A draft human pangenome reference.

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.

Semi-automated assembly of high-quality diploid human reference genomes.

The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society1,2. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals3,4. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome5. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity6. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent-child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements.

Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies.

In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) for Leishmania and show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multiple Leishmania species residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. SWGA carried out directly on skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive genomic diversity. Finally, as a proof-of-concept, we demonstrated that SWGA data can be integrated with published whole genome data from cultured parasite isolates to identify variants unique to specific geographic regions in Brazil where treatment failure rates are known to be high. SWGA provides a relatively simple method to generate Leishmania genomes directly from patient samples, unlocking the potential to link parasite genetics with host clinical phenotypes.

Functional network dynamics revealed by EEG microstates reflect cognitive decline in amyotrophic lateral sclerosis.

Recent electroencephalography (EEG) studies have shown that patterns of brain activity can be used to differentiate amyotrophic lateral sclerosis (ALS) and control groups. These differences can be interrogated by examining EEG microstates, which are distinct, reoccurring topographies of the scalp's electrical potentials. Quantifying the temporal properties of the four canonical microstates can elucidate how the dynamics of functional brain networks are altered in neurological conditions. Here we have analysed the properties of microstates to detect and quantify signal-based abnormality in ALS. High-density resting-state EEG data from 129 people with ALS and 78 HC were recorded longitudinally over a 24-month period. EEG topographies were extracted at instances of peak global field power to identify four microstate classes (labelled A-D) using K-means clustering. Each EEG topography was retrospectively associated with a microstate class based on global map dissimilarity. Changes in microstate properties over the course of the disease were assessed in people with ALS and compared with changes in clinical scores. The topographies of microstate classes remained consistent across participants and conditions. Differences were observed in coverage, occurrence, duration, and transition probabilities between ALS and control groups. The duration of microstate class B and coverage of microstate class C correlated with lower limb functional decline. The transition probabilities A to D, C to B and C to B also correlated with cognitive decline (total ECAS) in those with cognitive and behavioural impairments. Microstate characteristics also significantly changed over the course of the disease. Examining the temporal dependencies in the sequences of microstates revealed that the symmetry and stationarity of transition matrices were increased in people with late-stage ALS. These alterations in the properties of EEG microstates in ALS may reflect abnormalities within the sensory network and higher-order networks. Microstate properties could also prospectively predict symptom progression in those with cognitive impairments.

Fiber-taper collected emission from NV centers in high-Q/V diamond microdisks.

Fiber-coupled microdisks are a promising platform for enhancing the spontaneous emission from color centers in diamond. The measured cavity-enhanced emission from the microdisk is governed by the effective volume (V) of each cavity mode, the cavity quality factor (Q), and the coupling between the microdisk and the fiber. Here we observe room temperature photoluminescence from an ensemble of nitrogen-vacancy centers into high Q/V microdisk modes, which when combined with coherent spectroscopy of the microdisk modes, allows us to elucidate the relative contributions of these factors. The broad emission spectrum acts as an internal light source facilitating mode identification over several cavity free spectral ranges. Analysis of the fiber taper collected microdisk emission reveals spectral filtering both by the cavity and the fiber taper, the latter of which we find preferentially couples to higher-order microdisk modes. Coherent mode spectroscopy is used to measure Q ∼ 1 × 105 - the highest reported values for diamond microcavities operating at visible wavelengths. With realistic optimization of the microdisk dimensions, we predict that Purcell factors of ∼50 are within reach.

On-chip hybrid integration of swept frequency distributed-feedback laser with silicon photonic circuits using photonic wire bonding.

This paper presents a novel co-packaging approach through on-chip hybrid laser integration with photonic circuits using photonic wire bonding. The process involves die-bonding a low-cost semiconductor distributed-feedback (DFB) laser into a deep trench on a silicon-on-insulator (SOI) chip and coupling it to the silicon circuitry through photonic wire bonding (PWB). After characterizing the power-current-voltage (LIV) and optical spectrum of the laser, a wavelength-current relationship utilizing its tunability through self-heating a swept-frequency laser (SFL) is developed. Photonic integrated circuit (PIC) resonators are successfully characterized using the SFL method, demonstrating signal detection with a quality factor comparable to measurements conducted with an off-chip benchtop laser.

A fast machine-learning-guided primer design pipeline for selective whole genome amplification.

Addressing many of the major outstanding questions in the fields of microbial evolution and pathogenesis will require analyses of populations of microbial genomes. Although population genomic studies provide the analytical resolution to investigate evolutionary and mechanistic processes at fine spatial and temporal scales-precisely the scales at which these processes occur-microbial population genomic research is currently hindered by the practicalities of obtaining sufficient quantities of the relatively pure microbial genomic DNA necessary for next-generation sequencing. Here we present swga2.0, an optimized and parallelized pipeline to design selective whole genome amplification (SWGA) primer sets. Unlike previous methods, swga2.0 incorporates active and machine learning methods to evaluate the amplification efficacy of individual primers and primer sets. Additionally, swga2.0 optimizes primer set search and evaluation strategies, including parallelization at each stage of the pipeline, to dramatically decrease program runtime. Here we describe the swga2.0 pipeline, including the empirical data used to identify primer and primer set characteristics, that improve amplification performance. Additionally, we evaluate the novel swga2.0 pipeline by designing primer sets that successfully amplify Prevotella melaninogenica, an important component of the lung microbiome in cystic fibrosis patients, from samples dominated by human DNA.

Cortico-muscular coherence in primary lateral sclerosis reveals abnormal cortical engagement during motor function beyond primary motor areas.

Primary lateral sclerosis (PLS) is a slowly progressing disorder, which is characterized primarily by the degeneration of upper motor neurons (UMNs) in the primary motor area (M1). It is not yet clear how the function of sensorimotor networks beyond M1 are affected by PLS. The aim of this study was to use cortico-muscular coherence (CMC) to characterize the oscillatory drives between cortical regions and muscles during a motor task in PLS and to examine the relationship between CMC and the level of clinical impairment. We recorded EEG and EMG from hand muscles in 16 participants with PLS and 18 controls during a pincer-grip task. In PLS, higher CMC was observed over contralateral-M1 (α- and γ-band) and ipsilateral-M1 (ß-band) compared with controls. Significant correlations between clinically assessed UMN scores and CMC measures showed that higher clinical impairment was associated with lower CMC over contralateral-M1/frontal areas, higher CMC over parietal area, and both higher and lower CMC (in different bands) over ipsilateral-M1. The results suggest an atypical engagement of both contralateral and ipsilateral M1 during motor activity in PLS, indicating the presence of pathogenic and/or adaptive/compensatory alterations in neural activity. The findings demonstrate the potential of CMC for identifying dysfunction within the sensorimotor networks in PLS.

Disentangling direct and indirect effects of landscape structure on urban bird richness and functional diversity.

As fragmented landscapes become increasingly common around the world, managing the spatial arrangement of landscape elements (i.e., landscape configuration) may help to promote the conservation of biodiversity. However, the relative effects of landscape configuration on different dimensions of biodiversity across species assemblages are largely unknown. Thus, a key challenge consists in understanding when it is necessary to focus on landscape configuration, in addition to landscape composition, to achieve multifunctional landscapes. We tested the effects of landscape composition (the percentage of tree cover and built infrastructure) and landscape configuration (degree of fragmentation) on landscape-level species richness and different metrics of functional diversity of urban birds. We collected data on different bird guilds (nectarivores/frugivores, insectivores) from Brisbane, Australia. Using structural equation models, we found that landscape structure (landscape composition and configuration) affected functional diversity via two main pathways: (1) through effects of landscape composition, mediated by landscape configuration (indirect effects), and (2) through direct ("independent") effects of landscape composition and configuration, filtering species with extreme trait values. Our results show that landscape-level species richness declined with the extent of built infrastructure, but patterns of trait diversity did not necessarily correlate with this variable. Landscape configuration had a stronger mediating effect on some metrics of the functional diversity of insectivores than on the functional diversity of frugivores/nectarivores. In addition, fragmentation increased the effects of built infrastructure for some traits (body size and dispersal capacity), but not for others (habitat plasticity and foraging behavior). These results suggest that differential approaches to managing landscape structure are needed depending on whether the focus is on protecting functional diversity or species richness and what the target guild is. Managing landscape fragmentation in areas with high levels of built infrastructure is important if the objective is to protect insectivore species with uncommon traits, even if it is not possible to preserve high levels of species richness. However, if the target is to enhance both functional diversity and species richness of multiple guilds, the focus should be on improving composition through the reduction of negative effects of built infrastructure, rather than promoting specific landscape configurations in growing cities.

Drivers of fine-scale diurnal space use by a coral-reef mesopredatory fish.

The habitat preferences of many reef fishes are well established, but the use of space within these habitats by non-site-attached species is poorly studied. The authors examined the space use of a functionally important mesopredator, graysby (Cephalopholis cruentata), on six patch reefs in the Florida Keys. A 1 m2 -scale grid was constructed on each reef and 16 individual C. cruentata were tracked diurnally in situ to identify space use. At the patch reef scale, larger C. cruentata were more active and had larger observed home ranges, although home ranges were also affected by fish density and the abundances of prey and predators. The total time in each 1 m2 grid cell was regressed against a range of fine-scale biotic variables, including multiple variables derived from structure-from-motion three-dimensional digital reconstructions of each reef. Nonetheless, time in grid cells (preferred microhabitats) was only significantly positively correlated with the height of carbonate structures, likely because the cavities they enclose are particularly suitable for predator avoidance, resting and ambushing prey. The ongoing flattening of reefs in the region caused by negative carbonate budgets is thus likely to have significant effects on the abundance and space use of C. cruentata. In addition to examining spatial patterns, we analysed C. cruentata waiting times in each grid cell before moving. These times were best approximated by a truncated power-law (heavy-tailed) distribution, indicating a "bursty" pattern of relatively long periods of inactivity interspersed with multiple periods of activity. Such a pattern has previously been identified in a range of temperate ambush predators, and the authors extend this move-wait behaviour, which may optimize foraging success, to a reef fish for the first time. Understanding how C. cruentata uses space and time is critical to fully identify their functional role and better predict the implications of fishing and loss of reef structure.

4E-BP1 Protects Neurons from Misfolded Protein Stress and Parkinson's Disease Toxicity by Inducing the Mitochondrial Unfolded Protein Response.

Decline of protein quality control in neurons contributes to age-related neurodegenerative disorders caused by misfolded proteins. 4E-BP1 is a key node in the regulation of protein synthesis, as activated 4E-BP1 represses global protein translation. Overexpression of 4E-BP1 mediates the benefits of dietary restriction and can counter metabolic stress, and 4E-BP1 disinhibition on mTORC1 repression may be neuroprotective; however, whether 4E-BP1 overexpression is neuroprotective in mammalian neurons is yet to be fully explored. To address this question, we generated 4E-BP1-overexpressing transgenic mice and confirmed marked reductions in protein translation in 4E-BP1-overexpressing primary neurons. After documenting that 4E-BP1-overexpressing neurons are resistant to proteotoxic stress elicited by brefeldin A treatment, we exposed primary neurons to three different Parkinson's disease (PD)-linked toxins (rotenone, maneb, or paraquat) and documented significant protection in neurons from newborn male and female 4E-BP1-OE transgenic mice. We observed 4E-BP1-dependent upregulation of genes encoding proteins that comprise the mitochondrial unfolded protein response, and noted 4E-BP1 overexpression required activation of the mitochondrial unfolded protein response for neuroprotection against rotenone toxicity. We also tested whether 4E-BP1 could prevent α-synuclein neurotoxicity by treating 4E-BP1-overexpressing primary neurons with α-synuclein preformed fibrils, and we observed marked reductions in α-synuclein aggregation and neurotoxicity, thus validating that 4E-BP1 is a powerful suppressor of PD-linked pathogenic insults. Our results indicate that increasing 4E-BP1 expression or enhancing 4E-BP1 activation can robustly induce the mitochondrial unfolded protein response and thus could be an appealing strategy for treating a variety of neurodegenerative diseases, including especially PD.SIGNIFICANCE STATEMENT In neurodegenerative disease, misfolded proteins accumulate and overwhelm normal systems of homeostasis and quality control. One mechanism for improving protein quality control is to reduce protein translation. Here we investigated whether neuronal overexpression of 4E-BP1, a key repressor of protein translation, can protect against misfolded protein stress and toxicities linked to Parkinson's disease, and found that 4E-BP1 overexpression prevented cell death in neurons treated with brefeldin A, rotenone, maneb, paraquat, or preformed fibrils of α-synuclein. When we sought the basis for 4E-BP1 neuroprotection, we discovered that 4E-BP1 activation promoted the mitochondrial unfolded protein response. Our findings highlight 4E-BP1 as a therapeutic target in neurodegenerative disease and underscore the importance of the mitochondrial unfolded protein response in neuroprotection against various insults.

Assessment of the effects of repeated freeze thawing and extended bench top processing of plasma samples using untargeted metabolomics.

INTRODUCTION: Clinical metabolomics has utility as a screen for inborn errors of metabolism (IEM) and variant classification in patients with rare disease. It is important to understand and characterize preanalytical factors that influence assay performance during patient sample testing. OBJECTIVES: To evaluate the impact of extended thawing of human EDTA plasma samples on ice prior to extraction as well as repeated freeze-thaw cycling of samples to identify compounds that are unstable prior to metabolomic analysis. METHODS: Twenty-four (24) donor EDTA plasma samples were collected and immediately frozen at - 80 °C. Twelve samples were thawed on ice and extracted for analysis at time 0, 2, 4, and 6 h. Twelve other donor samples were repeatedly thawed and frozen up to four times and analyzed at each cycle. Compound levels at each time point/freeze-thaw cycle were compared to the control samples using matched-paired t tests to identify analytes affected by each condition. RESULTS: We identified 1026 biochemicals across all samples. Incubation of thawed EDTA plasma samples on ice for up to 6 h resulted in < 1% of biochemicals changing significantly. Freeze-thaw cycles affected a greater percentage of the metabolome; ~ 2% of biochemicals changed after 3 freeze-thaw cycles. CONCLUSIONS: Our study highlights that the number and magnitude of these changes are not as widespread as other aspects of improper sample handling. In total, < 3% of the metabolome detected on our clinical metabolomics platform should be disqualified when multiple freeze-thaw cycles or extended thawing at 4 °C are performed on a given sample.

Floquet Solitons and Dynamics of Periodically Driven Matter Waves with Negative Effective Mass.

We experimentally study the dynamics of weakly interacting Bose-Einstein condensates of cesium atoms in a 1D optical lattice with a periodic driving force. After a sudden start of the driving, we observe the formation of stable wave packets at the center of the first Brillouin zone (BZ) in momentum space, and we interpret these as Floquet solitons in periodically driven systems. The wave packets become unstable when we add a trapping potential along the lattice direction, leading to a redistribution of atoms within the BZ. The concept of a negative effective mass and the resulting changes to the interaction strength and effective trapping potential are used to explain the stability and the time evolution of the wave packets. We expect that similar states of matter waves exist for discrete breathers and other types of lattice solitons in periodically driven systems.

Discharge Practices for COVID-19 Patients: Rapid Review of Published Guidance and Synthesis of Documents and Practices at 22 US Academic Medical Centers.

BACKGROUND: There are currently no evidence-based guidelines that provide standardized criteria for the discharge of COVID-19 patients from the hospital. OBJECTIVE: To address this gap in practice guidance, we reviewed published guidance and collected discharge protocols and procedures to identify and synthesize common practices. DESIGN: Rapid review of existing guidance from US and non-US public health organizations and professional societies and qualitative review using content analysis of discharge documents collected from a national sample of US academic medical centers with follow-up survey of hospital leaders SETTING AND PARTICIPANTS: We reviewed 65 websites for major professional societies and public health organizations and collected documents from 22 Academic Medical Centers (AMCs) in the US participating in the HOspital MEdicine Reengineering Network (HOMERuN). RESULTS: We synthesized data regarding common practices around 5 major domains: (1) isolation and transmission mitigation; (2) criteria for discharge to non-home settings including skilled nursing, assisted living, or homeless; (3) clinical criteria for discharge including oxygenation levels, fever, and symptom improvement; (4) social support and ability to perform activities of daily living; (5) post-discharge instructions, monitoring, and follow-up. LIMITATIONS: We used streamlined methods for rapid review of published guidance and collected discharge documents only in a focused sample of US academic medical centers. CONCLUSION: AMCs studied showed strong consensus on discharge practices for COVID-19 patients related to post-discharge isolation and transmission mitigation for home and non-home settings. There was high concordance among AMCs that discharge practices should address COVID-19-specific factors in clinical, functional, and post-discharge monitoring domains although definitions and details varied.

Collisionally Inhomogeneous Bose-Einstein Condensates with a Linear Interaction Gradient.

We study the evolution of a collisionally inhomogeneous matter wave in a spatial gradient of the interaction strength. Starting with a Bose-Einstein condensate with weak repulsive interactions in quasi-one-dimensional geometry, we monitor the evolution of a matter wave that simultaneously extends into spatial regions with attractive and repulsive interactions. We observe the formation and the decay of solitonlike density peaks, counterpropagating self-interfering wave packets, and the creation of cascades of solitons. The matter-wave dynamics is well reproduced in numerical simulations based on the nonpolynomial Schrödinger equation with three-body loss, allowing us to better understand the underlying behavior based on a wavelet transformation. Our analysis provides new understanding of collapse processes for solitons, and opens interesting connections to other nonlinear instabilities.

Hexagonal Boron Nitride Cavity Optomechanics.

Hexagonal boron nitride (hBN) is an emerging layered material that plays a key role in a variety of two-dimensional devices, and has potential applications in nanophotonics and nanomechanics. Here, we demonstrate the first cavity optomechanical system incorporating hBN. Nanomechanical resonators consisting of hBN beams with average dimensions of 12 µm × 1.2 µm × 28 nm and minimum predicted thickness of 8 nm were fabricated using electron beam induced etching and positioned in the optical near-field of silicon microdisk cavities. Of the multiple devices studied here a maximum 0.16 pm/[Formula: see text] sensitivity to the hBN nanobeam motion is demonstrated, allowing observation of thermally driven mechanical resonances with frequencies between 1 and 23 MHz, and largest mechanical quality factor of 1100 for a 23 MHz mode, at room temperature in high vacuum. In addition, the role of air damping is studied via pressure dependent measurements. Our results constitute an important step toward realizing integrated optomechanical circuits employing hBN.

Glycogen synthase kinase-3 (GSK-3) activity regulates mRNA methylation in mouse embryonic stem cells.

Glycogen synthase kinase-3 (GSK-3) activity regulates multiple signal transduction pathways and is also a key component of the network responsible for maintaining stem cell pluripotency. Genetic deletion of Gsk-3α and Gsk-3ß or inhibition of GSK-3 activity via small molecules promotes stem cell pluripotency, yet the mechanism underlying the role for GSK-3 in this process remains ambiguous. Another cellular process that has been shown to affect stem cell pluripotency is mRNA methylation (m6A). Here, we describe an intersection between these components, the regulation of m6A by GSK-3. We find that protein levels for the RNA demethylase, FTO (fat mass and obesity-associated protein), are elevated in Gsk-3α;Gsk-3ß-deficient mouse embryonic stem cells (ESCs). FTO is normally phosphorylated by GSK-3, and MS identified the sites on FTO that are phosphorylated in a GSK-3-dependent fashion. GSK-3 phosphorylation of FTO leads to polyubiquitination, but in Gsk-3 knockout ESCs, that process is impaired, resulting in elevated levels of FTO protein. As a consequence of altered FTO protein levels, mRNAs in Gsk-3 knockout ESCs have 50% less m6A than WT ESCs, and m6A-Seq analysis reveals the specific mRNAs that have reduced m6A modifications. Taken together, we provide the first evidence for how m6A demethylation is regulated in mammalian cells and identify a putative novel mechanism by which GSK-3 activity regulates stem cell pluripotency.

"It's Like Riding Out the Chaos": Caring for Socially Complex Patients in an Ambulatory Intensive Care Unit (A-ICU).

PURPOSE: High-need high-cost (HNHC) patients consume a large proportion of health resources but often receive suboptimal care in traditional primary care. Intensive ambulatory care interventions attempt to better meet these patients' needs, but we know little about how teams delivering these interventions in clinics serving socially complex patient populations perceive their work. METHODS: We performed a qualitative study of multidisciplinary staff experiences at a Federally Qualified Health Center (FQHC) caring for predominantly homeless HNHC patients in the context of an ongoing implementation of an ambulatory intensive care unit (A-ICU) intervention. We conducted semistructured interviews with 9 ambulatory intensive care team members and 6 "usual care" members. We conducted a thematic analysis, using an inductive approach, at a semantic level. RESULTS: Staff viewed complexity as a combination of social, behavioral, and medical challenges that lead to patient-health care system mismatch. Staff perceive the following as key ingredients in caring for HNHC patients: addressing both psychosocial and clinical needs together; persistence in staying connected to patients through chaotic periods; shared commitment and cohesion among interdisciplinary team members; and flexibility to tailor care to patients' individual situations. Participants' definitions of success focused more on improving patient engagement than reducing utilization or cost. CONCLUSION: FQHC staff working with HNHC patients perceive mismatch between the health care system and patients' clinical and social needs as the key driver of poor outcomes for these patients. Intensive ambulatory care teams may bridge mismatch through provision of psychosocial supports, flexible care delivery, and fostering team cohesion to support patient engagement.

The Effects of Selenomethionine on the Escape Behaviours of Fathead Minnows.

Selenium (Se) is an essential micronutrient for animals and yet becomes toxic with only a small increase in concentration. Toxicological studies have reported various effects of Se on fishes, including developmental impacts and deformities of the musculature and sensory systems. This paper investigates the impact of sublethal concentrations of Se on the ability of the Fathead Minnow (Pimephales promelas) to perform escape responses, a routine behaviour important to predator-prey dynamics. Predation is among the strongest evolutionary driving forces in nature. Changes to this dynamic can have effects that cascade through the ecosystem. We used responses to mechanical and visual stimuli to determine the impact of environmentally relevant concentrations of dietary selenomethionine on the behaviour of minnows. Latency to respond to the stimulus and kinematic performance were assessed. Our results indicated that there was no significant effect of selenomethionine on either the visual response to a threat or burst swimming behaviours of the fast-start response in minnows. Levels of Se in tissues approached that of tissue-specific guidelines set by regulatory bodies across North America. This suggests that current regulations are adequately protecting this key component of predator avoidance in Fathead Minnows.

Impact of a Hospital Evidence-Based Practice Center (EPC) on Nursing Policy and Practice.

BACKGROUND: In 2006, our healthcare system created a hospital Evidence-based Practice Center (EPC) to support the local delivery of high-quality, safe and high value patient care. Since then, the importance of healthcare staff work life has also been highlighted, and together these four elements form the Quadruple Aim framework. Synergistic to this Aim, the Magnet® program promotes and recognizes organizational nursing excellence. OBJECTIVE: To examine the EPC's work to inform nursing policy and practice in support of the goals of the Quadruple Aim framework and Magnet® designation. METHODS: Methods used included the following: (1) descriptive analysis of the hospital EPC's database of rapid reviews; and (2) administration of a 40-item electronic questionnaire to nurses who requested an EPC review during fiscal years (FY) 2015 and 2016. RESULTS: Of 308 rapid reviews completed in the EPC's first 10 years, 59 (19%) addressed nursing topics. The proportion of reviews relevant to nursing increased from 5% (2/39) in the center's first 2 years to 44% (25/60) in FY 2015-2016. The majority of nursing reviews (39/59) examined processes of care. Of 23 nurses eligible to participate in the survey, 21 responded (91%). Nurses with administrative or managerial responsibilities requested 70% of reviews; clinical nurse specialists and bedside nurses requested 17% and 9%, respectively. Reviews were used to support clinical program development (48%), provide clinical guidance (33%), update nursing policies or procedures (24%) and develop training and curricula (24%). Nurses were satisfied with the hospital EPC reviews (mean; 4.7/5), and 95% indicated they were likely to request a future review. LINKING EVIDENCE TO ACTION: A dedicated hospital EPC in partnership with nursing offers a unique mechanism for promoting a culture of evidence-based practice. Nurses at all organizational levels use the services of a hospital EPC to inform nursing policy and practice and are highly satisfied with the process, supporting the Quadruple Aim and Magnet® designation.