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The Patagonian longfin squid Doryteuthis gahi has an annual life cycle with two seasonal cohorts (autumn and spring spawners). Earlier studies on the Patagonian shelf found a predominance of Euphausiacea in the D. gahi diet, but no studies to date have investigated differences between feeding spectra of the two cohorts or decadal diet shifts. The present study investigated differences in diet of D. gahi on the Patagonian shelf sampled two decades apart, and differences between seasonal cohorts. Classical stomach content analysis and generalized additive models were used to investigate and model the influence of mantle length, sampling period and spawning cohort on the diet. Results revealed an ontogenetic diet change from ~70% Frequency of Occurrence of Euphausiacea in small squid to more than 60% FO of fish and Cephalopoda at larger sizes. Cannibalism was also frequently observed. Euphausiacea were ingested more frequently and in higher amounts during the austral summer and therefore were consumed more by the autumn spawning cohort, whereas fish was more frequently fed upon during austral winter and also by the spring spawning cohort. Cannibalism was also recorded more in austral winter months but, contrary to feeding on fish, was more prevalent in the autumn spawning cohort. Increased predation of Munida gregaria was observed in 2020 compared with 2001. This study is an important step towards improving the knowledge of D. gahi's two seasonal cohorts, providing data that can be used for future ecosystem modelling.
Depression and anxiety are common in adolescents, but most affected will not get any formal help. Digital mental health technologies (i.e. resources and interventions to support and improve mental health) are a potential way to extend the reach and increase adolescents’ access to therapies, at a relatively low cost. Many young people can access the internet and mobile technologies, including in low- and middle-income countries. There has been increased interest in integrating technologies in a range of settings, especially because of the effect of the COVID-19 pandemic on adolescent mental health, at a time when services are under pressure. This clinical review gives an overview of digital technologies to support the prevention and management of depression and anxiety in adolescence. The technologies are presented in relation to their technological approaches, underlying psychological or other theories, setting, development, evaluations to date and how they might be accessed. There is also a discussion of the potential benefits, challenges and future developments in this field.
Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).
Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.
In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).
Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.
This chapter synthesises insights from the Deep Decarbonisation Pathways Project (DDPP), which provided detailed analysis of how 16 countries representing three-quarters of global emissions can transition to very low-carbon economies. The four ‘pillars’ of decarbonisation are identified as: achieving low or zero-carbon electricity supply; electrification and fuel switching in transport, industry and housing; ambitious energy efficiency improvements; and reducing non-energy emissions. The chapter focuses on decarbonisation scenarios for Australia. It shows that electricity supply can be readily decarbonised and greatly expanded to cater for electrification of transport, industry and buildings. There would be remaining emissions principally from industry and agriculture, these could be fully compensated through land-based carbon sequestration. The analysis shows that such decarbonisation would be consistent with continued growth in GDP and trade, and would require very little change in economic structure of Australia’s economy. Australia is rich in renewable energy potential, which could re-enable new industries such as energy-intensive manufacturing for export
In this study, atom probe tomography (APT) was used to investigate strontium-containing bioactive glass particles (BG-Sr10) and strontium-releasing bioactive glass-based scaffolds (pSrBG), both of which are attractive biomaterials with applications in critical bone damage repair. We outline the challenges and corresponding countermeasures of this nonconductive biomaterial for APT sample preparation and experiments, such as avoiding direct contact between focussed ion beam micromanipulators and the extracted cantilever to reduce damage during liftout. Using a low imaging voltage (≤3 kV) and current (≤500 pA) in the scanning electron microscope and a low acceleration voltage (≤2 kV) and current (≤200 pA) in the focussed ion beam prevents tip bending in the final stages of annular milling. To optimize the atom probe experiment, we considered five factors: total detected hits, multiple hits, the background level, the charge-state ratio, and the accuracy of the measured compositions, to explore the optimal laser pulse for BG-Sr10 bioactive glass. We show that a stage temperature of 30 K, 200–250 pJ laser pulse energy, 0.3% detection rate, and 200 kHz pulse rate are optimized experimental parameters for bioactive glass. The use of improved experimental preparation methods and optimized parameters resulted in a 90% successful yield of pSrBG samples by APT.
Zirconium alloys are common fuel claddings in nuclear fission reactors and are susceptible to the effects of hydrogen embrittlement. There is a need to be able to detect and image hydrogen at the atomic scale to gain the experimental evidence necessary to fully understand hydrogen embrittlement. Through the use of deuterium tracers, atom probe tomography (APT) is able to detect and spatially locate hydrogen at the atomic scale. Previous works have highlighted issues with quantifying deuterium concentrations using APT due to complex peak overlaps in the mass-to-charge-state ratio spectrum between molecular hydrogen and deuterium (H2 and D). In this work, we use new methods to analyze historic and simulated atom probe data, by applying currently available data analysis tools, to optimize solving peak overlaps to improve the quantification of deuterium. This method has been applied to literature data to quantify the deuterium concentrations in a concentration line profile across an α-Zr/deuteride interface.
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.
We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders.
There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88).
Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Nonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents.
Computerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance. Participants were adolescents aged 15 to 17 with (n = 50) and without (n = 190) NSSI history, sampled from the ROOTS project which recruited adolescents from secondary schools in Cambridgeshire, UK. NSSI was categorized as sporadic (1-3 instances per year) or repetitive (4 or more instances per year). Analyses were carried out in a series of linear and negative binomial regressions, controlling for age, gender, intelligence, and recent depressive symptoms.
Adolescents with lifetime NSSI, and repetitive NSSI specifically, made significantly more perseverative errors on the Probabilistic Reversal Task and exhibited significantly lower quality of decision making on the Cambridge Gambling Task compared to no-NSSI controls. Those with sporadic NSSI did not significantly differ from no-NSSI controls on task performance. NSSI was not associated with behavioral measures of impulsivity.
Repetitive NSSI is associated with increased behavioral compulsivity and disadvantageous decision making, but not with behavioral impulsivity. Future research should continue to investigate how neurocognitive phenotypes contribute to the onset and maintenance of NSSI, and determine whether compulsivity and addictive features of NSSI are potential targets for treatment.
Coil complexity is a critical consideration in stellarator design. The traditional two-step optimization approach, in which the plasma boundary is optimized for physics properties and the coils are subsequently optimized to be consistent with this boundary, can result in plasma shapes which cannot be produced with sufficiently simple coils. To address this challenge, we propose a method to incorporate considerations of coil complexity in the optimization of the plasma boundary. Coil complexity metrics are computed from the current potential solution obtained with the REGCOIL code (Landreman, Nucl. Fusion, vol. 57, 2017, 046003). While such metrics have previously been included in derivative-free fixed-boundary optimization (Drevlak et al., Nucl. Fusion, vol. 59, 2018, 016010), we compute the local sensitivity of these metrics with respect to perturbations of the plasma boundary using the shape gradient (Landreman & Paul, Nucl. Fusion, vol. 58, 2018, 076023). We extend REGCOIL to compute derivatives of these metrics with respect to parameters describing the plasma boundary. In keeping with previous research on winding surface optimization (Paul et al., Nucl. Fusion, vol. 58, 2018, 076015), the shape derivatives are computed with a discrete adjoint method. In contrast with the previous work, derivatives are computed with respect to the plasma surface parameters rather than the winding surface parameters. To further reduce the resolution required to compute the shape gradient, we present a more efficient representation of the plasma surface which uses a single Fourier series to describe the radial distance from a coordinate axis and a spectrally condensed poloidal angle. This representation is advantageous over the standard cylindrical representation used in the VMEC code (Hirshman & Whitson, Phys. Fluids, vol. 26, 1983, pp. 3553–3568), as it provides a uniquely defined poloidal angle, eliminating a null space in the optimization of the plasma surface. In comparison with previous spectral condensation methods (Hirshman & Breslau, Phys. Plasmas, vol. 5, 1998, p. 2664), the modified poloidal angle is obtained algebraically rather than through the solution of a nonlinear optimization problem. The resulting shape gradient highlights features of the plasma boundary that are consistent with simple coils and can be used to couple coil and fixed-boundary optimization.
Mental health policy makers require evidence-based information to optimise effective care provision based on local need, but tools are unavailable.
To develop and validate a population-level prediction model for need for early intervention in psychosis (EIP) care for first-episode psychosis (FEP) in England up to 2025, based on epidemiological evidence and demographic projections.
We used Bayesian Poisson regression to model small-area-level variation in FEP incidence for people aged 16–64 years. We compared six candidate models, validated against observed National Health Service FEP data in 2017. Our best-fitting model predicted annual incidence case-loads for EIP services in England up to 2025, for probable FEP, treatment in EIP services, initial assessment by EIP services and referral to EIP services for ‘suspected psychosis’. Forecasts were stratified by gender, age and ethnicity, at national and Clinical Commissioning Group levels.
A model with age, gender, ethnicity, small-area-level deprivation, social fragmentation and regional cannabis use provided best fit to observed new FEP cases at national and Clinical Commissioning Group levels in 2017 (predicted 8112, 95% CI 7623–8597; observed 8038, difference of 74 [0.92%]). By 2025, the model forecasted 11 067 new treated cases per annum (95% CI 10 383–11 740). For every 10 new treated cases, 21 and 23 people would be assessed by and referred to EIP services for suspected psychosis, respectively.
Our evidence-based methodology provides an accurate, validated tool to inform clinical provision of EIP services about future population need for care, based on local variation of major social determinants of psychosis.
Perceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority.
We used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case−control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-effects logistic regression models. We used stratified and mediation analyses to explore differences for minority ethnic groups.
Reporting any perceived experience of major discrimination (e.g. unfair treatment by police, not getting hired) was higher in cases than controls (41.8% v. 34.2%). Pervasive experiences of discrimination (≥3 types) were also higher in cases than controls (11.3% v. 5.5%). In fully adjusted models, the odds of psychosis were 1.20 (95% CI 0.91–1.59) for any discrimination and 1.79 (95% CI 1.19–1.59) for pervasive discrimination compared with no discrimination. In stratified analyses, the magnitude of association for pervasive experiences of discrimination appeared stronger for minority ethnic groups (OR = 1.73, 95% CI 1.12–2.68) than the ethnic majority (OR = 1.42, 95% CI 0.65–3.10). In exploratory mediation analysis, pervasive discrimination minimally explained excess risk among minority ethnic groups (5.1%).
Pervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.
Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration.
We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case–control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models.
In total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06–2.44, p = 0.027) and post-migration social disadvantages (OR 1.89, 95% CI 1.02–3.51, p = 0.044), along with expectations/achievements mismatch (OR 1.14, 95% CI 1.03–1.26, p = 0.014) were all significantly associated with psychosis. Migration adversities (OR 1.18, 95% CI 0.672–2.06, p = 0.568) were not significantly related to the outcome. Finally, we found a dose–response effect between the number of adversities across all phases and odds of psychosis (⩾6: OR 14.09, 95% CI 2.06–96.47, p = 0.007).
The cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may reduce the excess of psychosis in migrants.
The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach.
AESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time.
We had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory.
Our current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers.
Disease transmission and behaviour change are both fundamentally social phenomena. Behaviour change can have profound consequences for disease transmission, and epidemic conditions can favour the more rapid adoption of behavioural innovations. We analyse a simple model of coupled behaviour change and infection in a structured population characterised by homophily and outgroup aversion. Outgroup aversion slows the rate of adoption and can lead to lower rates of adoption in the later-adopting group or even behavioural divergence between groups when outgroup aversion exceeds positive ingroup influence. When disease dynamics are coupled to the behaviour-adoption model, a wide variety of outcomes are possible. Homophily can either increase or decrease the final size of the epidemic depending on its relative strength in the two groups and on R0 for the infection. For example, if the first group is homophilous and the second is not, the second group will have a larger epidemic. Homophily and outgroup aversion can also produce dynamics suggestive of a ‘second wave’ in the first group that follows the peak of the epidemic in the second group. Our simple model reveals dynamics that are suggestive of the processes currently observed under pandemic conditions in culturally and/or politically polarised populations such as the USA.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
This work investigated the photophysical pathways for light absorption, charge generation, and charge separation in donor–acceptor nanoparticle blends of poly(3-hexylthiophene) and indene-C60-bisadduct. Optical modeling combined with steady-state and time-resolved optoelectronic characterization revealed that the nanoparticle blends experience a photocurrent limited to 60% of a bulk solution mixture. This discrepancy resulted from imperfect free charge generation inside the nanoparticles. High-resolution transmission electron microscopy and chemically resolved X-ray mapping showed that enhanced miscibility of materials did improve the donor–acceptor blending at the center of the nanoparticles; however, a residual shell of almost pure donor still restricted energy generation from these nanoparticles.
In Europe, the incidence of psychotic disorder is high in certain migrant and minority ethnic groups (hence: ‘minorities’). However, it is unknown how the incidence pattern for these groups varies within this continent. Our objective was to compare, across sites in France, Italy, Spain, the UK and the Netherlands, the incidence rates for minorities and the incidence rate ratios (IRRs, minorities v. the local reference population).
The European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study was conducted between 2010 and 2015. We analyzed data on incident cases of non-organic psychosis (International Classification of Diseases, 10th edition, codes F20–F33) from 13 sites.
The standardized incidence rates for minorities, combined into one category, varied from 12.2 in Valencia to 82.5 per 100 000 in Paris. These rates were generally high at sites with high rates for the reference population, and low at sites with low rates for the reference population. IRRs for minorities (combined into one category) varied from 0.70 (95% CI 0.32–1.53) in Valencia to 2.47 (95% CI 1.66–3.69) in Paris (test for interaction: p = 0.031). At most sites, IRRs were higher for persons from non-Western countries than for those from Western countries, with the highest IRRs for individuals from sub-Saharan Africa (adjusted IRR = 3.23, 95% CI 2.66–3.93).
Incidence rates vary by region of origin, region of destination and their combination. This suggests that they are strongly influenced by the social context.
Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
OBJECTIVES/GOALS: Innovations with positive health impact are a high priority for NCATS and CTSAs. Program design that uses the Causal Pathway approach incorporates performance indicators that assess impact. We applied Causal Pathway thinking to an ongoing national program to enhance the evaluation of program impact. We report Lessons Learned. METHODS/STUDY POPULATION: We conducted a day-long onsite workshop to introduce the model to the project team, build capacity, and map the existing program elements to Logic Models representing program Specific Aims. A local Causal Pathway (CP) champion was identified. Alignment of the Logic Models with the CP approach (input→activities→ outputs→effects/impact) developed iteratively through biweekly, then monthly conferral among stakeholders. Key tasks included distinguishing among activities, outputs, and effects (impacts), and identification of performance indicators for each stage of the Causal Pathway. Visualization tools and an additional late stage half-day workshop were used to foster consensus. Implementation of the CP model tested the feasibility of collecting specific indicators and prompted model revisions. RESULTS/ANTICIPATED RESULTS: Program leadership and team members (n = 30) participated in the kick-off workshop. Four Specific Aims were mapped to Logic Models. Multiple Causal Pathway (CP) diagrams, one for each project in the program, were developed and mapped to Aims. Alignment of CP threads to Aims and identification of performance indicators required iteration. CP threads converged onto common final Impacts, sometimes crossing to another Aim. Performance indicators for operations were readily accessible to team members, and less so for impacts. Assumptions about program effects were subjected to specific indicators. Over time, Leadership noticed more expression of CP thinking in daily activities. New projects developed during this period incorporated the CP approach. Teams were able to streamline and simplify Logic/CP models. DISCUSSION/SIGNIFICANCE OF IMPACT: Through capacity-building and mentored exercises, an innovation team was able to infuse CP thinking into the evaluation of their ongoing program. The CP approach to design and evaluation maps progress and indicators across the life of a program from initial activities to its ultimate impact.