Reversible Photochromism of 4,4'-Disubstituted 2,2'-Bipyridine in the Presence of SO3.

We report an unusual photochromic behavior of 4,4'-disubstituted-2,2'-bipyridine. It was found that in the presence of a SO3 source and HCl, 2,2'-bipyridine-4,4'-dibutyl ester undergoes a color change from yellow to magenta in solution with maximum absorbance at 545 nm upon irradiation with 395 nm light. The photochromism is thermally reversible in solution. Different from the known bipyridine-based photoswitching pathways, the photo response does not involve any metal which form colored complexes or the formation of colored free radical cations like the photo-reduction of viologens. A combination of experimental and computational analysis was used to probe the mechanism. The results suggest the colored species to be a complex formed between N-oxide of the 2,2'-bipyridine-4,4'-dibutyl ester and SO2; the N-oxide and SO2 are formed from photoactivated oxidation of the bipyridine with SO3 serving as the oxygen source. This complex represents a new addition to the library of photoswitches that is easy to synthesize, reversible in solution, and of high fatigue resistance, making it a promising candidate for applications in photo-switchable materials and SO3 detection. We also demonstrated experimentally similar photochromic behaviors with 2,2'-bipyridine-containing polymers.

End of Life Outcomes Following Comfort Care Orders: A Single Center Experience.

Background: Few studies have explored the outcomes of patients placed on comfort care with respect to hospice disposition. The objective of this study was to perform a retrospective analysis of patients who transitioned to comfort care. Methods: We conducted a retrospective study of patients placed on the comfort care order set between July 1st, 2021, until June 30th, 2022. Each individual patient chart was then analyzed to collect multiple clinical variables. IRB approval was obtained as per institutional guidelines. Results: 541 patients were included in the analysis. An average of 1.5 patients were placed on comfort care a day. 424 (78.37%) patients died while in the hospital. The median time on comfort care was 1 day. For subspecialty and hospital medicine patients the median time was 2 days. 40% of non-ICU patients were discharged with hospice services. 60% of patients were in the intensive care unit (ICU) and spent a median of 2.33 hours on comfort care. 19% of these patients were on comfort care for over 12 hours. 94% of the patients placed on comfort care in the ICU died in the hospital as compared to 53% of subspecialty and 59% of hospital medicine patients. Conclusions: The majority of patients placed on comfort care died during their hospitalization demonstrating a real need for comprehensive end of life care and immediate hospice services. For those discharged with hospice services, they spent an excessive amount of time in the hospital waiting for services to be arranged.

A phase-separated protein hub modulates resistance to Fusarium head blight in wheat.

Fusarium head blight (FHB) is a devastating wheat disease. Fhb1, the most widely applied genetic locus for FHB resistance, is conferred by TaHRC of an unknown mode of action. Here, we show that TaHRC alleles distinctly drive liquid-liquid phase separation (LLPS) within a proteinaceous complex, determining FHB susceptibility or resistance. TaHRC-S (susceptible) exhibits stronger LLPS ability than TaHRC-R (resistant), and this distinction is further intensified by fungal mycotoxin deoxynivalenol, leading to opposing FHB symptoms. TaHRC recruits a protein class with intrinsic LLPS potentials, referred to as an "HRC-containing hub." TaHRC-S drives condensation of hub components, while TaHRC-R comparatively suppresses hub condensate formation. The function of TaSR45a splicing factor, a hub member, depends on TaHRC-driven condensate state, which in turn differentially directs alternative splicing, switching between susceptibility and resistance to wheat FHB. These findings reveal a mechanism for FHB spread within a spike and shed light on the roles of complex condensates in controlling plant disease.

The knowns and unknowns of callose biosynthesis in terrestrial plants.

Callose, a linear (1,3)-ß-glucan, is an indispensable carbohydrate polymer required for plant growth and development. Advances in biochemical, genetic, and genomic tools, along with specific antibodies, have significantly enhanced our understanding of callose biosynthesis. As additional components of the callose synthase machinery emerge, the elucidation of molecular biosynthetic mechanisms is expected to follow. Short-term objectives involve defining the stoichiometry and turnover rates of callose synthase subunits. Long-term goals include generating recombinant callose synthases to elucidate their biochemical properties and molecular mechanisms, potentially culminating in the determination of callose synthase three-dimensional structure. This review delves into the structures and intricate molecular processes underlying callose biosynthesis, emphasizing regulatory elements and assembly mechanisms.

Integrated care system leadership: a rapid realist review.

PURPOSE: Given the complex nature of integrated care systems (ICSs), the geographical spread and the large number of organisations involved in partnership delivery, the importance of leadership cannot be overstated. This paper aims to present novel findings from a rapid realist review of ICS leadership in England. The overall review question was: how does leadership in ICSs work, for whom and in what circumstances? DESIGN/METHODOLOGY/APPROACH: Development of initial programme theories and associated context-mechanism-outcome configurations (CMOCs) were supported by the theory-gleaning activities of a review of ICS strategies and guidance documents, a scoping review of the literature and interviews with key informants. A refined programme theory was then developed by testing these CMOCs against empirical data published in academic literature. Following screening and testing, six CMOCs were extracted from 18 documents. The study design, conduct and reporting were informed by the Realist And Metanarrative Evidence Syntheses: Evolving Standards (RAMESES) training materials (Wong et al., 2013). FINDINGS: The review informed four programme theories explaining that leadership in ICSs works when ICS leaders hold themselves and others to account for improving population health, a sense of purpose is fostered through a clear vision, partners across the system are engaged in problem ownership and relationships are built at all levels of the system. RESEARCH LIMITATIONS/IMPLICATIONS: Despite being a rigorous and comprehensive investigation, stakeholder input was limited to one ICS, potentially restricting insights from varied geographical contexts. In addition, the recent establishment of ICSs meant limited literature availability, with few empirical studies conducted. Although this emphasises the importance and originality of the research, this scarcity posed challenges in extracting and applying certain programme theory elements, particularly context. ORIGINALITY/VALUE: This review will be of relevance to academics and health-care leaders within ICSs in England, offering critical insights into ICS leadership, integrating diverse evidence to develop new evidence-based recommendations, filling a gap in the current literature and informing leadership practice and health-care systems.

A Study of Cross-Protection between Eimeria maxima Immunovariants.

For reasons unknown, Eimeria maxima is unique among Eimeria species infecting chickens in the immunovariability it displays among isolates from different geographical areas. Eimeria maxima oocysts (named EmaxAPU3) were isolated late in grow-out (6 weeks) from litter in a commercial broiler operation that was using Eimeria vaccination as the coccidiosis control program. Cross-protection studies (n = 4) were conducted in immunologically naïve chickens between EmaxAPU3 and two E. maxima lab strains (EmaxAPU1, EmaxAPU2) by immunizing with one E. maxima strain and challenging with either the homologous or heterologous E. maxima. As measured by oocyst output, immunization with EmaxAPU1 protected against homologous challenge (EmaxAPU1) and against heterologous challenge with EmaxAPU3, but not against EmaxAPU2. Similarly, immunization with EmaxAPU3 protected against homologous challenge (EmaxAPU3) and against heterologous challenge with EmaxAPU1, but not against EmaxAPU2. Immunization of chickens with EmaxAPU2 elicited a protective response against homologous challenge (EmaxAPU2), but not against EmaxAPU1 nor EmaxAPU3. The most plausible explanation for the appearance of this immunovariant late in grow-out is that E. maxima APU3 escaped immunity directed to E. maxima antigenic types in the commercial vaccine.

Atomic and Electronic Structure in MgO-SiO2.

Understanding disordered structure is difficult due to insufficient information in experimental data. Here, we overcome this issue by using a combination of diffraction and simulation to investigate oxygen packing and network topology in glassy (g-) and liquid (l-) MgO-SiO2 based on a comparison with the crystalline topology. We find that packing of oxygen atoms in Mg2SiO4 is larger than that in MgSiO3, and that of the glasses is larger than that of the liquids. Moreover, topological analysis suggests that topological similarity between crystalline (c)- and g-(l-) Mg2SiO4 is the signature of low glass-forming ability (GFA), and high GFA g-(l-) MgSiO3 shows a unique glass topology, which is different from c-MgSiO3. We also find that the lowest unoccupied molecular orbital (LUMO) is a free electron-like state at a void site of magnesium atom arising from decreased oxygen coordination, which is far away from crystalline oxides in which LUMO is occupied by oxygen's 3s orbital state in g- and l-MgO-SiO2, suggesting that electronic structure does not play an important role to determine GFA. We finally concluded the GFA of MgO-SiO2 binary is dominated by the atomic structure in terms of network topology.

Outstanding Energy-Storage Density Together with Efficiency of above 90% via Local Structure Design.

Dielectric ceramic capacitors with high recoverable energy density (Wrec) and efficiency (η) are of great significance in advanced electronic devices. However, it remains a challenge to achieve high Wrec and η parameters simultaneously. Herein, based on density functional theory calculations and local structure analysis, the feasibility of developing the aforementioned capacitors is demonstrated by considering Bi0.25Na0.25Ba0.5TiO3 (BNT-50BT) as a matrix material with large local polarization and structural distortion. Remarkable Wrec and η of 16.21 J/cm3 and 90.5% have been achieved in Bi0.25Na0.25Ba0.5Ti0.92Hf0.08O3 via simple chemical modification, which is the highest Wrec value among reported bulk ceramics with η greater than 90%. The examination results of local structures at lattice and atomic scales indicate that the disorderly polarization distribution and small nanoregion (∼3 nm) lead to low hysteresis and high efficiency. In turn, the drastic increase in local polarization activated via the ultrahigh electric field (80 kV/mm) leads to large polarization and superior energy storage density. Therefore, this study emphasizes that chemical design should be established on a clear understanding of the performance-related local structure to enable a targeted regulation of high-performance systems.

Behavioral and neuropathological features of Alzheimer's disease are attenuated in 5xFAD mice treated with intranasal GHK peptide.

Efforts to find disease modifying treatments for Alzheimer's disease (AD) have met with limited success in part because the focus has been on testing drugs that target a specific pathogenic mechanism. Multiple pathways have been implicated in the pathogenesis of AD. Hence, the probability of more effective treatment for AD is likely increased by using an intervention that targets more than one pathway. The naturally occurring peptide GHK (glycyl-L-histidyl-L-lysine), as a GHK-Cu complex, supports angiogenesis, remodeling, and tissue repair, has anti-inflammatory and antioxidant properties, and has been shown to improve cognitive performance in aging mice. In order to test GHK-Cu as a neurotherapeutic for AD, male and female 5xFAD transgenic mice on the C57BL/6 background at 4 months of age were given 15 mg/kg GHK-Cu intranasally 3 times per week for 3 months until 7 months of age. Results showed that intranasal GHK-Cu treatment delayed cognitive impairment, reduced amyloid plaques, and lowered inflammation levels in the frontal cortex and hippocampus. These observations suggest additional studies are warranted to investigate the potential of GHK-Cu peptide as a promising treatment for AD.

Chromosomal scale assembly reveals localized structural variants in avian caecal coccidian parasite Eimeria tenella.

Eimeria tenella is a major cause of caecal coccidiosis in commercial poultry chickens worldwide. Here, we report chromosomal scale assembly of Eimeria tenella strain APU2, a strain isolated from commercial broiler chickens in the U.S. We obtained 100× sequencing Oxford Nanopore Technology (ONT) and more than 800× Coverage of Illumina Next-Seq. We created the assembly using the hybrid approach implemented in MaSuRCA, achieving a contiguous 51.34 Mb chromosomal-scale scaffolding enabling identification of structural variations. The AUGUSTUS pipeline predicted 8060 genes, and BUSCO deemed the genomes 99% complete; 6278 (78%) genes were annotated with Pfam domains, and 1395 genes were assigned GO-terms. Comparing E. tenella strains (APU2, US isolate and Houghton, UK isolate) derived Houghton strain of E. tenella revealed 62,905 high stringency differences, of which 45,322 are single nucleotide polymorphisms (SNPs) (0.088%). The rate of transitions/transversions among the SNPs are 1.63 ts/tv. The strains possess conserved gene order but have profound sequence heterogeneity in a several chromosomal segments (chr 2, 11 and 15). Genic and intergenic variation in defined gene families was evaluated between the two strains to possibly identify sequences under selection. The average genic nucleotide diversity of 2.8 with average 2 kb gene length (0.145%) at genic level. We examined population structure using available E. tenella sequences in NCBI, revealing that the two E. tenella isolates from the U.S. (E. tenella APU2 and Wisconsin, "ERR296879") share a common maternal inheritance with the E. tenella Houghton. Our chromosomal level assembly promotes insight into Eimeria biology and evolution, hastening drug discovery and vaccine development.

Intranasal GHK peptide enhances resilience to cognitive decline in aging mice.

Brain aging and cognitive decline are aspects of growing old. Age-related cognitive impairment entails the early stages of cognitive decline, and is extremely common, affecting millions of older people. Investigation into early cognitive decline as a treatable condition is relevant to a wide range of cognitive impairment conditions, since mild age-related neuropathology increases risk for more severe neuropathology and dementia associated with Alzheimer's Disease. Recent studies suggest that the naturally occurring peptide GHK (glycyl-L-histidyl-L-lysine) in its Cu-bound form, has the potential to treat cognitive decline associated with aging. In order to test this concept, male and female C57BL/6 mice, 20 months of age, were given intranasal GHK-Cu, 15 mg/kg daily, for two months. Results showed that mice treated with intranasal GHK-Cu had an enhanced level of cognitive performance in spatial memory and learning navigation tasks, and expressed decreased neuroinflammatory and axonal damage markers compared to mice treated with intranasal saline. These observations suggest that GHK-Cu can enhance resilience to brain aging, and has translational implications for further testing in both preclinical and clinical studies using an atomizer device for intranasal delivery.

Relationship between Eimeria oocyst infectivity for chickens and in vitro excystation of E. acervulina, E. maxima, and E. tenella oocyst during long-term storage.

Vaccination of chickens against avian coccidiosis in chickens often involves storing Eimeria oocysts for months after oocyst propagation and sporulation. The purpose of this study was to determine how long E. acervulina, E. maxima, and E. tenella oocysts remained viable when stored at refrigeration (4°C) or egg room (20°C) temperatures. Separate tubes containing E. acervulina, E. maxima, or E. tenella oocysts were stored at these temperatures and a sample removed every 3 mo for inoculating chickens for evidence of a patent infection. Also, an aliquot of each Eimeria species at each time-temperature combination was subjected to in vitro excystation to quantify the relative number of released sporozoites to intact (nonexcysted) sporocysts. Eimeria tenella appeared to be most susceptible to storage in that no oocyst production was observed at 9 mo at either temperature. Although E. maxima oocysts were viable at 9 mo, no oocyst production was observed at 12 mo storage at these 2 temperatures. Quite unexpected was that E. acervulina was much more stable than E. tenella and E. maxima remaining viable up to and including 27 mo at 4°C and up to and including 12 mo at 20°C. No consistent correlation was observed between in vivo oocyst production and in vitro excystation arising from these 2 respective temperatures (E. acervulina r = 0.58, r = 0.54; E. maxima r = 0.90, r = 0.54; E. tenella r = 0.38, r = 0.90). These data indicate that attention must be paid to time and temperature of Eimeria oocyst storage, and that sporozoite excystation may not be a good indicator of oocyst viability, particularly at later timepoints in incubation.

Group physical therapy for knee osteoarthritis: protocol for a hybrid type III effectiveness-implementation trial.

BACKGROUND: Knee osteoarthritis (OA) is a leading cause of chronic pain and disability and one of the most common conditions treated in outpatient physical therapy (PT). Because of the high and growing prevalence of knee OA, there is a need for efficient approaches for delivering exercise-based PT to patients with knee OA. A prior randomized controlled trial (RCT) showed that a 6-session Group Physical Therapy Program for Knee OA (Group PT) yields equivalent or greater improvements in pain and functional outcomes compared with traditional individual PT, while requiring fewer clinician hours per patient to deliver. This manuscript describes the protocol for a hybrid type III effectiveness-implementation trial comparing two implementation packages to support delivery of Group PT. METHODS: In this 12-month embedded trial, a minimum of 16 Veterans Affairs Medical Centers (VAMCs) will be randomized to receive one of two implementation support packages for their Group PT programs: a standard, low-touch support based on Replicating Effective Programs (REP) versus enhanced REP (enREP), which adds tailored, high-touch support if sites do not meet Group PT adoption and sustainment benchmarks at 6 and 9 months following launch. Implementation outcomes, including penetration (primary), adoption, and fidelity, will be assessed at 6 and 12 months (primary assessment time point). Additional analyses will include patient-level effectiveness outcomes (pain, function, satisfaction) and staffing and labor costs. A robust qualitative evaluation of site implementation context and experience, as well as site-led adaptations to the Group PT program, will be conducted. DISCUSSION: To our knowledge, this study is the first to evaluate the impact of tailored, high-touch implementation support on implementation outcomes when compared to standardized, low-touch support for delivering a PT-based intervention. The Group PT program has strong potential to become a standard offering for PT, improving function and pain-related outcomes for patients with knee OA. Results will provide information regarding the effectiveness and value of this implementation approach and a deeper understanding of how healthcare systems can support wide-scale adoption of Group PT. TRIAL REGISTRATION: This study was registered on March 7, 2022 at ClinicalTrials.gov (identifier NCT05282927 ).

MADS8 is indispensable for female reproductive development at high ambient temperatures in cereal crops.

Temperature is a major factor that regulates plant growth and phenotypic diversity. To ensure reproductive success at a range of temperatures, plants must maintain developmental stability of their sexual organs when exposed to temperature fluctuations. However, the mechanisms integrating plant floral organ development and temperature responses are largely unknown. Here, we generated barley and rice loss-of-function mutants in the SEPALLATA-like MADS-box gene MADS8. The mutants in both species form multiple carpels that lack ovules at high ambient temperatures. Tissue-specific markers revealed that HvMADS8 is required to maintain floral meristem determinacy and ovule initiation at high temperatures, and transcriptome analyses confirmed that temperature-dependent differentially expressed genes in Hvmads8 mutants predominantly associate with floral organ and meristem regulation. HvMADS8 temperature-responsive activity relies on increased binding to promoters of downstream targets, as revealed by a cleavage under targets and tagmentation (CUT&Tag) analysis. We also demonstrate that HvMADS8 directly binds to 2 orthologs of D-class floral homeotic genes to activate their expression. Overall, our findings revealed a new, conserved role for MADS8 in maintaining pistil number and ovule initiation in cereal crops, extending the known function of plant MADS-box proteins in floral organ regulation.

Examining the residual radiological footprint of a former colliery: An industrial nuclear archaeology investigation.

Nuclear industrial archaeology utilises radiation mapping and characterisation technologies to gain an insight into the radiological footprint of industrial heritage sites. Increased concentrations of naturally occurring radioactive materials at legacy mine sites are the result of elemental enrichment during coal mining and subsequent combustion. Public safety is of concern around these sites, and therefore, an increased understanding of their associated hazard is essential. Using coincident laser scanning and gamma detection technologies, this study sought to assess the radiological legacy of a coal mine located in Bristol, UK. From this, we can increase our understanding of the residual footprints associated with the local coal mining industry. Samples taken from inside the site were characterised using high resolution gamma spectrometry, wherein the radionuclide content and activities of samples were then quantified. An area of elevated low-level radioactivity was observed at and around buildings believed to belong to the colliery, while Th, U, and K are confirmed at the site from photopeak's of daughter radionuclides. Activities of the radionuclides K-40, U-238, and Th-232 were further quantified during subsequent laboratory analysis. Results highlight an enrichment of naturally occurring radionuclides when compared with global averages for unburned coal. Employing these techniques at further legacy sites would enable an increased understanding of the lasting traces of the coal mining industry, with a focus on NORM enrichment in residual fly ash.

Implementation intensification to disseminate a skills-based caregiver training program: protocol for a type III effectiveness-implementation hybrid trial.

BACKGROUND: Family caregiver training decreases caregiver psychological burden and improves caregiver depressive symptoms and health-related quality of life. Caregivers FIRST is an evidence-based group skills training curriculum for family caregivers and was announced for national dissemination in partnership with the Veterans Health Administration (VHA) National Caregiver Support Program (CSP). Previous evaluations of Caregivers FIRST implementation highlighted that varying support was needed to successfully implement the program, ranging from minimal technical assistance to intensive assistance and support. However, we do not know the optimal level of support needed to inform cost-effective national scaling of the program. We describe a protocol for randomizing 24 non-adopting VA medical centers 1:1 to a tailored, high-touch implementation support or a standard, low-touch implementation support to test the primary hypothesis that high-touch support increases Caregivers FIRST penetration, fidelity, and adoption. Additionally, we describe the methods for evaluating the effect of Caregivers FIRST participation on Veteran outcomes using a quasi-experimental design and the methods for a business case analysis to examine cost of delivery differences among sites assigned to a low or high-touch implementation support. METHODS: We use a type III hybrid implementation-effectiveness study design enrolling VA medical centers that do not meet Caregivers FIRST adoption benchmarks following the announcement of the program as mandated within the CSP. Eligible medical centers will be randomized to receive a standard low-touch implementation support based on Replicating Effective Programs (REP) only or to an enhanced REP (high-touch) implementation support consisting of facilitation and tailored technical assistance. Implementation outcomes include penetration (primary), fidelity, and adoption at 12 months. Mixed methods will explore sites' perceptions and experiences of the high-touch intensification strategy. Additional analyses will include a patient-level effectiveness outcome (Veteran days at home and not in an institution) and a business case analysis using staffing and labor cost data. DISCUSSION: This pragmatic trial will lead to the development and refinement of implementation tools to support VA in spreading and sustaining Caregivers FIRST in the most efficient means possible. TRIAL REGISTRATION: This study was registered on April 8, 2022, at ClinicalTrials.gov (identifier NCT05319535).

Genetic and Phenotypic Analysis of Ovule Development in Arabidopsis.

The plant seed is a remarkable structure that represents the single most important energy source in global diets. The stages of reproductive growth preceding seed formation are particularly important since they influence the number, size, and quality of seed produced. The progenitor of the seed is the ovule, a multicellular organ that produces a female gametophyte while maintaining a range of somatic ovule cells to protect the seed and ensure it receives maternal nourishment. Ovule development has been well characterized in Arabidopsis using a range of molecular, genetic, and cytological assays. These can provide insight into the mechanistic basis for ovule development, and opportunities to explore its evolutionary conservation. In this chapter, we describe some of these methods and tools that can be used to investigate early ovule development and cell differentiation.

HvSL1 and HvMADS16 promote stamen identity to restrict multiple ovary formation in barley.

Correct floral development is the result of a sophisticated balance of molecular cues. Floral mutants provide insight into the main genetic determinants that integrate these cues, as well as providing opportunities to assess functional variation across species. In this study, we characterize the barley (Hordeum vulgare) multiovary mutants mov2.g and mov1, and propose causative gene sequences: a C2H2 zinc-finger gene HvSL1 and a B-class gene HvMADS16, respectively. In the absence of HvSL1, florets lack stamens but exhibit functional supernumerary carpels, resulting in multiple grains per floret. Deletion of HvMADS16 in mov1 causes homeotic conversion of lodicules and stamens into bract-like organs and carpels that contain non-functional ovules. Based on developmental, genetic, and molecular data, we propose a model by which stamen specification in barley is defined by HvSL1 acting upstream of HvMADS16. The present work identifies strong conservation of stamen formation pathways with other cereals, but also reveals intriguing species-specific differences. The findings lay the foundation for a better understanding of floral architecture in Triticeae, a key target for crop improvement.

Inhibition of vibrational energy flow within an aromatic scaffold via heavy atom effect.

The regulation of intramolecular vibrational energy redistribution (IVR) to influence energy flow within molecular scaffolds provides a way to steer fundamental processes of chemistry, such as chemical reactivity in proteins and design of molecular diodes. Using two-dimensional infrared (2D IR) spectroscopy, changes in the intensity of vibrational cross-peaks are often used to evaluate different energy transfer pathways present in small molecules. Previous 2D IR studies of para-azidobenzonitrile (PAB) demonstrated that several possible energy pathways from the N3 to the cyano-vibrational reporters were modulated by Fermi resonance, followed by energy relaxation into the solvent [Schmitz et al., J. Phys. Chem. A 123, 10571 (2019)]. In this work, the mechanisms of IVR were hindered via the introduction of a heavy atom, selenium, into the molecular scaffold. This effectively eliminated the energy transfer pathway and resulted in the dissipation of the energy into the bath and direct dipole-dipole coupling between the two vibrational reporters. Several structural variations of the aforementioned molecular scaffold were employed to assess how each interrupted the energy transfer pathways, and the evolution of 2D IR cross-peaks was measured to assess the changes in the energy flow. By eliminating the energy transfer pathways through isolation of specific vibrational transitions, through-space vibrational coupling between an azido (N3) and a selenocyanato (SeCN) probe is facilitated and observed for the first time. Thus, the rectification of this molecular circuitry is accomplished through the inhibition of energy flow using heavy atoms to suppress the anharmonic coupling and, instead, favor a vibrational coupling pathway.

Ready, set, go! The role of organizational readiness to predict adoption of a family caregiver training program using the Rogers' diffusion of innovation theory.

BACKGROUND: Caregivers FIRST is an evidence-based program addressing gaps in caregivers' skills. In 2020, the Veterans Health Administration Caregiver Support Program (CSP) nationally endorsed Caregivers FIRST, offering credit in leadership performance plans to encourage all VA medical centers (VAMCs) to implement locally. This study examines the association of organizational readiness with VAMC adoption of Caregivers FIRST. METHODS: In a cohort observational study, we surveyed CSP managers about their facilities' readiness to implement using the Organizational Readiness for Implementing Change (ORIC) instrument and compared change commitment and change efficacy domains among VAMCs "adopters" defined as delivering Caregivers FIRST within 1 year of the national announcement to those that did not ("non-adopters"). Within "adopters," we categorized time to adoption based on Rogers' diffusion of innovation theory including "innovators," "early adopters," "early majority," "late adopters," and "laggards." Organizational readiness and site characteristics (facility complexity, staffing levels, volume of applications for caregiver assistance services) were compared between "adopters," "non-adopters," and between time to adoption subcategories. Separate logistic regression models were used to assess whether ORIC and site characteristics were associated with early adoption among "adopters." RESULTS: Fifty-one of 63 (81%) VAMCs with CSP manager survey respondents adopted Caregivers FIRST during the first year. ORIC change commitment and efficacy were similar for "adopters" and "non-adopters." However, sites that adopted earlier (innovators and early adopters) had higher ORIC change commitment and efficacy scores than the rest of the "adopters." Logistic regression results indicated that higher ORIC change commitment (odds ratio [OR] = 2.57; 95% confidence interval [CI], 1.11-5.95) and ORIC change efficacy (OR = 2.60; 95% CI, 1.12-6.03) scores were associated with increased odds that a VAMC was an early adopter (categorized as an "innovator," "early adopter", or "early majority"). Site-level characteristics were not associated with Caregivers FIRST early adoption. CONCLUSIONS: To our knowledge, this study is the first to prospectively assess organizational readiness and the timing of subsequent program adoption. Early adoption was associated with higher ORIC change commitment and change efficacy and not site-level characteristics. These findings yield insights into the role of organizational readiness to accelerate program adoption. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03474380. Registered on March 22, 2018.