Using policy codesign to achieve multi-sector alignment in adolescent behavioral health: a study protocol

Background: Policymaking is quickly gaining focus in the field of implementation science as a potential opportunity for aligning cross-sector systems and introducing incentives to promote population health, including substance use disorders (SUD) and their prevention in adolescents. Policymakers are seen as holding the necessary levers for realigning service infrastructure to more rapidly and effectively address adolescent behavioral health across the continuum of need (prevention through crisis care, mental health, and SUD) and in multiple locations (schools, primary care, community settings). The difficulty of aligning policy intent, policy design, and successful policy implementation is a well-known challenge in the broader public policy and public administration literature that also affects local behavioral health policymaking. This study will examine a blended approach of coproduction and codesign (i.e., Policy Codesign), iteratively developed over multiple years to address problems in policy formation that often lead to poor implementation outcomes. The current study evaluates this scalable approach using reproducible measures to grow the knowledge base in this field of study. Methods: This is a single-arm, longitudinal, staggered implementation study to examine the acceptability and short-term impacts of Policy Codesign in resolving critical challenges in behavioral health policy formation. The aims are to (1) examine the acceptability, feasibility, and reach of Policy Codesign within two geographically distinct counties in Washington state, USA; (2) examine the impact of Policy Codesign on multisector policy development within these counties using social network analysis; and (3) assess the perceived replicability of Policy Codesign among leaders and other staff of policy-oriented state behavioral health intermediary organizations across the USA. Discussion: This study will assess the feasibility of a specific approach to collaborative policy development, Policy Codesign, in two diverse regions. Results will inform a subsequent multi-state study measuring the impact and effectiveness of this approach for achieving multi-sector and evidence informed policy development in adolescent SUD prevention and treatment

Graphene-Based Energy Storage Devices for Space Applications

No abstract availabl

Pleistocene environments, climate, and human activity in Britain during Marine Isotope Stage 7: insights from Oak Tree Fields, Cerney Wick, Gloucestershire

Investigations at Oak Tree Fields, Cerney Wick, Gloucestershire, in western England have revealed a sequence of fluvial deposits dating from Marine Oxygen Isotope Stage (MIS) 7 to 5. At the base of the sequence, a series of gravel and sand facies were deposited, initially as part of a meandering river. Reductions in flow energy of the latter and avulsion led to the development of short-lived channels and episodic backwater environments, the deposits of which are recorded as Facies Associations 1–3. Poorly sorted, probably colluvial deposits formed beyond the limit of the channel (Facies Association 4). Mollusca, Coleoptera, plant macrofossils, pollen and vertebrates recovered from the channel facies indicate broadly similar climatic conditions throughout accretion. Temperature ranges derived from mutual climatic range analysis of the Coleoptera almost completely overlap with those of Cerney Wick at the present day, albeit that winters may have been cooler when the channel was active. Further, the floral and faunal data suggest that the meandering river flowed through an open grassland environment, the latter heavily grazed by large vertebrates, most notably mammoth. Most of the botanical and faunal remains, together with four optically stimulated luminescence (OSL) age estimates ranging from 225 ± 23 to 187 ± 19 ka, suggest correlation of the channel deposits with MIS 7. The basal deposits (Facies Association 1) yielded the majority of vertebrate remains and all the lithic artefacts, most of which seem likely to have travelled only a short distance. Although only a few artefacts were recovered, they add to the relatively limited evidence of human activity from the upper Thames. The channel deposits are overlain by sheet gravels (Facies Association 5) which are attributed to the Northmoor Member of the Upper Thames Formation. These were likely to have been deposited as bedload in a braided stream environment, while two OSL age estimates of 129 ± 14 and 112 ± 11 ka suggest accumulation during MIS 5

Computational modeling suggests binding-induced expansion of Epsin disordered regions upon association with AP2.

Intrinsically disordered regions (IDRs) are prevalent in the eukaryotic proteome. Common functional roles of IDRs include forming flexible linkers or undergoing allosteric folding-upon-binding. Recent studies have suggested an additional functional role for IDRs: generating steric pressure on the plasma membrane during endocytosis, via molecular crowding. However, in order to accomplish useful functions, such crowding needs to be regulated in space (e.g., endocytic hotspots) and time (e.g., during vesicle formation). In this work, we explore binding-induced regulation of IDR steric volume. We simulate the IDRs of two proteins from Clathrin-mediated endocytosis (CME) to see if their conformational spaces are regulated via binding-induced expansion. Using Monte-Carlo computational modeling of excluded volumes, we generate large conformational ensembles (3 million) for the IDRs of Epsin and Eps15 and dock the conformers to the alpha subunit of Adaptor Protein 2 (AP2α), their CME binding partner. Our results show that as more molecules of AP2α are bound, the Epsin-derived ensemble shows a significant increase in global dimensions, measured as the radius of Gyration (RG) and the end-to-end distance (EED). Unlike Epsin, Eps15-derived conformers that permit AP2α binding at one motif were found to be more likely to accommodate binding of AP2α at other motifs, suggesting a tendency toward co-accessibility of binding motifs. Co-accessibility was not observed for any pair of binding motifs in Epsin. Thus, we speculate that the disordered regions of Epsin and Eps15 perform different roles during CME, with accessibility in Eps15 allowing it to act as a recruiter of AP2α molecules, while binding-induced expansion of the Epsin disordered region could impose steric pressure and remodel the plasma membrane during vesicle formation

Computational modeling suggests binding-induced expansion of Epsin disordered regions upon association with AP2

10.1371/journal.pcbi.1008474PLoS Computational Biology171-Dece100847

Importance of the Penultimate Positive Charge in Mouse Hepatitis Coronavirus A59 Membrane Protein▿

The coronavirus membrane (M) protein carboxy tail interacts with the nucleocapsid during virus assembly. Previous studies demonstrated that the two terminal residues are important, and the charged residue (R227) in the penultimate position in the mouse hepatitis coronavirus (MHV) A59 M protein was suggested to participate in intermolecular interactions with negative charges in the nucleocapsid (N) protein. To determine the significance of the positive charge at position 227, we substituted the arginine with lysine (K), aspartic acid (D), glutamic acid (E), or alanine (A) and studied these by reverse genetics in the context of a MHV full-length infectious clone. Viruses with wild-type phenotype were readily recovered with the K or A substitutions. In contrast, negative-charge substitutions were not tolerated as well. In all recovered R227D viruses the negative charge was replaced with heterologous residues resulting from apparent template switching during negative-strand synthesis of subgenomic RNA 7. An additional second-site compensatory V202I substitution was present in some viruses. Recovered R227E viruses had second-site changes within the M protein carboxy tail that were partially compensatory. Significantly, most of the second site changes in the R227E mutant viruses were previously shown to compensate for the removal of negative charges in the N protein. Our results strongly indicate that a positive charge is not absolutely required. It is clear that other regions within the tail must also be involved in helping mediate interactions between the M protein and the nucleocapsid

Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection

Granulocyte colony-stimulating factor (G-CSF) regulates the production, maturation, and function of neutrophils. Its expression is often induced during infection, resulting in high concentrations of G-CSF in inflammatory exudates and in the blood, suggesting that it may regulate both local and systemic neutrophil responses. Herein, we characterize the neutrophil response in G-CSFR(−/−) mice following intratracheal injection with Pseudomonas aeruginosa–laden agarose beads, modeling the pulmonary infection observed in many patients with cystic fibrosis. G-CSFR(−/−) mice are markedly susceptible to bronchopulmonary P aeruginosa infection, exhibiting decreased survival and bacterial clearance as well as extensive damage to lung tissue. The systemic neutrophil response was mediated primarily by enhanced neutrophil release from the bone marrow rather than increased neutrophil production and was attenuated in G-CSFR(−/−) mice. Despite normal to increased local production of inflammatory chemokines, neutrophil accumulation into the infected lung of G-CSFR(−/−) mice was markedly reduced. Moreover, the percentage of apoptotic neutrophils in the lung was elevated, suggesting that G-CSF signals may play an important role in regulating neutrophil survival at the inflammatory site. Collectively, these data provide new evidence that G-CSF signals play important but specific roles in the regulation of the systemic and local neutrophil response following infection

Predicting Parcel-Scale Redevelopment Using Linear and Logistic Regression—the Berkeley Neighborhood Denver, Colorado Case Study

Many watershed challenges can be associated with the increased impervious cover that accompanies urban development. This study establishes a methodology of evaluating the spatial and temporal distribution of infill re-development on a parcel scale, using publicly available urban planning data. This was achieved through a combination of linear and logistic regression. First, a “business as usual„ linear growth scenario was developed based on available building coverage data. Then, a logistic regression model of historic redevelopment, as a function of various parcel attributes, was used to predict each parcel’s probability of future redevelopment. Finally, the linear growth model forecasts were applied to the parcels with the greatest probability of future redevelopment. Results indicate that building cover change within the study site, from 2004–2014, followed a linear pattern (R2 = 0.98). During this period the total building cover increased by 17%, or 1.7% per year on average. Applying the linear regression model to the 2014 building coverage data resulted in an increase of 820,498 sq. ft. (18.8 acres) in building coverage over a ten-year period, translating to a 14% overall increase in impervious neighborhoods. The parcel and building variables selected for inclusion in the logistic regression model during the model calibration phase were total value, year built, percent difference between current and max building cover, and the current use classifications—rowhome and apartment. The calibrated model was applied to a validation dataset, which predicted redevelopment accuracy at 81%. This method will provide municipalities experiencing infill redevelopment a tool that can be implemented to enhance watershed planning, management, and policy development