disease groups. In Section 3, I extend the work in Section 2 by examining whether quantitative morphology (morphometry) of the striatum correlates to endophenotypic cognitive, emotional, behavioural and motoric manifestations of the specific neurodegenerative diseases. In Section 4, the theoretical underpinning of the conceptualisation of the thalamus as another target for quantitative morphology and correlation to endophenotype, as well as the development of an innovative quantitative manual measurement method for the thalamus, is described. Through the works in Sections 1-4, I had come to conceptualise a subcortical connectome (Section 5): a quantitative mapping of the hubs and spokes of recurrent neuroanatomical circuits, as well as potentially the spaces between the structures underlying and connecting to the cortex. In Section 5, I also describe the development of a further vision for my collaborative research program. Section 1: The first two chapters describe the theory and hypotheses underpinning my research on the quantitative morphometry (measurement of shape and volume) of fronto-striato-pallido-thalamo-cortical (frontostriatal) circuit hubs in neurodegenerative disease. Chapter 1 describes the conceptual background for the study of striatal morphology, a key hub of frontostriatal circuits, as a potential biomarker in neurodegenerative disease. Chapter 2 extends the striatal morphology biomarker model to the frontotemporal dementias towards establishing potential intermediate phenotypes (endophenotypes). Chapter 3 describes the Australian, US, Scandinavian Imaging Exchange (AUSSIE) research network I established to conduct the research program and to expand our knowledge of the role of the subcortical connectome as a potential biomarker in neurodegenerative disease. Section 2: Chapters 4-7 describe the application of the theory and methods outlined in section 1, initially in differentiating between neurodegenerative disease groups that have striatal morphologic change implicated as part of disease progression. Chapters 3 and 4 describe cross-sectional studies of differential striatal morphometry in frontotemporal dementia subtypes and Alzheimer’s disease (AD). Chapter 5 describes the application of striatal morphometry to progressive supranuclear palsy (PSP), whilst Chapter 6 describes cross-sectional studies of differential striatal morphometry in Huntington’s disease (HD), frontotemporal dementia (FTD) and Alzheimer’s disease. Section 3: Chapters 8-10 describe the extension of the striatal morphometric work to investigate functional correlations of morphology with clinical manifestations of the cognitive, emotional and motor circuits subserved by frontostriatal circuits, i.e. towards establishing an endophenotype. Chapters 7 and 8 describe correlations of striatal morphometry with executive dysfunction and gait disturbance in a cohort of persons with age-related white matter change respectively. Chapter 9 describes correlations of striatal morphometry with measures of behavioural change in frontotemporal dementia. Section 4: Chapters 11-12 describe development of methods for further research into another hub in fronto-striatal circuits (Chapter 10). Chapter 10 describes the characterisation of another crucial hub in frontostriatal circuits, the thalamus, and the rationale for further investigation. Chapter 11 describes the development of a method for manual neuroanatomical measurement of the thalamus for quantification of its shape and volume, i.e. morphology, in neurodegenerative disease. Section 5: Chapter 13 describes the conceptualisation of the overarching concept of the subcortical connectome to direct further research extending to other key subcortical structures and spaces in neurodegenerative disease. This thesis describes the development of quantitative measures of the shape and volume of crucial brain neurocircuit hubs (quantified morphology = morphometry) in human neurodegenerative disease that correlate to clinical cognitive, emotional, behavioural and motoric manifestations of disease aimed towards developing endophenotypes.

PRACTICAL DESIGN PROCEDURES FOR SEMI-CONTINUOUS BRACED FRAMES

Master'sMASTER OF ENGINEERIN

Interpretation of morphological descriptors on nanocellulose from oil palm frond fibers under weak acid, strong acid, and enzymatic treatments

Surface properties of the nanocellulose network from oil palm frond fibers have been modeled in this work by using a fractal model namely the generalized Cauchy process (GCP) to investigate the local fiber distribution and their geometrical effect on the loading capacity. Using the GCP model, the performance of the nanocellulose network under different treatment processes is quantified by interpreting the dual-fractal properties, namely power-law scaling in the local growth (variance) and correlation function, with independent scaling parameters. Our observations indicated a strong correlation between the fractal dimension of nanocellulose and the type and concentration of treatment chemicals, underlining its sensitivity to treatment variations. Additionally, we investigated the organization of cellulose nanocrystals within the morphological structure through simulated three-dimensional network topology, offering insights into pore distribution and aggregation formation. Furthermore, we delved into the influence of crosslinking on loading capacity. Our findings demonstrated a significant reduction in loading test result inconsistencies, emphasizing the enhanced stability and reliability of crosslinked nanocellulose. This research also highlighted the controlled release capabilities of crosslinked nanocellulose, positioning it as a promising candidate for tailored applications in sustained delivery systems

Explicating factual and subjective science knowledge : knowledge as a mediator of news attention and attitudes

Communication scholars have conflicting views on the relationship between exposure to science news and knowledge, and its subsequent influence on attitudes. Such mixed sentiments could arise from the vague definition of knowledge. Therefore, this paper explicates science knowledge into factual knowledge and subjective knowledge. It also compares the mediating roles of both types of knowledge between news attention and public support for science and technology (S&T). A survey of 967 Singaporeans showed that news attention was positively related to both factual and subjective knowledge. The findings revealed a stronger relationship between subjective knowledge and news attention than factual knowledge and news attention. Additionally, factual knowledge was positively related to public support for S&T, but subjective knowledge was negatively related to public support for S&T. The contrasting directions of these associations demonstrate that factual and subjective knowledge are two distinct dimensions of knowledge. Practically, the findings can inform policymakers and communication practitioners about effective public education and engagement initiatives. This study also provided guidelines for newsmakers in news reporting about S&T.MOE (Min. of Education, S’pore)Accepted versio

Care, competency, or honesty? Framing emergency preparedness messages and risks for nuclear energy in Singapore

It is imperative to provide emergency preparedness messages so that the public can react appropriately to potential nuclear crises. Considering the mass media's extensive audience outreach, this study investigates how emergency preparedness message frames and the type of communication channels can influence individuals’ trust in government, risk perceptions, and acceptance of nuclear energy development in a neighboring country. A 4 (Emergency preparedness message frame: competence vs. care vs. honesty vs. control) × 2 (Communication channel: social media vs. traditional media) between-subjects factorial experiment was conducted online with 600 participants. Messages centered on care influenced participants’ trust in government the most. Messages disseminated through traditional media impacted participants’ trust in government more than social media. Participants’ trust in government and risk perceptions mediated the relationship between message frames and the types of communication channel on their acceptance of nuclear energy development in a neighboring country. Theoretical implications, practical implications, and directions for future research are discussed.NRF (Natl Research Foundation, S’pore)Accepted versio