Genetic testing in Marfan syndrome

Genetic testing is aiding rapid diagnosis of Marfan syndrome as a basis for management of eye, heart and skeletal disease. The affected patient's mutation can be used as a basis for prenatal or postnatal diagnosis of offspring. Preimplantation genetic diagnosis, the technique of choice, can ensure an unaffected pregnancy

The Multi-center Evaluation of the Accuracy of the Contrast MEdium INduced Pd/Pa RaTiO in Predicting FFR (MEMENTO-FFR) Study.

AIMS: Adenosine administration is needed for the achievement of maximal hyperaemia fractional flow reserve (FFR) assessment. The objective was to test the accuracy of Pd/Pa ratio registered during submaximal hyperaemia induced by non-ionic contrast medium (contrast FFR [cFFR]) in predicting FFR and comparing it to the performance of resting Pd/Pa in a collaborative registry of 926 patients enrolled in 10 hospitals from four European countries (Italy, Spain, France and Portugal). METHODS AND RESULTS: Resting Pd/Pa, cFFR and FFR were measured in 1,026 coronary stenoses functionally evaluated using commercially available pressure wires. cFFR was obtained after intracoronary injection of contrast medium, while FFR was measured after administration of adenosine. Resting Pd/Pa and cFFR were significantly higher than FFR (0.93±0.05 vs. 0.87±0.08 vs. 0.84±0.08, p<0.001). A strong correlation and a close agreement at Bland-Altman analysis between cFFR and FFR were observed (r=0.90, p<0.001 and 95% CI of disagreement: from -0.042 to 0.11). ROC curve analysis showed an excellent accuracy (89%) of the cFFR cut-off of ≤0.85 in predicting an FFR value ≤0.80 (AUC 0.95 [95% CI: 0.94-0.96]), significantly better than that observed using resting Pd/Pa (AUC: 0.90, 95% CI: 0.88-0.91; p<0.001). A cFFR/FFR hybrid approach showed a significantly lower number of lesions requiring adenosine than a resting Pd/Pa/FFR hybrid approach (22% vs. 44%, p<0.0001). CONCLUSIONS: cFFR is accurate in predicting the functional significance of coronary stenosis. This could allow limiting the use of adenosine to obtain FFR to a minority of stenoses with considerable savings of time and costs.info:eu-repo/semantics/publishedVersio

Explicit flock solutions for Quasi-Morse potentials

We consider interacting particle systems and their mean-field limits, which are frequently used to model collective aggregation and are known to demonstrate a rich variety of pattern formations. The interaction is based on a pairwise potential combining short-range repulsion and long-range attraction. We study particular solutions, that are referred to as flocks in the second-order models, for the specific choice of the Quasi-Morse interaction potential. Our main result is a rigorous analysis of continuous, compactly supported flock profiles for the biologically relevant parameter regime. Existence and uniqueness is proven for three space dimension, whilst existence is shown for the two-dimensional case. Furthermore, we numerically investigate additional Morse-like interactions to complete the understanding of this class of potentials.Comment: 26 page

The application of a cavity ring-down spectrometer to measurements of ambient ammonia using traceable primary standard gas mixtures

A correction for the undesirable effects of direct and indirect cross-interference from water vapour on ammonia (NH$_3$) measurements was developed using an optical laser sensor based on cavity ring-down spectroscopy. This correction relied on new measurements of the collisional broadening due to water vapour of two NH$_3$ spectral lines in the near infra-red (6548.6 and 6548.8 cm$^{−1}$), and on the development of novel stable primary standard gas mixtures (PSMs) of ammonia prepared by gravimetry in passivated gas cylinders at 100 μmol mol$^{−1}$. The PSMs were diluted dynamically to provide calibration mixtures of dry and humidified ammonia atmospheres of known composition in the nmol mol$^{−1}$ range and were employed as part of establishing a metrological traceability chain to improve the reliability and accuracy of ambient ammonia measurements. The successful implementation of this correction will allow the extension of this rapid on-line spectroscopic technique to exposure chamber validation tests under controlled conditions and ambient monitoring in the field.We gratefully acknowledge the funding received from the Chemical and Biological Metrology Programme of the UK Department for Business, Innovation and Skills (BIS) and the European Metrology Research Programme (EMRP) of the European Union. The EMRP is jointly funded by the EMRP participating countries within EURAMET and the European Union.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00340-016-6486-

Deubiquitylating enzymes and drug discovery: emerging opportunities

More than a decade after a Nobel Prize was awarded for the discovery of the ubiquitin-proteasome system and clinical approval of proteasome and ubiquitin E3 ligase inhibitors, first-generation deubiquitylating enzyme (DUB) inhibitors are now approaching clinical trials. However, although our knowledge of the physiological and pathophysiological roles of DUBs has evolved tremendously, the clinical development of selective DUB inhibitors has been challenging. In this Review, we discuss these issues and highlight recent advances in our understanding of DUB enzymology and biology as well as technological improvements that have contributed to the current interest in DUBs as therapeutic targets in diseases ranging from oncology to neurodegeneration.The authors thank L. Greger for the generation of the phylogenic tree. Research in the S.P.J. laboratory is funded by the Cancer Research UK (CRUK) Program Grant C6/A18796 and a Wellcome Trust Investigator Award (206388/Z/17/Z), and institute core infrastructure funding is provided by the CRUK (C6946/A24843) and the Wellcome Trust (WT203144)

Rapid Spatial Mapping of Focused Ultrasound Fields Using a Planar Fabry-Pérot Sensor

Measurement of high acoustic pressures is necessary in order to fully characterise clinical high-intensity focused ultrasound (HIFU) fields, and for accurate validation of computational models of ultrasound propagation. However, many existing measurement devices are unable to withstand the extreme pressures generated in these fields, and those that can often exhibit low sensitivity. Here, a planar Fabry-Pérot interferometer with hard dielectric mirrors and spacer was designed, fabricated, and characterised and its suitability for measurement of nonlinear focused ultrasound fields was investigated. The noise equivalent pressure of the scanning system scaled with the adjustable pressure detection range between 49 kPa for pressures up to 8 MPa and 152 kPa for measurements up to 25 MPa, over a 125 MHz measurement bandwidth. Measurements of the frequency response of the sensor showed that it varied by less than 3 dB in the range 1 - 62 MHz. The effective element size of the sensor was 65 μm and waveforms were acquired at a rate of 200 Hz. The device was used to measure the acoustic pressure in the field of a 1.1 MHz single element spherically focused bowl transducer. Measurements of the acoustic field at low pressures compared well with measurements made using a PVDF needle hydrophone. At high pressures, the measured peak focal pressures agreed well with the focal pressure modelled using the Khokhlov-Zabolotskaya-Kuznetsov equation. Maximum peak positive pressures of 25 MPa, and peak negative pressures of 12 MPa were measured, and planar field scans were acquired in scan times on the order of 1 minute. The properties of the sensor and scanning system are well suited to measurement of nonlinear focused ultrasound fields, in both the focal region and the low pressure peripheral regions. The fast acquisition speed of the system and its low noise equivalent pressure are advantageous, and with further development of the sensor, it has potential in application to HIFU metrology

Self-beating instabilities in bistable devices

Since the observation of optical bistability by Gibbs et al., optical bistability has been the field where researchers from many fields have found a common place to work. More recently, when Ikeda and co-workers discussed the effect of a delayed feedback on instability of a ring cavity containing a non linear dielectric medium, and pointed out that the transmitted light from the ring cavity can be periodic or chaotic in time under a certain condition, optical bistable devices have shown new possibilities to be applied in many different fields. The novel phenomenon has been predicted to be observed in the hybrid optical device and has been confirmed by Gibbs et al. Moreover, as we have shown, a similar effect can be obtained when liquid crystal cells are employed as non linear element

Clarification of Pseudologia Fantastica, a study of two cases of fantastic pseudology.

The term pseudologia fantastica has been fairly widely used despite the lack of consensus as to its definition. Little attention has been paid to its diagnostic significance. As a presenting symptom it can be confused with delusional psychosis, confabulation, malingering, or mere lying. In this article the literature is briefly reviewed, and the diagnostic significance of pseudologia fantastica in cases of neuropsychiatric, delusional, and personality disorders is illustrated with two clinical vignettes.</p