Democracy, Bureaucracy, and Criminal Justice Reform

American criminal justice systems blend elected or politically appointed leaders with career civil servants. This organizational hybrid creates challenges at the intersection of democratic accountability and enforcement discretion. In moments of stasis in the politics of criminal justice, those challenges are largely invisible: the public, elected officials, and civil servants generally share a unity of interest, borne of like-minded policy commitments that have developed over time. But in moments of political transition—that is, when public preferences on criminal justice policy are in flux—the relationship between bureaucracy and democracy can be fraught. Public demand for change may or may not accord with the commitments, ideals, and culture of the bureaucracy’s front-line actors. Elected leaders are voted in with high expectations for transformative change, but may be stymied by institutional resistance to it. The bureaucracy, in turn, may seek to alter the political narrative that is fueling the political transition, further complicating the democratic process. And in a system in which criminal lawmaking and enforcement power is spread across three different levels of government—local, state, and federal—with overlapping authority yet different constituencies, the complexity of interplay between “public” and bureaucracy deepens. Across America, a growing number of jurisdictions are entering moments of political transition in criminal justice. This Article explores the political and institutional arrangements that alternatively impede, permit, or even accelerate a resulting change in criminal enforcement on the ground. Drawing on the democracy/bureaucracy framework developed in the fields of political theory and public administration, the Article considers how these fields and others can enrich our understanding of current political and institutional dynamics in American criminal justice. The Article then reflects on these dynamics’ implications for democratic responsiveness and systemic legitimacy, arguing, counterintuitively, that the very features of the democracy/bureaucracy relationship capable of slowing democratically sanctioned change in criminal enforcement can also end up hastening political shifts; and that, properly leveraged, the criminal enforcement bureaucracy can help realize deliberative and participatory democratic ideals

Type I Interferon in Children with Viral or Bacterial Infections.

BACKGROUND: Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians' decisions and limit antibiotic overuse. METHODS: Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. RESULTS: Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P 0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). CONCLUSIONS: IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov (NCT03163628)

Epithelial-Mesenchymal Transition in Cells Expanded In Vitro from Lineage-Traced Adult Human Pancreatic Beta Cells

BACKGROUND: In-vitro expansion of functional beta cells from adult human islets is an attractive approach for generating an abundant source of cells for beta-cell replacement therapy of diabetes. Using genetic cell-lineage tracing we have recently shown that beta cells cultured from adult human islets undergo rapid dedifferentiation and proliferate for up to 16 population doublings. These cells have raised interest as potential candidates for redifferentiation into functional insulin-producing cells. Previous work has associated dedifferentiation of cultured epithelial cells with epithelial-mesenchymal transition (EMT), and suggested that EMT generates cells with stem cell properties. Here we investigated the occurrence of EMT in these cultures and assessed their stem cell potential. METHODOLOGY/PRINCIPAL FINDINGS: Using cell-lineage tracing we provide direct evidence for occurrence of EMT in cells originating from beta cells in cultures of adult human islet cells. These cells express multiple mesenchymal markers, as well as markers associated with mesenchymal stem cells (MSC). However, we do not find evidence for the ability of such cells, nor of cells in these cultures derived from a non-beta-cell origin, to significantly differentiate into mesodermal cell types. CONCLUSIONS/SIGNIFICANCE: These findings constitute the first demonstration based on genetic lineage-tracing of EMT in cultured adult primary human cells, and show that EMT does not induce multipotency in cells derived from human beta cells

Insulin-Producing Cells Generated from Dedifferentiated Human Pancreatic Beta Cells Expanded In Vitro

Expansion of beta cells from the limited number of adult human islet donors is an attractive prospect for increasing cell availability for cell therapy of diabetes. However, attempts at expanding human islet cells in tissue culture result in loss of beta-cell phenotype. Using a lineage-tracing approach we provided evidence for massive proliferation of beta-cell-derived (BCD) cells within these cultures. Expansion involves dedifferentiation resembling epithelial-mesenchymal transition (EMT). Epigenetic analyses indicate that key beta-cell genes maintain open chromatin structure in expanded BCD cells, although they are not transcribed. Here we investigated whether BCD cells can be redifferentiated into beta-like cells.Redifferentiation conditions were screened by following activation of an insulin-DsRed2 reporter gene. Redifferentiated cells were characterized for gene expression, insulin content and secretion assays, and presence of secretory vesicles by electron microscopy. BCD cells were induced to redifferentiate by a combination of soluble factors. The redifferentiated cells expressed beta-cell genes, stored insulin in typical secretory vesicles, and released it in response to glucose. The redifferentiation process involved mesenchymal-epithelial transition, as judged by changes in gene expression. Moreover, inhibition of the EMT effector SLUG (SNAI2) using shRNA resulted in stimulation of redifferentiation. Lineage-traced cells also gave rise at a low rate to cells expressing other islet hormones, suggesting transition of BCD cells through an islet progenitor-like stage during redifferentiation.These findings demonstrate for the first time that expanded dedifferentiated beta cells can be induced to redifferentiate in culture. The findings suggest that ex-vivo expansion of adult human islet cells is a promising approach for generation of insulin-producing cells for transplantation, as well as basic research, toxicology studies, and drug screening