Investigating the Impact of the Nursing Practice Environment (NPE) on Central Line-Associated Bloodstream Infections (CLABSI) among Older Adults in the Intensive Care Unit (ICU)

Background: Health care–associated infections, resulting from treatment received for medical or surgical conditions in a health care setting, represent a critical public health and patient safety issue, exacting substantial medical, social, and economic costs. The costliest among the leading causes of preventable health care-associated infections is central-line associated bloodstream infections (CLABSI), to which older adults (age 65 years and older) are particularly susceptible, especially during intensive care unit (ICU) stays. A rich body of research has empirically linked the quality of the nursing practice environment (NPE) in hospitals to both positive and negative patient outcomes; yet, surprisingly few studies have sought to examine relations between the hospital NPE and older adult CLABSI outcomes. This study aimed to fill this gap through analysis of de-identified data from the 2011 national Prevention of Nosocomial Infections and Cost-Effectiveness Refined (PNICER) study, provided by the Columbia University School of Nursing. PNICER was a three-year, mixed-methods study aimed at assessing infection prevention efforts at eligible National Healthcare Safety Network hospitals. In the present study, analyses included the following data from 739 PNICER participating hospitals: self-reported data on the organizational work climate—a measure of the NPE—from 1,665 hospital infection preventionists, most of whom were nurses, and data on ICU CLABSI occurrence among 19,383 Medicare patients. Specific research aims included: AIM 1: Investigate the construct validity and test latent constructs of two healthcare organizational work climate instruments—the Leading a Culture of Quality Instrument for Infection Prevention (LCQ-IP) and the Relational Coordination Survey (RCS)—across PNICER-participating hospitals using Exploratory Factor Analysis (EFA). AIM 2: Investigate whether LCQ-IP and RCS instrument items are predictors of hospitalized older adult ICU CLABSI outcomes across PNICER-participating hospitals using multivariate logistic regression. AIM 3: Employ mediation analyses to examine whether LCQ-IP and RCS constructs mediate relations between hospital characteristics and older adult ICU CLABSI outcomes. Methods: Aim 1 analyses involved Exploratory Factor Analysis (EFA) to investigate the construct validity of two PNICER healthcare organizational work climate instruments, the LCQ-IP and RCS. Two LCQ-IP EFA models were run, one including 20 unit-level variables, and one including seven individual-level variables, and an EFA was run on all 28 RCS items. Aim 2 analyses involved multivariate logistic regression to explore relations between eight organizational work climate domains—based on LCQ-IP and RCS factors identified during Aim 1—hospital characteristics, and older adult ICU CLABSI occurrence. A stepwise series of models were run that included various work climate and covariate permutations to assess the relative impact on CLABSI occurrence. Finally, building on findings from Aim 2, Aim 3 analyses employed the Joint Significance Test of mediation to investigate whether three organizational work climate domains identified during Aim 1—Quality Prioritization, Personal Satisfaction, and RN Relational Coordination—mediated the relations between select structural hospital characteristics and older adult CLABSI occurrence in order to obtain greater insight into how associations between these variables of interest operate. All analyses were conducted in SAS® 9.4. Results: Exploratory Factor Analyses confirmed the construct validity and reliability of both the LCQ-IP and RCS instruments, capturing four-factor solutions for each. The four LCQ-IP factors included Psychological Safety, Quality Prioritization, Leadership and Change Orientation, and Personal Satisfaction, with acceptable internal consistency (Cronbach’s α = 0.909). The four RCS factors included Hospital Administration Relational Coordination, Environmental Services Relational Coordination, Physician (MD) Relational Coordination, and Bedside nurse (RN) Relational Coordination, also with acceptable internal consistency (Cronbach’s α = 0.768). Select organizational work climate domains were found to be statistically significant with CLABSI during multivariate logistic regression analyses—namely, Quality Prioritization, Personal Satisfaction, and Bedside Nurse Relational Coordination—although the magnitude and direction of those associations varied. Numerous structural hospital and infection prevention program department and policy covariates were found to impact the outcome, as well. However, goodness of fit statistics indicated that overall model fit was poor, with the fully adjusted and pruned regression models only explaining 5% of the variance of the CLABSI outcome variable, suggesting that indicators not assessed during the present study, such as patient and nurse-related characteristics, play an influential role in the work climate-CLABSI causal pathway. Results from Joint Significance Tests of mediation did not confirm the presence of mediation. Conclusion: This research provided critical insight into the associations between elements of the hospital NPE and CLABSI among hospitalized older adults, thus contributing to the public health, nursing, and gerontological literature. The LCQ-IP and RCS EFAs validated the psychometric properties of these instruments, indicating their utility for researchers and providers seeking to assess the quality of the hospital organizational climate related to infection prevention. To the researcher’s knowledge, this was the first investigation of the PNICER LCQ-IP that demonstrated the construct validity of the full 27-item scale, which may enhance its variability and sensitivity, as well as improve its theoretical structure since identified constructs are more fully represented. RCS EFA findings further validated that this tool has utility in addressing core elements of interdisciplinary practice in hospitals surrounding infection prevention efforts, especially in regard to collaboration and communication. The inconsistent findings related to organizational work environment-CLABSI associations that were observed during multivariate logistic were unexpected given that such a robust body of literature has documented the influential role that hospital work environment factors have on patient health care-associated infections, as well as that prior EFAs confirmed the psychometric properties of the LCQ-IP and RCS employed during PNICER. However, since goodness of fit tests revealed poor model fit, findings should be interpreted with caution. Additional research is needed to probe the nuanced associations between structural, organizational, and individual-level determinants of older patient safety and quality outcomes, such as CLABSI. Results from the Joint Significance Test of mediation did not provide enough evidence to reject the null hypothesis and confirm a mediating effect among any of these factors. Despite these findings, the analyses offer important theoretical and scientific contributions to the nursing and patient safety literature. As structural hospital characteristics are often incorporated into analyses for descriptive purposes or as covariates in regression analyses but rarely as explanatory variables, this study’s inclusion of these variables as key predictors provides a foundation for future scientific inquiry into how such factors impact patient safety outcomes. Additionally, to the researcher’s knowledge, this was the first study to examine the hypothesized mediating role of the NPE on the hospital characteristics-older adult CLABSI outcome causal pathway. Despite its infrequent use in nursing research, mediation analyses, such as these, enable researchers to ask and answer more nuanced and arguably more meaningful research questions that extend beyond how one variable influences a particular outcome, thereby advancing the scope of scientific inquiry. Findings from this study raise important questions surrounding what dimensions of the NPE are most consequential for older adult healthcare-associated infection occurrence in the ICU and how these NPE dimensions manifest within pre-existing hospital structures to shape patient outcomes. Additionally, analyses point towards the important yet overlooked role of nurse and patient characteristics in both shaping NPEs and driving outcomes. The complexity of these associations reinforces the need for further scientific investigation in this area, which should include advanced quantitative statistical methods aimed at teasing apart the nuance of these structural, organizational, and individual-level factors, in addition to qualitative methods, to provide important contextualization to the dynamics at play between these constructs. Such insights will help to highlight key areas for clinical and practice intervention to redress negative older adult patient outcomes and promote enhanced cultures of safety in ICUs and across hospital wards

The Progression of β-amyloid Deposition in the Frontal Cortex of the Aged Canine

Brains from 41 aged canines (≥10 years of age) were examined immunohistochemically to characterize the laminar distribution and age-related progression of β-amyloid (Aβ) in frontal cortex. We classified the Aβ patterns into four distinct types. Type I was characterized by small, faint deposits of Aβ in deep cortical layers. Type II consisted of diffuse deposits of Aβ mainly in layers V and VI. Type III had both dense plaques in superficial layers, and diffuse deposits in deep layers. Finally, Type IV had solely dense plaques throughout all layers of cortex. We compared the Aβ distribution pattern between the Old canines (10–15 years, n=22) and the Very Old canines (\u3e15 years, n=19). The Old group primarily had negative staining, or Type I and Type II patterns of amyloid deposition (73%). Conversely, the Very Old group had predominantly Types II, III and IV deposits (89.5%), a difference that was significant (Pβ deposition in canine frontal cortex is a progressive age-related process beginning with diffuse deposits in the deep cortical layers followed by the development of deposits in outer layers. In support of this hypothesis, the deeper layer diffuse plaques in the Very Old group of dogs also contain the largest proportion of β-amyloid with an isomerized aspartic acid residue at position 7, indicating that these deposits had been present for some time. We also observed fiber-like Aβ immunoreactivity within regions of diffuse Aβ deposits. These fibers appeared to be degenerating neurites, which were negative for hyperphosphorylated tau. Therefore, these fibers may represent a very early form of neuritic change that precede tau hyperphosphorylation or develop by an alternative pathway

Long-term Aquatic Invertebrate Monitoring at Buffalo National River, Arkansas

Aquatic invertebrate community structure was used to assess long-term water quality integrity in the mainstem of the Buffalo National River, Arkansas from 2005 to 2013. Nine benthic invertebrate samples were collected from each of six sampling sites using a Slack-Surber sampler. The Stream Condition Index (SCI) developed for Ozark streams was used to assess integrity of the invertebrate communities. This index is calculated using taxa richness, EPT (Ephemeroptera, Plecoptera, Trichoptera) Richness, Shannon’s Diversity Index, and Hilsenhoff Biotic Index (HBI). Sørensen’s similarity index was used to assess community similarity among sites, and scores were then analyzed using ascendant hierarchical cluster analysis. The benthic invertebrate fauna was diverse with 167 distinct taxa identified from all sites, with similarities ranging from 70% to 83%. Cluster analysis showed that sites were clustered in a longitudinal progression, with those sites closest to one another in linear distance generally being the most closely related. Overall, the invertebrate taxa of the Buffalo River are largely intolerant (mean tolerance value= 4.38). Taxa richness was typically greater than 20 among samples, and EPT richness values consistently were greater than 12 for all sites in most years. Shannon’s diversity index values generally ranged from 2.0 to 2.5 among sites and years. Metric values tended to decrease in a downstream direction to Site 4, and then increase to levels observed upstream. The exception was for HBI, which did not show this response and values for this metric generally were below 5. SCI scores among sampling sites were variable but not generally impaired and were fully biologically-supporting. Water quality (temperature, dissolved oxygen, specific conductance, pH, turbidity) met state standards in all instances. Habitat data were summarized, but found to be poorly correlated with invertebrate metrics (\u3c30% significant). Although the condition of invertebrate communities and water quality in the Buffalo River are largely sound and have high integrity, numerous ongoing and projected threats to these resources remain, and those threats largely originate outside of the park’s jurisdictional boundaries. Inherent variability of invertebrate community diversity and density across sites and years highlights the importance of using multi-metric assessment and multiyear monitoring to support management decisions

Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice.

BackgroundAlzheimer disease (AD) is characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which together lead to neurodegeneration and cognitive decline. Current therapeutic approaches have primarily aimed to reduce pathological aggregates of either Aβ or tau, yet phase 3 clinical trials of these approaches have thus far failed to delay disease progression in humans. Strong preclinical evidence indicates that these two abnormally aggregated proteins interact synergistically to drive downstream neurodegeneration. Therefore, combinatorial therapies that concurrently target both Aβ and tau might be needed for effective disease modification.MethodsA combinatorial vaccination approach was designed to concurrently target both Aβ and tau pathologies. Tau22/5xFAD (T5x) bigenic mice that develop both pathological Aβ and tau aggregates were injected intramuscularly with a mixture of two MultiTEP epitope vaccines: AV-1959R and AV-1980R, targeting Aβ and tau, respectively, and formulated in AdvaxCpG, a potent polysaccharide adjuvant. Antibody responses of vaccinated animals were measured by ELISA, and neuropathological changes were determined in brain homogenates of vaccinated and control mice using ELISA and Meso Scale Discovery (MSD) multiplex assays.ResultsT5x mice immunized with a mixture of Aβ- and tau-targeting vaccines generated high Aβ- and tau-specific antibody titers that recognized senile plaques and neurofibrillary tangles/neuropil threads in human AD brain sections. Production of these antibodies in turn led to significant reductions in the levels of soluble and insoluble total tau, and hyperphosphorylated tau as well as insoluble Aβ42, within the brains of bigenic T5x mice.ConclusionsAV-1959R and AV-1980R formulated with AdvaxCpG adjuvant are immunogenic and therapeutically potent vaccines that in combination can effectively reduce both of the hallmark pathologies of AD in bigenic mice. Taken together, these findings warrant further development of this vaccine technology for ultimate testing in human AD

Mechanism of Neuroprotective Mitochondrial Remodeling by PKA/AKAP1

The mitochondrial signaling complex PKA/AKAP1 protects neurons against mitochondrial fragmentation and cell death by phosphorylating and inactivating the mitochondrial fission enzyme Drp1

Protocol for Monitoring Aquatic Invertebrates of Small Streams in the Heartland Inventory & Monitoring Network, Version 2.1

Executive Summary The Heartland Inventory and Monitoring Network (HTLN) is a component of the National Park Service’s (NPS) strategy to improve park management through greater reliance on scientific information. The purposes of this program are to design and implement long-term ecological monitoring and provide information for park managers to evaluate the integrity of park ecosystems and better understand ecosystem processes. Concerns over declining surface water quality have led to the development of various monitoring approaches to assess stream water quality. Freshwater streams in network parks are threatened by numerous stressors, most of which originate outside park boundaries. Stream condition and ecosystem health are dependent on processes occurring in the entire watershed as well as riparian and floodplain areas; therefore, they cannot be manipulated independently of this interrelationship. Land use activities—such as timber management, landfills, grazing, confined animal feeding operations, urbanization, stream channelization, removal of riparian vegetation and gravel, and mineral and metals mining—threaten stream quality. Accordingly, the framework for this aquatic monitoring is directed towards maintaining the ecological integrity of the streams in those parks. Invertebrates are an important tool for understanding and detecting changes in ecosystem integrity, and they can be used to reflect cumulative impacts that cannot otherwise be detected through traditional water quality monitoring. The broad diversity of invertebrate species occurring in aquatic systems similarly demonstrates a broad range of responses to different environmental stressors. Benthic invertebrates are sensitive to the wide variety of impacts that influence Ozark streams. Benthic invertebrate community structure can be quantified to reflect stream integrity in several ways, including the absence of pollution sensitive taxa, dominance by a particular taxon combined with low overall taxa richness, or appreciable shifts in community composition relative to reference condition. Furthermore, changes in the diversity and community structure of benthic invertebrates are relatively simple to communicate to resource managers and the public. To assess the natural and anthropogenic processes influencing invertebrate communities, this protocol has been designed to incorporate the spatial relationship of benthic invertebrates with their local habitat including substrate size and embeddedness, and water quality parameters (temperature, dissolved oxygen, pH, specific conductance, and turbidity). Rigid quality control and quality assurance are used to ensure maximum data integrity. Detailed standard operating procedures (SOPs) and supporting information are associated with this protocol

Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes.

BACKGROUND: Tendon injuries occur frequently in human and equine athletes. Treatment options are limited, and the prognosis is often poor with functionally deficient scar tissue resulting. Fetal tendon injuries in contrast are capable of healing without forming scar tissue. Embryonic stem cells (ESCs) may provide a potential cellular therapeutic to improve adult tendon regeneration; however, whether they can mimic the properties of fetal tenocytes is unknown. To this end, understanding the unique expression profile of normal adult and fetal tenocytes is crucial to allow validation of ESC-derived tenocytes as a cellular therapeutic. METHODS: Equine adult, fetal and ESC-derived tenocytes were cultured in a three-dimensional environment, with histological, morphological and transcriptomic differences compared. Additionally, the effects on gene expression of culturing adult and fetal tenocytes in either conventional two-dimensional monolayer culture or three-dimensional culture were compared using RNA sequencing. RESULTS: No qualitative differences in three-dimensional tendon constructs generated from adult, fetal and ESCs were found using histological and morphological analysis. However, genome-wide transcriptomic analysis using RNA sequencing revealed that ESC-derived tenocytes' transcriptomic profile more closely resembled fetal tenocytes as opposed to adult tenocytes. Furthermore, this study adds to the growing evidence that monolayer cultured cells' gene expression profiles converge, with adult and fetal tenocytes having only 10 significantly different genes when cultured in this manner. In contrast, when adult and fetal tenocytes were cultured in 3D, large distinctions in gene expression between these two developmental stages were found, with 542 genes being differentially expressed. CONCLUSION: The information provided in this study makes a significant contribution to the investigation into the differences between adult reparative and fetal regenerative cells and supports the concept of using ESC-derived tenocytes as a cellular therapy. Comparing two- and three-dimensional culture also indicates three-dimensional culture as being a more physiologically relevant culture system for determining transcriptomic difference between the same cell types from different developmental stages

Reducing AD-Like Pathology in 3xTg-AD Mouse Model by DNA Epitope Vaccine — A Novel Immunotherapeutic Strategy

BACKGROUND: The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Abeta antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Abeta(42) (Abeta(1-11)) , a non-self T helper cell epitope (PADRE), and macrophage-derived chemokine (MDC/CCL22) as a molecular adjuvant to promote a strong anti-inflammatory Th2 phenotype. METHODS AND FINDINGS: We generated pMDC-3Abeta(1-11)-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Abeta antibody, which in turn inhibited accumulation of Abeta pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages. CONCLUSIONS: Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30