Witness: The Modern Writer as Witness

Editor\u27s Note [Excerpt] The United States, as a society, is on the brink of profound and positive change. Demographically and culturally, things are improving, and the reason is obvious to people who study history: Conflict pushes us to be better, to strive for principled goals. Consider the inspired eco-advocacy of Greta Thunberg. Or the swearing in of most diverse class of lawmakers in history into the 116th Congress. Or billionaire Robert F. Smith’s pledge to pay off every Morehouse College (in Atlanta, Georgia) student’s debt. Indeed, there are many good people helping and great moments happening in spite of a bleak 24-hour news cycle designed to ruin happiness and to limit our understanding of our human potential. We at Witness see this yearning for transformation in the works we selected. The doorway must be crossed, and the voices and characters we featured in our Winter 2019 issue stand at the vestibule, ready for the light to warm them, primed to fight for that necessary illumination.https://digitalscholarship.unlv.edu/witness/1000/thumbnail.jp

Variegate porphyria in South Africa, 1688 - 1996 - new developments in an old disease

Variegate porphyria, an autosomal dominant inherited trait resulting in decreased activity of protoporphyrinogen oxidase, the penuttimate haem biosynthetic enzyme, is characterised clinically by photosensitive skin disease and a propensity to acute neurovisceral crises. The disease has an exceptionally high frequency in South Africa,owing to a founder effect. The specific mutation in the protoporphynnogen oxidase gene sequence which represents this founder gene has been identified. Genetic diagnosis is therefore now possible in families in whom the gene defect is known. However, the exact nature and degree of activity of the porphyria can only be determined by detailed quantitative biochemical analysis of excreted porphyrins. The relative contributions of the acute attack and the skin disease to the total disease burden of patients with variegate porphyria is not static, and in South Africa there have been significant changes over the past 25 years, with fewer patients presenting with acute attacks, leaving a greater proportion to present with skin disease or to remain asymptomatic with the diagnosis being made in the laboratory. The most common precipitating cause of the acute attack of VP is administration of porphyrinogenic drugs. Specific suppression of haem synthesis with intravenous haem arginate is the most useful treatment of a moderate or severe acute attack. Although cutaneous lesions are limited to the sun-exposed areas, management of the skin disease of VP remains inadequate

Regulatory Approved Monoclonal Antibodies Contain Framework Mutations Predicted From Human Antibody Repertoires

Monoclonal antibodies (mAbs) are an important class of therapeutics used to treat cancer, inflammation, and infectious diseases. Identifying highly developable mAb sequences in silico could greatly reduce the time and cost required for therapeutic mAb development. Here, we present position-specific scoring matrices (PSSMs) for antibody framework mutations developed using baseline human antibody repertoire sequences. Our analysis shows that human antibody repertoire-based PSSMs are consistent across individuals and demonstrate high correlations between related germlines. We show that mutations in existing therapeutic antibodies can be accurately predicted solely from baseline human antibody sequence data. We find that mAbs developed using humanized mice had more human-like FR mutations than mAbs originally developed by hybridoma technology. A quantitative assessment of entire framework regions of therapeutic antibodies revealed that there may be potential for improving the properties of existing therapeutic antibodies by incorporating additional mutations of high frequency in baseline human antibody repertoires. In addition, high frequency mutations in baseline human antibody repertoires were predicted in silico to reduce immunogenicity in therapeutic mAbs due to the removal of T cell epitopes. Several therapeutic mAbs were identified to have common, universally high-scoring framework mutations, and molecular dynamics simulations revealed the mechanistic basis for the evolutionary selection of these mutations. Our results suggest that baseline human antibody repertoires may be useful as predictive tools to guide mAb development in the future. &nbsp;</p

ENhancing Assessment of Common Therapeutic factors (ENACT) tool: adaptation and psychometric properties in South Africa

BACKGROUND: The ENhancing Assessment of Common Therapeutic factors (ENACT) tool measures a set of therapeutic competencies required for the effective psychological intervention, including delivery by non-specialists. This paper describes the systematic adaptation of the ENACT for the South African (SA) context and presents the tool's initial psychometric properties. METHODS: We employed a four-step process: (1) Item generation: 204 therapeutic factors were generated by SA psychologists and drawn from the original ENACT as potential items; (2) Item relevance: SA therapists identified 96 items that were thematically coded according to their relationship to one another and were assigned to six domains; (3) Item utility: The ENACT-SA scale was piloted by rating recordings of psychological therapy sessions and stakeholder input; and (4) Psychometric properties: Internal consistency and inter-rater reliability of the final 12-item ENACT-SA were explored using Cronbach's alpha and intraclass correlation co-efficient (ICC) for both clinical psychologists and registered counsellors. RESULTS: Although the original ENACT provided a framework for developing a tool for use in SA, several modifications were made to improve the applicability of the tool for the SA context, and optimise its adaptability other contexts. The adapted 12-item tool's internal consistency was good, while the inter-rater reliability was acceptable for both clinical psychologists and registered counsellors. CONCLUSION: The ENACT-SA is a reliable tool to assess common factors in psychological treatments. It is recommended that the tool be used in conjunction with assessment protocols and treatment-specific competency measures to fully assess implementation fidelity and potential mechanisms of therapeutic change

Contributions of Muscles and External Forces to Medial Knee Load Reduction Due to Osteoarthritis Braces

Background Braces for medial knee osteoarthritis can reduce medial joint loads through a combination of three mechanisms: application of an external brace abduction moment, alteration of gait dynamics, and reduced activation of antagonistic muscles. Although the effect of knee bracing has been reported independently for each of these parameters, no previous study has quantified their relative contributions to reducing medial knee loads. Methods In this study, we used a detailed musculoskeletal model to investigate immediate changes in medial and lateral loads caused by two different knee braces: OA Assist and OA Adjuster 3 (DJO Global). Seventeen osteoarthritis subjects and eighteen healthy controls performed overground gait trials in unbraced and braced conditions. Results Across all subjects, bracing reduced medial loads by 0.1 to 0.3 times bodyweight (BW), or roughly 10%, and increased lateral loads by 0.03 to 0.2 BW. Changes in gait kinematics due to bracing were subtle, and had little effect on medial and lateral joint loads. The knee adduction moment was unaltered unless the brace moment was included in its computation. Only one muscle, biceps femoris, showed a significant change in EMG with bracing, but this did not contribute to altered peak medial contact loads. Conclusions Knee braces reduced medial tibiofemoral loads primarily by applying a direct, and substantial, abduction moment to each subject's knee. To further enhance brace effectiveness, future brace designs should seek to enhance the magnitude of this unloader moment, and possibly exploit additional kinematic or neuromuscular gait modifications

Urinary tract infections and antibiotic use in pregnancy - qualitative analysis of online forum content

Background Antibiotics are standard treatment for asymptomatic and symptomatic urinary tract infections (UTIs) in pregnancy. Their overuse, however, can contribute to antimicrobial resistance (AMR) and expose the foetus to drugs that might affect its development. Preventative behaviours are currently the best option to reduce incidences of UTIs and to avoid the use of antibiotics in pregnancy. The aim of this study was to explore women’s experiences of UTIs in pregnancy to develop an understanding of their concerns and to optimise and encourage behaviours that facilitate appropriate use of antibiotics. Methods An online pregnancy forum in the United Kingdom (UK) was used to collect data on women’s discussions of UTIs. A total of 202 individual threads generated by 675 different usernames were selected for analysis. The data was organised using NVivo 11® software and then analysed qualitatively using inductive thematic analysis. Results Women’s perceptions of UTIs and antibiotic use in pregnancy were driven by their pre-natal attachment to the foetus. UTIs were thought to be common and high risk in pregnancy, which meant that antibiotics were viewed as essential in the presence of suspected symptoms. The dominant view about antibiotics was that their use was safe and of little concern in pregnancy. Women reported an emotional reaction to developing a UTI. They coped by seeking information about behaviour change strategies to assist with recovery and through emotional support from the online forum. Conclusions Women face dual risks when they experience UTIs; the risk from the infection and the risk from antibiotic treatment. Pre-natal attachment to the foetus is highlighted in the decision making process. The focus is on the shorter term risk from UTIs while undermining the longer term risks from antibiotic use, especially the risk of AMR. A balanced view needs to be presented, and evidence-based infection prevention strategies should be promoted, to women to ensure appropriate antibiotic use in pregnancy, to address the global challenge of AMR

How Strong a Kick Should be to Topple Northeastern's Tumbling Robot?

Rough terrain locomotion has remained one of the most challenging mobility questions. In 2022, NASA's Innovative Advanced Concepts (NIAC) Program invited US academic institutions to participate NASA's Breakthrough, Innovative \& Game-changing (BIG) Idea competition by proposing novel mobility systems that can negotiate extremely rough terrain, lunar bumpy craters. In this competition, Northeastern University won NASA's top Artemis Award award by proposing an articulated robot tumbler called COBRA (Crater Observing Bio-inspired Rolling Articulator). This report briefly explains the underlying principles that made COBRA successful in competing with other concepts ranging from cable-driven to multi-legged designs from six other participating US institutions