Telescope to Observe Planetary Systems (TOPS): a high throughput 1.2-m visible telescope with a small inner working angle

The Telescope to Observe Planetary Systems (TOPS) is a proposed space mission to image in the visible (0.4-0.9 micron) planetary systems of nearby stars simultaneously in 16 spectral bands (resolution R~20). For the ~10 most favorable stars, it will have the sensitivity to discover 2 R_E rocky planets within habitable zones and characterize their surfaces or atmospheres through spectrophotometry. Many more massive planets and debris discs will be imaged and characterized for the first time. With a 1.2m visible telescope, the proposed mission achieves its power by exploiting the most efficient and robust coronagraphic and wavefront control techniques. The Phase-Induced Amplitude Apodization (PIAA) coronagraph used by TOPS allows planet detection at 2 lambda/d with nearly 100% throughput and preserves the telescope angular resolution. An efficient focal plane wavefront sensing scheme accurately measures wavefront aberrations which are fed back to the telescope active primary mirror. Fine wavefront control is also performed independently in each of 4 spectral channels, resulting in a system that is robust to wavefront chromaticity.Comment: 12 pages, SPIE conference proceeding, May 2006, Orlando, Florid

Physicians Infrequently Adhere to Hepatitis Vaccination Guidelines for Chronic Liver Disease

Background and Goals:Hepatitis A (HAV) and hepatitis B (HBV) vaccination in patients with chronic liver disease is an accepted standard of care. We determined HAV and HBV vaccination rates in a tertiary care referral hepatology clinic and the impact of electronic health record (EHR)-based reminders on adherence to vaccination guidelines.Methods:We reviewed the records of 705 patients with chronic liver disease referred to our liver clinic in 2008 with at least two follow-up visits during the subsequent year. Demographics, referral source, etiology, and hepatitis serology were recorded. We determined whether eligible patients were offered vaccination and whether patients received vaccination. Barriers to vaccination were determined by a follow-up telephone interview.Results:HAV and HBV serologic testing prior to referral and at the liver clinic were performed in 14.5% and 17.7%; and 76.7% and 74% patients, respectively. Hepatologists recommended vaccination for HAV in 63% and for HBV in 59.7% of eligible patients. Patient demographics or disease etiology did not influence recommendation rates. Significant variability was observed in vaccination recommendation amongst individual providers (30-98.6%), which did not correlate with the number of patients seen by each physician. Vaccination recommendation rates were not different for Medicare patients with hepatitis C infection for whom a vaccination reminder was automatically generated by the EHR. Most patients who failed to get vaccination after recommendation offered no specific reason for noncompliance; insurance was a barrier in a minority.Conclusions:Hepatitis vaccination rates were suboptimal even in an academic, sub-speciality setting, with wide-variability in provider adherence to vaccination guidelines. © 2013 Thudi et al

Development of evidence-based clinical practice guidelines (CPGs): comparing approaches

<p>Abstract</p> <p>Background</p> <p>While the potential of clinical practice guidelines (CPGs) to support implementation of evidence has been demonstrated, it is not currently being achieved. CPGs are both poorly developed and ineffectively implemented. To improve clinical practice and health outcomes, both well-developed CPGs and effective methods of CPG implementation are needed. We sought to establish whether there is agreement on the fundamental characteristics of an evidence-based CPG development process and to explore whether the level of guidance provided in CPG development handbooks is sufficient for people using these handbooks to be able to apply it.</p> <p>Methods</p> <p>CPG development handbooks were identified through a broad search of published and grey literature. Documents published in English produced by national or international organisations purporting to support development of evidence-based CPGs were included. A list of 14 key elements of a CPG development process was developed. Two authors read each handbook. For each handbook a judgement was made as to how it addressed each element; assigned as: 'mentioned and clear guidance provided', 'mentioned but limited practical detail provided ', or 'not mentioned'.</p> <p>Results</p> <p>Six CPG development handbooks were included. These were produced by the Council of Europe, the National Health and Medical Research Council of Australia, the National Institute for Health and Clinical Excellence in the UK, the New Zealand Guidelines Group, the Scottish Intercollegiate Guideline Network, and the World Health Organization (WHO).</p> <p>There was strong concordance between the handbooks on the key elements of an evidence-based CPG development process. All six of the handbooks require and provide guidance on establishment of a multidisciplinary guideline development group, involvement of consumers, identification of clinical questions or problems, systematic searches for and appraisal of research evidence, a process for drafting recommendations, consultation with others beyond the guideline development group, and ongoing review and updating of the CPG.</p> <p>Conclusion</p> <p>The key elements of an evidence-based CPG development process are addressed with strong concordance by existing CPG development handbooks. Further research is required to determine why these key elements are often not addressed by CPG developers.</p

The systematic guideline review: method, rationale, and test on chronic heart failure

Background: Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources-especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development-the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF). Methods: A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline. Results: Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) - the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer. Conclusion: The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines

TOPS: a small space telescope using phase induced-amplitude apodization (PIAA) to image rocky and giant exo-planets

The Telescope to Observe Planetary Systems (TOPS) is a proposed space mission to image planetary systems of nearby stars simultaneously in a few wide spectral bands covering the visible light (0.4-0.9 μm). It achieves its power by combining a high accuracy wavefront control system with a highly efficient Phase-Induced Amplitude Apodization (PIAA) coronagraph which provides strong suppression very close to the star (within 2 λ/D). The PIAA coronagraphic technique opens the possibility of imaging Earthlike planets in visible light with a smaller telescope than previously supposed. If sized at 1.2-m, TOPS would image and characterize many Jupiter-sized planets, and discover 2 RE rocky planets within habitable zones of the ≈10 most favorable stars. With a larger 2-m aperture, TOPS would have the sensitivity to reveal Earth-like planets in the habitable zone around ≈20 stars, and to characterize any found with low resolution spectroscopy. Unless the occurrence of Earth-like planets is very low (η⊕ <~ 0.2), a useful fraction of the TPF-C scientific program would be possible with aperture much smaller than the baselined 8 by 3.5m for TPF, with its more conventional coronagraph. An ongoing laboratory experiment has successfully demonstrated high contrast coronagraphic imaging within 2 λ/d with the PIAA coronagraph / focal plane wavefront sensing scheme envisioned for TOPS

Automated Builder and Database of Protein/Membrane Complexes for Molecular Dynamics Simulations

Molecular dynamics simulations of membrane proteins have provided deeper insights into their functions and interactions with surrounding environments at the atomic level. However, compared to solvation of globular proteins, building a realistic protein/membrane complex is still challenging and requires considerable experience with simulation software. Membrane Builder in the CHARMM-GUI website (http://www.charmm-gui.org) helps users to build such a complex system using a web browser with a graphical user interface. Through a generalized and automated building process including system size determination as well as generation of lipid bilayer, pore water, bulk water, and ions, a realistic membrane system with virtually any kinds and shapes of membrane proteins can be generated in 5 minutes to 2 hours depending on the system size. Default values that were elaborated and tested extensively are given in each step to provide reasonable options and starting points for both non-expert and expert users. The efficacy of Membrane Builder is illustrated by its applications to 12 transmembrane and 3 interfacial membrane proteins, whose fully equilibrated systems with three different types of lipid molecules (DMPC, DPPC, and POPC) and two types of system shapes (rectangular and hexagonal) are freely available on the CHARMM-GUI website. One of the most significant advantages of using the web environment is that, if a problem is found, users can go back and re-generate the whole system again before quitting the browser. Therefore, Membrane Builder provides the intuitive and easy way to build and simulate the biologically important membrane system

Continuum Molecular Simulation of Large Conformational Changes during Ion–Channel Gating

A modeling framework was developed to simulate large and gradual conformational changes within a macromolecule (protein) when its low amplitude high frequency vibrations are not concerned. Governing equations were derived as alternative to Langevin and Smoluchowski equations and used to simulate gating conformational changes of the Kv7.1 ion-channel over the time scale of its gating process (tens of milliseconds). The alternative equations predict the statistical properties of the motion trajectories with good accuracy and do not require the force field to be constant over the diffusion length, as assumed in Langevin equation. The open probability of the ion–channel was determined considering cooperativity of four subunits and solving their concerted transition to the open state analytically. The simulated open probabilities for a series of voltage clamp tests produced current traces that were similar to experimentally recorded currents