3,791 research outputs found
Current status and advances in esophageal drug delivery technology:influence of physiological, pathophysiological and pharmaceutical factors
Diseases affecting the esophagus are common. However, targeted drug delivery to the esophagus is challenging due to the anatomy and physiology of this organ. Current pharmacological treatment for esophageal diseases predominantly relies on the off-label use of drugs in various dosage forms, including those for systemic drug delivery (e.g. oral tablets, sublingual tablets, and injections) and topical drug delivery (e.g. metered dose inhaler, viscous solution or suspension, and endoscopic injection into the esophagus). In general, systemic therapy has shown the most efficacy but requires the use of high drug doses to achieve effective concentrations in the esophagus, which increases the risk of adverse effects and toxicity. Topical drug delivery has enormous potential in improving the way we treat patients with acute and chronic esophageal diseases, especially those requiring drugs that have low therapeutic index and/or significant adverse effects to non-targeted organs and tissues. This review will address the physiological, pathophysiological, and pharmaceutical considerations influencing topical drug delivery in the esophagus. The main conventional (e.g. liquid formulations, orodispersible tablets, lozenges, pastilles, troches, chewing gum) and innovative (e.g. stent-based, film-based, nanoparticulate-based) drug delivery approaches will be comprehensively discussed, along with the developments to improve their effectiveness for topical esophageal drug delivery. The translational challenges and future clinical advances of this research will also be discussed.</p
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Designing theoretically-informed implementation interventions
Clinical and health services research is continually producing new findings that may contribute to effective and efficient patient care. However, the transfer of research findings into practice is unpredictable and can be a slow and haphazard process. Ideally, the choice of implementation strategies would be based upon evidence from randomised controlled trials or systematic reviews of a given implementation strategy. Unfortunately, reviews of implementation strategies consistently report effectiveness some, but not all of the time; possible causes of this variation are seldom reported or measured by the investigators in the original studies. Thus, any attempts to extrapolate from study settings to the real world are hampered by a lack of understanding of the effects of key elements of individuals, interventions, and the settings in which they were trialled. The explicit use of theory offers a way of addressing these issues and has a number of advantages, such as providing: a generalisable framework within which to represent the dimensions that implementation studies address, a process by which to inform the development and delivery of interventions, a guide when evaluating, and a way to allow for an exploration of potential causal mechanisms. However, the use of theory in designing implementation interventions is methodologically challenging for a number of reasons, including choosing between theories and faithfully translating theoretical constructs into interventions. The explicit use of theory offers potential advantages in terms of facilitating a better understanding of the generalisability and replicability of implementation interventions. However, this is a relatively unexplored methodological area
XMM-Newton observation of the ultraluminous quasar SDSS J010013.02+280225.8 at redshift 6.326
A brief Chandra observation of the ultraluminous quasar SDSS J010013.02+280225.8 at redshift 6.326 showed it to be a relatively bright, soft X-ray source with a count rate of about 1 count ks−1. In this article, we present results for the quasar from a 65-ks XMM–Newton observation, which constrains its spectral shape well. The quasar is clearly detected with a total of ~460 net counts in the 0.2–10 keV band. The spectrum is characterized by a simple power-law model with a photon index of = 2.30+0.10 −0.10 and the intrinsic 2–10 keV luminosity is 3.14 × 1045 erg s−1. The 1σ upper limit to any intrinsic absorption column density is NH = 6.07 × 1022 cm−2. No significant iron emission lines were detected. We derive an X-rayto-optical flux ratio αox of −1.74 ± 0.01, consistent with the values found in other quasars of comparable ultraviolet luminosity. We did not detect significant flux variations either in the XMM–Newton exposure or between XMM–Newton and Chandra observations, which are separated by ∼8 months. The X-ray observation enables the bolometric luminosity to be calculated after modelling the spectral energy distribution: the accretion rate is found to be sub-Eddington
Undergraduate medical textbooks do not provide adequate information on intravenous fluid therapy: a systematic survey and suggestions for improvement
<b>Background</b><p></p>
Inappropriate prescribing of intravenous (IV) fluid, particularly 0.9% sodium chloride, causes post-operative complications. Fluid prescription is often left to junior medical staff and is frequently poorly managed. One reason for poor intravenous fluid prescribing practices could be inadequate coverage of this topic in the textbooks that are used.<p></p>
<b>Methods</b><p></p>
We formulated a comprehensive set of topics, related to important common clinical situations involving IV fluid therapy, (routine fluid replacement, fluid loss, fluids overload) to assess the adequacy of textbooks in common use. We assessed 29 medical textbooks widely available to students in the UK, scoring the presence of information provided by each book on each of the topics. The scores indicated how fully the topics were considered: not at all, partly, and adequately. No attempt was made to judge the quality of the information, because there is no consensus on these topics.<p></p>
<b>Results</b><p></p>
The maximum score that a book could achieve was 52. Three of the topics we chose were not considered by any of the books. Discounting these topics as “too esoteric”, the maximum possible score became 46. One textbook gained a score of 45, but the general score was poor (median 11, quartiles 4, 21). In particular, coverage of routine postoperative management was inadequate.<p></p>
<b>Conclusions</b><p></p>
Textbooks for undergraduates cover the topic of intravenous therapy badly, which may partly explain the poor knowledge and performance of junior doctors in this important field. Systematic revision of current textbooks might improve knowledge and practice by junior doctors. Careful definition of the remit and content of textbooks should be applied more widely to ensure quality and “fitness for purpose”, and avoid omission of vital knowledge
The Effect of Transposable Element Insertions on Gene Expression Evolution in Rodents
Background:Many genomes contain a substantial number of transposable elements (TEs), a few of which are known to be involved in regulating gene expression. However, recent observations suggest that TEs may have played a very important role in the evolution of gene expression because many conserved non-genic sequences, some of which are know to be involved in gene regulation, resemble TEs. Results:Here we investigate whether new TE insertions affect gene expression profiles by testing whether gene expression divergence between mouse and rat is correlated to the numbers of new transposable elements inserted near genes. We show that expression divergence is significantly correlated to the number of new LTR and SINE elements, but not to the numbers of LINEs. We also show that expression divergence is not significantly correlated to the numbers of ancestral TEs in most cases, which suggests that the correlations between expression divergence and the numbers of new TEs are causal in nature. We quantify the effect and estimate that TE insertion has accounted for ~20% (95% confidence interval: 12% to 26%) of all expression profile divergence in rodents. Conclusions:We conclude that TE insertions may have had a major impact on the evolution of gene expression levels in rodents
Using psychological theory to understand the clinical management of type 2 diabetes in Primary Care : a comparison across two European countries
Peer reviewedPublisher PD
Current status and advances in esophageal drug delivery technology: influence of physiological, pathophysiological and pharmaceutical factors
Diseases affecting the esophagus are common. However, targeted drug delivery to the esophagus is challenging due to the anatomy and physiology of this organ. Current pharmacological treatment for esophageal diseases predominantly relies on the off-label use of drugs in various dosage forms, including those for systemic drug delivery (e.g. oral tablets, sublingual tablets, and injections) and topical drug delivery (e.g. metered dose inhaler, viscous solution or suspension, and endoscopic injection into the esophagus). In general, systemic therapy has shown the most efficacy but requires the use of high drug doses to achieve effective concentrations in the esophagus, which increases the risk of adverse effects and toxicity. Topical drug delivery has enormous potential in improving the way we treat patients with acute and chronic esophageal diseases, especially those requiring drugs that have low therapeutic index and/or significant adverse effects to non-targeted organs and tissues. This review will address the physiological, pathophysiological, and pharmaceutical considerations influencing topical drug delivery in the esophagus. The main conventional (e.g. liquid formulations, orodispersible tablets, lozenges, pastilles, troches, chewing gum) and innovative (e.g. stent-based, film-based, nanoparticulate-based) drug delivery approaches will be comprehensively discussed, along with the developments to improve their effectiveness for topical esophageal drug delivery. The translational challenges and future clinical advances of this research will also be discussed
Motivations and barriers to prosthesis users participation in physical activity, exercise and sport : a review of the literature
The UK will host the Paralympics in 2012 and the Commonwealth Games in 2014 showcasing the talents of elite athletes and aiming to inspire the population to become involved. However, low levels of physical activity (PA) are prevalent: only 40% of men and 28% of women meet the minimum UK recommendations. The limb absent population is no exception. To determine if people with limb amputations are participating in physical activity and sport; whether post-amputation activity levels match pre-amputation levels; and if there are motivations and barriers to participation. Study design: Literature review Five reviewers systematically search of peer reviewed and gray literature in seven bibliographic databases and the Cochrane Library. Results: Following rigorous elimination, 12 articles were finally included in the review and critically appraised. Four themes were identified: components, rehabilitation outcomes, body image and motivations and barriers to participation. People with limb absence are not participating in PA conducive to health benefits, and only a minority participate in exercise and sports. Participation following amputation does not mirror that of pre-amputation levels, and more barriers than motivations exist to adopting and maintaining a physically active lifestyle. This literature review aims to inform those involved in rehabilitation and ongoing care of those with limb absence about what motivates or precludes their participation in physical activity, exercise and sport. Such knowledge could be applied to improving health and well being in this population
Astronomical Spectroscopy
Spectroscopy is one of the most important tools that an astronomer has for
studying the universe. This chapter begins by discussing the basics, including
the different types of optical spectrographs, with extension to the ultraviolet
and the near-infrared. Emphasis is given to the fundamentals of how
spectrographs are used, and the trade-offs involved in designing an
observational experiment. It then covers observing and reduction techniques,
noting that some of the standard practices of flat-fielding often actually
degrade the quality of the data rather than improve it. Although the focus is
on point sources, spatially resolved spectroscopy of extended sources is also
briefly discussed. Discussion of differential extinction, the impact of
crowding, multi-object techniques, optimal extractions, flat-fielding
considerations, and determining radial velocities and velocity dispersions
provide the spectroscopist with the fundamentals needed to obtain the best
data. Finally the chapter combines the previous material by providing some
examples of real-life observing experiences with several typical instruments.Comment: An abridged version of a chapter to appear in Planets, Stars and
Stellar Systems, to be published in 2011 by Springer. Slightly revise
Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors
MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UV–vis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately -500 mV (vs. the standard hydrogen electrode). Across this potential window the UV–vis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled low-spin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate
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