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The vast majority of gene mutations and/or gene knockouts result in either no observable changes, or significant deficits in molecular, cellular, or organismal function. However, in a small number of cases, mutant animal models display enhancements in specific behaviors such as learning and memory. To date, most gene deletions shown to enhance cognitive ability generally affect a limited number of pathways such as NMDA receptor- and translation-dependent plasticity, or GABA receptor- and potassium channel-mediated inhibition. While endolysosomal trafficking of AMPA receptors is a critical mediator of synaptic plasticity, mutations in genes that affect AMPAR trafficking either have no effect or are deleterious for synaptic plasticity, learning and memory. NSG2 is one of the three-member family of Neuron-specific genes (NSG1-3), which have been shown to regulate endolysosomal trafficking of a number of proteins critical for neuronal function, including AMPAR subunits (GluA1-2). Based on these findings and the largely universal expression throughout mammalian brain, we predicted that genetic knockout of NSG2 would result in significant impairments across multiple behavioral modalities including motor, affective, and learning/memory paradigms. However, in the current study we show that loss of NSG2 had highly selective effects on associative learning and memory, leaving motor and affective behaviors intact. For instance, NSG2 KO animals performed equivalent to wild-type C57Bl/6n mice on rotarod and Catwalk motor tasks, and did not display alterations in anxiety-like behavior on open field and elevated zero maze tasks. However, NSG2 KO animals demonstrated enhanced recall in the Morris water maze, accelerated reversal learning in a touch-screen task, and accelerated acquisition and enhanced recall on a Trace Fear Conditioning task. Together, these data point to a specific involvement of NSG2 on multiple types of associative learning, and expand the repertoire of pathways that can be targeted for cognitive enhancement.

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OBJECTIVE: Posttraumatic stress disorder (PTSD) has been linked to deficits in executive functioning, but the literature suggests these associations are inconsistent. Results vary depending on the task used, test modality, and the specific subdomain being measured, such as inhibitory control (interference resolution, response inhibition) or set shifting (task switching, rule switching). Notably, deficits are more consistently observed in computerized tasks that measure precise reaction times (RTs) than in classic paper-and-pencil measures, but few studies have parsed specific executive functioning deficits in PTSD using detailed analyses of RT data. METHOD: The present study used a cued-switching Stroop Task to examine both interference resolution and task switching in 28 veterans with PTSD and 28 age-matched controls. Each trial required attending to a randomly presented cue and responding to the specified target while ignoring irrelevant or opposing information. Analyses of RT distributions estimated both Gaussian (normal) and ex-Gaussian (exponential) parameters. RESULTS: Veterans with PTSD had slower and more variable RTs than the controls on trials that required ignoring conflicting information (interference resolution, d' = .68). These effects were confined to the normal distribution, not to excessively slow responses (as estimated by ex-Gaussian parameters). Veterans with PTSD also showed modestly slower RTs on trials that required switching between cues, but Bayesian evidence for this was weak, and measures by ex-Gaussian parameters were not significant. CONCLUSIONS: These results highlight the importance of examining executive functioning in PTSD with a more nuanced approach, as clarity around these deficits may have important implications for future intervention and rehabilitation strategies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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The Global Biodiversity Framework (GBF), signed in 2022 by Parties to the Convention on Biological Diversity, recognized the importance of area-based conservation, and its goals and targets specify the characteristics of protected and conserved areas (PCAs) that disproportionately contribute to biodiversity conservation. To achieve the GBF's target of conserving a global area of 30% by 2030, this Essay argues for recognizing these characteristics and scaling them up through the conservation of areas that are: extensive (typically larger than 5,000 km2); have interconnected PCAs (either physically or as part of a jurisdictional network, and frequently embedded in larger conservation landscapes); have high ecological integrity; and are effectively managed and equitably governed. These areas are presented as "Nature's Strongholds," illustrated by examples from the Congo and Amazon basins. Conserving Nature's Strongholds offers an approach to scale up initiatives to address global threats to biodiversity.

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Sexual health is a concern that often goes unaddressed among female cancer survivors. Management of these issues depends upon the type of malignancy, stage and other tumor characteristics, treatment, and the history, concerns, and goals of the individual patient.

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Although most studies have shown that newcomers benefit from proactive behaviors, these behaviors are not always viewed positively by colleagues, resulting in negative consequences for newcomers. Drawing on uncertainty reduction and social cognitive theories, we contend that newcomer proactive behaviors are viewed positively by competent leaders and peers but negatively by those with low competence. Further, we argue that newcomer proactive behaviors impact leader and peer threat perceptions, affecting subsequent workplace relationships, which in turn influence newcomer voluntary turnover. We empirically test our hypotheses in a three-time multisource study, utilizing a sample of 377 newcomers, 132 leaders, and 721 peers. Supporting our hypotheses, when leaders and peers are less competent, newcomer proactive behaviors, through impacting leader and peer threat perceptions, result in lower quality relationships with leaders and peers. These cascading effects positively correlate with newcomer voluntary turnover. Conversely, opposite effects arise for more competent leaders and peers. Implications of how newcomer proactive behaviors impact workplace relationships and turnover are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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The robust control of genotoxic N-nitrosamine (NA) impurities is an important safety consideration for the pharmaceutical industry, especially considering recent drug product withdrawals. NAs belong to the 'cohort of concern' list of genotoxic impurities (ICH M7) because of the mutagenic and carcinogenic potency of this chemical class. In addition, regulatory concerns exist regarding the capacity of the Ames test to predict the carcinogenic potential of NAs because of historically discordant results. The reasons postulated to explain these discordant data generally point to aspects of Ames test study design. These include vehicle solvent choice, liver S9 species, bacterial strain, compound concentration, and use of pre-incubation versus plate incorporation methods. Many of these concerns have their roots in historical data generated prior to the harmonization of Ames test guidelines. Therefore, we investigated various Ames test assay parameters and used qualitative analysis and quantitative benchmark dose modelling to identify which combinations provided the most sensitive conditions in terms of mutagenic potency. Two alkyl-nitrosamines, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) were studied. NDMA and NDEA mutagenicity was readily detected in the Ames test and key assay parameters were identified that contributed to assay sensitivity rankings. The pre-incubation method (30-min incubation), appropriate vehicle (water or methanol), and hamster-induced liver S9, alongside Salmonella typhimurium strains TA100 and TA1535 and Escherichia coli strain WP2uvrA(pKM101) provide the most sensitive combination of assay parameters in terms of NDMA and NDEA mutagenic potency in the Ames test. Using these parameters and further quantitative benchmark dose modelling, we show that N-nitrosomethylethylamine (NMEA) is positive in Ames test and therefore should no longer be considered a historically discordant NA. The results presented herein define a sensitive Ames test design that can be deployed for the assessment of NAs to support robust impurity qualifications.

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Chronic graft-versus-host disease is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 U.S. Food and Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of chronic graft-versus-host disease. Part II discusses disease grading and therapeutic management.

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Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 Federal Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of cGVHD. Part II discusses disease grading and therapeutic management.

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BACKGROUND: While it is established that video monitoring technology (compared with the use of in-person sitters) is a safe and cost-effective solution for hospitals, little is known about the impact of these approaches on nurses' stress and well-being. PURPOSE: To compare the use of video monitoring technology and in-person sitters (likely a resource reallocated from nurses) for monitoring patients on nurses' emotional labor and burnout. METHOD: An experience sampling method was conducted by surveying nurses twice a day for 3 weeks, resulting in 524 survey administrations provided by 74 nurses. The surveys included measures of daily video monitoring technology and in-person sitter use, emotional labor, emotional exhaustion, and nurse career commitment. FINDINGS: There were positive effects from video monitoring technology and negative effects of in-person sitters on emotional labor and emotional exhaustion, particularly for nurses lower in commitment. DISCUSSION: Hospital adoption of video monitoring technology has a positive impact on nurses compared with in-person sitter use.

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Quantifying the strength and efficiency of the Southern Ocean biological carbon pump (BCP) and its response to predicted changes in the Earth's climate is fundamental to our ability to predict long-term changes in the global carbon cycle and, by extension, the impact of continued anthropogenic perturbation of atmospheric CO2. There is little agreement, however, in climate model projections of the sensitivity of the Southern Ocean BCP to climate change, with a lack of consensus in even the direction of predicted change, highlighting a gap in our understanding of a major planetary carbon flux. In this review, we summarize relevant research that highlights the important role of fine-scale dynamics (both temporal and spatial) that link physical forcing mechanisms to biogeochemical responses that impact the characteristics of the seasonal cycle of phytoplankton and by extension the BCP. This approach highlights the potential for integrating autonomous and remote sensing observations of fine scale dynamics to derive regionally optimized biogeochemical parameterizations for Southern Ocean models. Ongoing development in both the observational and modelling fields will generate new insights into Southern Ocean ecosystem function for improved predictions of the sensitivity of the Southern Ocean BCP to climate change. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

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The biological carbon pump (BCP) in the Southern Ocean is driven by phytoplankton productivity and is a significant organic matter sink. However, the role of particle-attached (PA) and free-living (FL) prokaryotes (bacteria and archaea) and their diversity in influencing the efficiency of the BCP is still unclear. To investigate this, we analyzed the metagenomes linked to suspended and sinking marine particles from the Sub-Antarctic Southern Ocean Time Series (SOTS) by deploying a Marine Snow Catcher (MSC), obtaining suspended and sinking particulate material, determining organic carbon and nitrogen flux, and constructing metagenome-assembled genomes (MAGs). The suspended and sinking particle-pools were dominated by bacteria with the potential to degrade organic carbon. Bacterial communities associated with the sinking fraction had more genes related to the degradation of complex organic carbon than those in the suspended fraction. Archaea had the potential to drive nitrogen metabolism via nitrite and ammonia oxidation, altering organic nitrogen concentration. The data revealed several pathways for chemoautotrophy and the secretion of recalcitrant dissolved organic carbon (RDOC) from CO2, with bacteria and archaea potentially sequestering particulate organic matter (POM) via the production of RDOC. These findings provide insights into the diversity and function of prokaryotes in suspended and sinking particles and their role in organic carbon/nitrogen export in the Southern Ocean. IMPORTANCE The biological carbon pump is crucial for the export of particulate organic matter in the ocean. Recent studies on marine microbes have shown the profound influence of bacteria and archaea as regulators of particulate organic matter export. Yet, despite the importance of the Southern Ocean as a carbon sink, we lack comparable insights regarding microbial contributions. This study provides the first insights regarding prokaryotic contributions to particulate organic matter export in the Southern Ocean. We reveal evidence that prokaryotic communities in suspended and sinking particle fractions harbor widespread genomic potential for mediating particulate organic matter export. The results substantially enhance our understanding of the role played by microorganisms in regulating particulate organic matter export in suspended and sinking marine fractions in the Southern Ocean.

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INTRODUCTION: Children's physical activity, especially play, is important for healthy physical, social, and psychological development. Playgrounds are public spaces for children, but not all playgrounds are conducive to play and physical activity. We examined "playability," the ability of a space to promote active play, and associations with moderate-to-vigorous physical activity (MVPA) and energy expenditure. METHODS: This cross-sectional study assessed playground features with the Play Space Audit Tool; we calculated playability scores from audit data, overall and by domain (general amenities, surface, path, and play structure), from playgrounds in 70 parks in Chicago, Illinois, in 2017. We observed 2,712 individuals during the audits and used the System for Observing Play and Recreation in Communities tool to assess MVPA and energy expenditure. We used generalized estimating equation negative binomial regression to calculate incidence rate ratios for MVPA and mixed effects models to calculate energy expenditure (in kcal/kg/min) associated with playability scores. RESULTS: General amenities and play structure scores were associated with 1.28 (95% CI, 1.08-1.52) and 1.15 (95% CI, 1.00-1.31) times as many individuals (any age) engaged in MVPA, respectively. The general amenities score was significantly associated with 0.51 (95% CI, 0.24-0.79) and 0.42 (95% CI, 0.15-0.68) higher energy expenditure in renovated playgrounds and in all playgrounds, respectively. CONCLUSION: Overall, general amenities and play structure scores were associated with MVPA and were robust to adjustment for weather, neighborhood socioeconomic characteristics, and crime. These playground playability indices may strengthen future evaluations of community infrastructure for children's physical activity.

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The Southern Ocean is a major sink of anthropogenic CO2 and an important foraging area for top trophic level consumers. However, iron limitation sets an upper limit to primary productivity. Here we report on a considerably dense late summer phytoplankton bloom spanning 9000 km2 in the open ocean of the eastern Weddell Gyre. Over its 2.5 months duration, the bloom accumulated up to 20 g C m-2 of organic matter, which is unusually high for Southern Ocean open waters. We show that, over 1997-2019, this open ocean bloom was likely driven by anomalies in easterly winds that push sea ice southwards and favor the upwelling of Warm Deep Water enriched in hydrothermal iron and, possibly, other iron sources. This recurring open ocean bloom likely facilitates enhanced carbon export and sustains high standing stocks of Antarctic krill, supporting feeding hot spots for marine birds and baleen whales.

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Southern Ocean primary productivity is principally controlled by adjustments in light and iron limitation, but the spatial and temporal determinants of iron availability, accessibility, and demand are poorly constrained, which hinders accurate long-term projections. We present a multidecadal record of phytoplankton photophysiology between 1996 and 2022 from historical in situ datasets collected by Biogeochemical Argo (BGC-Argo) floats and ship-based platforms. We find a significant multidecadal trend in irradiance-normalized nonphotochemical quenching due to increasing iron stress, with concomitant declines in regional net primary production. The observed trend of increasing iron stress results from changing Southern Ocean mixed-layer physics as well as complex biological and chemical feedback that is indicative of important ongoing changes to the Southern Ocean carbon cycle.

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OBJECTIVES: As the aging population increases, it is critical to find ways to sustain older adults' health and well-being. Mindfulness-Based Stress Reduction (MBSR) may be one approach, but its effects are difficult to discern because few studies have conducted randomized controlled trials with an active control group and blinded examiners. We begin to address these gaps with a pilot study examining the feasibility of conducting an MBSR intervention with an active control condition in healthy older adults. METHODS: Participants were randomly assigned to one of two classes, MBSR or Brain Health education. Classes were matched for time, format, and instructor. The study examined acceptability, practicality, implementation, and preliminary efficacy using a range of participant questionnaires, instructor ratings, cognitive measures assessed by blinded examiners, and attendance. RESULTS: Both MBSR and the Brain Health class evidenced high rates of recruitment, participant satisfaction, and retention. Implementation procedures were successful, and preliminary results revealed similar levels of efficacy across both classes. CONCLUSIONS: This study demonstrates the feasibility of an MBSR intervention in healthy older adults. CLINICAL IMPLICATIONS: MBSR, with its focus on improving stress and self-awareness, has the potential to be an approach that can improve aging adults' health and coping skills.

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INTRODUCTION: Loneliness is a powerful predictor of several medical and psychiatric conditions that are highly prevalent in Veterans, including depression and PTSD. Despite this, few studies have examined loneliness in Veterans or how best to intervene upon Veteran loneliness. Additional empirical research is needed in these areas in order to define clear intervention targets and improve Veteran care. MATERIALS AND METHODS: In this pilot study, we used 62 Veterans' self-reported loneliness and symptoms of post-traumatic stress to examine whether specific symptom clusters of post-traumatic stress were associated with greater loneliness. Post-traumatic stress was measured using the PTSD Checklist for DSM-5, and responses were further parsed into four symptom clusters: intrusions, avoidance, negative alterations in mood and cognition (excluding the social withdrawal item), and alterations in arousal and reactivity. RESULTS: Results revealed that only the negative alterations in mood and cognition symptom cluster was associated with increased Veteran loneliness, even after adjusting for sociodemographic factors, social isolation, and symptoms of depression. These analyses were also repeated using a subset of our sample (n = 29) who completed repeated measures of the PTSD Checklist. Results again revealed that the same symptom cluster predicted Veteran loneliness over 1 year later. CONCLUSIONS: This pilot study demonstrates the value of a publicly available PTSD measure for identifying lonely Veterans and highlights how reducing negative alterations in mood and cognition may serve as a potentially critical target for future Veteran loneliness interventions.

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OBJECTIVES: Heavy demands upon dementia caregivers can lead to a number of poor health outcomes including declines in physical, mental, and brain health. Although dementia affects people from all backgrounds, research in the US has largely focused on European American caregivers. This has made providing culturally-competent care more difficult. This study begins to address this issue by empirically examining how culturally-shaped beliefs can influence loneliness in family caregivers of people with dementia. METHODS: We conducted a preliminary questionnaire study with Chinese American and European American family caregivers of people with dementia (N = 72). RESULTS: Chinese American caregivers were more concerned than European American caregivers about losing face, which in turn, was associated with greater loneliness. This pattern remained when accounting for caregiver gender, age, and relationship to the person with dementia. CONCLUSIONS: These preliminary findings highlight the role that cultural beliefs can play in adverse caregiver outcomes, and suggest that addressing concerns about losing face may be an important way for healthcare providers to help reduce loneliness among Chinese American caregivers. CLINICAL IMPLICATIONS: Understanding how cultural beliefs influence caregiver outcomes is critical as healthcare professionals work to provide culturally-competent care and design culturally-sensitive interventions.

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This study identifies a unique bias faced by Black employees which makes it challenging for this group to manage their professional image. Integrating research on racial backlash, image management, and expectancy violation theory, we argue that self-promotion by Black employees will result in detrimental outcomes for this group compared to White, Hispanic, and Asian employees. Due to negative racial stereotypes related to their job competence, we hypothesize that self-promotion by Black employees will be viewed by their White managers as a violation of stereotypically appropriate behavior and will result in a backlash in the form of lower job-related outcomes. We propose that the process by which these effects occur is through manager assessments of their employees on agentic and communal traits. Our hypothesized model was tested with a stratified sample of manager-employee dyads of a large financial institution. Results indicated that self-promotion by Black employees was associated with lower job performance and person-organization fit ratings, as well as fewer idiosyncratic deals with their immediate managers compared to White, Hispanic, and Asian employees. Implications of the divergent consequences of self-promotion for Black employees relative to other racial groups are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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Researchers typically study physiological responses either after stimulus onset or when the emotional valence of an upcoming stimulus is revealed. Yet, participants may also respond when they are told that an emotional stimulus is about to be presented even without knowing its valence. Increased physiological responding during this time may reflect a 'preparation for action'. The generation of such physiological responses may be supported by frontotemporal regions of the brain that are vulnerable to damage in frontotemporal lobar degeneration. We examined preparatory physiological responses and their structural and functional neural correlate in five frontotemporal lobar degeneration clinical subtypes (behavioural variant frontotemporal dementia, n = 67; semantic variant primary progressive aphasia, n = 35; non-fluent variant primary progressive aphasia, n = 30; corticobasal syndrome, n = 32; progressive supranuclear palsy, n = 30). Comparison groups included patients with Alzheimer's disease (n = 56) and healthy controls (n = 35). Preparatory responses were quantified as cardiac interbeat interval decreases (i.e. heart rate increases) from baseline to an 'instruction period', during which participants were told to watch the upcoming emotional film but not provided the film's valence. Patients' behavioural symptoms (apathy and disinhibition) were also evaluated via a caregiver-reported measure. Compared to healthy controls and Alzheimer's disease, the frontotemporal lobar degeneration group showed significantly smaller preparatory responses. When comparing each frontotemporal lobar degeneration clinical subtype with healthy controls and Alzheimer's disease, significant group differences emerged for behavioural variant frontotemporal dementia and progressive supranuclear palsy. Behavioural analyses revealed that frontotemporal lobar degeneration patients showed greater disinhibition and apathy compared to Alzheimer's disease patients. Further, these group differences in disinhibition (but not apathy) were mediated by patients' smaller preparatory responses. Voxel-based morphometry and resting-state functional MRI analyses revealed that across patients and healthy controls, smaller preparatory responses were associated with smaller volume and lower functional connectivity in a circuit that included the ventromedial prefrontal cortex and cortical and subcortical regions of the salience network. Diminished preparatory physiological responding in frontotemporal lobar degeneration may reflect a lack of preparation for actions that are appropriate for an upcoming situation, such as approaching or withdrawing from emotional stimuli. The ventromedial prefrontal cortex and salience network are critical for evaluating stimuli, thinking about the future, triggering peripheral physiological responses, and processing and interpreting interoceptive signals. Damage to these circuits in frontotemporal lobar degeneration may impair preparatory responses and help explain often-observed clinical symptoms such as disinhibition in these patients.

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BACKGROUND: Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin. METHODS: Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied. RESULTS: Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, -5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001). CONCLUSIONS: No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.