Expanding Public Safety in the Era of Black Lives Matter

The narrative of "Black Lives Matter" offers a new framework for policymakers, activists, practitioners, and other stakeholders to think about a public safety strategy that is not solely defined by arrests and admissions to prison. This essay provides an overview of evidence-based approaches for public safety interventions that exist outside of law enforcement interactions

Expanding Public Safety in the Era of Black Lives Matter

Traditional public safety responses to crime involve interactions with the criminal justice system. However, recent killings by police of unarmed black men, women, and children have led to a national dialogue on the fundamental strategy of public safety. The narrative of “Black Lives Matter” offers a new framework for policymakers, activists, practitioners, and other stakeholders to think about a public safety strategy that is not solely defined by arrests and admissions to prison. This essay provides an overview of evidence-based approaches for public safety interventions that exist outside of law enforcement interactions

Greenways of Saudi Arabia: Activating their transportation potential

Since the early 1970s, auto-centric planning in Saudi Arabia (SA) has created car-dependent lifestyles, resulting in health and environmental problems. In the past decade, ambitious policies (e.g., The Saudi Vision 2030), regulations, awareness campaigns, city plans, and projects have sought to address this problem by transitioning to sustainable urban mobility. One form of this is active transportation (AT) via networks of greenways, which is currently being promoted in Saudi cities. However, the contemporary use of greenways for AT - for example, commuting by bike or walking - is extremely low in SA. Additionally, there is limited research on greenways in Middle Eastern countries. Thus, this paper aims to examine the factors hindering the use and development of greenways as AT corridors in SA, thereby informing efforts to unlock their AT potential. After outlining how the forms and functions of greenways in SA evolved compared to their international counterparts, we present Jeddah city as a case study, a city with low rates of AT. Drawing on recent empirical mixed-methods research, an overview and synthesis of factors explaining the low utilisation rate of Jeddah’s greenways as AT corridors is presented. Barriers to AT are categorised as site-specific (e.g., greenway design, safety, maintenance), contextual (e.g., neighbourhood walkability/accessibility, weather), behavioural and perceptual (e.g., conflicts between greenway users and perceptions). In addition to user-based evidence, we identify broader development-related challenges of building a greenway network for AT in Jeddah city, including spatial connectivity, lack of integration with the concerned authorities, limited budgets, and securing and regulating land. Results show that multidimensional impediments to active commuting via greenways in SA are similar to those globally, for example, greenway’s proximity to home addresses (Krizek and Johnson 2007; Wolch et al. 2010). However, other factors are specific to the Saudi context. These include, but are not limited to, the perception of privacy, unsuitability of formal Saudi attire for riding bicycles, and fear of public judgement. We conclude with a comprehensive model that summarises all the factors influencing greenway use for active transport in SA, which can inform future research and practice in this domain

Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process.

To understand the impact of epigenetics on human misfolding disease, we apply Gaussian-process regression (GPR) based machine learning (ML) (GPR-ML) through variation spatial profiling (VSP). VSP generates population-based matrices describing the spatial covariance (SCV) relationships that link genetic diversity to fitness of the individual in response to histone deacetylases inhibitors (HDACi). Niemann-Pick C1 (NPC1) is a Mendelian disorder caused by >300 variants in the NPC1 gene that disrupt cholesterol homeostasis leading to the rapid onset and progression of neurodegenerative disease. We determine the sequence-to-function-to-structure relationships of the NPC1 polypeptide fold required for membrane trafficking and generation of a tunnel that mediates cholesterol flux in late endosomal/lysosomal (LE/Ly) compartments. HDACi treatment reveals unanticipated epigenomic plasticity in SCV relationships that restore NPC1 functionality. GPR-ML based matrices capture the epigenetic processes impacting information flow through central dogma, providing a framework for quantifying the effect of the environment on the healthspan of the individual

Viral Networks: Connecting Digital Humanities and Medical History

This volume of original essays explores the power of network thinking and analysis for humanities research. Contributing authors are all scholars whose research focuses on a medical history topic—from the Black Death in fourteenth-century Provence to psychiatric hospitals in twentieth-century Alabama. The chapters take readers through a variety of situations in which scholars must determine if network analysis is right for their research; and, if the answer is yes, what the possibilities are for implementation. Along the way, readers will find practical tips on identifying an appropriate network to analyze, finding the best way to apply network analysis, and choosing the right tools for data visualization. All the chapters in this volume grew out of the 2018 Viral Networks workshop, hosted by the History of Medicine Division of the National Library of Medicine (NIH), funded by the Office of Digital Humanities of the National Endowment for the Humanities, and organized by Virginia Tech

A site assessment tool for inpatient controlled human infection models for enteric disease pathogens

The use of the controlled human infection model to facilitate product development and to advance understanding of host-pathogen interactions is of increasing interest. While administering a virulent (or infective) organism to a susceptible host necessitates an ongoing evaluation of safety and ethical considerations, a central theme in conducting these studies in a safe and ethical manner that yields actionable data is their conduct in facilities well-suited to address their unique attributes. To that end, we have developed a framework for evaluating potential sites in which to conduct inpatient enteric controlled human infection model to ensure consistency and increase the likelihood of success.publishedVersio

A triple nucleus in the Brightest Cluster Galaxy in Abell 193

We present a ground-based near-infrared K-band image and an HST/WFPC2 image of the brightest cluster galaxy in Abell 193 (IC 1695). This object was selected as the central cluster galaxy using X-ray information. Both images reveal a triple nucleus structure. Previously, this galaxy was thought to have only 2 nuclei. We present colours and magnitudes and a colour plot of the three nuclei. The nuclear structure and colours of the nuclei in this galaxy suggest that a merger may have taken place in its recent history.Comment: 5 pages, 3 figures, accepted for publication in MNRA

Human and mouse neuroinflammation markers in Niemann‐Pick disease, type C1

Niemann‐Pick disease, type C1 (NPC1) is an autosomal recessive lipid storage disorder in which a pathological cascade, including neuroinflammation occurs. While data demonstrating neuroinflammation is prevalent in mouse models, data from NPC1 patients is lacking. The current study focuses on identifying potential markers of neuroinflammation in NPC1 from both the Npc1 mouse model and NPC1 patients. We identified in the mouse model significant changes in expression of genes associated with inflammation and compared these results to the pattern of expression in human cortex and cerebellar tissue. From gene expression array analysis, complement 3 (C3) was increased in mouse and human post‐mortem NPC1 brain tissues. We also characterized protein levels of inflammatory markers in cerebrospinal fluid (CSF) from NPC1 patients and controls. We found increased levels of interleukin 3, chemokine (C‐X‐C motif) ligand 5, interleukin 16 and chemokine ligand 3 (CCL3), and decreased levels of interleukin 4, 10, 13 and 12p40 in CSF from NPC1 patients. CSF markers were evaluated with respect to phenotypic severity. Miglustat treatment in NPC1 patients slightly decreased IL‐3, IL‐10 and IL‐13 CSF levels; however, further studies are needed to establish a strong effect of miglustat on inflammation markers. The identification of inflammatory markers with altered levels in the cerebrospinal fluid of NPC1 patients may provide a means to follow secondary events in NPC1 disease during therapeutic trials.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147148/1/jimd0083.pd

Bioinformatic and Genetic Association Analysis of MicroRNA Target Sites in One-Carbon Metabolism Genes

One-carbon metabolism (OCM) is linked to DNA synthesis and methylation, amino acid metabolism and cell proliferation. OCM dysfunction has been associated with increased risk for various diseases, including cancer and neural tube defects. MicroRNAs (miRNAs) are ∼22 nt RNA regulators that have been implicated in a wide array of basic cellular processes, such as differentiation and metabolism. Accordingly, mis-regulation of miRNA expression and/or activity can underlie complex disease etiology. We examined the possibility of OCM regulation by miRNAs. Using computational miRNA target prediction methods and Monte-Carlo based statistical analyses, we identified two candidate miRNA “master regulators” (miR-22 and miR-125) and one candidate pair of “master co-regulators” (miR-344-5p/484 and miR-488) that may influence the expression of a significant number of genes involved in OCM. Interestingly, miR-22 and miR-125 are significantly up-regulated in cells grown under low-folate conditions. In a complementary analysis, we identified 15 single nucleotide polymorphisms (SNPs) that are located within predicted miRNA target sites in OCM genes. We genotyped these 15 SNPs in a population of healthy individuals (age 18–28, n = 2,506) that was previously phenotyped for various serum metabolites related to OCM. Prior to correction for multiple testing, we detected significant associations between TCblR rs9426 and methylmalonic acid (p  =  0.045), total homocysteine levels (tHcy) (p  =  0.033), serum B12 (p < 0.0001), holo transcobalamin (p < 0.0001) and total transcobalamin (p < 0.0001); and between MTHFR rs1537514 and red blood cell folate (p < 0.0001). However, upon further genetic analysis, we determined that in each case, a linked missense SNP is the more likely causative variant. Nonetheless, our Monte-Carlo based in silico simulations suggest that miRNAs could play an important role in the regulation of OCM

Defining Natural History: Assessment of the Ability of College Students to Aid in Characterizing Clinical Progression of Niemann-Pick Disease, Type C

Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease