RESUMEN
While today it is universally acknowledged that COVID-19 has generated immense challenges for businesses and societies worldwide, public perceptions varied significantly at the time of the pandemic's initial appearance, even among democratic societies with comparable media systems. The growing scholarship on grand societal challenges in management and organization studies, however, tends to neglect the initial social construction of issues as complex, uncertain, evaluative, and widespread. We address this shortcoming by exploring the initial communicative enactment of COVID-19 in the media-based public discourse in Switzerland, Germany, and the United Kingdom. By applying a social problem work lens, we identify three mechanisms that explain the maturation of COVID-19 into a grand challenge, further showing how these are contextually dependent on differences in discourse quality. We add to research on grand challenges, issue maturation, and framing dynamics by theorizing how issues become constructed and acknowledged as grand challenges in the first place.
RESUMEN
Some patients diagnosed with benign IgA nephropathy (IgAN) develop a progressive clinical course, not predictable by known clinical or histopathological parameters. To assess if gene expression can differentiate between progressors and non-progressors with assumed benign IgAN, we tested microdissected glomeruli from archival kidney biopsy sections from adult patients with stable clinical remission (21 non-progressors) or from 15 patients that had undergone clinical progression within a 25-year time frame. Based on 1 240 differentially expressed genes from patients with suitable sequencing results, we identified eight IgAN progressor and nine non-progressor genes using a two-component classifier. These genes, including APOL5 and ZXDC, predicted disease progression with 88% accuracy, 75% sensitivity and 100% specificity on average 21.6 years before progressive disease was clinically documented. APOL lipoproteins are associated with inflammation, autophagy and kidney disease while ZXDC is a zinc-finger transcription factor modulating adaptive immunity. Ten genes from our transcriptomics data overlapped with an external genome wide association study dataset, although the gene set enrichment test was not statistically significant. We also identified 45 drug targets in the DrugBank database, including angiotensinogen, a target of sparsentan (dual antagonist of the endothelin type A receptor and the angiotensin II type 1 receptor) currently investigated for IgAN treatment. Two validation cohorts were used for substantiating key results, one by immunohistochemistry and the other by nCounter technology. Thus, glomerular mRNA sequencing from diagnostic kidney biopsies from patients with assumed benign IgAN can differentiate between future progressors and non-progressors at the time of diagnosis.
