Background: Long-term efficacy of inebilizumab (INEB), an anti-CD19+ B cell-depleting antibody approved for the treatment of seropositive-aquaporin-4-antibody (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) was evaluated over N-MOmentum (NCT02200770) open-label period (OLP) vs azathioprine and other immunosuppressants (AZA/IST) and vs PBO. Methods: Two historical comparator groups (HCGs), AZA/IST (N=132) and PBO (N=106), derived from published NMOSD studies, were used to compare efficacy of INEB (N=208) over the OLP. Hazard ratios (HR) for INEB vs HCGs were estimated using Cox proportional hazards (PH) regression. Time to NMOSD attack was analysed using parametric and flexible survival (spline) models. Results: Time to NMOSD attack for N-MOmentum PBO compared to PBO was HR 1.15;(95% CI:0.67–1.91; P=0.58). The HRs for time to NMOSD attack for INEB vs AZA/IST and PBO groups were 0.29(95% CI:0.17, 0.42; P<0.001) and 0.15 (95% CI:0.10, 0.21; P<0.001). At 4 years, estimated attack-free survival was 77% (95% CI:71, 83) for INEB, 36% (95% CI:27, 46) for AZA/IST, and 12% (95% CI:7, 20) for PBO. Conclusions: INEB was associated with a statistically significant reduction in risk of an NMOSD attack and provided a long-term attack-free probability over the OLP compared to the relative short-term benefit observed with AZA/IST.

Background: The long-term outcomes of inebilizumab in participants from the N-MOmentum trial with a history of immunosuppressant therapy as compared to those without was evaluated. Methods: N-MOmentum (NCT02200770) was a 28-week randomized phase 2/3 trial of inebilizumab vs placebo, with an optional Open-Label Period (OLP) (>2 years). In this post hoc analysis, AQP4+ participants who received inebilizumab (through the OLP) were grouped by no history of immunosuppression therapy beyond treatment of acute NMOSD attacks (naïve), or prior azathioprine (AZA) and/or mycophenolate mofetil (MMF) therapy. Results: Among participants who received inebilizumab during the study, 94 received prior AZA/MMF and 103 were immunosuppressant naïve. Annualized relapse rate (95%CI) for participants with prior AZA/MMF was 0.11 (0.07, 0.17), compared to 0.08 (0.05, 0.14) for naïve. The hospitalization rate (annualized rate [95% CI]) for prior AZA/MMF was 0.15 (0.08, 0.27), and 0.12 (0.06, 0.22) for naïve. Participants with ≥1 study drug-related-treatment-emergent-adverse-event (TEAE) was 30.9% (29/94) in prior AZA/MMF and 46.6% (48/103) of naïve. Most adverse events were infection-related for both groups; 72.3% (68/94) for prior AZA/MMF and 77.7% (80/94) for naïve. Conclusions: This post hoc analysis evaluating long-term outcomes of inebilizumab in AQP4+ NMOSD participants treated with prior AZA/MMF therapy demonstrated a similar efficacy and safety profile as participants without prior immunosuppressant therapy.

OBJECTIVES/GOALS: Well-appearing febrile infants are a model for exploring communication, bias, and health disparities in the pediatric emergency department (ED). Using mixed methods, we will perform an in-depth analysis of disparities and shared decision making, a potentially modifiable driver of inequities. METHODS/STUDY POPULATION: We will conduct a multicenter cross-sectional chart review study of well-appearing febrile infants 29-60 days old treated in the ED and apply multivariable logistic regression to assess the association between 1) race/ethnicity and 2) limited English proficiency with the primary outcome, discharge to home without lumbar puncture and without antibiotics (standard of care). We will concurrently perform an interpretive study using purposive sampling to conduct interviews with: 1) minority parents of febrile infants and 2) ED physicians. By capturing dyadic data, we will triangulate perspectives to elucidate disparities and bias that can emerge in the shared decision making process. RESULTS/ANTICIPATED RESULTS: Forty member institutions of the Pediatric Emergency Medicine Collaborative Research Committee are participating, providing a projected cohort of 3000 infants. In the 6 months since site recruitment, 235 eligible infants have been entered into the dataset (43% minority race/ethnicity, 6% language other than English), 61% of whom received the primary outcome. Chart review has the benefits of 1) ensuring exclusion of ill infants, 2) providing data on interpreter use that is unavailable in administrative datasets, and 3) allowing an analysis of shared decision making. These findings will inform an interpretive study of parent and provider experiences of bias in shared decision making. DISCUSSION/SIGNIFICANCE: We demonstrate the feasibility of a large-scale manual chart review to analyze disparities within a shared decision making context. Partnered with qualitative scholarship, this research will support the development of communication interventions to mitigate implicit bias in the clinical encounter.

OBJECTIVES/GOALS: Commercial health insurance payers invest in disease management programs (DM) to coordinate care for complex patients. To overcome gaps in connecting patients hospitalized with heart failure to DM, we implemented a novel warm handoff referral between hospital providers and payer DM using the Implementation Research Logic Model (IRLM). METHODS/STUDY POPULATION: A research and quality improvement team collaborated with champions from one hospital and three payers to build and pilot an inpatient-based referral for hospitalized patients with heart failure who were beneficiaries of one of three payers. The standard process of payers initiating contact with patients by phone was restructured to enable inpatient teams to initiate referrals by screening eligible patients prior to discharge. Between August 2020 and October 2021, 285 patients were hospitalized and eligible for screening. Patient registries were built to track patient referral, eligibility, and enrollment status. Monthly stakeholder meetings were used to collect referral rates and review barriers and facilitators related to implementation. RESULTS/ANTICIPATED RESULTS: Of the 63.6% (N=168) patients screened, 31.4% (N=83) were referred, 17.4% (N=46) declined referral, and 14.8% (N=39) were deemed ineligible by payers. Inpatient screenings were challenged by variability across five units with incomplete/missed referrals, primarily attributed to COVID-19-related staff shortages. Payers were challenged by delayed/incomplete referrals and varying access to the hospitals EHRs. Building patient registries helped inpatient champions track eligibility and referral status, and centralizing screening to one champion improved screening rates and reduced incomplete referrals. Additional challenges being addressed include clarifying each payers unique eligibility requirements, refining payers review of referral emails, and creating descriptions of DM for patients. DISCUSSION/SIGNIFICANCE: Implementing inpatient-based DM referrals requires patient and staff engagement, real-time data sharing, and iterative process improvement. Referrals using robust health IT systems could improve patient engagement by connecting payers, providers, and patients; and improve evaluation efforts with real-time process and outcome data.

Adolescent risk for self-injurious thoughts and behaviors (STBs) involves disturbance across multiple systems (e.g., affective valence, arousal regulatory, cognitive and social processes). However, research integrating information across these systems is lacking. Utilizing a multiple-levels-of-analysis approach, this person-centered study identified psychobiological stress response profiles and linked them to cognitive processes, interpersonal behaviors, and STBs. At baseline, adolescent girls (N = 241, Mage = 14.68 years, Range = 12–17) at risk for STBs completed the Trier Social Stress Test (TSST), questionnaires, and STB interviews. Positive affect (PA), negative affect (NA), and salivary cortisol (SC) were assessed before and after the TSST. STBs were assessed again during 3, 6, and 9 month follow-up interviews. Multitrajectory modeling of girls’ PA, NA, and SC revealed four profiles, which were compared on cognitive and behavioral correlates as well as STB outcomes. Relative to normative, girls in the affective distress, hyperresponsive, and hyporesponsive subgroups were more likely to report negative cognitive style (all three groups) and excessive reassurance seeking (hyporesponsive only) at baseline, as well as nonsuicidal self-injury (all three groups) and suicidal ideation and attempt (hyporesponsive only) at follow-up. Girls’ close friendship characteristics moderated several profile–STB links. A synthesis of the findings is presented alongside implications for person-centered tailoring of intervention efforts.

Habitat loss and fragmentation are major threats to biodiversity worldwide, and little is known about their effects on bats in Africa. We investigated effects of forest fragmentation on bat assemblages at Kakamega Forest, western Kenya, examining captures at edge and interior locations in three forest fragments (Buyangu, 3950 ha; Kisere, 400 ha; and Malava, 100 ha) varying in forest area and human-use regimes. Basal area, canopy cover, tree density and intensity of human use were used as predictors of bat abundance and species richness. A total of 3456 mist-net hours and 3168 harp-trap hours resulted in the capture of 4983 bats representing 26 species, eight families and four foraging ensembles (frugivores, forest-interior insectivores, forest-edge insectivores and open-space insectivores). Frugivores were frequently captured at the edges of the larger, better-protected forests, but also in the interior of the smaller, more open fragment. Forest-interior insectivores and narrow-space foragers predominated in the interiors of larger fragments but avoided the smallest one. Forest specialists showed positive associations with forest variables (canopy cover, basal area and tree density), whereas frugivores responded positively to the human-use indicators. On these bases, specialist species appear to be especially vulnerable to forest fragmentation.

We consider transport networks with nodes scattered at random in a large domain. At certain local rates, the nodes generate traffic flows according to some navigation scheme in a given direction. In the thermodynamic limit of a growing domain, we present an asymptotic formula expressing the local traffic flow density at any given location in the domain in terms of three fundamental characteristics of the underlying network: the spatial intensity of the nodes together with their traffic generation rates, and of the links induced by the navigation. This formula holds for a general class of navigations satisfying a link-density and a sub-ballisticity condition. As a specific example, we verify these conditions for navigations arising from a directed spanning tree on a Poisson point process with inhomogeneous intensity function.

A 3-year study was conducted in irrigated potato to compare weed control efficacy and economics of hilling plus one or two cultivations with the standard treatment of hilling plus a preemergence application of pendimethalin plus metribuzin. Trials were conducted under both weedy and weed-free conditions. Common lambsquarters and redroot pigweed were present in weedy treatments each year; significant populations of hairy nightshade and green foxtail also were present one year. When weed populations were low or moderate (< 45 plants/m2), total weed biomass in the hilling plus one cultivation treatment was reduced 98 to 99% relative to the weedy control, and U.S. No. 1 tuber yields were equal to the standard treatment. However, when weed populations were high (145 plants/m2), hilling plus one cultivation and hilling plus two cultivations provided only 30% and 61% reduction in weed biomass, respectively, and U.S. No. 1 tuber yields were 35% and 13% less, respectively, than the standard treatment. The standard treatment provided 99% reduction in total weed biomass each year, and yields were equal to the weed-free, hill plus no cultivation control. Net return was $37 to $100/ha higher for the hilling plus one cultivation treatment compared to the standard treatment when weed populations were moderate or low, but was $808/ha less than the standard treatment when weed populations were high.

A study of the C4 plant itchgrass (Rottboellia exaltata L.f.) grown under 100%, 60%, 25% and 2% sunlight revealed differences in the anatomy and cytology of the foliar mesophyll and vascular bundles associated with shading. In the bundle sheath, shading caused a reduction in thickness of the cell walls, shrinkage of plastids, rearrangement of plastid thylakoids, a reduction in starch deposits and vacuolization of the cytoplasm. In general, plastids and mitochondria retained membrane integrity but underwent stromal deterioration. Shading effects on cytoplasm were similar for mesophyll and bundle sheath cells. Mesophyll chloroplasts lost starch grains and the peripheral reticulum tended to decrease with greater shading. Grana were well developed at all irradiances, although the chloroplasts themselves decreased in size with shading. Movement of mesophyll chloroplasts away from bundle sheath-mesophyll borders was pronounced at 60% sunlight and was progressively greater at the two lower irradiances. These observations suggest that the structural relationships thought to be necessary for the intercellular transfer of C4 acids and the functioning of the C4 photosynthetic pathway were disrupted by shading.

Increasingly, evidence suggests that computerized Cognitive Behavioural Therapy (cCBT) is effective at reducing adolescent anxiety and depression for young people in the general population or those ‘at risk’. However, less is known about the acceptability, feasibility and effectiveness of cCBT for adolescents with clinically significant levels of impairment. This study aimed to investigate the feasibility of using a novel cCBT intervention, ‘Pesky gNATs’, with adolescents aged between 13–18 years with anxiety and/or depression who met the criteria for specialist mental health services. Eleven participants were recruited from a Tier 3 child and adolescent mental health service (CAMHS). Recruitment, attendance and retention rates were recorded and qualitative feedback about the benefits and disadvantages of completing cCBT were obtained during the final session. In addition, a number of outcome measures were completed pre- and post- intervention to assess reliable and clinically significant change. The intervention was very brief comprising of just seven sessions. Participants showed high recruitment and retention rates. All participants who started the intervention completed it. All described the programme as useful and the majority identified several benefits. Four of 11 participants demonstrated reliable reductions in symptoms of depression and anxiety and six of 11 showed decreases in parent-reported symptoms of anxiety and depression following the seven-session intervention. This study demonstrates the acceptability and feasibility of using cCBT in a Tier 3 CAMHS setting. Further research is required to investigate the effect of Pesky gNATs on anxiety and depression in other Tier 3 settings.

We study large deviation principles for a model of wireless networks consisting of Poisson point processes of transmitters and receivers. To each transmitter we associate a family of connectable receivers whose signal-to-interference-and-noise ratio is larger than a certain connectivity threshold. First, we show a large deviation principle for the empirical measure of connectable receivers associated with transmitters in large boxes. Second, making use of the observation that the receivers connectable to the origin form a Cox point process, we derive a large deviation principle for the rescaled process of these receivers as the connection threshold tends to 0. Finally, we show how these results can be used to develop importance sampling algorithms that substantially reduce the variance for the estimation of probabilities of certain rare events such as users being unable to connect.

This study compares two methods of estimating a reduced form model of fresh tomato marketing margins: an econometric and an artificial neural network (ANN) approach. Model performance is evaluated by comparing out-of-sample forecasts for the period of January 1992 to December 1994. Parameter estimates using the econometric model fail to reject a dynamic, imperfectly competitive, uncertain relative price spread margin specification, but misspecification tests reject both linearity and log-linearity. This nonlinearity suggests that an inherently nonlinear method, such as a neural network, may be of some value. The neural network is able to forecast with approximately half the mean square error of the econometric model, but both are equally adept at predicting turning points in the time series.

The Fuji apple variety is relatively new in the U.S. As a new product, questions concern the relative impact of consumer learning by experience, by variety-specific promotion, or by generic apple promotion. A two-stage (LES/LAIDS) model incorporating both types of promotion is used to estimate the effect of generic and variety specific promotion, as well as consumer experience, on the demand for Fuji apples. Estimates show each to have a positive impact, and also show new or specialty apple varieties to be relatively price inelastic, but income elastic. Grower returns to promotion are calculated with an equilibrium displacement model of price changes and producer surplus. Changes in producer surplus provide a base-scenario benefit:cost ratio of 6.33:1.

Consumers the world over are becoming more homogeneous thanks to the unifying forces of travel, media, technology, information transfer and the like. Furthermore, today customers have higher expectations than ever before regarding the quality of service they should receive from a wide range of service organisations (professional as well as non-professional). As customers are increasingly exposed to world best practice in a wide range of service industries, expectations spiral upwards. Slow, discourteous, unresponsive and unprofessional service will no longer be tolerated - but especially when the service is highly customised, complex, costly and high involvement, professional service.

Few, if any, studies have examined service quality issues for professional services in an international context. Hence, this case study documents the problems experienced by the Australian Trade Commission's (Austrade) Bangkok, Thailand Post in providing a level of service consistent with clients' (and senior managements') expectations, the steps taken to overcome these long standing service quality shortcomings, as well as the key lessons to be learnt from the process. Today Austrade provides a professional consulting service and thus possesses similar characteristics to many professional service firms (project management, engineering consulting, general management consulting, etc.) and thus the lessons from this successful change management program may be generalisable to other professional services. Furthermore, the lessons should prove invaluable for Australian firms operating in South-East Asia staffed by expatriates and local nationals.

Consumer product manufacturers often compete in dynamic, multi-firm oligopolies using multiple strategic tools. While existing empirical models of strategic interaction typically consider only parts of the more general problem, this paper presents a more comprehensive alternative. Marketing decisions are dynamically optimal, consistent with optimal consumer choice, and responsive to rival decisions. Using a single-market case study that consists of five years of four-weekly data on ready-to-eat cereal sales, prices, and new brand introductions, we test several hypotheses regarding the nature of strategic interaction among several rival manufacturers. We find that cereal manufacturers price and introduce new brands cooperatively in the same period, but behave more competitively when dynamic reactions are included.

“Commodity promotion” consists of many activities, each designed to contribute to a consumer's product knowledge or influence tastes. However, both knowledge and tastes are unobservable, or latent, variables influencing demand. This paper specifies a dynamic structural model of fresh fruit demand that treats promotion and other socioeconomic variables as “causal” variables influencing these latent variables. Estimating this state-space model using a Kalman filter approach provides estimates of both the system parameters and a latent variable series. The results show that these latent effects contribute positively to apple and other fruit consumption, while reducing banana consumption.