Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field

Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials

BACKGROUND: Randomized controlled trials play a central role in evidence-based practice, but recruitment of participants, and retention of them once in the trial, is challenging. Moreover, there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies. As with other healthcare initiatives, the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives, which for recruitment would mean embedding a recruitment trial within an ongoing host trial. Systematic reviews indicate that such studies are rare. Embedded trials are largely delivered in an ad hoc way, with interventions almost always developed in isolation and tested in the context of a single host trial, limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to researchers working in different contexts. METHODS/DESIGN: The Systematic Techniques for Assisting Recruitment to Trials (START) program is funded by the United Kingdom Medical Research Council (MRC) Methodology Research Programme to support the routine adoption of embedded trials to test standardized recruitment interventions across ongoing host trials. To achieve this aim, the program involves three interrelated work packages: (1) methodology - to develop guidelines for the design, analysis and reporting of embedded recruitment studies; (2) interventions - to develop effective and useful recruitment interventions; and (3) implementation - to recruit host trials and test interventions through embedded studies. DISCUSSION: Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or, potentially, other types of intervention linked to trial conduct. It will also increase the evidence base for two types of recruitment intervention. TRIAL REGISTRATION: The START protocol covers the methodology for embedded trials. Each embedded trial is registered separately or as a substudy of the host trial

Antimony-doped graphene nanoplatelets

Heteroatom doping into the graphitic frameworks have been intensively studied for the development of metal-free electrocatalysts. However, the choice of heteroatoms is limited to non-metallic elements and heteroatom-doped graphitic materials do not satisfy commercial demands in terms of cost and stability. Here we realize doping semimetal antimony (Sb) at the edges of graphene nanoplatelets (GnPs) via a simple mechanochemical reaction between pristine graphite and solid Sb. The covalent bonding of the metalloid Sb with the graphitic carbon is visualized using atomic-resolution transmission electron microscopy. The Sb-doped GnPs display zero loss of electrocatalytic activity for oxygen reduction reaction even after 100,000 cycles. Density functional theory calculations indicate that the multiple oxidation states (Sb3+ and Sb5+) of Sb are responsible for the unusual electrochemical stability. Sb-doped GnPs may provide new insights and practical methods for designing stable carbon-based electrocatalystsclose0

Strain- and Adsorption-Dependent Electronic States and Transport or Localization in Graphene

The chapter generalizes results on influence of uniaxial strain and adsorption on the electron states and charge transport or localization in graphene with different configurations of imperfections (point defects): resonant (neutral) adsorbed atoms either oxygen- or hydrogen-containing molecules or functional groups, vacancies or substitutional atoms, charged impurity atoms or molecules, and distortions. To observe electronic properties of graphene-admolecules system, we applied electron paramagnetic resonance technique in a broad temperature range for graphene oxides as a good basis for understanding the electrotransport properties of other active carbons. Applied technique allowed observation of possible metal-insulator transition and sorption pumping effect as well as discussion of results in relation to the granular metal model. The electronic and transport properties are calculated within the framework of the tight-binding model along with the Kubo-Greenwood quantum-mechanical formalism. Depending on electron density and type of the sites, the conductivity for correlated and ordered adsorbates is found to be enhanced in dozens of times as compared to the cases of their random distribution. In case of the uniaxially strained graphene, the presence of point defects counteracts against or contributes to the band-gap opening according to their configurations. The band-gap behaviour is found to be nonmonotonic with strain in case of a simultaneous action of defect ordering and zigzag deformation. The amount of localized charge carriers (spins) is found to be correlated with the content of adsorbed centres responsible for the formation of potential barriers and, in turn, for the localization effects. Physical and chemical states of graphene edges, especially at a uniaxial strain along one of them, play a crucial role in electrical transport phenomena in graphene-based materials.Comment: 16 pages, 10 figure

Enhanced convective heat transfer using graphene dispersed nanofluids

Nanofluids are having wide area of application in electronic and cooling industry. In the present work, hydrogen exfoliated graphene (HEG) dispersed deionized (DI) water, and ethylene glycol (EG) based nanofluids were developed. Further, thermal conductivity and heat transfer properties of these nanofluids were systematically investigated. HEG was synthesized by exfoliating graphite oxide in H2 atmosphere at 200°C. The nanofluids were prepared by dispersing functionalized HEG (f-HEG) in DI water and EG without the use of any surfactant. HEG and f-HEG were characterized by powder X-ray diffractometry, electron microscopy, Raman and FTIR spectroscopy. Thermal and electrical conductivities of f-HEG dispersed DI water and EG based nanofluids were measured for different volume fractions and at different temperatures. A 0.05% volume fraction of f-HEG dispersed DI water based nanofluid shows an enhancement in thermal conductivity of about 16% at 25°C and 75% at 50°C. The enhancement in Nusselts number for these nanofluids is more than that of thermal conductivity

Direct nitrogen fixation at the edges of graphene nanoplatelets as efficient electrocatalysts for energy conversion

Nitrogen fixation is essential for the synthesis of many important chemicals (e.g., fertilizers, explosives) and basic building blocks for all forms of life (e.g., nucleotides for DNA and RNA, amino acids for proteins). However, direct nitrogen fixation is challenging as nitrogen (N2) does not easily react with other chemicals. By dry ball-milling graphite with N2, we have discovered a simple, but versatile, scalable and eco-friendly, approach to direct fixation of N2 at the edges of graphene nanoplatelets (GnPs). The mechanochemical cracking of graphitic C-C bonds generated active carbon species that react directly with N2 to form five- and six-membered aromatic rings at the broken edges, leading to solution-processable edge-nitrogenated graphene nanoplatelets (NGnPs) with superb catalytic performance in both dye-sensitized solar cells and fuel cells to replace conventional Pt-based catalysts for energy conversion.open302

Antimicrobial management and appropriateness of treatment of urinary tract infection in general practice in Ireland

<p>Abstract</p> <p>Background</p> <p>Urinary tract infections (UTIs) are the second most common bacterial infections in general practice and a frequent indication for prescription of antimicrobials. Increasing concern about the association between the use of antimicrobials and acquired antimicrobial resistance has highlighted the need for rational pharmacotherapy of common infections in general practice.</p> <p>Methods</p> <p>Management of urinary tract infections in general practice was studied prospectively over 8 weeks. Patients presenting with suspected UTI submitted a urine sample and were enrolled with an opt-out methodology. Data were collected on demographic variables, previous antimicrobial use and urine samples. Appropriateness of different treatment scenarios was assessed by comparing treatment with the laboratory report of the urine sample.</p> <p>Results</p> <p>A total of 22 practices participated in the study and included 866 patients. Bacteriuria was established for 21% of the patients, pyuria without bacteriuria for 9% and 70% showed no laboratory evidence of UTI. An antimicrobial agent was prescribed to 56% (481) of the patients, of whom 33% had an isolate, 11% with pyuria only and 56% without laboratory evidence of UTI. When taking all patients into account, 14% patients had an isolate identified and were prescribed an antimicrobial to which the isolate was susceptible. The agents most commonly prescribed for UTI were co-amoxyclav (33%), trimethoprim (26%) and fluoroquinolones (17%). Variation between practices in antimicrobial prescribing as well as in their preference for certain antimicrobials, was observed. Treatment as prescribed by the GP was interpreted as appropriate for 55% of the patients. Three different treatment scenarios were simulated, i.e. if all patients who received an antimicrobial were treated with nitrofurantoin, trimethoprim or ciprofloxacin only. Treatment as prescribed by the GP was no more effective than treatment with nitrofurantoin for all patients given an antimicrobial or treatment with ciprofloxacin in all patients. Prescribing cost was lower for nitrofurantoin. Empirical treatment of all patients with trimethoprim only was less effective due to the higher resistance levels.</p> <p>Conclusions</p> <p>There appears to be considerable scope to reduce the frequency and increase the quality of antimicrobial prescribing for patients with suspected UTI.</p

Magnetodielectric effect of Graphene-PVA Nanocomposites

Graphene-Polyvinyl alcohol (PVA) nanocomposite films with thickness $120 \mu m$ were synthesized by solidification of PVA in a solution with dispersed graphene nanosheets. Electrical conductivity data were explained as arising due to hopping of carriers between localized states formed at the graphene-PVA interface. Dielectric permittivity data as a function of frequency indicated the occurrence of Debye-type relaxation mechanism. The nanocomposites showed a magnetodielectric effect with the dielectric constant changing by 1.8% as the magnetic field was increased to 1 Tesla. The effect was explained as arising due to Maxwell-Wagner polarization as applied to an inhomogeneous two-dimensional,two-component composite model. This type of nanocomposite may be suitable for applications involving nanogenerators.Comment: 13 pages, 11 figure

Visualizing Graphene Based Sheets by Fluorescence Quenching Microscopy

Graphene based sheets have stimulated great interest due to their superior mechanical, electrical and thermal properties. A general visualization method that allows quick observation of these single atomic layers would be highly desirable as it can greatly facilitate sample evaluation and manipulation, and provide immediate feedback to improve synthesis and processing strategies. Here we report that graphene based sheets can be made highly visible under a fluorescence microscope by quenching the emission from a dye coating, which can be conveniently removed afterwards by rinsing without disrupting the sheets. Current imaging techniques for graphene based sheets rely on the use of special substrates. In contrast, the fluorescence quenching mechanism is no longer limited by the types of substrates. Graphene, reduced graphene oxide, or even graphene oxide sheets deposited on arbitrary substrates can now be readily visualized by eye with good contrast for layer counting. Direct observation of suspended sheets in solution was also demonstrated. The fluorescence quenching microscopy offers unprecedented imaging flexibility and could become a general tool for characterizing graphene based materials.Comment: J. Am. Chem. Soc., Article ASA

Longitudinal unzipping of carbon nanotubes to form graphene nanoribbons.

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