A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve.

AimsThe mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.Materials and resultsRandomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041).ConclusionsIn this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects.Trial registrationclinicaltrials.gov Identifier: NCT01342029

Spin gap in the Quasi-One-Dimensional S=1/2 Antiferromagnet: Cu2(1,4-diazacycloheptane)2Cl4

Cu_{2}(1,4-diazacycloheptane)_{2}Cl_{4} contains double chains of spin 1/2 Cu^{2+} ions. We report ac susceptibility, specific heat, and inelastic neutron scattering measurements on this material. The magnetic susceptibility, $\chi(T)$, shows a rounded maximum at T = 8 K indicative of a low dimensional antiferromagnet with no zero field magnetic phase transition. We compare the $\chi(T)$ data to exact diagonalization results for various one dimensional spin Hamiltonians and find excellent agreement for a spin ladder with intra-rung coupling $J_1 = 1.143(3)$ meV and two mutually frustrating inter-rung interactions: $J_2 = 0.21(3)$ meV and $J_3 = 0.09(5)$ meV. The specific heat in zero field is exponentially activated with an activation energy $\Delta = 0.89(1)$ meV. A spin gap is also found through inelastic neutron scattering on powder samples which identify a band of magnetic excitations for $0.8 < \hbar\omega < 1.5$ meV. Using sum-rules we derive an expression for the dynamic spin correlation function associated with non-interacting propagating triplets in a spin ladder. The van-Hove singularities of such a model are not observed in our scattering data indicating that magnetic excitations in Cu_{2}(1,4-diazacycloheptane)_{2}Cl_{4} are more complicated. For magnetic fields above $H_{c1} \simeq 7.2$ T specific heat data versus temperature show anomalies indicating a phase transition to an ordered state below T = 1 K.Comment: 9 pages, 8 postscript figures, LaTeX, Submitted to PRB 8/4/97, e-mail Comments to [email protected]

Excitation Spectrum and Superexchange Pathways in the Spin Dimer VODPO_4 . 1/2 D_2O

Magnetic excitations have been investigated in the spin dimer material VODPO_4 \cdot 1/2 D_2O using inelastic neutron scattering. A dispersionless magnetic mode was observed at an energy of 7.81(4) meV. The wavevector dependence of the scattering intensityfrom this mode is consistent with the excitation of isolated V^{4+} spin dimers with a V-V separation of 4.43(7) \AA. This result is unexpected since the V-V pair previously thought to constitute themagnetic dimer has a separation of 3.09 \AA. We identify an alternative V-V pair as the likely magnetic dimer, which involves superexchange pathways through a covalently bonded PO_4 group. This surprising result casts doubt on the interpretation of (VO)_2P_2O_7 as a spin ladder.Comment: 4 pages, 4 postscript figures - identical to previous paper but figure 2 and 3 hopefully more compatible .p

Recent advances in electronic structure theory and their influence on the accuracy of ab initio potential energy surfaces

Recent advances in electronic structure theory and the availability of high speed vector processors have substantially increased the accuracy of ab initio potential energy surfaces. The recently developed atomic natural orbital approach for basis set contraction has reduced both the basis set incompleteness and superposition errors in molecular calculations. Furthermore, full CI calculations can often be used to calibrate a CASSCF/MRCI approach that quantitatively accounts for the valence correlation energy. These computational advances also provide a vehicle for systematically improving the calculations and for estimating the residual error in the calculations. Calculations on selected diatomic and triatomic systems will be used to illustrate the accuracy that currently can be achieved for molecular systems. In particular, the F+H2 yields HF+H potential energy hypersurface is used to illustrate the impact of these computational advances on the calculation of potential energy surfaces

Innovation in assessment: building student confidence in preparation for unfamiliar assessment methods

Innovative assessment methods in which students are active participants promote deeper learning. A group debate and a webfolio were implemented as methods of assessment in the 2015 undergraduate midwifery curriculum, with the assessment tools being evaluated by students. Thematic analysis of the evaluations showed students enjoyed undertaking innovative methods of assessment, they developed confidence and engaged meaningfully with the content to be assessed. Students also commented they developed multiple skills required for future professional practice as a midwife. Thorough preparation of students to undertake an innovative method of assessment however is vital in fostering student confidence

The K2 M67 Study: A Curiously Young Star in an Eclipsing Binary in an Old Open Cluster

We present an analysis of a slightly eccentric ($e=0.05$), partially eclipsing long-period ($P = 69.73$ d) main sequence binary system (WOCS 12009, Sanders 1247) in the benchmark old open cluster M67. Using Kepler K2 and ground-based photometry along with a large set of new and reanalyzed spectra, we derived highly precise masses ($1.111\pm0.015$ and $0.748\pm0.005 M_\odot$) and radii ($1.071\pm0.008\pm0.003$ and $0.713\pm0.019\pm0.026 R_\odot$, with statistical and systematic error estimates) for the stars. The radius of the secondary star is in agreement with theory. The primary, however, is approximately $15\%$ smaller than reasonable isochrones for the cluster predict. Our best explanation is that the primary star was produced from the merger of two stars, as this can also account for the non-detection of photospheric lithium and its higher temperature relative to other cluster main sequence stars at the same $V$ magnitude. To understand the dynamical characteristics (low measured rotational line broadening of the primary star and the low eccentricity of the current binary orbit), we believe that the most probable (but not the only) explanation is the tidal evolution of a close binary within a primordial triple system (possibly after a period of Kozai-Lidov oscillations), leading to merger approximately 1Gyr ago. This star appears to be a future blue straggler that is being revealed as the cluster ages and the most massive main sequence stars die out.Comment: 33 pages, 11 figures, accepted to AJ, photometry files will be available with the electronic journal articl

From the cell membrane to the nucleus: unearthing transport mechanisms for Dynein

Mutations in the motor protein cytoplasmic dynein have been found to cause Charcot-Marie-Tooth disease, spinal muscular atrophy, and severe intellectual disabilities in humans. In mouse models, neurodegeneration is observed. We sought to develop a novel model which could incorporate the effects of mutations on distance travelled and velocity. A mechanical model for the dynein mediated transport of endosomes is derived from first principles and solved numerically. The effects of variations in model parameter values are analysed to find those that have a significant impact on velocity and distance travelled. The model successfully describes the processivity of dynein and matches qualitatively the velocity profiles observed in experiments

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods