The Doolittle, Wherry-Doolittle, and Summerfield-Lubin methods of multiple correlation are compared theoretically as well as by an application in which a set of predictors is selected. Wherry's method and the Summerfield-Lubin method are shown to be equivalent; the relationship of these methods to the Doolittle method is indicated. The Summerfield-Lubin method, because of its compactness and ease of computation, and because of the meaningfulness of the interim computational values, is recommended as a convenient least squares method of multiple correlation and predictor selection.

A solution is presented to the problem of determining a proper correction for spuriousness in correlation coefficients. The general case developed is the estimate of correlation between u and v, both being linear functions of the same set of variables. Special formulae relate to overlapping scales correlations, part-whole correlations, and item-total test correlations.

Geometrical properties and relationships of the Doolittle and square root methods of multiple correlation, as represented in the variable subspace of an orthogonal person space, are shown. The method of representation is also useful for depicting zero-order and partial correlations, as well as for the more general problem of the combination of variables.

Opioid antagonists block opioid receptors, a mechanism associated with utility in several therapeutic indications. Here, we review the sites of action, clinical uses, pharmacology, and general safety profiles of US Food and Drug Administration (FDA)-approved opioid antagonists. A review of the literature and product labels of opioid antagonists was conducted. The unique clinical uses of approved opioid antagonists are related to their ability to block opioid receptors centrally and/or peripherally. Centrally acting opioid antagonists treat opioid and alcohol use disorders (AUDs) and reverse opioid overdose. Because the opioid system influences weight and metabolism, one opioid antagonist combination product is approved for chronic weight management; another, approved for adults with schizophrenia or bipolar I disorder, mitigates olanzapine-associated weight gain. Peripherally acting opioid antagonists are approved for opioid-induced constipation; another accelerates gastrointestinal recovery after bowel surgery. Opioid antagonists are generally well tolerated; they are not associated with physiologic dependence or abuse. However, opioid antagonists can precipitate acute opioid withdrawal in patients using or undergoing withdrawal from opioid agonists. Likewise, their use can confer a risk for opioid overdose if attempts are made to overcome opioid antagonist blockade of opioid receptors via the intake of additional opioids. Opioid receptor antagonists have diverse therapeutic benefits based on their respective pharmacology and sites of action; understanding their respective nuances facilitates the safe and effective use of these agents.

Identifying long-term care facility (LTCF)-exposed inpatients is important for infection control research and practice, but ascertaining LTCF exposure is challenging. Across a large validation study, electronic health record data fields identified 76% of LTCF-exposed patients compared to manual chart review.

OBJECTIVES/GOALS: Since 2017, we have used the Design Lab methodology to support investigators taking innovative approaches to clinical effectiveness trial design. To date we have held 12 Design Labs and this year we are creating a handbook that will support dissemination of this approach across the Clinical and Translational Science Award consortium. METHODS/STUDY POPULATION: The Clinical Trial Design Lab brings together a multi-stakeholder group to consider innovative and impactful clinical trial designs. An investigative team is selected from a competitive pool of applicants, after which expert-led consultations support the investigator team to think about evidence generation in the context of the full treatment development pathway. Teams map the stakeholders at each step of this pathway (e.g. clinicians, patients, researchers, funders, industry experts, policy experts, regulatory experts, payers) and consider innovative design solutions. These consultations prepare investigators for an event that involves all stakeholders in a structured and facilitated discussion about trial designs that generate the best evidence and increase potential for health impact. RESULTS/ANTICIPATED RESULTS: The result of our work will be a set of Design Lab principles, a handbook with templates that support stakeholder mapping and structured discussions, and educational resources to accompany the handbook. The work is supported by a literature review that characterizes the multi-component processes included in the Design Lab, situates them within the larger context of team science interventions, and lays groundwork for the development of process metrics and impact evaluation criteria to assess the Design Lab method. In this poster presentation, we will share our multi-component broadly engaged team science approach, provide a brief outline of the principles and educational resources, and include an early version of the evaluation criteria. DISCUSSION/SIGNIFICANCE: Broadly engaged team science supports innovative thinking about study design and is especially important in the development of clinical trials. We have grown the Design Lab program of work over the past seven years and are now able to characterize our team science methodology and support others to use this approach to innovate for health impact.

OBJECTIVES/GOALS: Childhood Sjögren’s disease (cSD) is a rare autoimmune disease. Despite the profound impact on children and their families, pediatric-specific clinical trials to inform therapeutic strategies in cSD are lacking. In 2022 we participated in the Trial Innovation Network (TIN) Design Lab with the purpose of designing a series of N-of-1 trials for cSD. METHODS/STUDY POPULATION: New medications have the potential to be safe/effective treatments for cSD but must be evaluated in randomized trials. To overcome limitations of traditional parallel-group designs given the rarity of cSD, we developed an N-of-1 trial approach. Our proposal was selected by the Tufts TIN Design Lab. The Design Lab multi-stakeholder process involved parents of and patients with cSD, pediatric and adult rheumatologists, and experts in clinical trial design and outcomes. We engaged all stakeholders in protocol development to maximize the impact of the proposed approach on clinical care, ensure a successful recruitment plan, and inform the choice of endpoints as there are no widely accepted cSD outcome measures to determine treatment efficacy. RESULTS/ANTICIPATED RESULTS: Using the Design Lab methodology, we clarified the N-of-1 study goals and engaged in an iterative process to develop a “briefing book” that ensured a sound premise for our study. We reviewed and accumulated published literature to support our focus on mucosal/glandular manifestations, identified potential interventions to be used in the N-of-1 trials, and enumerated possible outcomes, including outcomes important to patient/parents. This work culminated in a full-day Design Lab event that included multiple stakeholders who provided expertise from different perspectives on the full drug development pathway. Study design feedback focused on three specific areas. 1) Inclusion and exclusion criteria; 2) Identification of outcome measures; 3) Treatment and washout periods. DISCUSSION/SIGNIFICANCE: To address the critical need and move treatment of cSD forward, we are designing a prototype N-of-1 trial in children with rheumatic disease. We will continue to engage stakeholders by using a series of Delphi surveys and an in-person meeting to create composite outcome measures to test cSD therapies in personalized trials.

The name volkonskoite was first used in 1830 to describe a bright blue-green, chromiumbearing clay material from the Okhansk region, west of the Ural Mountains, U.S.S.R. Since that time, the name has been applied to numerous members of the smectite group of clay minerals, although the reported chromium content has ranged from 1% to about 30% Cr2O3. The name has also been applied to some chromian chlorites. Because volkonskoite has been used for materials that differ not only in their chromium content but also in their basic structure, the species status of the mineral has been unclear.

To resolve this uncertainty, two specimens of volkonskoite from (1) Mount Efimiatsk, the type locality in the Soviet Union (USNM 16308) and (2) the Okhansk region in the Perm Basin, U.S.S.R. (USNM R4820), were examined by several mineralogical techniques. Neotype sample 16308 has the following structural formula:

$({\text{Ca}}_{0.11}{\text{Mg}}_{0.11}{\text{Fe}}^{2+}{\hspace{0.17em}}_{0.03}{\text{K}}_{0.02})({\text{Cr}}_{1.18}{\text{Mg}}_{0.78}{\text{Fe}}^{3+}{\hspace{0.17em}}_{0.29}\text{Ca}{}_{0.02})({\text{Si}}_{3.50}{\text{Al}}_{0.51}){\text{O}}_{10}{(\text{OH})}_2\cdot 3.64{\text{H}}_2\text{O}.$

Sample R4820 has the following structural formula:

$({\text{Ca}}_{0.25}{\text{Mg}}_{0.05}{\text{Fe}}^{2+}{\hspace{0.17em}}_{0.01}{\text{K}}_{0.03}{\text{Mn}}_{0.01})({\text{Cr}}_{1.07}{\text{Mg}}_{0.75}{\text{Fe}}^{3+}{\hspace{0.17em}}_{0.35}({\text{Si}}_{3.59}{\text{Al}}_{0.43}){\text{O}}_{10}{(\text{OH})}_2\cdot 4.22{\text{H}}_2\text{O}.$

Mössbauer spectroscopy indicates that 91% and 98% of the iron is present as Fe3+ in samples 16308 and R4820, respectively. X-ray powder diffraction patterns of both samples have broad lines corresponding to minerals of the smectite group.

On the basis of these data, volkonskoite appears to be a dioctahedral member of the smectite group that contains chromium as the dominant cation in the octahedral layer. Smectites containing less than this amount of octahedral chromium should not be called volkonskoite, but should be named by chemical element adjectives, e.g., chromian montmorillonite, chromian nontronite.

Hydroxy-interlayered vermiculite (HIV) is a ubiquitous phyllosilicate in the <0.05-mm fraction of sandy soils on the U.S. southeastern coastal plain. Extensive areas of soils with abundant HIV (i.e., peninsular Florida) have no detectable mica; yet the coarseness, platy habit, and nonexchangeable K associated with HIV grains suggest a mica precursor. The objectives of this study were: (1) to probe for mica zones (1.0-nm) within HIV grains, using high-resolution transmission electron microscopy (HRTEM), and (2) to determine intragrain elemental distributions via electron microprobe analysis (EMA). HIV grains from a Quartzipsamment medium-silt fraction, which contained no detectable mica by X-ray diffraction (XRD), were concentrated via high-density liquid separation. EMA transects and X-ray dot maps showed zonation or trends of K depletion near edges of some grains, with K2O contents ranging from trace levels to >40 g kg-1. Elemental oxide data indicated a dioctahedral phyllosilicate structure, with some octahedral substitution of Fe and Mg for Al. Intermittent 1.0-nm lattice-fringe images obtained by HRTEM supported the presence of mica zones within grains. There were no detectable 1.4-nm fringes, despite the dominance of a 1.4-nm XRD peak, indicating the instability of the HIV specimen under the electron beam. Results support a transformational link between mica and HIV in these soils. Rapid incursion and polymerization of Al following loss of K from mica may limit the extent of the vermiculite intermediate. The latter idea is consistent with the paucity of vermiculite in Florida soils. Traces of occluded mica may be the last remnants of the precursor grain. A sand-sized mica precursor would likely have weathered in place during the period when colloidal components such as kaolinite illuviated to deeper zones. Thus, the transformation product (HIV) would comprise a significant proportion of the <0.05-mm fraction persisting in sandy eluvial horizons.

Antimicrobial resistance (AMR) is a pressing global health issue with serious implications for health, food security, and livelihoods. Collective action, from local to global, that draws on the One Health (OH) approach to facilitate collaboration between the human, animal, and environmental sectors is required to inform initiatives to mitigate AMR. For AMR surveillance, this involves applying an intersectoral, multistakeholder perspective to guide the co-creation of knowledge and policy around the collection, analysis, and application of surveillance data to detect, monitor, and prevent AMR health threats. Currently, there is little available evidence on how to operationalize a OH approach to support integrated AMR surveillance systems, or on how the governance of such systems facilitates intersectoral action on AMR. We conducted a scoping review of the literature to identify the governance domains most relevant to applying the OH approach to the design and evaluation of AMR surveillance systems. We found that governance is a crucial component of the development of surveillance systems equipped to tackle complex, structural issues such as AMR. The governance domains identified include participation, coordination and collaboration, management, sustainability, accountability and transparency, and equity. These domains are relevant throughout all stages of policy design, implementation, and evaluation of AMR surveillance systems. Equity is both a domain and an essential component of the other domains. All the domains are interdependent and co-constitutive, so that progress in one domain can accelerate progress in another. The conceptual framework presented in this article can inform the design and evaluation of OH AMR governance systems and other complex health challenges that have similar barriers and facilitators to OH governance. The qualitative evaluation questions developed for each domain facilitate assessment of the breadth (the range of actors involved in governance) and depth (how meaningful their engagement is) for each domain relevant to OH governance. Finally, the prioritization of formal, sustainable, and democratic governance of AMR can help to facilitate achievement of the sustainable development goals (SDGs) and promote conservation of the use of antimicrobials for future generations.

A dense Ecklonia radiata (Laminariales) kelp forest extending at least 35 km has been found between 45 and 60 m depth range within the mesophotic zone inside the iSimangaliso marine-protected area (MPA) at the iSimangaliso Wetland park World Heritage Site on the east coast of South Africa. This is the first visual confirmation of the occurrence of E. radiata beds in subtropical South Africa, in an area situated between the tropical and subtropical bioregions, in an area that spans the Natal and Delagoa bioregions of the south-western Indian Ocean, more than 350 km north of its previously documented South African range. The kelp was found to be present across the length of the MPA, but dense beds were present only in the southern Natal bioregion, with sparse occurrences observed elsewhere on soft-coral and sponge-dominated reefs in the upper mesophotic zone. The footage was collected in November 2020, May 2021 and November 2022 during remotely operated vehicle and drop camera surveys of the mesophotic zone inside the MPA. This discovery adds to the body of knowledge on the global distribution of Laminariales populations in deep tropical and subtropical settings and the diversity of habitats within South Africa's largest coastal MPA.