Evidence into action: a policy brief exemplar supporting attainment of nursing now.

AIM: To provide a framework for the production of policy briefs, and offer a practical example of how evidence can be turned into a succinct document to inform policy and bring about change targeted at delivering universal health coverage. INTRODUCTION: Policymakers are too busy, or do not have the necessary expertise, to read and comprehend complex scientific papers. As a result, policy briefs that capture and present the essential points are needed if evidence-informed policy is to be developed and implemented. METHOD: A two-page example of how evidence from meta-analytical and systematic reviews can be presented to identify options and recommendations to address a major global disease burden. RESULTS: The example uses a simple, seven-section template for developing a policy brief. The essential characteristics of each section are provided. The briefing, targeted at the global level, provides information on the major challenges associated with the treatment of individuals with diabetes. DISCUSSION AND CONCLUSIONS: This paper demonstrates how to use existing research evidence to address the pursuit of UHC relevant to a wide range of geographies, settings or disadvantaged groups. IMPLICATIONS FOR POLICY: Gaps in universal health coverage and major disease burdens such as diabetes can be pursued through entities such as country-based Nursing Now groups. In addition, ongoing opportunities exist through the International Council of Nurses annual International Nurses Day and WHO's regular regional meetings to inform and influence policy discussions at national and subnational levels. By focusing on a small number of global topics each year, measurable changes in addressing the burden of disease can be achieved while simultaneously keeping the nursing profession's contribution centre stage.

Evidence-based policy: nursing now and the importance of research synthesis.

AIM: This study explores how scholarship relating to meta-analytical studies and systematic and integrative reviews can inform nursing's contribution to universal health coverage. INTRODUCTION: As nursing globally embraces the 200th anniversary of the birth of Florence Nightingale, the Nursing Now social movement has called for the profession to improve universal health coverage through increasing nursing's policy voice. METHODS: In determining how the Nursing Now social movement could pursue the aim of this study, researchers undertook a comparative bibliometric analysis of scholarship relating to the systematic curation of evidence. This study uses a mixed-method analysis of the bibliometric data available through extracting and synthesizing information from one of the commercially produced indexing and citation databases. RESULTS: Generally, medicine has contributed far more synthesized contributions than nursing, except in the case of integrative reviews. Co-occurrence analysis of nursing literature through examination of key terms yielded a complex visualization of 11 specific clusters of scholarship (Care of the Older Person, Nurse Education, Emergency and Critical Care, Occupational Health and Safety, Rural Services, Anxiety and Depression, Measurement, Newborn and Post-natal Health, Cardiovascular Disease, Preventative Health and Cancer Care). DISCUSSION AND CONCLUSIONS: Bibliometric analysis of curated evidence demonstrates that there is ample nursing-relevant material to inform evidence-based policy change directed towards the attainment of universal health coverage and several of the Sustainable Development Goals. IMPLICATIONS FOR POLICY: Nursing literature is available to support policy change directed towards the pursuit of universal health coverage and sustainable development goals. Leveraging existing networks of research collaboration to increase research capacity through communities of scholarship or by twinning experienced and neophyte contributors is possible. Further work is needed to equip nurses with the competencies to navigate the policy environment and develop and deliver impactful policy messaging.

Relation between image charge and potential alignment corrections for charged defects in periodic boundary conditions.

Charged defects are often studied within the periodic density functional theory (DFT), but this introduces strong finite-size artifacts. In this work, we develop an electrostatic image interaction correction (IIC) method based on the direct solution of the Poisson equation for charge models constructed directly from DFT calculations. These IICs are found to be detail-insensitive, depending almost entirely on bulk dielectric properties. As these IICs are not able to fully explain the observed finite-size scaling, we explore potential alignment in detail and introduce a novel decomposition to separate out different contributions. We find that the two main sources of potential alignment are defect image interactions and changes in the number of atoms present in the supercell. This first effect is accurately predicted by the periodic part of our IIC. The second contribution is unrelated to the IIC and justifies the common observation that the magnitude of finite-size dependence can strongly vary between vacancy and interstitial defects. It can be approximately predicted using atomic radius, but is strongly sensitive to the pseudopotential employed. Combined, these developments provide a new justification for known finite-size scaling rules. Our results suggest that for cubic supercells, the Lany-Zunger IIC, combined with simplified potential alignment between neutral systems, can yield accurate corrections in spite of the simplicity of the approach.

Influence of ions on two-dimensional and three-dimensional atomic force microscopy at fluorite-water interfaces.

Recent advancement in liquid-environment atomic force microscopy (AFM) has enabled us to visualize three-dimensional (3D) hydration structures as well as two-dimensional (2D) surface structures with subnanometer-scale resolution at solid-water interfaces. However, the influence of ions present in solution on the 2D- and 3D-AFM measurements has not been well understood. In this study, we perform atomic-scale 2D- and 3D-AFM measurements at fluorite-water interfaces in pure water and a supersaturated solution of fluorite. The images obtained in these two environments are compared to understand the influence of the ions in solution on these measurements. In the 2D images, we found clear difference in the nanoscale structures but no significant difference in the atomic-scale contrasts. However, the 3D force images show clear difference in the subnanometer-scale contrasts. The force contrasts measured in pure water largely agree with those expected from the molecular dynamics simulation and the solvent tip approximation model. In the supersaturated solution, an additional force peak is observed over the negatively charged fluorine ion site. This location suggests that the observed force peak may originate from cations adsorbed on the fluorite surface. These results demonstrate that the ions can significantly alter the subnanometer-scale force contrasts in the 3D-AFM images.

Engineering Polarons at a Metal Oxide Surface.

Polarons in metal oxides are important in processes such as catalysis, high temperature superconductivity, and dielectric breakdown in nanoscale electronics. Here, we study the behavior of electron small polarons associated with oxygen vacancies at rutile TiO_{2}(110), using a combination of low temperature scanning tunneling microscopy (STM), density functional theory, and classical molecular dynamics calculations. We find that the electrons are symmetrically distributed around isolated vacancies at 78 K, but as the temperature is reduced, their distributions become increasingly asymmetric, confirming their polaronic nature. By manipulating isolated vacancies with the STM tip, we show that particular configurations of polarons are preferred for given locations of the vacancies, which we ascribe to small residual electric fields in the surface. We also form a series of vacancy complexes and manipulate the Ti ions surrounding them, both of which change the associated electronic distributions. Thus, we demonstrate that the configurations of polarons can be engineered, paving the way for the construction of conductive pathways relevant to resistive switching devices.

PILOT EVALUATION OF A SIMPLE ADJUNCTIVE METHOD FOR IMPROVED REMOVAL OF ORAL BIOFILM DURING CONVENTIONAL SCALING AND ROOT PLANING THERAPY.

Various studies have evaluated the adjunctive use of chemical and antimicrobial treatments to assist in the mechanical removal of oral microbial biofilm from tissue surfaces during scaling and root planning therapy (SRP). The current study demonstrates the elimination of two classes of surrogate molecular markers from periodontal disease sites. This suggests the current agent may be a more effective adjunctive cleansing agent for complete biofilm removal. A patient with advanced chronic periodontitis was subjected to standard SRP therapy, supplemented by irrigation with HYBENX® (HBX). Samples of gingival crevicular fluid were collected with triplicate absorbent paper points from each of three quadrants at three time points: 1) at baseline prior to treatment; 2) after irrigation with the topical agent for 20 seconds and rinsing; and 3) after SRP followed by a second irrigation/rinsing treatment with the agent. Paper points were extracted to assess the presence of 13 bacterial species known to be primarily associated with periodontal disease using DNA pyrosequencing. In addition, the presence of Matrix Metalloproteinase-8 (MMP8), as well as IL-1ß, IL-6, and TNF-alpha were also assessed by immunoassay of the paper point sample extracts. The combined adjunctive treatment indicated a complete absence of detectable bacterial DNA and the four inflammatory mediators from samples taken from the gingival sulci treated with HBX. The advantage of the current adjunctive topical treatment technique is that it is simple and easy to administer in conjunction with standard SRP techniques. It appears to provide a level of cleanliness not currently achieved with other SRP adjunctive procedures.

Molecular phylogeny and evolution of the cone snails (Gastropoda, Conoidea).

We present a large-scale molecular phylogeny that includes 320 of the 761 recognized valid species of the cone snails (Conus), one of the most diverse groups of marine molluscs, based on three mitochondrial genes (COI, 16S rDNA and 12S rDNA). This is the first phylogeny of the taxon to employ concatenated sequences of several genes, and it includes more than twice as many species as the last published molecular phylogeny of the entire group nearly a decade ago. Most of the numerous molecular phylogenies published during the last 15years are limited to rather small fractions of its species diversity. Bayesian and maximum likelihood analyses are mostly congruent and confirm the presence of three previously reported highly divergent lineages among cone snails, and one identified here using molecular data. About 85% of the species cluster in the single Large Major Clade; the others are divided between the Small Major Clade (∼12%), the Conus californicus lineage (one species), and a newly defined clade (∼3%). We also define several subclades within the Large and Small major clades, but most of their relationships remain poorly supported. To illustrate the usefulness of molecular phylogenies in addressing specific evolutionary questions, we analyse the evolution of the diet, the biogeography and the toxins of cone snails. All cone snails whose feeding biology is known inject venom into large prey animals and swallow them whole. Predation on polychaete worms is inferred as the ancestral state, and diet shifts to molluscs and fishes occurred rarely. The ancestor of cone snails probably originated from the Indo-Pacific; rather few colonisations of other biogeographic provinces have probably occurred. A new classification of the Conidae, based on the molecular phylogeny, is published in an accompanying paper.

Full-genome dissection of an epidemic of severe invasive disease caused by a hypervirulent, recently emerged clone of group A Streptococcus.

Group A Streptococcus (GAS) causes an exceptionally broad range of infections in humans, from relatively mild pharyngitis and skin infections to life-threatening necrotizing fasciitis and toxic shock syndrome. An epidemic of severe invasive human infections caused by type emm59 GAS, heretofore an exceedingly rare cause of disease, spread west to east across Canada over a 3-year period (2006 to 2008). By sequencing the genomes of 601 epidemic, historic, and other emm59 organisms, we discovered that a recently emerged, genetically distinct emm59 clone is responsible for the Canadian epidemic. Using near-real-time genome sequencing, we were able to show spread of the Canadian epidemic clone into the United States. The extensive genome data permitted us to identify patterns of geographic dissemination as well as links between emm59 subclonal lineages that cause infections. Mouse and nonhuman primate models of infection demonstrated that the emerged clone is unusually virulent. Transmission of epidemic emm59 strains may have occurred primarily by skin contact, as suggested by an experimental model of skin transmission. In addition, the emm59 strains had a significantly impaired ability to persist in human saliva and to colonize the oropharynx of mice, and seldom caused human pharyngitis. Our study contributes new information to the rapidly emerging field of molecular pathogenomics of bacterial epidemics and illustrates how full-genome data can be used to precisely illuminate the landscape of strain dissemination during a bacterial epidemic.

Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group A Streptococcus.

Whole-genome sequencing of serotype M3 group A streptococci (GAS) from oropharyngeal and invasive infections in Ontario recently showed that the gene encoding regulator of protease B (RopB) is highly polymorphic in this population. To test the hypothesis that ropB is under diversifying selective pressure among all serotype M3 GAS strains, we sequenced this gene in 1178 strains collected from different infection types, geographic regions, and time periods. The results confirmed our hypothesis and discovered a significant association between mutant ropB alleles, decreased activity of its major regulatory target SpeB, and pharyngitis. Additionally, isoallelic strains with ropB polymorphisms were significantly less virulent in a mouse model of necrotizing fasciitis. These studies provide a model strategy for applying whole-genome sequencing followed by deep single-gene sequencing to generate new insight to the rapid evolution and virulence regulation of human pathogens.

Large variation of vacancy formation energies in the surface of crystalline ice.

Resolving the atomic structure of the surface of ice particles within clouds, over the temperature range encountered in the atmosphere and relevant to understanding heterogeneous catalysis on ice, remains an experimental challenge. By using first-principles calculations, we show that the surface of crystalline ice exhibits a remarkable variance in vacancy formation energies, akin to an amorphous material. We find vacancy formation energies as low as ~0.1-0.2 eV, which leads to a higher than expected vacancy concentration. Because a vacancy's reactivity correlates with its formation energy, ice particles may be more reactive than previously thought. We also show that vacancies significantly reduce the formation energy of neighbouring vacancies, thus facilitating pitting and contributing to pre-melting and quasi-liquid layer formation. These surface properties arise from proton disorder and the relaxation of geometric constraints, which suggests that other frustrated materials may possess unusual surface characteristics.

Chemical resolution at ionic crystal surfaces using dynamic atomic force microscopy with metallic tips.

We demonstrate that well prepared and characterized Cr tips can provide atomic resolution on the bulk NaCl(001) surface with dynamic atomic force microscopy in the noncontact regime at relatively large tip-sample separations. At these conditions, the surface chemical structure can be resolved yet tip-surface instabilities are absent. Our calculations demonstrate that chemical identification is unambiguous, because the interaction is always largest above the anions. This conclusion is generally valid for other polar surfaces, and can thus provide a new practical route for straightforward interpretation of atomically resolved images.

Deactivation of sodium tetradecyl sulphate injection by blood proteins.

OBJECTIVES: The aim of this work was to quantify the volume of blood required to deactivate 1 ml of 3% sodium tetradecyl sulphate (STS). DESIGN: A series of experiments were performed where the concentration of STS remaining in a stock solution was measured after adding increasing volumes of blood protein solutions. MATERIALS AND METHODS: Increasing volumes of bovine serum albumin, bovine erythrocytes and a mixture of both was added to a stock solution of STS. The BP manual titration method was used to measure the assay of the remaining STS. RESULTS: The method was reproducible and increasing volumes of blood protein lowered the STS concentration in a linear fashion. Approximately 2 ml of a 4% blood protein solution deactivates 1 ml of 3% STS, which means approximately 0.5 ml of whole blood will deactivate 1 ml of 3% STS. CONCLUSIONS: Sodium tetradecyl sulphate injection is deactivated by a relatively small volume of blood. The practical implication is that changes in technique to reduce the blood volume in larger veins and to introduce fresh aliquots of sclerosant along the length of the vein could improve the efficacy of sclerotherapy.

Reaginic antibody produced in mice with contact sensitivity.

Mice produced reaginic antibody within 1 wk of painting with the contact sensitizing agent picryl chloride. The titers, measured by passive cutaneous anaphylaxis in rats, increased after repeated applications of picryl chloride. In contrast, serum agglutinins did not increase after two applications of picryl chloride. Reagin was also elicited by another contact sensitizing agent, oxazolone. Some strain variation of the response to picryl chloride was found, with CBA mice being good responders and BALB/c and C57BL/10 mice being poor responders.

Developing evidence-based process maps for spinal cord injury rehabilitation.

STUDY DESIGN: Longitudinal audit. OBJECTIVES: To develop evidence-based maps of rehabilitation for different lesion categories. SETTING: Midlands, UK. METHODS: Over a 5-year period data for all newly injured neurologically damaged patients aged 18 years or more were collected and analyzed (n=280). Data were collected from a functional independence measure (the Needs Assessment Checklist), patient records (paper and electronic) and patient goal planning records. The patients were grouped into different lesion categories. Standard milestones that patients in a given category would be expected to reach in rehabilitation were identified using goals set at goal planning meetings. Time when patients reached these milestones and variation between patients around time in reaching these milestones were calculated. RESULTS: Median times from onset to admission, onset to rehabilitation and length of rehabilitation are given. Pictorial representations of rehabilitation (rehabilitation maps) were produced, using goals identified, median times of achievement and variation. This paper provides examples of these maps from one particular group, T8-T12 Frankel A. CONCLUSION: Pathways of care can be used in a number of ways: to identify the need for service change; to audit service change; to provide evidence-based expectations for staff, patients and external parties; to look at variances affecting care; to make this service transparent; to provide figures for comparison with other philosophies of care; and to ensure consistency across the service.

Soluble, semivolatile phenol and nitrogen compounds in milk-processing wastewaters.

Potable water is an essential and major input in processing our food supplies, and the continued growth in food manufacturing is placing increased pressure on this limited resource. Recycling and reuse of factory wastewater can lessen potable water use but requires a detailed understanding of wastewater properties. This study uses solid-phase extraction techniques with gas chromatography-mass spectrometry analysis to investigate trace-level semivolatile organic species in various waste and reference waters associated with the Burra Foods milk-processing plant located in Southeastern Australia. Our focus was on contaminants containing phenolic and heterocyclic nitrogen functional groups, which, because of their toxicity and persistence, may limit options for water recycling and reuse. Effluent from the wastewater treatment plant of the factory showed both the highest soluble carbon burden (47 mg/kg) and concentrations of target compounds. The target species found in these effluents included methyl phenol (13 mg/kg), hydroxy indole (9.8 mg/kg), synthetic tolyltriazoles (5.1 mg/kg) and alkyl phenol ethoxylates (0.2 mg/kg). Given the environmental stability of the tolyltriazoles, they may act as chemical markers where these effluents are used for purposes such as irrigation. Milk evaporator condensate waters, in contrast to the effluent, contained very few target species, with only low levels of pyrrolidine and piperidine derivatives such as ethylglutarimide (450 mug/L) detected. Although there were fewer target microcontaminants overall in the potable and creek reference waters, these samples had characteristic profiles. The potable water analysis revealed hydroxy cineole (2.1 microg/L) and the creek analysis revealed dichlorohydroxyacetophenone (0.3 microg/L), which were not detected in other waters. The compounds found in the wastewaters are likely to have been derived from milk or synthetic chemicals used in factory operations. The presence of nitrogen compounds in all the different milk-processing waters suggest their likely source was milk, probably milk phosphoproteins subjected to thermal, chemical, or microbial degradation. Our benign results for the condensates suggest it may be possible to substitute condensate for potable water with minimal pretreatment, both within the plant and in other applications, such as irrigation of recreation turf.

First-Principles Modeling of Polaron Formation in TiO2 Polymorphs.

We present a computationally efficient and predictive methodology for modeling the formation and properties of electron and hole polarons in solids. Through a nonempirical and self-consistent optimization of the fraction of Hartree-Fock exchange (α) in a hybrid functional, we ensure the generalized Koopmans' condition is satisfied and self-interaction error is minimized. The approach is applied to model polaron formation in known stable and metastable phases of TiO2 including anatase, rutile, brookite, TiO2(H), TiO2(R), and TiO2(B). Electron polarons are predicted to form in rutile, TiO2(H), and TiO2(R) (with trapping energies ranging from -0.02 eV to -0.35 eV). In rutile the electron localizes on a single Ti ion, whereas in TiO2(H) and TiO2(R) the electron is distributed across two neighboring Ti sites. Hole polarons are predicted to form in anatase, brookite, TiO2(H), TiO2(R), and TiO2(B) (with trapping energies ranging from -0.16 eV to -0.52 eV). In anatase, brookite, and TiO2(B) holes localize on a single O ion, whereas in TiO2(H) and TiO2(R) holes can also be distributed across two O sites. We find that the optimized α has a degree of transferability across the phases, with α = 0.115 describing all phases well. We also note the approach yields accurate band gaps, with anatase, rutile, and brookite within six percent of experimental values. We conclude our study with a comparison of the alignment of polaron charge transition levels across the different phases. Since the approach we describe is only two to three times more expensive than a standard density functional theory calculation, it is ideally suited to model charge trapping at complex defects (such as surfaces and interfaces) in a range of materials relevant for technological applications but previously inaccessible to predictive modeling.

A heterodyne dispersion interferometer for wide bandwidth density measurements on DIII-D.

In order to improve both the density and particularly the temporal resolution beyond previous dispersion interferometers (DIs), a heterodyne technique based on an acousto-optic (AO) cell has been added to the DI. A 40 MHz drive frequency for the AO cell allows density fluctuation measurements into the MHz range. A CO2 laser-based heterodyne DI (HDI) installed on DIII-D has demonstrated that the HDI is capable of tracking the density evolution throughout DIII-D discharges, including disruption events and other rapid transient phenomena. The data also show good agreement with independent density measurements obtained with the existing DIII-D two-color interferometer. The HDI line-integrated density resolution sampled over a 1 s interval is ∼9 × 1017 m-2. Density fluctuations induced by MHD instabilities are also successfully measured by the HDI.

Tests of a full-scale ITER toroidal interferometer and polarimeter (TIP) prototype on the DIII-D tokamak (invited).

A full-scale ITER toroidal interferometer and polarimeter (TIP) prototype, including an active feedback alignment system, has been installed and tested on the DIII-D tokamak. In the TIP prototype, a two-color interferometry measurement of line-integrated density is carried out at 10.59 µm and 5.22 µm using a CO2 and quantum cascade laser, respectively, while a separate polarimetry measurement of the plasma-induced Faraday effect is made at 10.59 µm. The TIP prototype is equipped with a piezo tip/tilt stage active feedback alignment system that minimizes noise in the measurement and keeps the diagnostic aligned throughout DIII-D discharges. The measured phase resolution for the polarimeter and interferometer is 0.05° (100 Hz bandwidth) and 1.9° (1 kHz bandwidth), respectively. The corresponding line-integrated density resolution for the vibration-compensated interferometer is δnL = 1.5 × 1018 m-2, and the magnetic field-weighted line-integrated density from the polarimeter is δnBL = 1.5 × 1019 Tm-2. Both interferometer and polarimeter measurements during DIII-D discharges compare well with the expectations based on calculations using Thomson scattering measured density profiles and magnetic equilibrium reconstructions. Additionally, larger bandwidth interferometer measurements show that the diagnostic is a sensitive monitor of core density fluctuations with demonstrated measurements of Alfvén eigenmodes and tearing modes.

A Cost-Effectiveness Analysis of Nintedanib in Idiopathic Pulmonary Fibrosis in the UK.

BACKGROUND: International guidelines recommend nintedanib (OFEV®) as an option for the treatment of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: The objective of this study was to assess the cost effectiveness of nintedanib versus pirfenidone, N-acetylcysteine and best supportive care (BSC) for the treatment of IPF from a UK payer's perspective. METHODS: A Markov model was designed to capture the changes in the condition of adults with IPF. Efficacy outcomes included mortality, lung function decline and acute exacerbations. Treatment safety (serious adverse events) and tolerability (overall discontinuation) were also considered. The baseline risk of these events was derived from patient-level data from the placebo arms of nintedanib clinical trials (TOMORROW, INPULSIS-1, INPULSIS-2). A network meta-analysis (NMA) was conducted to estimate the relative effectiveness of the comparator treatments. Quality of life and healthcare resource use data from the clinical trials were also incorporated in the economic model. RESULTS: Nintedanib showed statistically significant differences against placebo on acute exacerbation events avoided and lung function decline. In the cost-effectiveness analysis, the results were split between two treatments with relative low costs and modest effectiveness (BSC and N-acetylcysteine) and two that showed improved effectiveness (lung function) and higher costs (nintedanib and pirfenidone). All comparators were assumed to have similar projected survival and the difference in quality-adjusted life-years (QALYs) was driven by the acute exacerbations and lung function estimates. In the base-case deterministic pairwise comparison with pirfenidone, nintedanib was found to have fewer acute exacerbations and resulted in less costs and more QALYs gained. CONCLUSIONS: Compared with BSC (placebo), nintedanib and pirfenidone were the only treatments to show statistical significance in the efficacy parameters. We found substantial uncertainty in the overall cost-effectiveness results between nintedanib and pirfenidone. N-Acetylcysteine was largely similar to BSC but with a worse survival profile. INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.