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Stigma negatively shapes the lives of people who use substances through criminalization processes and criminal justice involvement. This chapter draws from the authors’ lived experiences to explore the harms created by stigma at the intersection of substance use and criminal justice. Stigma produces a social context contributing to high rates of criminal justice involvement among people who use substances through inequitable social conditions, criminalization of substances, and under-resourcing of substance use services. Substance use stigma is reinforced by harmful police practices, painful imprisonment experiences, and insufficient support offered to formerly incarcerated people living in the community. Approaches for reducing substance use stigma involve reforming drug policy to decriminalize substances, improving access to substance use treatment and harm reduction services, and involving people with lived and living experiences of substance use and criminal justice involvement in policymaking and service delivery.
OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
The chapter is a brief attempt to follow the development of Brent Shaw’s work from his first, splendidly iconoclastic revision of the role of pastoral nomadism in Roman North Africa and in the ancient world in general (from 1981 onward) to his recent pair of crowning masterpieces, both published in 2013 – the first, on religious violence in Roman North Africa in the time of Augustine; the second, on harvesting in the ancient world. In between, I have tried to do justice to the breadth and coherence of his principal concerns for major themes of ancient history – for the nature of power and of resistance to power, for the structures of the family, for the nature of the Roman economy, and for the mobilization of opinion (largely of hatred) in the interconfessional conflicts of the later empire.
To systematically review and synthesise qualitative evidence about determinants of self-management in adults with SMI. The goal is to use findings from this review to inform the design of effective self-management strategies for people with SMI and LTCs.
People living with serious mental illness (SMI) have a reduced life expectancy by around 15–20 years, mainly due to the high prevalence of long-term physical conditions such as diabetes and heart disease. People with SMI face many challenges when trying to manage their physical health. Little is known about the determinants of self-management – managing the emotional and practical issues – of long-term conditions (LTCs) for people with SMI.
Six databases, including CINAHL and MEDLINE, were searched to identify qualitative studies that explored people's perceptions about determinants of self-management in adults with SMI (with or without comorbid LTCs). Self-management was defined according to the American Association of Diabetes Educator's self-care behaviours (AADE7). Determinants were defined according to the Capabilities, Opportunity, Motivations and Behaviours (COM-B) framework. Eligible studies were purposively sampled for synthesis according to the richness of the data (assessed using Ames et al (2017)'s data richness scale), and thematically synthesised.
Twenty-six articles were included in the synthesis. Seven studies focused on self-management of LTCs, with the remaining articles exploring self-management of SMI. Six analytic themes and 28 sub-themes were identified from the synthesis. The themes included: the additional burden of SMI; living with comorbidities; beliefs and attitudes about self-management; support from others for self-management; social and environmental factors; routine, structure and planning. Capabilities for self-management were linked to people's perceptions about the support they received for their SMI and LTC from healthcare professionals, family and friends. Opportunities for self-management were more commonly expressed in the context of social and environmental factors. Motivation for self-management was influenced by beliefs and attitudes, whilst being closely related to the burden of SMI.
The themes identified from the synthesis suggest that capabilities, opportunities and motivations for self-management can be negatively influenced by the experience of SMI, whilst social and professional support, improved access to resources, and increased involvement in care, could promote self-management. Support programmes for people with SMI and LTCs need to account for these experiences and adapt to meet the unique needs of this population.
Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full two-dimensional (2D) image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields, and other sample-dependent properties. However, extracting this information requires complex analysis pipelines that include data wrangling, calibration, analysis, and visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open-source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail and present results from several experimental datasets. We also implement a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open-source HDF5 standard. We hope this tool will benefit the research community and help improve the standards for data and computational methods in electron microscopy, and we invite the community to contribute to this ongoing project.
Introduction to Education provides pre-service teachers with an overview of the context, craft and practice of teaching in Australian schools as they commence the journey from learner to classroom teacher. Each chapter poses questions about the nature of teaching students, and guides readers though the Australian Professional Standards for Teachers. Incorporating recent research and theoretical literature, Introduction to Education presents a critical consideration of the professional, policy and curriculum contexts of teaching in Australia. The book covers theoretical topics in chapters addressing assessment, planning, safe learning environments, and working with colleagues, families, carers and communities. More practical chapters discuss professional experience and building a career after graduation. Rigorous in conception and practical in scope, Introduction to Education welcomes new educators to the theory and practical elements of teaching, learning, and professional practice.