Early adolescents in adversity: A mixed methods approach to understanding psychosocial risks across four low- and middle-income countries

Early adolescents (ages 10-14) living in low- and middle-income countries (LMICs) have heightened vulnerability to psychosocial risks, but available evidence from these settings is limited. The objective of this dissertation is to contribute evidence on psychosocial risks among early adolescents living in four LMICs. Participants were drawn from the multi-country Global Early Adolescent Study and included 10,437 early adolescents from the Democratic Republic of Congo, Malawi, Indonesia, China. In Chapter One, we introduce the dissertation’s three specific research aims. In Chapter Two, we review the literature on central concepts related to these aims. In Chapter Three, we use latent class analysis (LCA) to characterize prototypical patterns of emotional and behavioral problems among early adolescents from the four included LMICs, and explore the extent to which these patterns vary by country and sex. Results supported the existence of four subgroups across countries: Well-Adjusted, Emotional Problems, Behavioral Problems (not present in China), and Maladjusted. Despite the consistency of these patterns, there were notable contextual differences. Further, tests of measurement invariance indicated that the prevalence and nature of these classes differed by sex within each country. In Chapter Four, we build on the LCA results from the preceding chapter, using multivariate latent class regression to assess the extent to which risk and protective factors across the family, peer, school, and neighborhood levels are associated with latent class membership. Across countries, we found that childhood adversity, peer bullying behaviors, and a perceived lack of school safety were consistently associated with psychosocial challenges. In Chapter Five, we explore Indonesian early adolescents’ motivations, perceptions, and beliefs regarding bullying involvement. Building on our prior quantitative findings, we use an explanatory sequential mixed methods approach to better understand the myriad ways in which bullying involvement ties into other psychosocial challenges. Qualitative interviews yielded contextual insights into adolescents’ definitions of bullying, related risk behaviors, key drivers, social and emotional consequences, and coping strategies. Lastly, in Chapter Six, we discuss the implications of these findings for researchers, practitioners, and policymakers focused on bolstering psychosocial adjustment among vulnerable early adolescents in low-resource settings worldwide

Intranasal Deferoxamine (IN DFO) as a Treatment for Neurodegenerative Disease

Faculty advisor: Jared FineThis research was supported by the Undergraduate Research Opportunities Program (UROP)

First Report of a Novel Hepatozoon sp. in Giant Pandas (Ailuropoda melanoleuca)

The first report of giant pandas (Ailuropoda melanoleuca) infected with a novel Hepatozoon species is presented. An intraleukocytic parasite was detected via routine blood smear from a zoo-housed giant panda at the National Zoological Park. Ribosomal DNA sequences indicated a previously undescribed Hepatozoon species. Phylogenetic and distance analyses of the sequences placed it within its own branch, clustered with Old World species with carnivore (primarily ursid and mustelid) hosts. Retrospective and opportunistic testing of other individuals produced additional positive detections (17/23, 73.9%), demonstrating 100% prevalence (14/14) across five institutions. All animals were asymptomatic at time of sampling, and health implications for giant pandas remain unknown

Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease

Identifying disease-modifying therapies for neurological diseases remains one of the greatest gaps in modern medicine. Herein, we present the rationale for intranasal (IN) delivery of deferoxamine (DFO), a high-affinity iron chelator, as a treatment for neurodegenerative and neurovascular disease with a focus on its novel mechanisms. Brain iron dyshomeostasis with iron accumulation is a known feature of brain aging and is implicated in the pathogenesis of a number of neurological diseases. A substantial body of preclinical evidence and early clinical data has demonstrated that IN DFO and other iron chelators have strong disease-modifying impacts in Alzheimer’s disease (AD), Parkinson’s disease (PD), ischemic stroke, and intracranial hemorrhage (ICH). Acting by the disease-nonspecific pathway of iron chelation, DFO targets each of these complex diseases via multifactorial mechanisms. Accumulating lines of evidence suggest further mechanisms by which IN DFO may also be beneficial in cognitive aging, multiple sclerosis, traumatic brain injury, other neurodegenerative diseases, and vascular dementia. Considering its known safety profile, targeted delivery method, robust preclinical efficacy, multiple mechanisms, and potential applicability across many neurological diseases, the case for further development of IN DFO is considerable

Targeting polyamine biosynthesis to stimulate beta cell regeneration in zebrafish

Type 1 diabetes (T1D) is a disease characterized by destruction of the insulin-producing beta cells. Currently, there remains a critical gap in our understanding of how to reverse or prevent beta cell loss in individuals with T1D. Previous studies in mice discovered that pharmacologically inhibiting polyamine biosynthesis using difluoromethylornithine (DFMO) resulted in preserved beta cell function and mass. Similarly, treatment of non-obese diabetic mice with the tyrosine kinase inhibitor Imatinib mesylate reversed diabetes. The promising findings from these animal studies resulted in the initiation of two separate clinical trials that would repurpose either DFMO (NCT02384889) or Imatinib (NCT01781975) and determine effects on diabetes outcomes; however, whether these drugs directly stimulated beta cell growth remained unknown. To address this, we used the zebrafish model system to determine pharmacological impact on beta cell regeneration. After induction of beta cell death, zebrafish embryos were treated with either DFMO or Imatinib. Neither drug altered whole-body growth or exocrine pancreas length. Embryos treated with Imatinib showed no effect on beta cell regeneration; however, excitingly, DFMO enhanced beta cell regeneration. These data suggest that pharmacological inhibition of polyamine biosynthesis may be a promising therapeutic option to stimulate beta cell regeneration in the setting of diabetes

Artwrite 38

This issue of Artwrite is the collective effort of students studying the Master of Art Administration in the College of Fine Arts, UNSW working under the direction of Associate Professor Joanna MendelssohnIt concerns exhibitions and issues current in Australian art in the first half of 2008, including the Biennale of Sydney, ethics and art practice