A research protocol for developing a Point-Of-Care Key Evidence Tool 'POCKET': a checklist for multidimensional evidence reporting on point-of-care in vitro diagnostics.

INTRODUCTION: Point-of-care in vitro diagnostics (POC-IVD) are increasingly becoming widespread as an acceptable means of providing rapid diagnostic results to facilitate decision-making in many clinical pathways. Evidence in utility, usability and cost-effectiveness is currently provided in a fragmented and detached manner that is fraught with methodological challenges given the disruptive nature these tests have on the clinical pathway. The Point-of-care Key Evidence Tool (POCKET) checklist aims to provide an integrated evidence-based framework that incorporates all required evidence to guide the evaluation of POC-IVD to meet the needs of policy and decisionmakers in the National Health Service (NHS). METHODS AND ANALYSIS: A multimethod approach will be applied in order to develop the POCKET. A thorough literature review has formed the basis of a robust Delphi process and validation study. Semistructured interviews are being undertaken with POC-IVD stakeholders, including industry, regulators, commissioners, clinicians and patients to understand what evidence is required to facilitate decision-making. Emergent themes will be translated into a series of statements to form a survey questionnaire that aims to reach a consensus in each stakeholder group to what needs to be included in the tool. Results will be presented to a workshop to discuss the statements brought forward and the optimal format for the tool. Once assembled, the tool will be field-tested through case studies to ensure validity and usability and inform refinement, if required. The final version will be published online with a call for comments. Limitations include unpredictable sample representation, development of compromise position rather than consensus, and absence of blinding in validation exercise. ETHICS AND DISSEMINATION: The Imperial College Joint Research Compliance Office and the Imperial College Hospitals NHS Trust R&D department have approved the protocol. The checklist tool will be disseminated through a PhD thesis, a website, peer-reviewed publication, academic conferences and formal presentations

ASTROD and ASTROD I -- Overview and Progress

In this paper, we present an overview of ASTROD (Astrodynamical Space Test of Relativity using Optical Devices) and ASTROD I mission concepts and studies. The missions employ deep-space laser ranging using drag-free spacecraft to map the gravitational field in the solar-system. The solar-system gravitational field is determined by three factors: the dynamic distribution of matter in the solar system; the dynamic distribution of matter outside the solar system (galactic, cosmological, etc.) and gravitational waves propagating through the solar system. Different relativistic theories of gravity make different predictions of the solar-system gravitational field. Hence, precise measurements of the solar-system gravitational field test all these. The tests and observations include: (i) a precise determination of the relativistic parameters beta and gamma with 3-5 orders of magnitude improvement over previous measurements; (ii) a 1-2 order of magnitude improvement in the measurement of G-dot; (iii) a precise determination of any anomalous, constant acceleration Aa directed towards the Sun; (iv) a measurement of solar angular momentum via the Lense-Thirring effect; (v) the detection of solar g-mode oscillations via their changing gravity field, thus, providing a new eye to see inside the Sun; (vi) precise determination of the planetary orbit elements and masses; (viii) better determination of the orbits and masses of major asteroids; (ix) detection and observation of gravitational waves from massive black holes and galactic binary stars in the frequency range 0.05 mHz to 5 mHz; and (x) exploring background gravitational-waves.Comment: 17 pages, 6 figures, presented to The Third International ASTROD Symposium on Laser Astrodynamics, Space Test of Relativity and Gravitational-Wave Astronomy, Beijing, July 14-16, 2006; International Journal of Modern Physics D, in press (2008

Mitochondrial dynamics and mitochondrial quality control

AbstractMitochondria are cellular energy powerhouses that play important roles in maintaining cell survival, cell death and cellular metabolic homeostasis. Timely removal of damaged mitochondria via autophagy (mitophagy) is thus critical for cellular homeostasis and function. Mitochondria are reticular organelles that have high plasticity for their dynamic structures and constantly undergo fission and fusion as well as movement through the cytoskeleton. In this review, we discuss the most recent progress on the molecular mechanisms and roles of mitochondrial fission/fusion and mitochondrial motility in mitophagy. We also discuss multiple pathways leading to the quality control of mitochondria in addition to the traditional mitophagy pathway under different conditions

Electronic Feedback or Handwritten Feedback: What Do Undergraduate Students Prefer and Why?

Giving feedback on students’ assignments is, by no means, new to faculty. Yet, when it comes to handwritten feedback delivered in person and typed feedback delivered electronically to students, faculty may not know what undergraduate students prefer and reasons behind their preferences. The present study explored which form of feedback, i.e., electronic or handwritten feedback, undergraduate students preferred and rationale behind their preferences. Two hundred fifty respondents completed an online survey, which consisted of three closed-ended questions and two open-ended questions. Nonparametric tests were used to analyze the quantitative data. Qualitative responses were read and analyzed by four researchers and six themes were identified. The qualitative data were rechecked against the six themes independently first and then collectively. Discrepancies were discussed before complete consensus was made. The study found that nearly 70% of the participants preferred e-feedback for its accessibility, timeliness, and legibility. Yet, with respect to the quality of feedback, the majority of handwritten supporters chose handwritten feedback, as they perceived this type of feedback as more personal. The article discusses the marked discrepancies between the two groups and ends with educational implications and suggestions for future research

Muon Spin Rotation Measurement of the Magnetic Field Penetration Depth in Ba(Fe0.93 Co0.07)2 As2 : Evidence for Multiple Superconducting Gaps

We have performed transverse field muon spin rotation measurements of single crystals of Ba(Fe$_{0.93}$Co$_{0.07})_2$As$_2$ with the applied magnetic field along the $\hat{c}$ direction. Fourier transforms of the measured spectra reveal an anisotropic lineshape characteristic of an Abrikosov vortex lattice. We have fit the $\mu$SRSR spectra to a microscopic model in terms of the penetration depth $\lambda$ and the Ginzburg-Landau parameter $\kappa$. We find that as a function of temperature, the penetration depth varies more rapidly than in standard weak coupled BCS theory. For this reason we first fit the temperature dependence to a power law where the power varies from 1.6 to 2.2 as the field changes from 200G to 1000G. Due to the surprisingly strong field dependence of the power and the superfluid density we proceeded to fit the temperature dependence to a two gap model, where the size of the two gaps is field independent. From this model, we obtained gaps of $2\Delta_1=3.7k_BT_c$ and $2\Delta_2=1.6k_BT_c$, corresponding to roughly 6 meV and 3 meV respectively

Optical pulse-shaping for internal cooling of molecules

We consider the use of pulse-shaped broadband femtosecond lasers to optically cool rotational and vibrational degrees of freedom of molecules. Since this approach relies on cooling rotational and vibrational quanta by exciting an electronic transition, it is most easily applicable to molecules with similar ground and excited potential energy surfaces, such that the vibrational state is usually unchanged during electronic relaxation. Compared with schemes that cool rotations by exciting vibrations, this approach achieves internal cooling on the orders-of- magnitude faster electronic decay timescale and is potentially applicable to apolar molecules. For AlH+, a candidate species, a rate-equation simulation indicates that rovibrational equilibrium should be achievable in 8 \mu s. In addition, we report laboratory demonstration of optical pulse shaping with sufficient resolution and power for rotational cooling of AlH+

Structures of monomeric and oligomeric forms of the Toxoplasma gondiiperforin-like protein 1

Toxoplasma and Plasmodium are the parasitic agents of toxoplasmosis and malaria, respectively, and use perforin-like proteins (PLPs) to invade host organisms and complete their life cycles. The Toxoplasma gondii PLP1 (TgPLP1) is required for efficient exit from parasitophorous vacuoles in which proliferation occurs. We report structures of the membrane attack complex/perforin (MACPF) and Apicomplexan PLP C-terminal β-pleated sheet (APCβ) domains of TgPLP1. The MACPF domain forms hexameric assemblies, with ring and helix geometries, and the APCβ domain has a novel β-prism fold joined to the MACPF domain by a short linker. Molecular dynamics simulations suggest that the helical MACPF oligomer preserves a biologically important interface, whereas the APCβ domain binds preferentially through a hydrophobic loop to membrane phosphatidylethanolamine, enhanced by the additional presence of inositol phosphate lipids. This mode of membrane binding is supported by site-directed mutagenesis data from a liposome-based assay. Together, these structural and biophysical findings provide insights into the molecular mechanism of membrane targeting by TgPLP1

Superfluid Density and Field-Induced Magnetism in Ba(Fe1-xCox)2As2 and Sr(Fe1-xCox)2As2 Measured with Muon Spin Relaxation

We report muon spin rotation ($\mu$SR) measurements of single crystal Ba(Fe$_{1-x}$Co$_x$)$_2$As$_2$ and Sr(Fe$_{1-x}$Co$_x$)$_2$As$_2$. From measurements of the magnetic field penetration depth $\lambda$ we find that for optimally- and over-doped samples, $1/\lambda(T\to 0)^2$ varies monotonically with the superconducting transition temperature T$_{\rm C}$. Within the superconducting state we observe a positive shift in the muon precession signal, likely indicating that the applied field induces an internal magnetic field. The size of the induced field decreases with increasing doping but is present for all Co concentrations studied.Comment: 7 pages, accepted for publication in Phys. Rev.

Prospects in the orbital and rotational dynamics of the Moon with the advent of sub-centimeter lunar laser ranging

Lunar Laser Ranging (LLR) measurements are crucial for advanced exploration of the laws of fundamental gravitational physics and geophysics. Current LLR technology allows us to measure distances to the Moon with a precision approaching 1 millimeter. As NASA pursues the vision of taking humans back to the Moon, new, more precise laser ranging applications will be demanded, including continuous tracking from more sites on Earth, placing new CCR arrays on the Moon, and possibly installing other devices such as transponders, etc. Successful achievement of this goal strongly demands further significant improvement of the theoretical model of the orbital and rotational dynamics of the Earth-Moon system. This model should inevitably be based on the theory of general relativity, fully incorporate the relevant geophysical processes, lunar librations, tides, and should rely upon the most recent standards and recommendations of the IAU for data analysis. This paper discusses methods and problems in developing such a mathematical model. The model will take into account all the classical and relativistic effects in the orbital and rotational motion of the Moon and Earth at the sub-centimeter level. The new model will allow us to navigate a spacecraft precisely to a location on the Moon. It will also greatly improve our understanding of the structure of the lunar interior and the nature of the physical interaction at the core-mantle interface layer. The new theory and upcoming millimeter LLR will give us the means to perform one of the most precise fundamental tests of general relativity in the solar system.Comment: 26 pages, submitted to Proc. of ASTROCON-IV conference (Princeton Univ., NJ, 2007