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OBJECTIVES:. To assess the added prognostic value of serial monitoring of urinary C-C motif chemokine ligand 14 (uCCL14) over that of single measurements, which have been shown to be prognostic for development of persistent severe acute kidney injury (AKI) in critically ill patients. DESIGN:. Retrospective observational study. SETTING:. Data derived from two multinational ICU studies (Ruby and Sapphire). PATIENTS:. Critically ill patients with early stage 2–3 AKI. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We analyzed three consecutive uCCL14 measurements at 12-hour intervals after diagnosis of stage 2–3 AKI by Kidney Disease Improving Global Outcomes criteria. Primary outcome was persistent severe AKI, defined as 72 consecutive hours of stage 3 AKI, death, or receipt of dialysis prior to 72 hours. uCCL14 was measured using the NEPHROCLEAR uCCL14 Test on the Astute 140 Meter (Astute Medical, San Diego, CA). Based on predefined, validated cutoffs, we categorized uCCL14 as: low (≤ 1.3 ng/mL), medium (> 1.3 to ≤ 13 ng/mL), or high (> 13 ng/mL). Seventy-five of 417 patients with three consecutive uCCL14 measurements developed persistent severe AKI. Initial uCCL14 category strongly correlated with primary endpoint and, in most cases (66%), uCCL14 category was unchanged over the first 24 hours. Compared with no change and accounting for baseline category, decrease in category was associated with decreased odds of persistent severe AKI (odds ratio [OR], 0.20; 95% CI, 0.08–0.45; p < 0.001) and an increase in category with increased odds (OR, 4.04; 95% CI, 1.75–9.46; p = 0.001). CONCLUSIONS:. In one-third of patients with moderate to severe AKI uCCL14 risk category altered over three serial measurements and such changes were associated with altered risk for persistent severe AKI. Serial CCL-14 measurement may detect progression or resolution of underlying kidney pathology and help refine AKI prognosis.

Objective Determine the pharmacokinetics (PK) and exposure–response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE).Methods We conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry with a diagnosis of pSLE were eligible if they were receiving HCQ as standard of care for ≥3 months. Biological samples were collected at up to four visits over a 6-month period. At each visit, plasma was obtained to measure the concentrations of HCQ and DHCQ, as well as cytokines. HCQ and DHCQ plasma PK data were analysed using a population PK modelling approach.Results Twenty-five subjects provided a total of 88 plasma concentrations for PK analysis. There was a poor linear fit between HCQ concentrations and total body weight (R2=0.03). There was a decline in both interferon (IFN)-alpha and IFN-gamma with higher concentrations of HCQ and DHCQ. Volume of distribution for HCQ in plasma was higher in children compared with published values in adults (73 000 L vs 44 000 L), but clearance values in children were similar to adults.Conclusions We report the first population PK model for HCQ and DHCQ in children using data from a novel direct-to-family clinical trial. We observed high interindividual variability in HCQ PK and found that weight-based dosing for HCQ is poorly correlated with drug concentrations, suggesting the need to use therapeutic drug monitoring to individualise dosing. Furthermore, our results suggest that the current weight-based dosing paradigm for HCQ may result in suboptimal drug exposures, particularly for children with obesity. Accordingly, additional studies of HCQ are needed in pSLE to determine the optimal drug concentration and dosing to reduce disease activity and improve outcomes.Trial registration number NCT04358302.

Rehearsal is a form of self-talk used to support short-term memory. Historically, the study of rehearsal development has diverged from the study of self-talk more generally. The current experiment examines whether two characteristics of self-talk (impact of task difficulty and self-talk's narrative vs. planning purpose) are also observed in rehearsal. Eighty children, ages 4-7, were tasked with remembering the three-item and six-item lists over a 15-s delay. Children's spontaneous use of fixed rehearsal (i.e., immediate repetition of a just-presented item) and cumulative rehearsal (i.e., cycling through multiple items at a time) was documented from video recordings. Four-year-olds narrated item presentations using fixed rehearsal. Six- and seven-year-olds proactively planned for recall by engaging cumulative rehearsal. Five-year-olds used both forms of rehearsal, but their frequency of cumulative rehearsal was dependent on list length. Therefore, rehearsal is susceptible to task manipulations that affect other forms of self-talk.

Abstract Background PSEN1, PSEN2, and APP mutations cause Alzheimer’s disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP. Methods We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer’s disease (FAD) patients harboring mutations in PSEN1 A79V , PSEN2 N141I , and APP V717I and mechanistically characterized by integrating RNA-seq and ATAC-seq. Results We identified common disease endotypes, such as dedifferentiation, dysregulation of synaptic signaling, repression of mitochondrial function and metabolism, and inflammation. We ascertained the master transcriptional regulators associated with these endotypes, including REST, ASCL1, and ZIC family members (activation), and NRF1 (repression). Conclusions FAD mutations share common regulatory changes within endotypes with varying severity, resulting in reversion to a less-differentiated state. The regulatory mechanisms described offer potential targets for therapeutic interventions.

A newly-discovered endemic tree species of Melicope from Kaua‘i, Hawaiian Islands, is described and illustrated with notes on its distribution, ecology, conservation status and phylogenetic placement. A modification to the existing key to Hawaiian Melicope is also provided. Melicope iolensis sp. nov. is a member of Stone’s Megacarpa group having carpels connate at base, capsules 4-lobed and leaves usually opposite. The new species differs from its Hawaiian congeners by its unique combination of abaxially glabrate to pilose-pubescent leaves with petioles up to 70 mm long, ramiflorous and axillary inflorescences, sepals on staminate flowers 0.3–0.5 mm long, capsules with green and purple streaking, 10–14 mm wide and seeds 3–3.5 mm long. Since its discovery in 2021, 15 individuals have been documented within a single remote windward hanging valley below the Kawaikini Summit of Kaua‘i. Melicope iolensis represents a new Critically Endangered (CR) single island endemic species in need of conservation.

During a survey by the National Tropical Botanical Garden drone team, an enigmatic Schiedea was observed in December 2021on steep, rocky cliff faces of the Waiahulu Valley in the Waimea Canyon of Kaua'i. Subsequently, another survey was conducted in March 2022 and, by use of a remotely controlled cutting device suspended below the drone, the first herbarium specimen was collected, as well as a seed collection of an undescribed cliff-dwelling species of Schiedea. Detailed study of the collections and plants grown at the University of California, Irvine greenhouse showed that it had enlarged, somewhat whitish sepals similar to those of cliff-dwelling S. attenuata (the sole species in sect. Leucocalyx), yet differed significantly from all other species in the genus. It also shares with S. attenuata a woody habit, hermaphroditic flowers, coloured nectar and styles 5 to 7 or 8. We describe it here as S. waiahuluensis given the only known localities are on the cliffs of this valley and place it in an enlarged sect. Leucocalyx. With the discovery of this new species, there are 36 species in this Hawaiian endemic genus.

Abstract The recently discovered interaction between presenilin 1 (PS1), a subunit of γ-secretase involved in amyloid-β (Aβ) peptide production, and GLT-1, the major brain glutamate transporter (EAAT2 in the human), may link two pathological aspects of Alzheimer’s disease: abnormal Aβ occurrence and neuronal network hyperactivity. In the current study, we employed a FRET-based fluorescence lifetime imaging microscopy (FLIM) to characterize the PS1/GLT-1 interaction in brain tissue from sporadic AD (sAD) patients. sAD brains showed significantly less PS1/GLT-1 interaction than those with frontotemporal lobar degeneration or non-demented controls. Familial AD (fAD) PS1 mutations, inducing a “closed” PS1 conformation similar to that in sAD brain, and gamma-secretase modulators (GSMs), inducing a “relaxed” conformation, respectively reduced and increased the interaction. Furthermore, PS1 influences GLT-1 cell surface expression and homomultimer formation, acting as a chaperone but not affecting GLT-1 stability. The diminished PS1/GLT-1 interaction suggests that these functions may not work properly in AD.

Abstract Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls. MSOT is compared with muscle magnetic resonance imaging (MRI), ultrasound, spirometry, muscle testing and quality of life scores. Next, results are validated in an independent LOPD patient cohort from a second clinical site. Our study demonstrates that MSOT enables imaging of subcellular disease pathology with increases in glycogen/water, collagen and lipid signals, providing higher sensitivity in detecting muscle degeneration than current methods. This translational approach suggests implementation in the complex care of these rare disease patients.

As more schools adopt inclusive practices, the need for schools to understand how students perceive these practices grows. The current study explores K-12 students' perceptions of co-teaching through a systematic review and thematic analysis of the literature. Through an analysis of quantitative, qualitative, and mixed-methods research from journals and dissertations, this review shows the importance of attending to contextual variables surrounding co-teaching and how these may serve as mediating factors for students' perceptions. Using an open-ended date range for studies and including gray literature allowed for robust findings that synthesize comprehensively how students view co-teaching. Key findings include students' perceived success academically and preference for co-teaching. Additionally, results indicated a pattern of students' negative perceptions of co-teaching when teachers experienced many professional demands. However, the lack of reported socially constructed contextual variables, such as race and gender, limited insights into how students make meaning of co-teaching. On the basis of these findings, we discuss implications for research, policy, and practice.

Preterm infants have an immature intestinal environment featuring microbial dysbiosis. Human milk can improve the composition of the neonatal gut microbiome by supporting commensal species. Milk free fatty acids (FFAs) provide nutritional energy, participate in endogenous signaling, and exert antimicrobial effects. This study examined the growth of individual commensal and pathobiont microbes in response to unesterified unsaturated FFAs found in milk: oleic, linoleic, arachidonic, and docosahexaenoic acid. Select species of commensal and pathobiont genera (Bifidobacterium, Lactobacillus, Streptococcus, Staphylococcus, Enterococcus, Acinetobacter, Pseudomonas, Escherichia, and Klebsiella) were cultured with FFAs. The growth of all commensals, except for L. johnsonii, was significantly inhibited by the highest concentration (1 %) of all FFAs. L. johnsonii was only inhibited by arachidonic acid. In contrast, suppression of pathobionts in response to FFAs was less pronounced. Higher concentrations (0.1 %, 1 %) of docosahexaenoic acid significantly inhibited the growth of five of eight pathobionts. Meanwhile, for oleic, linoleic, and arachidonic acid, only two of eight pathobionts were significantly affected. Intriguingly, the effects for these FFAs were highly complex. For example, S. agalactiae growth was enhanced with 1 % oleic acid but suppressed at 0.01 %; however, the effects were directionally opposite for linoleic acid, i.e., suppressed at 1 % but enhanced at 0.01 %. Our genome analyses suggest that pathobiont survival may be related to the number of gene copies for fatty acid transporters. Overall, the effect of FFAs was dose-dependent and species-specific, where commensal growth was broadly inhibited while pathobionts were either unaffected or exhibited complex, bi-directional responses.

Abstract Sero-monitoring provides context to the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and changes in population immunity following vaccine introduction. Here, we describe results of a cross-sectional hospital-based study of anti-spike seroprevalence in New York City (NYC) from February 2020 to July 2022, and a follow-up period from August 2023 to October 2023. Samples from 55,092 individuals, spanning five epidemiological waves were analyzed. Prevalence ratios (PR) were obtained using Poisson regression. Anti-spike antibody levels increased gradually over the first two waves, with a sharp increase during the 3rd wave coinciding with SARS-CoV-2 vaccination in NYC resulting in seroprevalence levels >90% by July 2022. Our data provide insights into the dynamic changes in immunity occurring in a large and diverse metropolitan community faced with a new viral pathogen and reflects the patterns of antibody responses as the pandemic transitions into an endemic stage.

Abstract Conventional magnetofossils are the remains of magnetotactic bacteria and giant magnetofossils are the remains of iron biomineralizing organisms that have not yet been identified. We report the oldest robust conventional and giant magnetofossil records, ~97 Ma, from marine sediments drilled in Holland Park, Virginia, USA. The Holland Park core records the Cenomanian-Turonian boundary and Oceanic-Anoxic Event 2 (OAE2). Magnetic datasets indicate single domain magnetite within the clay-rich sediments bookending OAE2. Electron microscopy images from these intervals highlight conventional and giant magnetofossil morphologies, including three potentially new giant magnetofossil morphologies: seeds, squash, and spades. There is an overall high abundance and morphological disparity of magnetofossils at Holland Park. However, we observe abundance, disparity, and preservation changes between the magnetofossil assemblages bookending OAE2. Our observations provide clues toward understanding the ecological thresholds of the enigmatic organisms that produce giant magnetofossils and evidence that magnetofossils may be widely distributed in the geologic record.

Abstract Background Clinical reasoning (CR) is a crucial ability that can prevent errors in patient care. Despite its important role, CR is often not taught explicitly and, even when it is taught, typically not all aspects of this ability are addressed in health professions education. Recent research has shown the need for explicit teaching of CR for both students and teachers. To further develop the teaching and learning of CR we need to improve the understanding of students' and teachers' needs regarding content as well as teaching and assessment methods for a student and trainer CR curriculum. Methods Parallel mixed-methods design that used web-surveys and semi-structured interviews to gather data from both students (nsurvey = 100; ninterviews = 13) and teachers (nsurvey = 112; ninterviews = 28). The interviews and surveys contained similar questions to allow for triangulation of the results. This study was conducted as part of the EU-funded project DID-ACT ( https://did-act.eu ). Results Both the surveys and interview data emphasized the need for content in a clinical reasoning (CR) curriculum such as “gathering, interpreting and synthesizing patient information”, “generating differential diagnoses”, “developing a diagnostic and a treatment plan” and “collaborative and interprofessional aspects of CR”. There was high agreement that case-based learning and simulations are most useful for teaching CR. Clinical and oral examinations were favored for the assessment of CR. The preferred format for a train-the-trainer (TTT)-course was blended learning. There was also some agreement between the survey and interview participants regarding contents of a TTT-course (e.g. teaching and assessment methods for CR). The interviewees placed special importance on interprofessional aspects also for the TTT-course. Conclusions We found some consensus on needed content, teaching and assessment methods for a student and TTT-course in CR. Future research could investigate the effects of CR curricula on desired outcomes, such as patient care.

Abstract It has been difficult to demonstrate that interprofessional education (IPE) and interprofessional collaboration (IPC) have positive effects on patient care quality, cost effectiveness of patient care, and healthcare provider satisfaction. Here we propose a detailed explanation for this difficulty based on an adjusted theory about cause and effect in the field of IPE and IPC by asking: 1) What are the critical weaknesses of the causal models predominantly used which link IPE with IPC, and IPE and IPC with final outcomes? 2) What would a more precise causal model look like? 3) Can the proposed novel model help us better understand the challenges of IPE and IPC outcome evaluations? In the format of a critical theoretical discussion, based on a critical appraisal of the literature, we first reason that a monocausal, IPE-biased view on IPC and IPC outcomes does not form a sufficient foundation for proper IPE and IPC outcome evaluations; rather, interprofessional organization (IPO) has to be considered an additional necessary cause for IPC; and factors outside of IPC additional causes for final outcomes. Second, we present an adjusted model representing the “multi-stage multi-causality” of patient, healthcare provider, and system outcomes. Third, we demonstrate the model’s explanatory power by employing it to deduce why misuse of the modified Kirkpatrick classification as a causal model in IPE and IPC outcome evaluations might have led to inconclusive results in the past. We conclude by applying the derived theoretical clarification to formulate recommendations for enhancing future evaluations of IPE, IPO, and IPC. Our main recommendations: 1) Focus should be placed on a comprehensive evaluation of factual IPC as the fundamental metric and 2) A step-by-step approach should be used that separates the outcome evaluation of IPE from that of IPC in the overarching quest for proving the benefits of IPE, IPO and IPC for patients, healthcare providers, and health systems. With this critical discussion we hope to enable more effective evaluations of IPE, IPO and IPC in the future.

Myrsine cirrhosa Lorence & K.R.Wood (Primulaceae), a new single-island endemic shrub species from Kaua‘i, Hawaiian Islands, is described and illustrated. Notes on its distribution, ecology and conservation status are included. The new species is known from an area with ca. 45 individuals, where it is restricted to the remote central windward region of Kaua‘i in open bogs and along open windy ridges. Suggested IUCN Red List status is CR (Critically Endangered). It differs from its Kaua‘i congeners by its longer petals and narrowly elliptic leaves with strongly undulate margins and tendril-like apex. Phylogenetic analysis using RADseq data supports the recognition of this new species.

Purpose: To validate the performance of the Notal OCT Analyzer (NOA) in processing self-administered OCT images from an OCT system designed for home use (home OCT [HOCT]) as part of a pivotal study aimed at achieving de novo United States Food and Drug Admininstration marketing authorization. Design: A prospective quantitative cross-sectional artificial intelligence study. Participants: The study enrolled adults aged ≥55 years diagnosed with neovascular age-related macular degeneration (nAMD) in ≥1 eligible eye with a best-corrected visual acuity of 20/320 or better. Methods: Participants self-imaged 4 times on each of 2 HOCT devices and once with an in-office OCT (IO-OCT) device during a single visit. Scans were segmented by the NOA and human graders at a certified reading center (RC). Main Outcome Measures: Intradevice and interdevice repeatability and reproducibility of total retinal hyporeflective (TRO) volume estimation by the NOA on HOCT-acquired images as compared with that of RC graders on IO-OCT-acquired images. Additionally, to assess the performance of the NOA in segmentation of TRO over multiple B-scans as compared with RC graders. Results: Self-imaging was performed successfully by 387 participants in 2451 of 2616 attempts (93.7%). For repeatability, the coefficient of variance for NOA was 11.1% for eyes with >10 volume units of TRO imaged with HOCT compared with 16.4% for RC graders segmenting IO-OCT images. The median DICE similarity coefficients for segmentation of TRO by NOA vs. Grader 1, Grader 2, and Grader 3; Grader 1 vs. Grader 2 and Grader 3; and Grader 2 vs. Grader 3 were 0.68, 0.68, 0.61, 0.72, 0.63, 0.70, respectively. Conclusions: The performance of NOA supports the intended use of the system as a tool to monitor TRO at home between routine clinical visits in support of the management of nAMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

BackgroundIntra-tumoral lymphocytes hold prognostic and predictive significance in colorectal cancer (CRC). The internationally validated Immunoscore™ predicts CRC survival risk by averaging percentile scores of tumor-associated CD3+ and CD8+ cell densities, but is limited by increased cost, intra-tumoral heterogeneity and omission of other immunologic variables of importance. To address these limitations, we sought to explore alternative prognostic markers based on CD3+ and CD8+ quantification in CRC.Methods201 resected CRCs were subjected to quantitative CD3/CD8 immunohistochemistry, from which percentile cell counts were averaged (“I-score”) in a manner analogous to the Immunoscore™. I-score and exploratory endpoints, including CD3+ and CD8+ cell densities/percentiles, CD3+-CD8+ density/percentile differences, and CD3+:CD8+ density/percentile ratios were tested for association with clinicopathologic and genomic correlates and disease-specific survival (DSS).ResultsCD3+ density among CRCs was right-skewed and potentially bimodal, while CD8+ density was right-skewed. Density and intra-tumoral variability for CD3+ and CD8+, as well as combination metrics including I-score, CD3+-CD8+ density/percentile differences, and CD3+-CD8+ density/percentile ratios showed distinct clinicopathologic and genomic associations, suggesting that each may hold unique biological significance. CD3+ density, CD8+ density/percentile, I-score and CD3+:CD8+ percentile ratio were associated with DSS; only CD3+:CD8+ percentile ratio was pTNM stage-independent on multivariable analysis. Independently, CD8+ density was as prognostic as I-score, questioning the necessity of CD3, or a combination metric.ConclusionsI-score, in our study, was closely associated with potentially confounding biologic variables such as sex, active smoking, pTNM stage, and mutations in BRAF, and MMR genes. More precise and biologically relevant biomarkers can be achieved by using data-driven CD3+/CD8+ density cutoffs and ratios, while controlling for important clinicopathologic and molecular variables in CRC. Independent validation and inclusion of other relevant immunocyte types could bring these findings closer to clinical utility in CRC.

Improving the scalability of tissue imaging throughput with bright, coherent X-rays requires identifying and mitigating artifacts resulting from the interactions between X-rays and matter. At synchrotron sources, long-term imaging of soft tissues in solution can result in gas bubble formation or cavitation, which dramatically compromises image quality and integrity of the samples. By combining in-line phase-contrast imaging with gas chromatography in real time, we were able to track the onset and evolution of high-energy X-ray-induced gas bubbles in ethanol-embedded soft tissue samples for tens of minutes (two to three times the typical scan times). We demonstrate quantitatively that vacuum degassing of the sample during preparation can significantly delay bubble formation, offering up to a twofold improvement in dose tolerance, depending on the tissue type. However, once nucleated, bubble growth is faster in degassed than undegassed samples, indicating their distinct metastable states at bubble onset. Gas chromatography analysis shows increased solvent vaporization concurrent with bubble formation, yet the quantities of dissolved gasses remain unchanged. By coupling features extracted from the radiographs with computational analysis of bubble characteristics, we uncover dose-controlled kinetics and nucleation site-specific growth. These hallmark signatures provide quantitative constraints on the driving mechanisms of bubble formation and growth. Overall, the observations highlight bubble formation as a critical yet often overlooked hurdle in upscaling X-ray imaging for biological tissues and soft materials and we offer an empirical foundation for their understanding and imaging protocol optimization. More importantly, our approaches establish a top-down scheme to decipher the complex, multiscale radiation–matter interactions in these applications.

Abstract Introduction The standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up). Methods In this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated. Discussion This is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option. Trial registration Clinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.

Abstract Background The analysis of dental caries has been a major focus of recent work on modeling dental defect data. While a dental caries focus is of major importance in dental research, the examination of developmental defects which could also contribute at an early stage of dental caries formation, is also of potential interest. This paper proposes a set of methods which address the appearance of different combinations of defects across different tooth regions. In our modeling we assess the linkages between tooth region development and both the type of defect and associations with etiological predictors of the defects which could be influential at different times during the tooth crown development. Methods We develop different hierarchical model formulations under the Bayesian paradigm to assess exposures during primary central incisor (PMCI) tooth development and PMCI defects. We evaluate the Bayesian hierarchical models under various simulation scenarios to compare their performance with both simulated dental defect data and real data from a motivating application. Results The proposed model provides inference on identifying a subset of etiological predictors of an individual defect accounting for the correlation between tooth regions and on identifying a subset of etiological predictors for the joint effect of defects. Furthermore, the model provides inference on the correlation between the regions of the teeth as well as between the joint effect of the developmental enamel defects and dental caries. Simulation results show that the proposed model consistently yields steady inferences in identifying etiological biomarkers associated with the outcome of localized developmental enamel defects and dental caries under varying simulation scenarios as deemed by small mean square error (MSE) when comparing the simulation results to real application results. Conclusion We evaluate the proposed model under varying simulation scenarios to develop a model for multivariate dental defects and dental caries assuming a flexible covariance structure that can handle regional and joint effects. The proposed model shed new light on methods for capturing inclusive predictors in different multivariate joint models under the same covariance structure and provides a natural extension to a nested hierarchical model.

Abstract Peritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with a poor prognosis and limited treatment options. Recent work identifying high concentrations of the cytokine interleukin-6 (IL-6) and its soluble receptor (sIL-6-Rα) in the peritoneal cavity of patients with PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides a comprehensive overview of the current understanding of the potential role of IL-6 in the development and progression of PC. We discuss mechansims by which the IL-6 pathway may contribute to peritoneal tumor dissemination, mesothelial adhesion and invasion, stromal invasion and proliferation, and immune response modulation. Finally, we review the prospects for targeting the IL-6 pathway in the treatment of PC, focusing on common sites of origin, including ovarian, gastric, pancreatic, colorectal and appendiceal cancer, and mesothelioma.

Introduction: The incidence of sexually transmitted infections (STI) increased in the United States between 2017–2021. There is limited data describing STI co-testing practices and the prevalence of STI co-infections in emergency departments (ED). In this study, we aimed to describe the prevalence of co-testing and co-infection of HIV, hepatitis C virus (HCV), syphilis, gonorrhea, and chlamydia, in a large, academic ED. Methods: This was a single-center, retrospective cross-sectional study of ED patients tested for HIV, HCV, syphilis, gonorrhea or chlamydia between November 27, 2018–May 26, 2019. In 2018, the study institution implemented an ED-based infectious diseases screening program in which any patient being tested for gonorrhea/chlamydia was eligible for opt-out syphilis screening, and any patient 18–64 years who was having blood drawn for any clinical purpose was eligible for opt-out HIV and HCV screening. We analyzed data from all ED patients ≥13 years who had undergone STI testing. The outcomes of interest included prevalence of STI testing/co-testing and the prevalence of STI infection/co-infection. We describe data with simple descriptive statistics. Results: During the study period there were 30,767 ED encounters for patients ≥13 years (mean age: 43 ± 14 years, 52% female), and 7,866 (26%) were tested for at least one of HIV, HCV, syphilis, gonorrhea, or chlamydia. We observed the following testing frequencies (and prevalence of infection): HCV, 7,539 (5.0%); HIV, 7,359 (0.9%); gonorrhea, 574 (6.1%); chlamydia, 574 (9.8%); and syphilis, 420 (10.5%). Infectious etiologies with universal testing protocols (HIV and HCV) made up the majority of STI testing. In patients with syphilis, co-infection with chlamydia (21%, 9/44) and HIV (9%, 4/44) was high. In patients with gonorrhea, co-infection with chlamydia (23%, 8/35) and syphilis (9%, 3/35) was high, and in patients with chlamydia, co-infection with syphilis (16%, 9/56) and gonorrhea (14%, 8/56) was high. Patients with HCV had low co-infection proportions (

The synthesis of heavy elements in supernovae is affected by low-energy (n,p) and (p,n) reactions on unstable nuclei, yet experimental data on such reaction rates are scarce. The SECAR (SEparator for CApture Reactions) recoil separator at FRIB (Facility for Rare Isotope Beams) was originally designed to measure astrophysical reactions that change the mass of a nucleus significantly. We used a novel approach that integrates machine learning with ion-optical simulations to find an ion-optical solution for the separator that enables the measurement of (p,n) reactions, despite the reaction leaving the mass of the nucleus nearly unchanged. A new measurement of the ^{58}Fe(p,n)^{58}Co reaction in inverse kinematics with a 3.66±0.12 MeV/nucleon ^{58}Fe beam (corresponding to 3.69±0.12 MeV proton energy in normal kinematics) yielded a cross-section of 20.3±6.3 mb and served as a proof of principle experiment for the new technique demonstrating its effectiveness in achieving the required performance criteria. This novel approach paves the way for studying astrophysically important (p,n) reactions on unstable nuclei produced at FRIB.

Abstract Current eddy‐permitting and eddy‐resolving ocean models require dissipation to prevent a spurious accumulation of enstrophy at the grid scale. We introduce a new numerical scheme for momentum advection in large‐scale ocean models that involves upwinding through a weighted essentially non‐oscillatory (WENO) reconstruction. The new scheme provides implicit dissipation and thereby avoids the need for an additional explicit dissipation that may require calibration of unknown parameters. This approach uses the rotational, “vector invariant” formulation of the momentum advection operator that is widely employed by global general circulation models. A novel formulation of the WENO “smoothness indicators” is key for avoiding excessive numerical dissipation of kinetic energy and enstrophy at grid‐resolved scales. We test the new advection scheme against a standard approach that combines explicit dissipation with a dispersive discretization of the rotational advection operator in two scenarios: (a) two‐dimensional turbulence and (b) three‐dimensional baroclinic equilibration. In both cases, the solutions are stable, free from dispersive artifacts, and achieve increased “effective” resolution compared to other approaches commonly used in ocean models.

Abstract Unusually large and enigmatic giant magnetofossils are well-documented in sediments deposited during and surrounding climatic events such as the Paleocene-Eocene Thermal Maximum (~56 Ma) and Middle Eocene Climatic Optimum (~40 Ma). However, the absence of giant magnetofossil modern analogues raises intriguing questions about their origin and formation mechanism. In this study, we report the discovery of giant magnetofossils within late Quaternary sediments retrieved from the Bay of Bengal (BoB), the youngest giant magnetofossils yet reported. First-order reversal curve diagrams of BoB sediments display a central ridge feature, a characteristic magnetic signature of non-interacting single domain magnetofossils. Scanning electron microscopy examinations reveal giant magnetofossils with needle, spindle, bullet, and spearhead shapes. We use high-resolution transmission electron microscopy, with electron diffraction and energy dispersive spectrometry, to confirm their distinctive morphologies and magnetite crystal structure. Our environmental magnetic and geochemical data suggest that an influx of fluvially derived reactive iron and organic carbon, combined with persistent suboxic conditions, supported the proliferation of giant magnetofossil-producing organisms. The discovery of a modern analogue to ancient giant magnetofossils expands our understanding of their temporal distribution within the geological record and is a promising step toward elucidating the nature of the organisms responsible for their formation.

Abstract The psychosocial underpinnings of vaccine hesitancy are complex. Research is needed to pinpoint the exact reasons why people hesitate to vaccinate themselves or their children against vaccine-preventable diseases. One possible reason are concerns that arise from a misunderstanding of vaccine science. We examined the impact of scientific reasoning on vaccine hesitancy and human papillomavirus (HPV) vaccination intent through a cross-sectional study of parents of vaccine-eligible children (N = 399) at immunization clinics in Shanghai, China. We assessed the relationship between science reasoning and both vaccine hesitancy and HPV vaccine acceptance using general additive models. We found a significant association between scientific reasoning and education level, with those with less than a high school education having a significantly lower scientific reasoning that those with a college education (ß = -1.31, p-value = 0.002). However, there was little evidence of a relationship between scientific reasoning and vaccine hesitancy. Scientific reasoning therefore appears not to exert primary influence on the formation of vaccine attitudes among the respondents surveyed. We suggest that research on vaccine hesitancy continues working to identify the styles of reasoning parents engage in when determining whether or not to vaccinate their children. This research could inform the development and implementation of tailored vaccination campaigns.

Invasive fungal infections pose significant morbidity and mortality risks, particularly those caused by moulds. Available antifungal classes are limited by toxicities and are increasingly susceptible to resistance, particularly amongst challenging fungal pathogens. The purpose of this case series and literature review was to characterize the use of a high-dose lipid formulation of amphotericin B. A case series is presented including patients who received high-dose lipid formulation amphotericin B (≥7.5 mg/kg/day) between June 2012 and August 2021. Additionally, a systematic literature review was conducted by searching the PubMed database for English-language studies involving individuals who received high-dose amphotericin B therapy (≥7.5 mg/kg) using lipid formulations. Nine patients were included in the case series, receiving an average of 8.9 ± 1.3 mg/kg liposomal amphotericin B over a mean of 11.0 ± 10.8 days predominantly for mould infections including Mucorales, aspergillosis and Fusarium. The patients were primarily cared for in intensive care units, with varying treatment histories and outcomes. A total of 11 studies (n=260 patients) met inclusion criteria for the literature review. Responses to high-dose liposomal amphotericin B ranged from 8% to 100%, often showing favourable outcomes. High doses of liposomal amphotericin B were well tolerated both in the case series and in published literature, with serum creatinine changes being the most commonly reported adverse event. However, multi-patient studies continue to report less than favourable (range 8–62%) response rates. High-dose liposomal amphotericin B, either alone or in combination with other antifungal agents, might be a viable strategy for managing invasive fungal infections when few treatment choices exist. This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections

Cyrtandra obliquifolia K.R. Wood & W.L. Wagner (Gesneriaceae), a new shrub species known only from Kaua‘i, Hawaiian Islands, is described and illustrated with notes on its distribution, ecology, and conservation status. The new species is morphologically most similar to Cyrtandra wawrae C.B. Clarke but differs by its unique combination of oblique, non-peltate, auriculate leaf bases, more deeply divided calyx lobes, inflorescence with fewer flowers and lacking profusely umbellate cymes. Cyrtandra obliquifolia is known from only two localities which have undergone severe habitat degradation from landslides and invasive plants and animals and is determined to be Critically Endangered (CR) when evaluated under IUCN criteria.

Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis worldwide, primarily transmitted through contaminated water and food. In patients with chronic liver disease (CLD), HEV infection might worsen the prognosis. This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in CLD patients. A decision tree–Markov cohort model was used to assess the cost-effectiveness of universal-vaccination, vaccination-following-screening, and no-vaccination strategies in 100,000 CLD patients over their lifetimes, simulating cohorts aged ≥16 years, ≥40 years, and ≥60 years, based on the licensed vaccination ages and typical ages of CLD onset, from a societal perspective. Model parameters were retrieved and estimated from previous publications and government data. The outcomes included HEV-related cases, costs, and the incremental cost-effectiveness ratio (ICER). Compared to no-vaccination, universal-vaccination reduced HEV-related cases by 32.8% to 39.6%, while vaccination-following-screening reduced them by 38.1% to 49.3%. Furthermore, universal-vaccination showed ICERs of USD 6898.33, USD 6638.91, and USD 6582.69 per quality-adjusted life year (QALY) for cohorts aged ≥16, ≥40, and ≥60 years, respectively. Moreover, the vaccination-following-screening strategy significantly enhanced cost-effectiveness, with ICERs decreasing to USD 6201.55, USD 5199.46, and USD 4919.87 per QALY for the cohorts. Additionally, one-way sensitivity analysis identified the discount rate and utility for CLD patients as the key factors influencing ICER. Probabilistic sensitivity analysis indicated the vaccination-following-screening strategy was cost-effective with probabilities of 92.50%, 95.70%, and 95.90% for each cohort. Hepatitis E vaccination in CLD patients costs less than GDP per capita for each QALY gained in China. The vaccination-following-screening strategy may be the optimal option, especially in those over 60 years.

Abstract Background The evening primrose family (Onagraceae) includes 664 species (803 taxa) with a center of diversity in the Americas, especially western North America. Ongoing research in Onagraceae includes exploring striking variation in floral morphology, scent composition, and breeding system, as well as the role of these traits in driving diversity among plants and their interacting pollinators and herbivores. However, these efforts are limited by the lack of a comprehensive, well-resolved phylogeny. Previous phylogenetic studies based on a few loci strongly support the monophyly of the family and the sister relationship of the two largest tribes but fail to resolve several key relationships. Results We used a target enrichment approach to reconstruct the phylogeny of Onagraceae using 303 highly conserved, low-copy nuclear loci. We present a phylogeny for Onagraceae with 169 individuals representing 152 taxa sampled across the family, including extensive sampling within the largest tribe, Onagreae. Deep splits within the family are strongly supported, whereas relationships among closely related genera and species are characterized by extensive conflict among individual gene trees. Conclusions This phylogenetic resource will augment current research projects focused throughout the family in genomics, ecology, coevolutionary dynamics, biogeography, and the evolution of characters driving diversification in the family.

Abstract Background Sexually transmitted infections (STIs) like chlamydia, gonorrhea, syphilis, and trichomoniasis contribute significantly to global morbidity and mortality. Researchers are pursuing vaccines for these STIs, and a clinical trial is currently underway for a chlamydia vaccine. However, there is little research available on individuals’ willingness to receive chlamydia, gonorrhea, syphilis, and trichomoniasis vaccines. The purpose of this analysis was to map the existing literature we have on individuals’ willingness to receive these bacterial/parasitic STI vaccines and understand what information on vaccine acceptability is still needed. Methods We searched seven databases for literature on STI vaccine acceptability, then conducted title/abstract and full-text reviews to assess eligibility. All reviews and abstractions were conducted blindly by two reviewers, with discrepancies settled by discussion or the input of a third reviewer. Results Eight of the original 2,259 texts of interest met inclusion criteria. After data abstraction, we found that gonorrhea was the most commonly examined, followed by chlamydia and syphilis. Trichomoniasis vaccine acceptability was not reported. Most texts reported high acceptability, but there did not appear to be data describing how vaccine characteristics affect acceptability. Similarly, while the literature covers a variety of populations, most of the study populations were based out of the United States or Canada and were patrons of healthcare facilities or participants from a larger health intervention study. Therefore, more information is needed on populations outside North America, and on groups with lower healthcare access and utilization. Conclusion As the incidence of bacterial and parasitic STIs increase, and as we grow nearer vaccines for these illnesses, understanding how likely the public is to accept and receive these vaccines is crucial to their success. While the existing literature describes STI vaccine acceptability in a variety of populations, their overall number is small. More research into STI vaccine acceptability outside of North America, and especially examining how factors like number of doses, timing, and cost influence vaccine acceptability is needed to ensure effective future vaccine rollouts.

Background: Exposure to breast surgical oncology (BSO) and the multidisciplinary management of patients with breast cancer is limited in medical school. The purpose of this study was to assess changes in student perceptions of BSO as a career following an interactive multidisciplinary workshop. Methods: Pre-clinical medical students participated in a multidisciplinary, hands-on workshop, composed of breast radiology (BR), breast surgical oncology (BSO) and breast plastic reconstructive surgery (B-PRS). BR presented students screening and diagnostic breast imaging followed by hands-on ultrasound-guided biopsy on phantom simulators. BSO demonstrated lumpectomy, mastectomy, sentinel lymph node biopsy, and axillary lymph node dissections while B-PRS demonstrated oncoplastic techniques and autologous flap reconstruction with cadavers. Pre-and post-workshop surveys assessed student opinions on surgery and BSO. Results were compared using Wilcoxon Signed Rank, Wilcoxon Rank Sum, and Fisher's Exact. Results: The workshop was attended by twenty-four students. There was a statistically significant increase in interest in BSO from 52% to 86% after the workshop (p = 0.003). The event improved understanding of the work and lifestyle in BSO for 79% (19/24). All students (100%) expressed interest to further explore BSO. The most common attractors to a career in BSO were impacts on patients’ lives (N = 23), intellectual stimulation (N = 22), and earnings (N = 20). The most reported deterrents were lack of personal time (N = 18) and stress (N = 15). Conclusion: An interactive, anatomically based exposure to multidisciplinary breast cancer surgery improves medical student perception and interest in BSO. Medical schools should consider incorporating similar events to foster interest in BSO and other surgical subspecialties.

Abstract Southern giant petrels (Macronectes giganteus) are important consumers that range across the oceans throughout the southern hemisphere. In Argentina, previous studies have shown they eat primarily pinnipeds and penguins, which they are assumed to scavenge, although there are occasional anecdotes of them attacking living penguins. Here we describe a predation attempt by a trio of southern giant petrels on a molting adult Magellanic penguin (Spheniscus magellanicus) at the large colony at Punta Tombo, Argentina. We relate giant petrel attendance patterns at the colony to the penguins' phenology, showing how giant petrel numbers rise with the increasing prevalence of vulnerable penguins. We suggest that living penguins—both fledglings and adults—may constitute a more seasonally significant proportion of the giant petrel diet than previously assumed, and their capture may represent a specialized predation technique.

In 2018, the US Congress enacted a policy permitting Medicare Advantage (MA) plans to cover telehealth services in a beneficiary’s home and through audio-only means as part of the basic benefit package of services, where prior to the policy change such benefits were only allowed to be covered as a supplemental benefit. MA plans were afforded 2 years of lead time for strategizing, negotiating, and capital investment prior to the start date (January 1, 2020) of the new coverage option. Our data analysis found basic benefit telehealth was offered by plans comprising 71% of enrollment in 2020 and increased to 95% in 2021. At the same time, remote access telehealth was offered as a supplemental benefit for 69% of enrollees in 2020, a decrease of 23% compared to 2019. These efforts by MA plans may have enabled traditional Medicare (TM) to leverage an existing telehealth infrastructure as a solution to the access issues created by public health policies requiring sheltering in place and social distancing during the COVID-19 pandemic. The success of this MA policy prompts consideration of additional flexibility beyond the standard basic benefit package, and whether such benefits reduce costs while improving access and/or outcomes in the context of a managed care environment like MA. Subject to oversight, such flexibility could potentially improve value in MA, and facilitate future changes in TM, as appropriate.

Multispectral optoacoustic tomography (MSOT) allows non-invasive molecular disease activity assessment in adults with inflammatory bowel disease (IBD). In this prospective pilot-study, we investigated, whether increased levels of MSOT haemoglobin parameters corresponded to inflammatory activity in paediatric IBD patients, too. 23 children with suspected IBD underwent MSOT of the terminal ileum and sigmoid colon with standard validation (e.g. endoscopy). In Crohn`s disease (CD) and ulcerative colitis (UC) patients with endoscopically confirmed disease activity, MSOT total haemoglobin (HbT) signals were increased in the terminal ileum of CD (72.1 ± 13.0 a.u. vs. 32.9 ± 15.4 a.u., p = 0.0049) and in the sigmoid colon of UC patients (62.9 ± 13.8 a.u. vs. 35.1 ± 16.3 a.u., p = 0.0311) as compared to controls, respectively. Furthermore, MSOT haemoglobin parameters correlated well with standard disease activity assessment (e.g. SES-CD and MSOT HbT (rs =0.69, p = 0.0075). Summarizing, MSOT is a novel technology for non-invasive molecular disease activity assessment in paediatric patients with inflammatory bowel disease.

Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach. While US provides morphologic information, SWL-OAI visualizes the absorption of pulsed laser light and the resulting sound waves from molecules undergoing thermoelastic expansion. US/SWL-OAI was compared to multispectral data, clinical disease severity, angiographic findings, phantom experiments, and histological examinations from calf muscle biopsies. We were able to show that synergistic use of US/SWL-OAI is most likely to map clinical degeneration of the muscle and progressive PAD.

Mobile air pollution measurements have the potential to provide a wide range of insights into emission sources and air pollution exposure. The analysis of mobile data is, however, highly challenging. In this work we develop a new regression-based framework for the analysis of mobile data with the aim of improving the potential to draw inferences from such measurements. A quantile regression approach is adopted to provide new insight into the distribution of NOx and CO emissions in Central and Outer London. We quantify the emissions intensity of NOx and CO (ΔNOx/ΔCO2 and ΔCO/ΔCO2) at different quantile levels (τ) to demonstrate how transient high-emission events can be examined in parallel to the average emission characteristics. We observed a clear difference in the emissions behaviour between both locations. On average, the median (τ = 0.5) ΔNOx/ΔCO2 in Central London was 2x higher than Outer London, despite the stringent emission standards imposed throughout the Ultra Low Emissions Zone. A comprehensive vehicle emission remote sensing data set (n ≈ 700,000) is used to put the results into context, providing evidence of vehicle behaviour which is indicative of poorly controlled emissions, equivalent to high-emitting classes of older vehicles. Our analysis suggests the coupling of a diesel-dominated fleet with persistently congested conditions, under which the operation of emissions after-treatment technology is non-optimal, leads to increased NOx emissions.

COVID-19 vaccination rates for children globally are relatively low. This study aimed to investigate parental vaccine hesitancy and parents' acceptance of a COVID-19 for their children for their children in the United States, China, Taiwan, India, Indonesia, and Malaysia.We analyzed data from an opt-in, internet-based cross-sectional study (n = 23,940). Parents were asked about their acceptance of a COVID-19 vaccine for their children, and if they would accept the vaccine with different risk and effectiveness profiles for themselves. Poisson regression was used to generate prevalence ratios (PR) of the relationship between vaccine acceptance for a child and vaccine profile, by country and waves and overall. Between August 2020 and June 2021, COVID-19 vaccine acceptance for children decreased in the United States (89% to 72%) and Taiwan (79% to 71%), increased in India (91% to 96%) and Malaysia (81% to 91%), and was stable in Indonesia (86%) and China (at 87%-90%). Vaccine risk and effectiveness profiles did not consistently affect parent's acceptance of a COVID-19 vaccine for their children. Instead, being not hesitant was a large driver of vaccine acceptance (PR: 1.24, 95% CI: 1.14, 1.36). Adolescent COVID-19 vaccination have already been established in many high and middle-income countries, but our study suggests that there is a movement of vaccine hesitancy which could impede the success of future pediatric and adolescent COVID-19 vaccination programs.

In the neonatal intensive care unit, adequate nutrition requires various enteral products, including human milk and formula. Human milk is typically fortified to meet increased calorie goals, and infants commonly receive vitamin mixes, iron supplements, and less frequently, thickening agents. We examined the growth of 16 commensal microbes and 10 pathobionts found in the premature infant gut and found that formula, freshly pasteurized milk, and donated banked milk generally increased bacterial growth. Fortification of human milk significantly elevated the growth of all microbes. Supplementation with thickeners or NaCl in general did not stimulate additional growth. Vitamin mix promoted the growth of several commensals, while iron promoted growth of pathobionts. These data indicate that pathobionts in the preterm gut have significant growth advantage with preterm formula, fortified donor milk, and supplemented iron and suggest that the choice of milk and supplements may impact the infant gut microbiota.

In April 2021, the US paused Janssen (J&J) COVID-19 vaccination because of reported blood clots post vaccination. This paper explores how vaccine decision-making--receiving a J&J vaccine right away vs waiting for a Pfizer vaccine--changed during the pause. In an opt-in internet-based survey April 2021 with 915 participants, 37 % were not vaccinated. Of these, 18 % would accept a J&J vaccine, 5 % would wait 1 month for a Pfizer vaccine, 25 % would wait 3 months, and 52 % would not want any vaccine. Among the unvaccinated, 56 % had heard of blood clots; 61 % of these did not want any vaccine, compared to 41 % of those who had not heard of blood clots. Moreover, among those vaccine hesitant in general, 11 % would still obtain a J&J vaccine if offered right away. These findings may suggest spillover of brand-specific adverse event concerns to the vaccine product as a whole.

Introduction: Diabetes and depression may present concurrently, and clinical pharmacists are well equipped to manage these conditions. Clinical pharmacists were grant funded to implement a diabetes-focused randomized controlled trial in a Federally Qualified Health Center. The objective of this analysis is to evaluate if glycemic control and depressive symptoms improve for patients with diabetes and depression with additional management from clinical pharmacists compared with those receiving the standard of care. Methods: This is a post hoc subgroup analysis of a diabetes-focused randomized controlled trial. Pharmacists enrolled patients with type 2 diabetes mellitus (T2DM) and a glycated hemoglobin (A1C) greater than 8% and randomly assigned them to 1 of 2 cohorts, one managed by the primary care provider alone and one with additional care from the pharmacist. Pharmacists completed encounters with patients who have T2DM with or without depression to comprehensively optimize pharmacotherapy while tracking glycemic and depressive outcomes throughout the study. Results: A1C improved from baseline to 6 months in patients with depressive symptoms who received additional care from pharmacists by -2.4 percentage points (SD, 2.41) compared with a -0.1 percentage point (SD, 1.78) reduction in the control arm (P .0081), and there was no change in depressive symptoms. Discussion: Patients with T2DM and depressive symptoms experienced better diabetes outcomes with additional pharmacist management compared with a similar cohort of patients with depressive symptoms, managed independently by primary care providers. These patients with diabetes and comorbid depression received a higher level of engagement and care from the pharmacists, which led to more therapeutic interventions.