The BOLD signal and neurovascular coupling in autism

BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging) is commonly used to study differences in neuronal activity between human populations. As the BOLD response is an indirect measure of neuronal activity, meaningful interpretation of differences in BOLD responses between groups relies upon a stable relationship existing between neuronal activity and the BOLD response across these groups. However, this relationship can be altered by changes in neurovascular coupling or energy consumption, which would lead to problems in identifying differences in neuronal activity. In this review, we focus on fMRI studies of people with autism, and comparisons that are made of their BOLD responses with those of control groups. We examine neurophysiological differences in autism that may alter neurovascular coupling or energy use, discuss recent studies that have used fMRI to identify differences between participants with autism and control participants, and explore experimental approaches that could help attribute between-group differences in BOLD signals to either neuronal or neurovascular factors

The design, development and evaluation of cross-platform mobile applications and services supporting social accountability monitoring

Local government processes require meaningful and effective participation from both citizens and their governments in order to remain truly democratic. This project investigates the use of mobile phones as a tool for supporting this participation. MobiSAM, a system which aims to enhance the Social Accountability Monitoring (SAM) methodology at local government level, has been designed and implemented. The research presented in this thesis examines tools and techniques for the development of cross-platform client applications, allowing access to the MobiSAM service, across heterogeneous mobile platforms, handsets and interaction styles. Particular attention is paid to providing an easily navigated user interface (UI), as well as offering clear and concise visualisation capabilities. Depending on the host device, interactivity is also included within these visualisations, potentially helping provide further insight into the visualised data. Guided by the results obtained from a comprehensive baseline study of the Grahamstown area, steps are taken in an attempt to lower the barrier of entry to using the MobiSAM service, potentially maximising its market reach. These include extending client application support to all identified mobile platforms (including feature phones); providing multi-language UIs (in English, isiXhosa and Afrikaans); as well as ensuring client application data usage is kept to a minimum. The particular strengths of a given device are also leveraged, such as its camera capabilities and built-in Global Positioning System (GPS) module, potentially allowing for more effective engagement with local municipalities. Additionally, a Short Message Service (SMS) gateway is developed, allowing all Global System for Mobile Communications (GSM) compatible handsets access to the MobiSAM service via traditional SMS. Following an iterative, user-centred design process, a thorough evaluation of the client application is also performed, in an attempt to gather feedback relating to the navigation and visualisation capabilities. The results of which are used to further refine its design. A comparative usability evaluation using two different versions of the cross-platform client application is also undertaken, highlighting the perceived memorability, learnabilitv and satisfaction of each. Results from the evaluation reveals which version of the client application is to be deployed during future pilot studies

A study of the cytoplasmic inclusions during oogenesis, spermatogenesis, maturation, fertilisation and the first cleavage division of the egg of the mouse (Mus musculus)

LISTS OF PAPERS EMBODIED IN THIS THESIS:"A Study of the Cytoplasmic Inclusions and Nucleolar Phenomena During the Oogenesis of the Mouse", 'Quart.Journ.Micr. Sci.' , vol.75, 1933."Effect of Ultra- centrifuging the Oocytes of the Mouse", 'Nature' , vol .142 , 1938."A Cytological Study of the Centrifuged Mouse", 'Quart. Journ. Micr. Aci.' , vo1.81,1940."A Study of the Cytoplasmic Inclusions during Maturation, Fertilisation and the First Cleavage Division of the Egg of the Mouse". Accepted for publication in Quart. Journ.Micr.Soi.1940.SUBMITTED AS ADDITIONAL EVIDEIVCE OF RESEARCH: "The Effect of Increased Daily Illumination and of Reversed Day and Night on the Oestrus Cycle of the Mouse (Mus musculus)", 'Proc. Roy. óc. Edin:r, vol.60, 1940

Identification and Functional Characterization of CNS Pericytes and the Role they Play in Neurovascular Coupling in Physiological and Pathological Conditions

Brain blood flow increases, evoked by neuronal activity, power neural computation and are the basis of BOLD functional imaging. However, it is controversial whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes. The experimental work within this thesis examines capillary pericytes, and the role they play in neurovascular coupling in physiological and pathological conditions. I show that pericytes can be identified using several protein markers and that, using the same technique, pericytes can be distinguished from other perivascular cell types. I demonstrate that pericytes respond to the neurotransmitters noradrenaline and glutamate. Noradrenaline depolarizes pericytes and constricts capillaries, and this constriction reflects pericyte contraction while glutamate, mimicking neuronal activity, hyperpolarizes pericytes and dilates capillaries, and this dilation reflects pericyte relaxation. Glutamate-evoked dilation is mediated by prostaglandin E₂ or a related compound acting at EP4 receptors, but requires nitric oxide release to suppress synthesis of the vasoconstrictor 20-HETE. In pathology, I show that pericytes die when exposed to ischaemia. This may lead to pericytes irreversibly constricting capillaries and to damage of the blood-brain barrier. Pericyte death increases on reperfusion after ischaemia, and is reduced by block of glutamate receptors or Ca2+ removal, but not by scavenging reactive oxygen species. These data establish pericytes as active regulators of capillary tone and thus as potential regulators of brain blood flow. My data also suggest prevention of pericyte death as a strategy to reduce the long-lasting blood flow decrease which contributes to neuronal death after stroke. This thesis also contains a discussion of how energy supply to the brain alters with age, and how this may affect the BOLD signal

Política exterior e paz: um jogo em dois níveis?

Durante los dos periodos presidenciales de Juan Manuel Santos, la política exterior colombiana dirigió una buena parte de sus esfuerzos a solidificar, a través del involucramiento de actores internacionales, las negociaciones que se llevaban a cabo con la otrora guerrilla de las Fuerzas Armadas Revolucionarias de Colombia (FARC-EP). En el presente texto se analiza ese proceso a través de la teoría de los dos niveles de juego (two-level game theory). Además, se considera que la organización de la política exterior colombiana alrededor de la solidificación de los Diálogos de La Habana respondió a la necesidad de consolidar este proceso, de dotarlo de legitimidad entre la población y de garantizar la implementación de lo acordado. Así, a través de acciones concretas y del proceso de internacionalización en sí mismo se construyó una suerte de 'blindaje internacional' que establece restricciones a la posibilidad de dar marcha atrás a lo establecido en el Acuerdo.During the two presidential terms of Juan Manuel Santos, Colombian foreign policy focused on solidifying, through the involvement of international actors, the negotiations that were taking place with the former guerrilla of the Revolutionary Armed Forces of Colombia (farc-ep, after the initials in Spanish). In the present text, the author analyzes the process of internationalization of the peace process and the subsequent implementation of what was agreed upon through the two-level game theory. Thus, it is considered that the organization of Colombian foreign policy around the solidification of the Dialogues of Havana responded to the need to consolidate them, give them legitimacy among the population and guarantee the implementation of what was agreed upon. In addition, through concrete actions and the process of internationalization itself, a kind of 'international armor' was built, which establishes restrictions from international politics on the possibility of reversing the provisions of the Agreement

Student Engagement and Learning Approaches during COVID-19: The Role of Study Resources, Burnout Risk, and Student Leader–Member Exchange as Psychological Conditions

Objectives: The primary objective of this study was to explore the interplay of psychological conditions that influenced personal engagement among university students. As a theoretical lens through which to investigate this, the study used the job demands-resources model, the study demands-resources model, and the leader–member exchange theory. This study further aimed to explore outcomes that supported students in becoming lifelong learners (i.e., deep-learning approach). Method: Participants were undergraduate students registered at a South African university. We used a purposive, non-probability sampling strategy and employed a cross-sectional survey research design. This study used Mplus version 8.6 for the statistical analyses. Results: Results showed that the psychological conditions of meaningfulness (study resources), availability (burnout risk), and safety (student–leader–member exchange) influenced student engagement. In addition, the results showed that study demands were positively associated with student engagement, although this association can be regarded as small. Furthermore, study resources and student engagement were associated with a deep approach to learning. Conclusions: Findings from the present study demonstrated that Kahn’s theory carried implications beyond the workplace and held true in a student learning environment. Further, an exploration of the psychological conditions that led to engagement showed that the job demands-resources model and the study demands-resources model could be used to operationalise study resources as psychological meaningfulness and burnout risk as availability. Similarly, in the context of exploring the student-lecturer relationship, student leader–member exchange could be operationalised as psychological safety. Implication for Practice: Leaders in higher education are encouraged to focus not only on ensuring that students receive adequate support in terms of structures and physical resources during periods of uncertainty, such as the global COVID-19 pandemic, but to adopt a holistic approach that includes considering all the psychological conditions that encourage and promote students’ engagement

ASCENSO DE LA ULTRADERECHA EN LATINOAMÉRICA: ARGENTINA, BRASIL Y CHILE EN PERSPECTIVA COMPARADA

Even though in Argentina, Brazil and Chile, after a left ́s predominance in the executive, right-wing politicians were elected in the most recent elections, in Brazil this turn brought to power Jair Bolsonaro, a politician close to the far- right. What explains this result in the Brazilian case? The authors conclude that, although in all three cases there is evidence of a crisis of democratic values, in Brazil there is also a deep decline in support for the political system and a rejection of traditional political parties. In this sense, Bolsonaro does not represent an ideological change among the population. It is, rather, a response against the system, not a transit in the value system

The HIV Genomic Incidence Assay Meets False Recency Rate and Mean Duration of Recency Infection Performance Standards.

HIV incidence is a primary metric for epidemic surveillance and prevention efficacy assessment. HIV incidence assay performance is evaluated via false recency rate (FRR) and mean duration of recent infection (MDRI). We conducted a meta-analysis of 438 incident and 305 chronic specimens' HIV envelope genes from a diverse global cohort. The genome similarity index (GSI) accurately characterized infection stage across diverse host and viral factors. All except one chronic specimen had GSIs below 0.67, yielding a FRR of 0.33 [0-0.98] %. We modeled the incidence assay biomarker dynamics with a logistic link function assuming individual variabilities in a Beta distribution. The GSI probability density function peaked close to 1 in early infection and 0 around two years post infection, yielding MDRI of 420 [361, 467] days. We tested the assay by newly sequencing 744 envelope genes from 59 specimens of 21 subjects who followed from HIV negative status. Both standardized residuals and Anderson-Darling tests showed that the test dataset was statistically consistent with the model biomarker dynamics. This is the first reported incidence assay meeting the optimal FRR and MDRI performance standards. Signatures of HIV gene diversification can allow precise cross-sectional surveillance with a desirable temporal range of incidence detection