A Mosquito Pick-and-Place System for PfSPZ-based Malaria Vaccine Production

The treatment of malaria is a global health challenge that stands to benefit from the widespread introduction of a vaccine for the disease. A method has been developed to create a live organism vaccine using the sporozoites (SPZ) of the parasite Plasmodium falciparum (Pf), which are concentrated in the salivary glands of infected mosquitoes. Current manual dissection methods to obtain these PfSPZ are not optimally efficient for large-scale vaccine production. We propose an improved dissection procedure and a mechanical fixture that increases the rate of mosquito dissection and helps to deskill this stage of the production process. We further demonstrate the automation of a key step in this production process, the picking and placing of mosquitoes from a staging apparatus into a dissection assembly. This unit test of a robotic mosquito pick-and-place system is performed using a custom-designed micro-gripper attached to a four degree of freedom (4-DOF) robot under the guidance of a computer vision system. Mosquitoes are autonomously grasped and pulled to a pair of notched dissection blades to remove the head of the mosquito, allowing access to the salivary glands. Placement into these blades is adapted based on output from computer vision to accommodate for the unique anatomy and orientation of each grasped mosquito. In this pilot test of the system on 50 mosquitoes, we demonstrate a 100% grasping accuracy and a 90% accuracy in placing the mosquito with its neck within the blade notches such that the head can be removed. This is a promising result for this difficult and non-standard pick-and-place task.Comment: 12 pages, 11 figures, Manuscript submitted for Special Issue of IEEE CASE 2019 for IEEE T-AS

Epidemiology of Injuries at a Tertiary Care Center in Malawi

Injury surveillance is an ongoing process required for primary, secondary, and tertiary injury prevention. In Malawi, hospital-based injury data are not available

Viral Response to Chemotherapy in Endemic Burkitt Lymphoma

Some Epstein-Barr virus (EBV)-directed therapies are predicted to be effective only when lytic viral replication occurs. We studied whether cyclophosphamide chemotherapy induces EBV to switch from latent to lytic phases of infection in a series of EBV-associated Burkitt lymphomas

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Dimensions of Urban Agriculture for Sustainable Development: A Case Study of "Aulas Ambientales" in Medellín, Colombia

I would like to take the time to thank all of those who helped me along this thesis exploration process. Thank you Dr. Wayne Decker for introducing me to International Studies and for pushing me explore Colombia. Thank you to professor Marcela Vasquez- León, the University of Arizona Department of Latin American Studies for guiding me through the pre-proposal as I set off for Medellín, Colombia. Also, a big thank you to professor Allison Hayes Conroy for offering me critical advice throughout my research in Medellín, Colombia and a for allowing me to shadow her research project, "Rural Strategies, Urban Struggles: Food Security among Women and Displaced Families in Medellín". None of this could have been possible without your advice, facilitation, and expertise

BrainSABER v0.99.5: Transcriptomic Similarity Assessment Toolkit and Web Application for Comparative Analysis against the BrainSpan Developmental Dataset

The Allen Brain Institute has used RNA sequencing and microarray technologies to sample the transcriptome of the developing human brain across sixteen cortical and subcortical regions for an age range of 8 weeks post conception through 40 years of age. The BrainSpan project is intended to give a baseline for the normal transcriptomic landscape of the human brain and is accompanied by a web interface that allows for the visualization of gene expression across brain ages and regions as well as differential comparisons between the sample sets. However, the current implementation does not allow for similarity assessment between user data and the BrainSpan dataset. To facilitate comparisons with outside user data, we developed the BrainSABER R package and Shiny web application. The BrainSABER package was designed to provide the user with a self-validating container for transcriptomic data, calculate the transcriptomic similarity between user data and the BrainSpan dataset across developmental ages and brain regions, and display the results using static and dynamic graphs. This package is split into a command-line accessible workflow for greater customization and a Shiny web application for ease of use. The command-line workflow utilizes Euclidean and cosine distances to evaluate similarity across all genes and the Shiny application evaluates cosine distance, Kendall’s Tau, and Spearman’s Rho for the 5000 genes with the highest stabilized variance across the BrainSpan dataset. Results are displayed as exportable static and dynamic heatmaps. Both Shiny and command-line workflows were self-validated as well as used for the secondary evaluation of samples from patients with atypical teratoid rhabdoid tumors (ATRT). The command-line BrainSABER package is available on Bioconductor (DOI: 10.18129/B9.bioc.BrainSABER), and the Shiny application can be accessed on the developmental “dev” branch of the bicbioeng/BrainSABER project on GitHub. This project was previously presented at the Bioc2020 conference (https://doi.org/10.7490/f1000research.1118072.1)

FRAMEWORK FOR THE EVALUATION OF PERTURBATIONS IN THE SYSTEMS BIOLOGY LANDSCAPE AND INTER-SAMPLE SIMILARITY FROM TRANSCRIPTOMIC DATASETS — A DIGITAL TWIN PERSPECTIVE

One approach to interrogating the complexities of human systems in their well-regulated and dysregulated states is through the use of digital twins. Digital twins are virtual representations of physical systems that are descriptive of an individual\u27s state of health, an object fundamentally related to precision medicine. A key element for building a functional digital twin type for a disease or predicting the therapeutic efficacy of a potential treatment is harmonized, machine-parsable domain knowledge. Hypothesis-driven investigations are the gold standard for representing subsystems, but their results encompass a limited knowledge of the full biosystem. Multi-omics data is one rich source of knowledge for characterizing disease- and therapy-induced shifts across the systems biology landscape. However, systematic biases in and between the data types limits the functionality of big multi-omics data. In this dissertation, the generation of and results from transcriptomic analysis pipelines are assessed in their biological context and respective to their usability for applications such as digital twins. This latter is achieved by assessing the adherence of the workflows to the FAIR principles --- Findability, Accessibility, Interoperability, and Reusability --- and the extent to which they connect to the broader systems biology landscape. The first two specific aims of this work emphasize the transcriptomic shifts induced by atypical teratoid rhabdoid tumors (ATRT) relative to the normal brain and those induced by treatment of tumor models by 4SC-202 across disease states including medulloblastoma, ATRT, triple negative breast cancer, osteosarcoma, and pancreatic cancer. These are problem-driven workflows, tightly connected to biological hypotheses that contribute to disease and therapy-specific domain knowledge. In contrast, the third specific aim introduces a domain-agnostic approach for developing transcriptomic pipelines to harmonize bulk RNA-sequencing datasets. This framework does not directly contribute to a given biological domain, but instead provides a generalized approach for integrating large RNA-sequencing datasets and assessing the resultant representation for biological meaningfulness. This harmonization framework may also have utility in assessing the clinical relevance of in vitro biomodels. Collectively, this work presents and assesses the efficacy of multiple transcriptomic workflows within their biological context and broader machine learning applicability

Influence of a Sleeping Verses Waking Retention Interval on Spatial Visual Auditory Memory Performance

We investigated the influence of a retention interoal spent sleeping or waking on participants\u27 performance in spatial, auditory, and visual tasks. Usingjenkins and Dallenbach \u27s research ( 1924) as a paradigm, we replicated and extended the original study using a 2 X 3 mixed design with repeated measures. The 2 independent variables were the activity during the retention interoal (i.e., sleeping or waking) and the 3 types of memory tasks (i.e., spatial, auditory, and visual). Fifty-seven undergraduate students participated in 2 sessions. Results indicate that a retention interoal spent sleeping had a beneficial effect on auditory memory performance. We did not find a significant effect for visual and spatial memory performance, but attribute this to ceiling effects within the experimental design