Search

Polycyclic aromatic hydrocarbons (PAHs) play a major role in the chemistry of combustion, pyrolysis, and the interstellar medium. Production (or activation) of radical PAHs and propagation of their resulting reactions require efficient dehydrogenation, but the preferred method of hydrogen loss is not well understood. Unimolecular hydrogen ejection (i.e., direct C─H bond fission) and bimolecular radical abstraction are two main candidate pathways. We performed a computational study to characterize the role of H ejection, particularly as a driver for radical-centric hydrocarbon-growth mechanisms and particle formation. Electronic structure calculations establish that C─H bond strengths span a broad range of energies, which can be weaker than 30 kcal/mol in some C9 and C13 PAH radicals. At T > 1200 K, calculated thermal rates for hydrogen ejection from weak C─H bonds at zigzag sites on PAH radicals are significantly larger than typical H-abstraction rates. These results are highly relevant in the context of chain reactions of radical species and soot inception under fuel-rich combustion conditions. Furthermore, calculated microcanonical rates that include the additional internal energy released by bond formation (e.g., ring closure to yield C9H9) yield significantly higher rates than those associated with full thermalization. These microcanonical considerations are relevant to the astrochemical processes associated with hydrocarbon growth and processing in the low-density interstellar environment.

Mortality disparities among persons with intellectual disability are important to guide health-care practices. The objective was to evaluate mortality patterns of persons with intellectual disability in a nationwide study from 1976 to 2020. This study establishes a Danish nationwide cohort of persons with intellectual disability and age- and sex-matched reference cohort through linkage between several registers. We established a cohort of 79,114 persons with intellectual disability. Standardized mortality ratios were increased for persons with intellectual disability, most pronounced among younger persons and among females. Life expectancies were markedly lower; among persons with intellectual disability 63.6 years among females and 59.8 years among males in 2016-2020 compared to 82.4 and 78.7 years among females and males in the reference cohort. Life expectancies decreased with severity of intellectual disability. This study reports the establishment of a nationwide Danish cohort of persons with intellectual disability.

UNLABELLED: PIK3CA (PI3Kα) is a lipid kinase commonly mutated in cancer, including ∼40% of hormone receptor-positive breast cancer. The most frequently observed mutants occur in the kinase and helical domains. Orthosteric PI3Kα inhibitors suffer from poor selectivity leading to undesirable side effects, most prominently hyperglycemia due to inhibition of wild-type (WT) PI3Kα. Here, we used molecular dynamics simulations and cryo-electron microscopy to identify an allosteric network that provides an explanation for how mutations favor PI3Kα activation. A DNA-encoded library screen leveraging electron microscopy-optimized constructs, differential enrichment, and an orthosteric-blocking compound led to the identification of RLY-2608, a first-in-class allosteric mutant-selective inhibitor of PI3Kα. RLY-2608 inhibited tumor growth in PIK3CA-mutant xenograft models with minimal impact on insulin, a marker of dysregulated glucose homeostasis. RLY-2608 elicited objective tumor responses in two patients diagnosed with advanced hormone receptor-positive breast cancer with kinase or helical domain PIK3CA mutations, with no observed WT PI3Kα-related toxicities. SIGNIFICANCE: Treatments for PIK3CA-mutant cancers are limited by toxicities associated with the inhibition of WT PI3Kα. Molecular dynamics, cryo-electron microscopy, and DNA-encoded libraries were used to develop RLY-2608, a first-in-class inhibitor that demonstrates mutant selectivity in patients. This marks the advance of clinical mutant-selective inhibition that overcomes limitations of orthosteric PI3Kα inhibitors. See related commentary by Gong and Vanhaesebroeck, p. 204 . See related article by Varkaris et al., p. 227 . This article is featured in Selected Articles from This Issue, p. 201.

Abstract: Background: Therapeutic climbing (TC) has been increasingly implemented in the context of mental health care, with promising effects. While most evaluation studies focus on symptom reduction, the specific elements and mechanisms that make climbing effective compared to other therapeutic sports remain unclear. This study explores the subjective experiences of participants of a climbing therapy program in order to explore the underlying processes and the subjectively perceived effects. Method: The study took place at an inpatient rehabilitation facility in southern Germany, where a weekly group TC program was part of the treatment for individuals with mental disorders. Data from 265 participants with ICD-10 mental disorders collected between 2010 and 2022 was analyzed via questionnaires quantitatively assessing physical, psychological, and social improvements with rating items. Additionally open answers on subjectively relevant psychological experiences were analyzed using a qualitative content analysis. Results: Climbing therapy was generally perceived as relevant to their rehabilitation and rated as influential in terms of improving physical and psychological condition as well as sociability. The qualitative analysis identified five main categories being “Successful coping and positive mood”, “Challenge and coping strategies”, “Self-reflection and self-perception”, “Social experiences and belaying” and “Letting go of worries and being in the moment”. Conclusion: The results support previous findings on the benefits of TC and highlight its relevance as a therapeutic tool. Participants with mental disorders reported various positive experiences, emphasizing the unique demands, motivational aspects and social context of climbing. Further high-quality research is needed to compare climbing’s potential with other therapeutic sports across different target groups.

We investigated the pyrolysis of propyne and propene using aerosol mass spectrometry coupled with tunable synchrotron vacuum ultraviolet photoionization. The results show that propyne forms particles at pyrolysis temperatures approximately 100 K below the lowest temperature at which propene produces particles. The aerosol mass spectra show that the carbon-to-hydrogen (C/H) ratios of the pyrolysis products from both reactants increase with temperature between the particle onset temperature and 1275 K. In this temperature range, the mass peaks corresponding to species with 18 or more carbon atoms are more saturated (i.e., have lower C/H ratios) than species predicted by the stabilomer grid. The observation of relatively high saturation (low C/H ratios) at temperatures near particle onset is consistent with the presence of aliphatically linked hydrocarbons during the preliminary stages of soot formation. The masses of the species presumed to be aliphatically linked suggest that these linked species are adducts of species smaller than chrysene (C18H12). We performed a comparative analysis of the initial PAH-growth pathways consistent with aerosol mass spectra and associated mass-specific photoionization-efficiency curves. The results from the comparative analysis indicate that the development of PAHs up to the size of acenaphthylene (C12H8) follow similar formation pathways for propyne and propene, but the isomeric composition of species larger than acenaphthylene diverges for the two reactants.

OBJECTIVE: Perianal Crohns disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in Complement Factor B (CFB). DESIGN: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed. Serological and clinical variables were analysed by regression analyses. Risk allele of rs4151651 was introduced into human CFB plasmid by site-directed mutagenesis. Binding of recombinant G252 or S252 CFB to C3b and its cleavage was determined in cell-free assays. Macrophage phagocytosis in presence of recombinant CFB or serum from CFB risk, or protective CD or healthy subjects was assessed by flow cytometry. RESULTS: Perianal complications were associated with colonic involvement, OmpC and ASCA serology, and serology quartile sum score. We identified a genetic association for pCD (rs4151651), a non-synonymous SNP (G252S) in CFB, in all three cohorts. Recombinant S252 CFB had reduced binding to C3b, its cleavage was impaired, and complement-driven phagocytosis and cytokine secretion were reduced compared with G252 CFB. Serine 252 generates a de novo glycosylation site in CFB. Serum from homozygous risk patients displayed significantly decreased macrophage phagocytosis compared with non-risk serum. CONCLUSION: pCD-associated rs4151651 in CFB is a loss-of-function mutation that impairs its cleavage, activation of alternative complement pathway, and pathogen phagocytosis thus implicating the alternative complement pathway and CFB in pCD aetiology.

Abstract Aims Decision‐makers still predominantly focus on the perspective of non‐patient stakeholders, which may deviate from the unique perspective of heart failure (HF) patients. To enhance patient‐centred decision‐making, there is a need for more patient‐based evidence derived directly from the patients themselves. Hence, this study aimed to understand (i) HF patients' unmet medical needs and preferred treatment outcomes; (ii) patients' risk tolerance; and (iii) their information needs, uncertainties and satisfaction towards HF treatment. Methods This qualitative patient preference study consisted of a literature review with a systematic search strategy and semi‐structured interviews with HF patients, analysed using the framework method. During the interviews, patients were asked to rank a predefined list of disease and treatment‐related characteristics informed by the literature review and were able to spontaneously raise additional characteristics. Results The study included 14 Belgian HF patients (age range: 58–79, mean age: 72). (i) Regarding their unmet medical needs, HF patients reported that the most important unmet medical needs were shortness of breath and fatigue, as they negatively impact their quality of life (QoL) and independence. In the ranking exercise, patients prioritized improvements in QoL over improvements in life expectancy, whereby the following characteristics received the highest cumulative score: (1) independence, (2) shortness of breath, (3) impaired renal function, (4) survival, (5) fatigue, (6) risk of hospitalization and (7) communication with and between physicians. Patients most often spontaneously raise characteristics related to the general care process. Mechanism of action, route of administration, dose frequency and weight fluctuations scored among the least important characteristics. (ii) Regarding patients' risk tolerance towards HF treatment, some of the patients expressed zero tolerance for side effects, as they had not yet experienced any discomfort caused by the treatment or disease. (iii) Regarding their information needs, patients voiced their desire to receive practical and comprehensible advice orally from their physician because they highly value individualized treatment decision‐making. Patients also expressed uncertainties regarding whether the experienced effects were due to their treatment, disease, ageing or other comorbidities. Conclusions This study shows that, besides increasing life expectancy, HF patients prioritize improvements in symptoms and side effects reducing their QoL and independence, such as shortness of breath and fatigue. The patient‐relevant characteristics identified in this study, from the perspective of HF patients themselves, may be useful to inform clinical trial endpoint selection and guide downstream drug development, evaluation and clinical decision‐making towards addressing the unmet medical needs and treatment outcomes of importance to HF patients.

Abstract Background Eating disorders (EDs) constitute a considerable burden for individuals and society, but adequate and timely professional treatment is rare. Evidence-based Digital Mental Health Interventions (DMHIs) have the potential both to reduce this treatment gap and to increase treatment effectiveness. However, their integration into routine care is lacking. Understanding practitioners’ attitudes towards DMHIs for EDs is crucial for their effective use. Aims To investigate the consensus among German ED treatment experts on the relevance of different influencing factors for DMHI use in EDs. Methods This Delphi study consisted of two rounds and was conducted online with an initial sample of N = 24 ED experts (M age=41.96, SD age=9.92, n = 22 female). Prior to the Delphi rounds, semi-structured qualitative telephone interviews were performed to explore participants’ attitudes, experiences, and expectations towards DMHIs. In order to construct the Delphi survey, content analysis was applied to a subset of ten interviews. A total of 63 influencing factors were identified and grouped into three main categories: contextual conditions, design, and content of DMHIs. In both Delphi rounds, the interview participants were subsequently invited to rate each of the factors with regard to their importance on 10-point scales. Group percentages and individual ratings of the first round (n = 23) were presented in the second round (n = 21). Consensus was calculated for each item (defined as IQR ≤ 2). Results Importance ratings were high across items (M = 7.88, SD = 2.07, Mdn = 8). In the first round, 48% of the items reached consensus, with its most important (Mdn = 10) factors referring to data security, evidence base, technical requirements, usability, and specific DMHI content (psychoeducation, crisis intervention). In the second Delphi round, a consensus was reached on 73% of the items. No consensus was reached on 17 items. Conclusions The findings on practitioners’ attitudes and priorities have relevant implications for subsequent DMHI development, dissemination, and implementation strategies, indicating that the highest-rated factors should be highlighted in the process.

This follow-up study presents a design-based research (DBR) setting implemented over a three-year project called 'eKidZ - Teach Your Parents Well' which uses research-based learning and follows the four phases of DBR. In an iterative cycle, 20 teenagers aged 14-16 took on the role of researchers and investigated intergenerational learning and the multiplier effects of students participating in the Climate Change Education project 'k.i.d.Z.21 - Competent into the Future' on their parents, using the complete research process. Simultaneously, scientists implemented and tested the DBR setting to validate student research findings and to evaluate the quality of the educational setting. In this fully integrated DBR, using multiple methods (quantitative and qualitative), educational and scientific perspectives are brought together to evaluate students' findings and draw conclusions regarding their learning effects. These research results demonstrate that not only did students generate valid and reliable research, but - when changing perspectives - teenagers also contribute to the discussion about closing the gaps in science education and practice. By examining young people's research on Climate Change Education and recognising their contribution in scientific discourse, this paper offers a host of new insights. Highlights: Teenagers take on the role of researchers and perform reliable and valid research results on intergenerational learning and multiplier effects in Climate Change Education, by completing all phases of research-based learning. Design-based research is an effective method to combine science and education and thus delivering novel insights into science education and practice. High-quality Climate Change Education fosters constructive cooperation among all participants with inter - and intragenerational learning and multiplier effects. Constructivism, transdisciplinarity and research-based learning form the basis for effective design-based research and Climate Change Education.

BackgroundNew ways of reimbursement for high-cost, one-shot curative therapies such as advanced therapy medicinal products (ATMPs) are a growing area of interest to stakeholders in market access such as industry representatives, legislative and accounting experts, physicians, hospital managers, hospital pharmacists, patient representatives, policymakers, and sickness funds. Due to the complex nature of ATMPs, new payment models and reimbursement modalities are proposed yet not widely applied across Europe.ObjectivesThis study aimed to elicit opinions on and insights into the governance aspect of implementing outcome-based spread payments (OBSP) in Belgium for the reimbursement of innovative therapies. Stakeholders’ responsibilities and roles were analysed and proposed solutions or general beliefs were assessed to identify necessary or sufficient conditions to establish outcome-based spread payments.MethodsSemi-structured interviews (n = 33) were conducted with physicians (n = 2), hospital pharmacists (n = 4), hospital managers (n = 2), Belgian policymakers (n = 6), legislative experts (n = 2), accounting experts (n = 5), representatives of patients (n = 3), of industry (n = 5), and sickness funds (n = 4). The interviews took place between July 2020 and October 2020. The framework method analysis was performed using Nvivo software (version 20.4.1.851). Statements were allocated into six main topics: payment structure, spread payments, outcome-based agreements, governance, transparency, and regulation.ResultsInterviews revealed the necessary conditions that, fulfilled together, are seen to be sufficient for the successful implementation of OBSP, including consensus on pricing, payment logistics, robust data infrastructure and financing, clear agreement terms (duration, outcome parameters, payment triggers), long-term patient follow-up solutions, an external multi-stakeholder governance body, and transparency regarding agreement types.ConclusionDespite the interest, the effective implementation of OBSP falls behind due to a lack of consensus on how this new reimbursement method can be a sustainable solution. By stating the necessary conditions that, when fulfilled together, are deemed sufficient for successful OBSP implementation, this study provides a framework towards overcoming implementation barriers and realizing the potential of OBSP in transforming healthcare reimbursement practices.

Summary: Background: The Bari-SolidAct randomized controlled trial compared baricitinib with placebo in patients with severe COVID-19. A post hoc analysis revealed a higher incidence of serious adverse events (SAEs) among SARS-CoV-2-vaccinated participants who had received baricitinib. This sub-study aimed to investigate whether vaccination influences the safety profile of baricitinib in patients with severe COVID-19. Methods: Biobanked samples from 146 participants (55 vaccinated vs. 91 unvaccinated) were analysed longitudinally for inflammation markers, humoral responses, tissue viral loads, and plasma viral antigens on days 1, 3, and 8. High-dimensional analyses, including RNA sequencing and flow cytometry, were performed on available samples. Mediation analyses were used to assess relationships between SAEs, baseline-adjusted biomarkers, and treatment-vaccination status. Findings: Vaccinated participants were older, more frequently hospitalized, had more comorbidities, and exhibited higher nasopharyngeal viral loads. Baricitinib treatment did not affect antibody responses or viral clearance, but reduced markers of T-cell and monocyte activation compared to placebo (sCD25, sCD14, sCD163, sTIM-3). Age, baseline levels of plasma viral antigen, and several inflammatory markers, as well as IL-2, IL-6, Neopterin, CXCL16, sCD14, and suPAR on day 8 were associated with the occurrence of SAEs. However, mediation analyses of markers linked to SAEs, baricitinib treatment, or vaccination status did not reveal statistically significant interactions between vaccination status and SAEs. Interpretation: This sub-study did not identify any virus- or host-related biomarkers significantly associated with the interaction between SARS-CoV-2 vaccination status and the safety of baricitinib. However, caution should be exercised due to the moderate sample size. Funding: EU Horizon 2020 (grant number 101015736).

Objectives The objective of this study was to assess the completeness of registration of secondary preventive variables comparing on-site visits with telephone consultations during follow-up after myocardial infarction.Design This was an observational study based on the Swedish quality registry SWEDEHEART.Setting and outcome measures We analysed the proportion of missing values for major secondary preventive target data registered at the 2-month and 1-year follow-up visits, during 2006–2022 (n=101 199). χ2 tests were used to compare differences in data registration comparing on-site visits with telephone consultations. Patient characteristics and time trends in the proportion of missing values were also analysed.Results Baseline characteristics for patients with on-site visits and telephone consultations were similar. At the 2-month follow-up, the proportion of missing data registered at on-site visits compared with telephone consultations was systolic blood pressure 2.4% (n=1729) vs 28.0% (n=5462), low-density lipoprotein cholesterol 9.1% (n=6525) vs 32.6% (n=6360), weight 20.1% (n=14 343) vs 43.0% (n=8401) and haemoglobin A1c for patients with diabetes mellitus 39.4% (n=4594) vs 69.4% (n=2225), p for all

Introduction Reviews of economic evaluations of telehealth interventions found that the current evidence is inconsistent with standard guidelines for conducting economic evaluation. The reviews conclude that most economic evaluations of telehealth interventions are small-scale and short-term. The choice of time horizon in economic evaluation, in general, is an important part. When using longer time horizons, it often involves extrapolating costs and effects, where assumptions are taken. Different tools for extrapolating cost and effects in economic evaluations exist. However, there is a heterogeneity in the methods used, which can create different results. Therefore, this study aims to review the design and conduct of existing long-term economic evaluations of telehealth interventions using extrapolation methods. Furthermore, the aim is to map the methods used for extrapolation.Methods and analysis A scoping review is conducted to investigate the aim of this study. To identify relevant studies for inclusion in the scoping review, a systematic literature search will be conducted in the electronic databases: Embase (Elsevier), PubMed (National Library of Medicine), EconLit (ProQuest), Web of Science (Clarivate), NHS Economic Evaluation Database (NHS Centre for Reviews and Dissemination) and CINAHL (EBSCO Industries). A grey literature search will be conducted in Google Scholar. The search will be supplemented with studies identified by reviewing the references in the included studies and reviewing the citations of the included studies. The extracted data from the studies in the scoping review will be presented in relevant descriptive tables and summarising descriptions. The results will be reported in correspondence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guideline.Ethics and dissemination Hence, the methodology used is a scoping review of the existing literature; no ethical or safety considerations are identified for this study. The plan for dissemination includes a peer-reviewed publication and possible poster or oral presentations.

Generally, with increasing elevation, there is a corresponding decrease in annual mean air and soil temperatures, resulting in an overall decrease in ecosystem carbon dioxide (CO2) exchange. However, there is a lack of knowledge on the variations in CO2 exchange along elevation gradients in tundra ecosystems. Aiming to quantify CO2 exchange along elevation gradients in tundra ecosystems, we measured ecosystem CO2 exchange in the peak growing season along an elevation gradient (9–387 m above sea level, m.a.s.l) in an arctic heath tundra, West Greenland. We also performed an ex-situ incubation experiment based on soil samples collected along the elevation gradient, to assess the sensitivity of soil respiration to changes in temperature and soil moisture. There was no apparent temperature gradient along the elevation gradient, with the lowest air and soil temperatures at the second lowest elevation site (83 m). The lowest elevation site exhibited the highest net ecosystem exchange (NEE), ecosystem respiration (ER) and gross ecosystem production (GEP) rates, while the other three sites generally showed intercomparable CO2 exchange rates. Topography aspect-induced soil microclimate differences rather than the elevation were the primary drivers for the soil nutrient status and ecosystem CO2 exchange. The temperature sensitivity of soil respiration above 0 °C increased with elevation, while elevation did not regulate the temperature sensitivity below 0 °C or the moisture sensitivity. Soil total nitrogen, carbon, and ammonium contents were the controls of temperature sensitivity below 0 °C. Overall, our results emphasize the significance of considering elevation and microclimate when predicting the response of CO2 balance to climate change or upscaling to regional scales, particularly during the growing season. However, outside the growing season, other factors such as soil nutrient dynamics, play a more influential role in driving ecosystem CO2 fluxes. To accurately upscale or predict annual CO2 fluxes in arctic tundra regions, it is crucial to incorporate elevation-specific microclimate conditions into ecosystem models.

Background: Women with South Asian ethnicity have a higher risk of developing type 2 diabetes mellitus (T2DM) compared with white women of European descent, especially after gestational diabetes mellitus (GDM). Central obesity and adipose tissue dysfunction have been linked to their higher risk of T2DM, but the mechanisms are not known. We hypothesize that low-grade, persistent immune cell activation is involved in metabolic disturbances following GDM with different influence according to ethnicity. Methods: We measured plasma levels of T cell exhaustion marker soluble T cell immunoglobin mucin domain 3 (sTIM-3), sCD25, sCD27 and soluble lymphocyte activation gene (sLAG)-3 in 266 women of South Asian (n = 160) and white Nordic (n = 106) ethnic background with a history of GDM. Results: Baseline plasma concentration of sTIM-3 was higher in South Asian women compared to Nordic women (p

Objectives To re-evaluate cut-offs for disease activity states according to the Axial Spondyloarthritis Disease Activity Score (ASDAS), and study the impact of sex, age, calendar time, disease and symptom duration on ASDAS and ASDAS cut-offs in a large contemporary cohort.Methods Data from 2939 patients with axial spondyloarthritis (axSpA) starting their first tumour necrosis factor inhibitor in nine European registries were pooled and analysed. Receiver operating characteristic analyses were performed to identify cut-offs against external criteria. Six-month data including patient and physician global assessments, both ≤1 (0–10 integer scale), and Assessment of SpondyloArthritis International Society partial remission were used for separation of inactive disease (ID) from low disease activity (LDA), while patient and physician global ≤3 were applied as external criteria to separate LDA from high disease activity (HDA). Patient and physician global ≥6 were applied to separate HDA from very high disease activity in baseline data.Results The three ASDAS cut-offs identified to separate the four disease activity states in the overall patient population were 3.5. Cut-offs for ID and LDA in women were higher (

Dealing with students' conceptions is one of the central elements of student-oriented teaching. To be able to organize learning processes efficiently, it is necessary to look at the learners in a differentiated way and to approach their conceptions individually. The first necessary step is the individual diagnosis of each student's conceptions. This article presents a qualitative study (n = 8) that focused on the development of drawing assignments for the diagnosis of conceptions on the topic of plant nutrition. Based on the conceptual metaphor theory (CMT), features were identified that are beneficial for the diagnosis of the conceptions. To achieve this goal, it was crucial to reliably diagnose existing conceptions with valid assignments, which can also be carried out in schools. Research about task design and the proceeding diagnosis of conceptions in the light of the CMT has received little attention so far. This article, therefore, deals predominantly with the question about the design of assignments in the context of conceptual change. Based on this, guidelines were derived for the design of assignments for practical use in science education. This study represents the basis for developing a Moodle-based digital learning environment for working with students' conceptions on the topic of plant nutrition in schools.

The Metropolitan Water District (MWD) serves local member agencies which in turn supply water to nearly half of California’s population. The MWD’s Local Resources Program (LRP) helps fund projects designed and proposed by its member agencies to produce more locally-sourced water in Southern California, to bolster the region’s self-resiliency and reduce reliance on imported water sources. As of 2022, MWD states that its LRP supports close to half of the recycled water and groundwater recovery production in the district’s service area (MWD CAP, 2022). Southern California has been in a state of water crisis since patterns of record-breaking drought began in the early 1990s.Southern California’s reliance upon imported water supplied from the State Water Project (SWP) and the Colorado River has come under threat. Faced with expanding cuts in water supplies delivered via the SWP, the region has needed to draw more and more water from the Colorado River to meet residential needs, putting water sources at risk of drying up or being unable to produce hydroelectric power. Hence, programs like the LRP which stand to help reduce water demand from member agencies have only grown in importance. Before our study, an independent, public analysis of LRP funding distribution and an in-depth survey concerning the perspectives of receiving member agencies had not yet been conducted. Accordingly, in this study, in cooperation with MWD and many of its member agencies, our research team assessed existing documents, conducted interviews, and performed statistical analyses on funding trends from the program’s inception in 1984 to today. In our evaluation of the LRP, the overarching question we are aiming to address is: “What has been the effectiveness of MWD’s Local Resources Program in terms of water resilience and equity, and can it be improved?” This research seeks to inform how the LRP fits into a comprehensive vision for Southern California of a long-term transition to local water resources.