Academic discussion of social challenges and the government interventions which might address them are overlooking social innovation as an option. Contemporary trends at the community-public management interface, however, show an upsurge of interest in social innovation as a way of simultaneously creating social benefit and economic opportunity. While this indicates that the idea has genuine substance our observation of international and Australian developments convinces us that there is now sufficient experience upon which to base an understanding of what social innovation is and why it has policy significance. In this article we identify some components of social innovation practice and indicate how these might be theorised into generally applicable models.

Randomized prospective studies represent the gold standard for experimental design. In this paper, we present a randomized prospective study to validate the benefits of combining rule-based and data-driven natural language understanding methods in a virtual patient dialogue system. The system uses a rule-based pattern matching approach together with a machine learning (ML) approach in the form of a text-based convolutional neural network, combining the two methods with a simple logistic regression model to choose between their predictions for each dialogue turn. In an earlier, retrospective study, the hybrid system yielded a nearly 50% error reduction on our initial data, in part due to the differential performance between the two methods as a function of label frequency. Given these gains, and considering that our hybrid approach is unique among virtual patient systems, we compare the hybrid system to the rule-based system by itself in a randomized prospective study. We evaluate 110 unique medical student subjects interacting with the system over 5,296 conversation turns, to verify whether similar gains are observed in a deployed system. This prospective study broadly confirms the findings from the earlier one but also highlights important deficits in our training data. The hybrid approach still improves over either rule-based or ML approaches individually, even handling unseen classes with some success. However, we observe that live subjects ask more out-of-scope questions than expected. To better handle such questions, we investigate several modifications to the system combination component. These show significant overall accuracy improvements and modest F1 improvements on out-of-scope queries in an offline evaluation. We provide further analysis to characterize the difficulty of the out-of-scope problem that we have identified, as well as to suggest future improvements over the baseline we establish here.

Pediatric antimicrobial stewardship programs (ASPs) improve antibiotic use for hospitalized children. Prescriber surveys indicate acceptance of ASPs, but data on infectious diseases (ID) physician opinions of ASPs are lacking. We conducted a survey of pediatric ID physicians, ASP and non-ASP, and their perceptions of ASP practices and outcomes.

In this survey of 41 hospitals, 18 (72%) of 25 respondents reporting utilization of National Healthcare Safety Network resources demonstrated accurate central-line–associated bloodstream infection reporting compared to 6 (38%) of 16 without utilization (adjusted odds ratio, 5.37; 95% confidence interval, 1.16–24.8). Adherence to standard definitions is essential for consistent reporting across healthcare facilities.

Children of women with pre-eclampsia have increased risk of cardiovascular (CV) and metabolic disease in adult life. Furthermore, the risk of pregnancy complications is higher in daughters born to women affected by pre-eclampsia than in daughters born after uncomplicated pregnancies. While aberrant inflammation contributes to the pathophysiology of pregnancy complications, including pre-eclampsia, the contribution of maternal inflammation to subsequent risk of CV and metabolic disease as well as pregnancy complications in the offspring remains unclear. Here, we demonstrate that 24-week-old female rats (F1) born to dams (F0) exposed to lipopolysaccharide (LPS) during pregnancy (to induce inflammation) exhibited mild systolic dysfunction, increased cardiac growth-related gene expression, altered glucose tolerance, and coagulopathy; whereas male F1 offspring exhibited altered glucose tolerance and increased visceral fat accumulation compared with F1 sex-matched offspring born to saline-treated dams. Both male and female F1 offspring born to LPS-treated dams had evidence of anemia. Fetuses (F2) from F1 females born to LPS-treated dams were growth restricted, and this reduction in fetal growth was associated with increased CD68 positivity (indicative of macrophage presence) and decreased expression of glucose transporter-1 in their utero-placental units. These results indicate that abnormal maternal inflammation can contribute to increased risk of CV and metabolic disease in the offspring, and that the effects of inflammation may cross generations. Our findings provide evidence in support of early screening for CV and metabolic disease, as well as pregnancy complications in offspring affected by pre-eclampsia or other pregnancy complications associated with aberrant inflammation.

We performed a survey of adult infectious diseases (ID) physicians to explore unintended consequences of antimicrobial stewardship programs (ASP). ID physicians worried about disagreement with colleagues, provider autonomy, and remote recommendations. Non-ASP ID physicians expressed more concern regarding ASPs focus on costs, provider efficiency, and unintended consequences of ASP guidance.

OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 μg/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 μm thick sagittal sections from each joint, 50 μm apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.

OBJECTIVES/GOALS: We have created the first-ever database for all patients who have acute peripheral nerve injuries. Our goal is to use this data to construct two clinical scoring systems to facilitate triaging by emergency room physicians by 1.) identifying patients who would likely benefit from a nerve surgery, and 2.) identify patients who are less likely to follow up. METHODS/STUDY POPULATION: Based on 2,606 consult emails from the Washington University in St. Louiss Division of Plastic and Reconstructive Surgery, from 2013 to 2019, we have identified more than 600 patient cases in which patients presented after an injury with any kind of nerve deficit. We have defined nerve deficits as any abnormality on motor or sensory exam of the extremities, excluding those younger than 18 years old and those with other disease processes that may affect function of the peripheral nervous system. Data for these patients was collected from electronic medical records and include handedness, nerve injured, operative details, area deprivation index decile, mechanism of injury, insurance and employment status, and whether injuries were a result of work or violence. RESULTS/ANTICIPATED RESULTS: Our plan is to provide the first descriptive statistics for such a population, as well as multiple regression analysis for our two endpoints, loss to follow up and need for surgery. Following regression analysis, we also look to perform cluster analysis to further study co-occurring clinical and social features that affect our endpoints. We are excitedly awaiting to perform the analysis after the final data has been collected. DISCUSSION/SIGNIFICANCE: Nerve injury is a common symptom of penetrating injuries. Many of the socioeconomic factors associated with increased risk for violent injury are also risk factors for decreased rates of follow up. This problem is particularly worrisome given that nerve repair surgery is only viable as an option to return function within the first year after injury.

Marine-terminating glaciers lose mass through melting and iceberg calving, and we find that meltwater drainage systems influence calving timing at Helheim Glacier, a tidewater glacier in East Greenland. Meltwater feeds a buoyant subglacial discharge plume at the terminus of Helheim Glacier, which rises along the glacial front and surfaces through the mélange. Here, we use high-resolution satellite and time-lapse imagery to observe the surface expression of this meltwater plume and how plume timing and location compare with that of calving and supraglacial meltwater pooling from 2011 to 2019. The plume consistently appeared at the central terminus even as the glacier advanced and retreated, fed by a well-established channelized drainage system with connections to supraglacial water. All full-thickness calving episodes, both tabular and non-tabular, were separated from the surfacing plume by either time or by space. We hypothesize that variability in subglacial hydrology and basal coupling drive this inverse relationship between subglacial discharge plumes and full-thickness calving. Surfacing plumes likely indicate a low-pressure subglacial drainage system and grounded terminus, while full-thickness calving occurrence reflects a terminus at or close to flotation. Our records of plume appearance and full-thickness calving therefore represent proxies for the grounding state of Helheim Glacier through time.

Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System. Monoclonal antibody implementation success factors included engagement with local medical providers, therapy batch preparation, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges included confirming patient severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, strained staff, scheduling, and pharmacy coordination. Infusion sites are effective when integrated into pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources.

This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.

The knowledge-centric theory of mind research program suggested by Phillips et al. stands to gain significant value by embracing a neurocognitive approach that takes full advantage of techniques such as fMRI and EEG. This neurocognitive approach has already begun providing important insights into the mechanisms of knowledge attribution, insights which support the claim that it is more basic than belief attribution.

Seed retention, and ultimately seed shatter, are extremely important for the efficacy of harvest weed seed control (HWSC) and are likely influenced by various agroecological and environmental factors. Field studies investigated seed-shattering phenology of 22 weed species across three soybean [Glycine max (L.) Merr.]-producing regions in the United States. We further evaluated the potential drivers of seed shatter in terms of weather conditions, growing degree days, and plant biomass. Based on the results, weather conditions had no consistent impact on weed seed shatter. However, there was a positive correlation between individual weed plant biomass and delayed weed seed–shattering rates during harvest. This work demonstrates that HWSC can potentially reduce weed seedbank inputs of plants that have escaped early-season management practices and retained seed through harvest. However, smaller individuals of plants within the same population that shatter seed before harvest pose a risk of escaping early-season management and HWSC.