BioMeT and algorithm challenges: A proposed digital standardized evaluation framework

Technology is advancing at an extraordinary rate. Continuous flows of novel data are being generated with the potential to revolutionize how we better identify, treat, manage, and prevent disease across therapeutic areas. However, lack of security of confidence in digital health technologies is hampering adoption, particularly for biometric monitoring technologies (BioMeTs) where frontline healthcare professionals are struggling to determine which BioMeTs are fit-for-purpose and in which context. Here, we discuss the challenges to adoption and offer pragmatic guidance regarding BioMeTs, cumulating in a proposed framework to advance their development and deployment in healthcare, health research, and health promotion. Furthermore, the framework proposes a process to establish an audit trail of BioMeTs (hardware and algorithms), to instill trust amongst multidisciplinary users

“Rogue” B cells: An investigation into B cells that break tolerance in autoimmune disease

A breakdown in B cell self-tolerance can lead to antibody-mediated autoimmune disease. This thesis aims to explore how B cell tolerance can be broken in two distinct, but complementary projects within the context of the Goodnow somatic mutation hypothesis. In both scenarios, B cells that escape self-tolerance and generate autoantibodies are referred to as “rogue” B cells. First, this thesis aimed to elucidate the precise steps undertaken by expanded rogue B cell clones in patients with chronic Hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis, an autoimmune disease characterised by the production of a rheumatoid factor cryoglobulin autoantibody. The rogue B cell clones in the HCV cryoglobulinemic vasculitis patients were confirmed to be the source of the autoantibody. The rogue B cell clone precursor antibodies failed to bind the HCV envelope glycoprotein E2, yet bound multimerised self-antigen IgG relative to membrane IgM density. These findings disfavour a molecular mimicry hypothesis, and instead indicate IgG immune complexes may be sufficient to drive recruitment of the rogue B cell clone precursors. Finally, the rogue B cells clones were found to carry somatic lymphoma-associated, non-immunoglobulin gene mutations and chromosomal aberrations, predicted to cause hyperactivation of the NF-kB signalling pathway and escape of B cell tolerance. This finding provides additional evidence in support of the Goodnow somatic mutation hypothesis. Second, this thesis examined rogue germinal centre (GC) B cells that arise in the absence of the receptor FAS. Rogue GC B cells loose specificity for the foreign antigen and incidentally generate autoantibodies. However, the accumulation of rogue GC B cells cannot be explained by our current understanding of affinity-based selection in the GC. This work revealed rogue GC B cells, unlike “conventional” GC B cells undergoing affinity maturation to the foreign antigen, can be identified by low expression of CD21 and high expression of B220 (CD21loB220hi). Moreover, rogue GC B cells were found to be rapidly entering cell cycle, enriched for a dark zone phenotype and T-cell dependent, reminiscent of positively selected GC B cells. Thus, rogue GC B cells typically removed by FAS, likely persist in the competitive GC microenvironment despite their loss of BCR specificity to foreign antigen, because they retain the capacity to undergo T-cell dependent positive GC selection

Isolation and Screening of Microbial Isolates from Kombucha Culture for Bacterial Cellulose Production in Sugarcane Molasses Medium

Kombucha tea is a traditional fermented beverage of Manchurian origins which is made of sugar and tea. The fermentation involves the application of a symbiotic consortium of bacteria and yeast (SCOBY) in which their metabolites provide health benefits for the consumer and subsequently allow the product to protect itself from contamination. Additionally, kombucha tea fermentation also produces a byproduct in the form of a pellicle composed of cellulose (Bacterial Cellulose, BC). Compared to plant cellulose, BC properties are more superior, which makes it industrially important. However, BC production at industrial scale has been faced with many challenges, including low yield and high fermentation medium cost. Many researchers have focused their studies on the use of alternative low cost media, such as molasses, which is a by-product   of sugar refining process. To  maximize the BC production in molasses medium, it    is important to select the microbial strains that can grow and produce BC at high yield in molasses. This study aimed to isolate and characterize BC-producing bacteria and a dominant yeast from kombucha culture which had been previously adapted in molasses medium. The isolation of bacteria was performed using Nutrient Agar (NA) and Hestrin and Schramm (HS) supplemented with cycloheximide, while yeast was isolated using Potato Dextrose Agar (PDA) supplemented with chloramphenicol. The most dominant colonies were isolated and then subjected to microscopic observation for morphological analysis. The pure bacteria and yeast isolates were then identified by sequencing the 16S rRNA gene and D1/D2 region of the 26S rRNA, respectively. The bacteria isolates obtained were all from closely related genera: Komagataeibacter sp. DS1MA.62A, Komagataeibacter xylinus, Komagataeibacter saccharivorans, Komagataeibacter xylinus and Gluconacetobacter saccharivorans. The single isolated yeast was identified as Brettanomyces bruxellensis. This study helps to elucidate  the BC-producing species which thrive in molasses medium for potential use in the BC production using molasses as alternative cheap carbon source. Also, the study revealed that the co-culture of Komagataeibacter sp. DS1MA.62A and B. bruxellensis could produce BC from molasses supplemented with caffeine and acetate buffer at an average yield of 27.7±1.83 g/L. Keywords: Kombucha, SCOBY, bacterial cellulose, Acetobacter, Komagataeibacter, Brettanomyces, alternative medium, molasses, caffeine, acetate buffer

Deriving a Preference-Based Measure for Myelofibrosis from the EORTC QLQ-C30 and the MF-SAF

AbstractBackgroundUtility values are required for economic evaluation using cost-utility analyses. Often, generic measures such as the EuroQol five-dimensional questionnaire are used, but this may not appropriately reflect the health-related quality of life of patients with cancer including myelofibrosis.ObjectiveTo derive a condition-specific preference-based measure for myelofibrosis using appropriate existing measures, the Myelofibrosis-Symptom Assessment Form and the European Organisation for Research and Treatment of Cancer Quality of Life 30 Questionnaire.MethodsData from the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment trial (n = 309) were used to derive the health state classification system. Psychometric and factor analyses were used to determine the dimensions of the classification system. Psychometric and Rasch analyses were then used to select an item to represent each dimension. Item selection was validated with experts. A selection of health states was valued by members of the general population using time trade-off. Finally, health state values were modeled using regression analysis to produce utility values for every state.ResultsThe Myelofibrosis 8 dimensions has eight dimensions: physical functioning, emotional functioning, fatigue, itchiness, pain under ribs on the left side, abdominal discomfort, bone or muscle pain, and night sweats. Regression models were estimated using time trade-off data from 246 members of the general population valuing a total of 33 states. The best performing model was a random effects maximum likelihood model producing utility values ranging from 0.089 to 1.ConclusionsThe Myelofibrosis 8 dimensions is a condition-specific preference-based measure for myelofibrosis. This measure can be used to generate utility values for myelofibrosis for any data set containing the Myelofibrosis-Symptom Assessment Form and the European Organisation for Research and Treatment of Cancer Quality of Life 30 Questionnaire data

Lessons Learned from Deploying an Analytical Task Management Database

Defining requirements, missions, technologies, and concepts for space exploration involves multiple levels of organizations, teams of people with complementary skills, and analytical models and simulations. Analytical activities range from filling a To-Be-Determined (TBD) in a requirement to creating animations and simulations of exploration missions. In a program as large as returning to the Moon, there are hundreds of simultaneous analysis activities. A way to manage and integrate efforts of this magnitude is to deploy a centralized database that provides the capability to define tasks, identify resources, describe products, schedule deliveries, and generate a variety of reports. This paper describes a web-accessible task management system and explains the lessons learned during the development and deployment of the database. Through the database, managers and team leaders can define tasks, establish review schedules, assign teams, link tasks to specific requirements, identify products, and link the task data records to external repositories that contain the products. Data filters and spreadsheet export utilities provide a powerful capability to create custom reports. Import utilities provide a means to populate the database from previously filled form files. Within a four month period, a small team analyzed requirements, developed a prototype, conducted multiple system demonstrations, and deployed a working system supporting hundreds of users across the aeros pace community. Open-source technologies and agile software development techniques, applied by a skilled team enabled this impressive achievement. Topics in the paper cover the web application technologies, agile software development, an overview of the system's functions and features, dealing with increasing scope, and deploying new versions of the system

“Life is at a standstill” Quality of life after lower extremity trauma in Malawi

Low- and middle-income countries face a disproportionate burden of death and disability from injuries, many of which are due to road traffic accidents or falls. Lower extremity injuries in particular have implications not only for physical disabilities affecting work and school performance, but also for quality of life (QOL) of the individual. This qualitative study explores the psychosocial impact and QOL changes due to lower extremity injuries among trauma patients in central Malawi

THE GREEN INFRASTRUCTURE OF A HIGHLY URBANIZED NEOTROPICAL CITY: THE ROLE OF THE URBAN VEGETATION IN PRESERVING NATIVE BIODIVERSITY

We mapped and described the composition of the urban vegetation that comprises the green infrastructure of a highly urbanized Neotropical city, and discussed how it can be used to preserve and maintain urban biodiversity. Almost half of our study area is occupied by 12 types of arboreal and herbaceous vegetation, composed mostly of urban parks, gardens and street trees. Forty-one percent of the almost 90,000 street trees are composed of 10 species with only 4 native species. These results show that this urban landscape is highly heterogeneous and has a great potential for biodiversity conservation. However, management strategies are needed, such as better planning of the urban forestry. This study is the first step towards a better understanding of how this landscape influences local biodiversity, and can be used as a management tool to increase urban resilience and functionality.The composition of the urban vegetation that comprises the green infrastructure of a highly urbanized Neotropical city was mapped and described in order to assess how it can be used to preserve and maintain urban biodiversity. Supervised classification was used, followed by Map Algebra methodology, to identify the elements that comprise the green infrastructure of the southern region of Belo Horizonte (Minas Gerais, Brazil). Species composition of the street trees community was also assessed. Almost half of the study area is occupied by 12 types of woody and herbaceous vegetation, composed mostly by urban parks and gardens. Forty-one percent of the almost 90,000 street trees is composed by 10 species from which only four are native. These results show that the green infrastructure of this urban landscape is comprised by a large amount of different types of green elements, and has a great potential for biodiversity conservation. However, management strategies are needed such as better planning of the urban afforestation process, increasing street tree species richness. This study is the first step towards a better understanding of how such urban landscape influences local biodiversity