Decreasing central-line-associated bloodstream infections in Connecticut intensive care units.

Central-line-associated bloodstream infections (CLABSIs) are a significant cause of preventable harm. A collaborative project involving a multifaceted intervention was used in the Michigan Keystone Project and associated with significant reductions in these infections. This intervention included the Comprehensive Unit-based Safety Program, a multifaceted approach to CLABSI prevention, and the monitoring and reporting of infections.

Principles for understanding the accuracy of SHAPE-directed RNA structure modeling.

Accurate RNA structure modeling is an important, incompletely solved, challenge. Single-nucleotide resolution SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) yields an experimental measurement of local nucleotide flexibility that can be incorporated as pseudo-free energy change constraints to direct secondary structure predictions. Prior work from our laboratory has emphasized both the overall accuracy of this approach and the need for nuanced interpretation of modeled structures.

Safety in numbers 4: The relationship between exposure to authentic and didactic environments and nursing students' learning of medication dosage calculation problem solving knowledge and skills.

Advancing the art and science of education practice requires a robust evaluation of the relationship between students' exposure to learning and assessment environments and the development of their cognitive competence (knowing that and why) and functional competence (know-how and skills). Healthcare education translation research requires specific education technology assessments and evaluations that consist of quantitative analyses of empirical data and qualitative evaluations of the lived student experience of the education journey and schemata construction (Weeks et al., 2013a).

Safety in numbers 7: Veni, vidi, duci: a grounded theory evaluation of nursing students' medication dosage calculation problem-solving schemata construction.

This paper evaluates nursing students' transition through schemata construction and competence development in medication dosage calculation problem-solving (MDC-PS). We advance a grounded theory from interview data that reflects the experiences and perceptions of two groups of undergraduate pre-registration nursing students: eight students exposed to a prototype authentic MDC-PS environment and didactic transmission methods of education and 15 final year students exposed to the safeMedicate authentic MDC-PS environment. We advance a theory of how classroom-based 'chalk and talk' didactic transmission environments offered multiple barriers to accurate MDC-PS schemata construction among novice students.

Statistical analysis of SHAPE-directed RNA secondary structure modeling.

The ability to predict RNA secondary structure is fundamental for understanding and manipulating RNA function. The information obtained from selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) experiments greatly improves the accuracy of RNA secondary structure prediction. Recently, Das and colleagues [Kladwang, W.

Safety in numbers 5: Evaluation of computer-based authentic assessment and high fidelity simulated OSCE environments as a framework for articulating a point of registration medication dosage calculation benchmark.

This paper reports a key educational initiative undertaken by NHS Education for Scotland (NES), based upon recommendations from a 'Numeracy in Healthcare' consultation. We report here the design of a web-based technical measurement authentic assessment environment evolved from the safeMedicate suite of programs that provided a model for an environment within which a medication dosage calculation problem-solving (MDC-PS) benchmark could be articulated. A sample of 63 third-year pre-registration nursing students was recruited from four participating universities in the UK.

Safety in numbers 2: Competency modelling and diagnostic error assessment in medication dosage calculation problem-solving.

Accurately defining and modelling competence in medication dosage calculation problem-solving (MDC-PS) is a fundamental pre-requisite to measuring competence, diagnosing errors and determining the necessary design and content of professional education programmes. In this paper we advance an MDC-PS competence model that illustrates the relationship between conceptual competence (dosage problem-understanding), calculation competence (dosage-computation) and technical measurement competence (dosage-measurement). To facilitate bridging of the theory-practice gap it is critical that such models are operationalised within a wider education framework that supports the learning, assessment and synthesis of cognitive competence (the knowing that and knowing why of MDC-PS) and functional competence (the know-how and skills associated with the professional practice of MDC-PS in clinical settings).

Safety in numbers 1: Essential numerical and scientific principles underpinning medication dose calculation.

Registered nurses spend up to 40% of their professional clinical practice engaged in the art and science of medication dosage calculation problem-solving (MDC-PS). In advancing this patient safety critical discipline it is our position that as a profession we must first situate MDC-PS within the context of the wider features of the nursing numeracy, medicines management and clinical pharmacokinetic domains that inform its practice. This paper focuses on the essential relationship between numeracy, healthcare numeracy, medicines management, pharmacokinetics and MDC-PS.

Safety in numbers 6: Tracking pre-registration nursing students' cognitive and functional competence development in medication dosage calculation problem-solving: the role of authentic learning and diagnostic assessment environments.

Tracking the progress of pre-registration nursing students' medication dosage calculation problem-solving (MDC-PS) competence development is critical both to ensure achievement of professional and regulatory requirements and to evaluate the validity and reliability of nursing education preparation programmes. This paper focuses on the outcomes of a three-year professional healthcare education evaluation study that tracked the progress of 210 nursing students following the foundation programme and child, adult, mental health and learning disability branch programmes of a UK undergraduate pre-registration nursing degree programme. Outcome measures indicated that despite many students displaying a range of arithmetical deficits on entry to the undergraduate programme, exposure to the safeMedicate environment and practice based learning environments facilitated all 210 participants demonstration of:

QuShape: rapid, accurate, and best-practices quantification of nucleic acid probing information, resolved by capillary electrophoresis.

Chemical probing of RNA and DNA structure is a widely used and highly informative approach for examining nucleic acid structure and for evaluating interactions with protein and small-molecule ligands. Use of capillary electrophoresis to analyze chemical probing experiments yields hundreds of nucleotides of information per experiment and can be performed on automated instruments. Extraction of the information from capillary electrophoresis electropherograms is a computationally intensive multistep analytical process, and no current software provides rapid, automated, and accurate data analysis.

Safety in numbers 3: Authenticity, Building knowledge & skills and Competency development & assessment: the ABC of safe medication dosage calculation problem-solving pedagogy.

When designing learning and assessment environments it is essential to articulate the underpinning education philosophy, theory, model and learning style support mechanisms that inform their structure and content. We elaborate on original PhD research that articulates the design rationale of authentic medication dosage calculation problem-solving (MDC-PS) learning and diagnostic assessment environments. These environments embody the principles of authenticity, building knowledge and skills and competency assessment and are designed to support development of competence and bridging of the theory-practice gap.

Fingerprinting noncanonical and tertiary RNA structures by differential SHAPE reactivity.

Many RNA structures are composed of simple secondary structure elements linked by a few critical tertiary interactions. SHAPE chemistry has made interrogation of RNA dynamics at single-nucleotide resolution straightforward. However, de novo identification of nucleotides involved in tertiary interactions remains a challenge.

Safety in numbers: an introduction to the Nurse Education in Practice series.

This paper introduces this Nurse Education in Practice 'Safety in Numbers' series. We introduce the background and seven papers that explore the outcomes of a 20-year programme of healthcare education translation research and education action research that focuses on medication dosage calculation problem-solving (MDC-PS) education.

Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin.

Follistatin is essential for skeletal muscle development and growth, but the intracellular signaling networks that regulate follistatin-mediated effects are not well defined. We show here that the administration of an adeno-associated viral vector expressing follistatin-288aa (rAAV6:Fst-288) markedly increased muscle mass and force-producing capacity concomitant with increased protein synthesis and mammalian target of rapamycin (mTOR) activation. These effects were attenuated by inhibition of mTOR or deletion of S6K1/2.

Phosphoinositide 3-kinase p110α is a master regulator of exercise-induced cardioprotection and PI3K gene therapy rescues cardiac dysfunction.

Background: Numerous molecular and biochemical changes have been linked with the cardioprotective effects of exercise, including increases in antioxidant enzymes, heat shock proteins, and regulators of cardiac myocyte proliferation. However, a master regulator of exercise-induced protection has yet to be identified. Here, we assess whether phosphoinositide 3-kinase (PI3K) p110α is essential for mediating exercise-induced cardioprotection, and if so, whether its activation independent of exercise can restore function of the failing heart.

Accelerometer-based, portable navigation vs imageless, large-console computer-assisted navigation in total knee arthroplasty: a comparison of radiographic results.

Computer-assisted surgery (CAS) systems improve alignment accuracy in total knee arthroplasty (TKA) but have not been widely implemented. Eighty knees underwent TKA using an accelerometer-based, portable navigation device (KneeAlign 2; OrthAlign Inc, Aliso Viejo, California), and the radiographic results were compared with 80 knees performed using a large-console, imageless CAS system (AchieveCAS; Smith and Nephew, Memphis, Tennessee). In the KneeAlign 2 cohort, 92.

Three-dimensional RNA structure refinement by hydroxyl radical probing.

Molecular modeling guided by experimentally derived structural information is an attractive approach for three-dimensional structure determination of complex RNAs that are not amenable to study by high-resolution methods. Hydroxyl radical probing (HRP), which is performed routinely in many laboratories, provides a measure of solvent accessibility at individual nucleotides. HRP measurements have, to date, only been used to evaluate RNA models qualitatively.

The mechanisms of RNA SHAPE chemistry.

The biological functions of RNA are ultimately governed by the local environment at each nucleotide. Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistry is a powerful approach for measuring nucleotide structure and dynamics in diverse biological environments. SHAPE reagents acylate the 2'-hydroxyl group at flexible nucleotides because unconstrained nucleotides preferentially sample rare conformations that enhance the nucleophilicity of the 2'-hydroxyl.

RNA-Puzzles: a CASP-like evaluation of RNA three-dimensional structure prediction.

We report the results of a first, collective, blind experiment in RNA three-dimensional (3D) structure prediction, encompassing three prediction puzzles. The goals are to assess the leading edge of RNA structure prediction techniques; compare existing methods and tools; and evaluate their relative strengths, weaknesses, and limitations in terms of sequence length and structural complexity. The results should give potential users insight into the suitability of available methods for different applications and facilitate efforts in the RNA structure prediction community in ongoing efforts to improve prediction tools.

Using the Opportunity Estimator tool to improve engagement in a quality and safety intervention.

Teams throughout the United States participating in a program to reduce central line-associated bloodstream infections (CLABSIs) are using the Opportunity Estimator. This web-based tool translates CLABSI-related data into "opportunity estimates" of the patient lives and money that could be saved by reducing these infections.

SHAPE-directed discovery of potent shRNA inhibitors of HIV-1.

The RNA interference (RNAi) pathway can be exploited using short hairpin RNAs (shRNAs) to durably inactivate pathogenic genes. Prediction of optimal target sites is notoriously inaccurate and current approaches applied to HIV-1 show weak correlations with virus inhibition. In contrast, using a high-content model for disrupting pre-existing intramolecular structure in the HIV-1 RNA, as achievable using high-resolution SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) chemical probing information, we discovered strong correlations between inhibition of HIV-1 production in a quantitative cell-based assay and very simple thermodynamic features in the target RNA.

Impact of age, race and decade of treatment on overall survival in a critical population analysis of 40,000 multiple myeloma patients.

With the availability of novel agents, the overall survival (OS) in patients diagnosed with multiple myeloma (MM) has improved over the last decade. Data on 40,294 MM patients in the years from 1973 to 2003 were obtained from the Surveillance, Epidemiology, and End Results Program (SEER) of the US National Cancer Institute. Statistical analyses evaluating gender, race, age, and year of diagnosis were performed using univariate and multivariate Cox regression models for the OS endpoint.