Impact of Local Tailoring on Acute Stroke Care in 21 Disparate Emergency Departments: A Prospective Stepped Wedge Type III Hybrid Effectiveness-Implementation Study.

BACKGROUND: Faster delivery of tPA (tissue-type plasminogen activator) results in better health outcomes for eligible patients with stroke. Standardization of stroke protocols in emergency departments (EDs) has been difficult, especially in nonstroke centers. We measured the effectiveness of a centrally led implementation strategy with local site tailoring to sustain adherence to an acute stroke protocol to improve door-to-needle (DTN) times across disparate EDs in a multihospital health system. METHODS: Prospective, type III hybrid effectiveness-implementation cohort study measuring performance at 21 EDs in Utah and Idaho (stroke centers [4]/nonstroke centers [17]) from January 2018 to February 2020 using a nonrandomized stepped-wedge design, monthly repeated site measures and multilevel hierarchical modeling. Each site received the implementation strategies in 1 of 6 steps providing control and intervention data. Co-primary outcomes were percentage of DTN times ≤60 minutes and median DTN time. Secondary outcomes included percentage of door-to-activation of neurological consult times ≤10 minutes and clinical effectiveness outcomes. Results were stratified between stroke and nonstroke centers. RESULTS: A total of 855 474 ED patient encounters occurred with 5325 code stroke activations (median age, 69 [IQR, 56-79] years; 51.8% female patients]. Percentage of door-to-activation times ≤10 minutes increased from 47.5% to 59.9% (adjusted odds ratio, 1.93 [95% CI, 1.40-2.67]). A total of 615 patients received tPA of ≤3 hours from symptom onset (median age, 71 [IQR, 58-80] years; 49.6% female patients). The percentage of DTN times ≤60 minutes increased from 72.5% to 86.1% (adjusted odds ratio, 3.38, [95% CI, 1.47-7.78]; stroke centers (77.4%-90.0%); nonstroke centers [59.3%-72.1%]). Median DTN time declined from 46 to 38 minutes (adjusted median difference, -9.68 [95% CI, -17.17 to -2.20]; stroke centers [41-35 minutes]; nonstroke centers [55-52 minutes]). No differences were observed in clinical effectiveness outcomes. CONCLUSIONS: A centrally led implementation strategy with local site tailoring led to faster delivery of tPA across disparate EDs in a multihospital system with no change in clinical effectiveness outcomes including rates of complication. Disparities in performance persisted between stroke and nonstroke centers.

Effect of copper on multiple successional stages of a marine fouling assemblage.

Copper based paints are used to prevent fouling on the hulls of ships. The widely documented effect of copper on hull assemblages may be primarily due to direct effects on the invertebrates themselves or indirect effects from copper absorbed into the microbial biofilm before settlement has commenced. Artificial units of habitat were exposed to varied regimes of copper to examine (1) the photosynthetic efficiency and pigments of early-colonising biofilms, and (2) subsequent macroinvertebrate assemblage change in response to the different regimes of copper. Macroinvertebrate assemblages were found to be less sensitive to the direct effects of copper than indirect effects as delivered through biofilms that have been historically exposed to copper, with some species more tolerant than others. This raises further concern for the efficacy of copper as a universal antifoulant on the hulls of ships, which may continue to assist the invasion of copper-tolerant invertebrate species.

Design, selection, and development of cyclic peptide ligands for human erythropoietin.

This work presents the selection and characterization of erythropoietin (EPO)-binding cyclic peptide ligands. The sequences were selected by screening a focused library of cyclic depsipeptides cyclo[(Nα-Ac)Dap(A)-X1-X6-AE], whose structure and amino acid compositions were tailored to mimic the EPO receptor. The sequences identified through library screening were synthesized on chromatographic resin and characterized via binding-and-elution studies against EPO to select a pool of candidate ligands. Sequences with higher hydrophobicity consistently showed stronger binding to EPO, with the exception of FSLLSH, which was noted for its lower hydrophobicity and high EPO binding. Mutagenesis studies performed on FSLLSH with natural and non-natural amino acid substitutions led to the identification of critical EPO-binding determinants, and the discovery of new peptide ligands. In particular, histidine-scanning mutagenesis performed on three lead sequences yielded the discovery of variants whose EPO-binding is more pH-sensitive, which facilitates EPO recovery. Selected ligands were studied to correlate the elution yield to the salinity of the binding buffer and the elution pH. Elution yields were consistently higher when EPO binding was performed at low ionic strength. The crystal structures of lead cyclic peptides were docked in silico against EPO to estimate the binding affinity in solution. Isotherm adsorption studies performed on FSLLSH indicated that the cyclic version of the ligand (KD=0.46µM) has a higher affinity for EPO than its corresponding linear variant (KD=1.44µM). Collectively, these studies set the stage for use of the cyclic peptide ligands as EPO purification and detection tools.

The lectotype of Goliathus drurii Westwood, 1837 (Coleoptera: Scarabaeidae: Cetoniinae) in the Macleay Museum, University of Sydney, Australia.

The lectotype of Goliathus drurii Westwood (Coleoptera: Scarabaeidae: Cetoniinae) has been located to the Macleay Museum, University of Sydney, Australia. Collected in 1775, this specimen represents the second species of Goliathus to be illustrated in European literature, however eluding a proper species description until 1837. This important specimen, overlooked by previous curators, represents another portion of the Dru Drury collections purchased by Alexander McLeay now held in the Macleay Museum.

An autophosphorylation site database for leucine-rich repeat receptor-like kinases in Arabidopsis thaliana.

Leucine-rich repeat receptor-like kinases (LRR RLKs) form a large family of plant signaling proteins consisting of an extracellular domain connected by a single-pass transmembrane sequence to a cytoplasmic kinase domain. Autophosphorylation on specific Ser and/or Thr residues in the cytoplasmic domain is often critical for the activation of several LRR RLK family members with proven functional roles in plant growth regulation, morphogenesis, disease resistance, and stress responses. While identification and functional characterization of in vivo phosphorylation sites is ultimately required for a full understanding of LRR RLK biology and function, bacterial expression of recombinant LRR RLK cytoplasmic catalytic domains for identification of in vitro autophosphorylation sites provides a useful resource for further targeted identification and functional analysis of in vivo sites. In this study we employed high-throughput cloning and a variety of mass spectrometry approaches to generate an autophosphorylation site database representative of more than 30% of the approximately 223 LRR RLKs in Arabidopsis thaliana. We used His-tagged constructs of complete cytoplasmic domains to identify a total of 592 phosphorylation events across 73 LRR RLKs, with 497 sites uniquely assigned to specific Ser (268 sites) or Thr (229 sites) residues in 68 LRR RLKs. Multiple autophosphorylation sites per LRR RLK were the norm, with an average of seven sites per cytoplasmic domain, while some proteins showed more than 20 unique autophosphorylation sites. The database was used to analyze trends in the localization of phosphorylation sites across cytoplasmic kinase subdomains and to derive a statistically significant sequence motif for phospho-Ser autophosphorylation.

Job Stress in the United Kingdom: Are Small and Medium-Sized Enterprises and Large Enterprises Different?

This paper examines the relationships between firm size and employees' experience of work stress. We used a matched employer-employee dataset (Workplace Employment Relations Survey 2011) that comprises of 7182 employees from 1210 private organizations in the United Kingdom. Initially, we find that employees in small and medium-sized enterprises experience lower level of overall job stress than those in large enterprises, although the effect disappears when we control for individual and organizational characteristics in the model. We also find that quantitative work overload, job insecurity and poor promotion opportunities, good work relationships and poor communication are strongly associated with job stress in the small and medium-sized enterprises, whereas qualitative work overload, poor job autonomy and employee engagements are more related with larger enterprises. Hence, our estimates show that the association and magnitude of estimated effects differ significantly by enterprise size.

Reversible cyclic peptide libraries for the discovery of affinity ligands.

A novel strategy is presented for the identification of cyclic peptide ligands from combinatorial libraries of reversible cyclic depsipeptides. A method for the solid-phase synthesis of individual cyclic depsipeptides and combinatorial libraries of these compounds is proposed, which employs lactic acid (Lact) and the dipeptide ester (Nα-Ac)-Ser(Ala)- as linkers for dilactonization. Upon alkaline treatment of the beads selected by screening a model library, the cyclic depsipeptides are linearized and released from the solid support to the liquid phase, to be sequenced via single-step tandem mass spectrometry (MS/MS). The protocol presented for library synthesis provides for wide structural diversity. Two model sequences, VVWVVK and AAWAAR, were chosen to present different structural examples for depsipeptide libraries and demonstrate the process of sequence determination by mass spectrometry. Further, a case study using the IgG binding cyclic depsipeptide cyclo[(Nα-Ac)-S(A)-RWHYFK-Lact-E] is presented to demonstrate the process of library screening and sequence determination on the selected beads. Finally, a method is shown for synthesis of the irreversible cyclic peptide corresponding to the proposed depsipeptide structure, to make the ligand stable to the aqueous acid and alkaline conditions encountered in affinity chromatographic applications. The cyclic peptide ligand was synthesized on a poly(methacrylate) resin and used for chromatographic binding of the target IgG.

Clinical documentation for patient care: models, concepts, and liability considerations for pharmacists.

PURPOSE: A guide to the appropriate documentation of the critical aspects of the patient medical record to ensure reimbursement and the reduction of medical liability is presented. SUMMARY: Several documentation styles can be adopted to record pharmacist interventions, including unstructured notes, semistructured notes, and systematic notes. Documentation should be clear, concise, legible, nonjudgmental, patient focused, and standardized, and it should ensure patient confidentiality. Systematic documentation styles include SOAP (subjective, objective, assessment, plan), TITRS (title, introduction, text, recommendation, signature), and FARM (findings, assessment, recommendations or resolutions, management). SOAP is the primary form for which payers traditionally reimburse. Systematic documentation should be used to demonstrate how pharmacist interventions improved patient care and should not just be used for reimbursement. Pharmacists have the opportunity to build a collaborative relationship with other professionals and with patients. Documentation can provide evidence of this symbiotic relationship where the pharmacist assists in providing a caring and compassionate environment for the patient's benefit. Professional liability, as it relates to clinical documentation, can be an issue. Documentation provides the necessary information to successfully manage the process of discovery and the review of the conduct of all parties involved in a liability issue. CONCLUSION: Documentation in a universal format allows for communication among health care practitioners. Written documentation is one key to a successful, open-communication partnership among providers. In addition, accurate, appropriate, and concise documentation is an essential component of ensuring that the patient care provided is evident, not only for patient safety and continuity but also for cases where reimbursement and quality of care are being challenged contractually or legally.

Explaining gender segregation.

Occupational gender segregation--the tendency for women and men to work in different occupations--is an important feature of all societies, and particularly the wealthy industrialized ones. To understand this segregation, and to explain its significance, we need to distinguish between vertical segregation entailing inequality and horizontal segregation representing difference without inequality, with overall segregation being the resultant of these components. Three major theoretical approaches to understanding occupational gender segregation are examined: human capital/rational choice, patriarchy, and preference theories. All are found to be inadequate; they tend to confuse overall segregation with its vertical component, and each entails a number of other faults. It is generally assumed or implied that greater empowerment of women would reduce gender segregation. This is the reverse of what actually happens; in countries where the degree of women's empowerment is greater, the level of gender segregation is also greater. An alternative theoretical approach based on processes of social reproduction is shown to be more useful.