Association of Socioeconomic, Racial, and Regional Factors with In-Hospital Management and Outcomes of Acute Myocardial Infarction Patients in the United States: National Analyses of 2.8 Million Admissions

Social determinants of health contribute to variations in clinical outcomes among acute myocardial infarction (AMI) patients. Using the National Inpatient Sample, we conducted retrospective cohort analyses to evaluate the association of income, race, and geography with in-hospital mortality and revascularization procedures among AMI admissions in the United States from 2015 to 2019. Multilevel logistic regression models were used while accounting for hospital clustering and relevant predictors. A sequential model-building approach produced model 1 (unadjusted patient-level exposures), model 2 (lifestyle factors), model 3 (clinical characteristics), and model 4 (fully adjusted hospital-level factors). We identified 2,798,225 AMI hospitalizations (≥18 years) with 1,567,575 undergoing revascularization procedures. Lowest-income, White, Asian or Pacific Islander, Native American, and Southern residents had higher in-hospital mortality, while higher-income, White, Midwestern, Southern, and Western residents had greater use of revascularization procedures. System-level strategies that improve structural factors are recommended to reduce disparities in AMI outcomes

BRINGING THE FUTURE TO LIFE Pervasive Transmedia Scenarios and the World of Worlding

A technique is described for applying design processes associated with transmedia storytelling to the materialization of speculative future scenarios. How could this technique could be used to engage mass audiences in decision-making processes and experiences simulating different possible futures? A case study is used to demonstrate how an interdisciplinary team led by Trevor Haldenby called The Mission Business used this technique to create a nine-month transmedia story about the future of the biotechnology industry called ZED.TO. This pervasive transmedia scenario spread across numerous narrative channels, and engaged thousands of active participants from the general public to some acclaim. The performance of ZED.TO is explored in qualitative and quantitative terms, and the project’s form and content are contrasted against the practices of contemporary designers, futurists, and storytellers

Genetic Analysis of RadB, a Paralogue of the Archaeal Rad51/RecA Homologue, RadA

The integrity of all genomes is under constant threat, with DNA double strand breaks being particularly dangerous. Double strand breaks can be repaired by homologous recombination, a process catalysed by recombinase proteins of the RecA family. The archaeal recombinase, RadA, is homologous to eukaryotic and bacterial Rad51/RecA. Euryarchaea encode an additional Rad51/RecA homologue, RadB. RadB shares homology with the core domain of RadA and has been shown to bind both single and double stranded DNA, binds ATP and possesses a very weak ATPase activity. However, RadB does not catalyse strand exchange. RadB has been shown to interact with RadA, a Holliday junction resolvase (Hjc) and a DNA polymerase (PolD), suggesting a role in recombination. In this study, radB was deleted from the halophilic archaeon, Haloferax volcanii. 'delta' radB strains were slow growing, sensitive to mitomycin C and UV irradiation, and deficient for both crossover and non-crossover recombination. Deletion of radA results in similar phenotypic characteristics, and complete abrogation of recombination. Strains deleted for both radA and radB are equally defective as 'delta' radA strains, demonstrating that RadA is epistatic to RadB. A suppressor of 'delta' radB was isolated and identified as a mutation in the polymerisation domain of RadA (RadA-A196V). radA-A196V suppresses the slow growth, crossover and non-crossover recombination defects associated with 'delta' radB, as well as UV and mitomycin C sensitivity phenotypes. On account of the nature of this suppressor, the observed interaction between RadA and RadB, and the epistatic relationship between RadA and RadB, a role for RadB as a recombination mediator protein is proposed. Finally, strains were deleted for hjc. 'delta' hjc strains exhibit no growth, crossover and non-crossover recombination defects and no UV and mitomycin C sensitivity. This suggests that another, as yet unidentified, Holliday junction resolvase is encoded by Haloferax volcanii

Genetic Analysis of RadB, a Paralogue of the Archaeal Rad51/RecA Homologue, RadA

The integrity of all genomes is under constant threat, with DNA double strand breaks being particularly dangerous. Double strand breaks can be repaired by homologous recombination, a process catalysed by recombinase proteins of the RecA family. The archaeal recombinase, RadA, is homologous to eukaryotic and bacterial Rad51/RecA. Euryarchaea encode an additional Rad51/RecA homologue, RadB. RadB shares homology with the core domain of RadA and has been shown to bind both single and double stranded DNA, binds ATP and possesses a very weak ATPase activity. However, RadB does not catalyse strand exchange. RadB has been shown to interact with RadA, a Holliday junction resolvase (Hjc) and a DNA polymerase (PolD), suggesting a role in recombination. In this study, radB was deleted from the halophilic archaeon, Haloferax volcanii. 'delta' radB strains were slow growing, sensitive to mitomycin C and UV irradiation, and deficient for both crossover and non-crossover recombination. Deletion of radA results in similar phenotypic characteristics, and complete abrogation of recombination. Strains deleted for both radA and radB are equally defective as 'delta' radA strains, demonstrating that RadA is epistatic to RadB. A suppressor of 'delta' radB was isolated and identified as a mutation in the polymerisation domain of RadA (RadA-A196V). radA-A196V suppresses the slow growth, crossover and non-crossover recombination defects associated with 'delta' radB, as well as UV and mitomycin C sensitivity phenotypes. On account of the nature of this suppressor, the observed interaction between RadA and RadB, and the epistatic relationship between RadA and RadB, a role for RadB as a recombination mediator protein is proposed. Finally, strains were deleted for hjc. 'delta' hjc strains exhibit no growth, crossover and non-crossover recombination defects and no UV and mitomycin C sensitivity. This suggests that another, as yet unidentified, Holliday junction resolvase is encoded by Haloferax volcanii

Panel sequencing links rare, likely damaging gene variants with distinct clinical phenotypes and outcomes in juvenile-onset SLE

OBJECTIVES: Juvenile-onset systemic lupus erythematosus (jSLE) affects 15–20% of lupus patients. Clinical heterogeneity between racial groups, age groups and individual patients suggests variable pathophysiology. This study aimed to identify highly penetrant damaging mutations in genes associated with SLE/SLE-like disease in a large national cohort (UK JSLE Cohort Study) and compare demographic, clinical and laboratory features in patient sub-cohorts with ‘genetic’ SLE vs remaining SLE patients. METHODS: Based on a sequencing panel designed in 2018, target enrichment and next-generation sequencing were performed in 348 patients to identify damaging gene variants. Findings were integrated with demographic, clinical and treatment related datasets. RESULTS: Damaging gene variants were identified in ∼3.5% of jSLE patients. When compared with the remaining cohort, ‘genetic’ SLE affected younger children and more Black African/Caribbean patients. ‘Genetic’ SLE patients exhibited less organ involvement and damage, and neuropsychiatric involvement developed over time. Less aggressive first line treatment was chosen in ‘genetic’ SLE patients, but more second and third line agents were used. ‘Genetic’ SLE associated with anti-dsDNA antibody positivity at diagnosis and reduced ANA, anti-LA and anti-Sm antibody positivity at last visit. CONCLUSION: Approximately 3.5% of jSLE patients present damaging gene variants associated with younger age at onset, and distinct clinical features. As less commonly observed after treatment induction, in ‘genetic’ SLE, autoantibody positivity may be the result of tissue damage and explain reduced immune complex-mediated renal and haematological involvement. Routine sequencing could allow for patient stratification, risk assessment and target-directed treatment, thereby increasing efficacy and reducing toxicity

Lignocellulose-Degrading Microbial Communities in Landfill Sites Represent a Repository of Unexplored Biomass- Degrading Diversity Emma

The microbial conversion of lignocellulosic biomass for biofuel production represents a renewable alternative to fossil fuels. However, the discovery of new microbial enzymes with high activity is critical for improving biomass conversion processes. While attempts to identify superior lignocellulose-degrading enzymes have focused predominantly on the animal gut, biomass-degrading communities in landfill sites represent an unexplored resource of hydrolytic enzymes for biomass conversion. Here, to address the paucity of information on biomass-degrading microbial diversity beyond the gastrointestinal tract, cellulose (cotton) “baits” were incubated in landfill leachate microcosms to enrich the landfill cellulolytic microbial community for taxonomic and functional characterization. Metagenome and 16S rRNA gene amplicon sequencing demonstrated the dominance of Firmicutes, Bacteroidetes, Spirochaetes, and Fibrobacteres in the landfill cellulolytic community. Functional metagenome analysis revealed 8,371 carbohydrate active enzymes (CAZymes) belonging to 244 CAZyme families. In addition to observing biomass-degrading enzymes of anaerobic bacterial “cellulosome” systems of members of the Firmicutes, we report the first detection of the Fibrobacter cellulase system and the Bacteroidetes polysaccharide utilization locus (PUL) in landfill sites. These data provide evidence for the presence of multiple mechanisms of biomass degradation in the landfill microbiome and highlight the extraordinary functional diversity of landfill microorganisms as a rich source of biomass-degrading enzymes of potential biotechnological significance