In Vivo Human Left-to-Right Ventricular Differences in Rate Adaptation Transiently Increase Pro-Arrhythmic Risk following Rate Acceleration

Left-to-right ventricular (LV/RV) differences in repolarization have been implicated in lethal arrhythmias in animal models. Our goal is to quantify LV/RV differences in action potential duration (APD) and APD rate adaptation and their contribution to arrhythmogenic substrates in the in vivo human heart using combined in vivo and in silico studies. Electrograms were acquired from 10 LV and 10 RV endocardial sites in 15 patients with normal ventricles. APD and APD adaptation were measured during an increase in heart rate. Analysis of in vivo electrograms revealed longer APD in LV than RV (207.8±21.5 vs 196.7±20.1 ms; P<0.05), and slower APD adaptation in LV than RV (time constant τs = 47.0±14.3 vs 35.6±6.5 s; P<0.05). Following rate acceleration, LV/RV APD dispersion experienced an increase of up to 91% in 12 patients, showing a strong correlation (r2 = 0.90) with both initial dispersion and LV/RV difference in slow adaptation. Pro-arrhythmic implications of measured LV/RV functional differences were studied using in silico simulations. Results show that LV/RV APD and APD adaptation heterogeneities promote unidirectional block following rate acceleration, albeit being insufficient for establishment of reentry in normal hearts. However, in the presence of an ischemic region at the LV/RV junction, LV/RV heterogeneity in APD and APD rate adaptation promotes reentrant activity and its degeneration into fibrillatory activity. Our results suggest that LV/RV heterogeneities in APD adaptation cause a transient increase in APD dispersion in the human ventricles following rate acceleration, which promotes unidirectional block and wave-break at the LV/RV junction, and may potentiate the arrhythmogenic substrate, particularly in patients with ischemic heart disease

Comparative Evaluation of Methodologies for T-wave Alternans Mapping in Electrograms.

Electrograms (EGM) recorded from the surface of the myocardium are becoming more and more accessible. T-wave alternans (TWA) is associated with increased vulnerability to ventricular tachycardia/fibrillation and it occurs before the onset of ventricular arrhythmias. Thus, accurate methodologies for time-varying alternans estimation/detection in EGM are needed. In this paper, we perform a simulation study based on epicardial EGM recorded in vivo in humans to compare the accuracy of four methodologies: the spectral method (SM), modified moving average method (MMA), laplacian likelihood ratio method (LLR) and a novel method based on time-frequency distributions (TFD). A variety of effects are considered, which include the presence of wide band noise, respiration and impulse artifacts. We found that (a) EGM-TWA can be detected accurately when the standard deviation of wide band noise is equal or smaller than 10 times the magnitude of EGM-TWA. (b) Respiration can be critical for EGM-TWA analysis, even at typical respiratory rates. (c) Impulse noise strongly reduces the accuracy of all methods, except LLR. (d) If depolarization time is used as a fiducial point, the localization of the T-wave is not critical for the accuracy of EGMTWA detection. (e) According to this study, all methodologies provided accurate EGM-TWA detection/quantification in ideal conditions, while LLR was the most robust, providing better detection-rates in noisy conditions. Application on epicardial mapping of the in-vivo human heart shows that EGM-TWA has heterogeneous spatio-temporal distribution

Proximity to Sports Facilities and Sports Participation for Adolescents in Germany

Objectives - To assess the relationship between proximity to specific sports facilities and participation in the corresponding sports activities for adolescents in Germany. Methods - A sample of 1,768 adolescents aged 11–17 years old and living in 161 German communities was examined. Distances to the nearest sports facilities were calculated as an indicator of proximity to sports facilities using Geographic Information Systems (GIS). Participation in specific leisure-time sports activities in sports clubs was assessed using a self-report questionnaire and individual-level socio-demographic variables were derived from a parent questionnaire. Community-level socio-demographics as covariates were selected from the INKAR database, in particular from indicators and maps on land development. Logistic regression analyses were conducted to examine associations between proximity to the nearest sports facilities and participation in the corresponding sports activities. Results - The logisitic regression analyses showed that girls residing longer distances from the nearest gym were less likely to engage in indoor sports activities; a significant interaction between distances to gyms and level of urbanization was identified. Decomposition of the interaction term showed that for adolescent girls living in rural areas participation in indoor sports activities was positively associated with gym proximity. Proximity to tennis courts and indoor pools was not associated with participation in tennis or water sports, respectively. Conclusions - Improved proximity to gyms is likely to be more important for female adolescents living in rural areas

High-sensitivity diamond magnetometer with nanoscale resolution

We present a novel approach to the detection of weak magnetic fields that takes advantage of recently developed techniques for the coherent control of solid-state electron spin quantum bits. Specifically, we investigate a magnetic sensor based on Nitrogen-Vacancy centers in room-temperature diamond. We discuss two important applications of this technique: a nanoscale magnetometer that could potentially detect precession of single nuclear spins and an optical magnetic field imager combining spatial resolution ranging from micrometers to millimeters with a sensitivity approaching few femtotesla/Hz$^{1/2}$.Comment: 29 pages, 4 figure

Valley-spin blockade and spin resonance in carbon nanotubes

Manipulation and readout of spin qubits in quantum dots made in III-V materials successfully rely on Pauli blockade that forbids transitions between spin-triplet and spin-singlet states. Quantum dots in group IV materials have the advantage of avoiding decoherence from the hyperfine interaction by purifying them with only zero-spin nuclei. Complications of group IV materials arise from the valley degeneracies in the electronic bandstructure. These lead to complicated multiplet states even for two-electron quantum dots thereby significantly weakening the selection rules for Pauli blockade. Only recently have spin qubits been realized in silicon devices where the valley degeneracy is lifted by strain and spatial confinement. In carbon nanotubes Pauli blockade can be observed by lifting valley degeneracy through disorder. In clean nanotubes, quantum dots have to be made ultra-small to obtain a large energy difference between the relevant multiplet states. Here we report on low-disorder nanotubes and demonstrate Pauli blockade based on both valley and spin selection rules. We exploit the bandgap of the nanotube to obtain a large level spacing and thereby a robust blockade. Single-electron spin resonance is detected using the blockade.Comment: 31 pages including supplementary informatio

Quantum control of proximal spins using nanoscale magnetic resonance imaging

Quantum control of individual spins in condensed matter systems is an emerging field with wide-ranging applications in spintronics, quantum computation, and sensitive magnetometry. Recent experiments have demonstrated the ability to address and manipulate single electron spins through either optical or electrical techniques. However, it is a challenge to extend individual spin control to nanoscale multi-electron systems, as individual spins are often irresolvable with existing methods. Here we demonstrate that coherent individual spin control can be achieved with few-nm resolution for proximal electron spins by performing single-spin magnetic resonance imaging (MRI), which is realized via a scanning magnetic field gradient that is both strong enough to achieve nanometric spatial resolution and sufficiently stable for coherent spin manipulations. We apply this scanning field-gradient MRI technique to electronic spins in nitrogen-vacancy (NV) centers in diamond and achieve nanometric resolution in imaging, characterization, and manipulation of individual spins. For NV centers, our results in individual spin control demonstrate an improvement of nearly two orders of magnitude in spatial resolution compared to conventional optical diffraction-limited techniques. This scanning-field-gradient microscope enables a wide range of applications including materials characterization, spin entanglement, and nanoscale magnetometry.Comment: 7 pages, 4 figure

Evaluation of the Re-entry Vulnerability Index to Predict Ventricular Tachycardia Circuits Using High Density Contact Mapping

BACKGROUND: Identifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The re-entry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for re-entrant arrhythmia initiation without inducing VT. OBJECTIVE: To provide the first assessment of RVI's capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate. METHODS: 18 VT ablation patients (16M, 72% ischemic) were studied. Unipolar electrograms were recorded during ventricular pacing and analysed off-line. Activation time (AT), activation-recovery interval (ARI), repolarization time (RT) were measured. Vulnerability to re-entry was mapped based on RVI and spatial distribution of AT, ARI and RT. The distance from sites identified as vulnerable to re-entry to the VT site of origin was measured, with distances 20 mm indicating accurate and inaccurate localization, respectively. RESULTS: The origin of 18 VTs was identified (n=6 entrainment, n=12 pace-mapping). RVI maps included 1012, 408-2098 (median, 1st-3rd quartiles) points/patient. RVI accurately localized 72.2% VT sites of origin, with median distance equal to 5.1, 3.2-10.1 mm. Inaccurate localization was significantly less frequent for RVI than AT (5.6% vs 33.3%, OR=0.12, P=0.035). Compared to RVI, distance to VT sites of origin was significantly larger for sites showing prolonged RT and ARI, and non-significantly larger for sites showing highest AT and ARI gradients. CONCLUSION: RVI identifies vulnerable regions closest to VT sites of origin. Activation-repolarization metrics may improve VT substrate delineation and inform novel ablation strategies

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Terpenoid biotransformations by Mucor species

Terpenoids are natural products of great interest due to their widespread use in agrochemicals, drugs, fragrances, flavouring and pigments. Biocatalysts are increasingly being used in the search for new derivatives with improved properties especially to obtain structurally novel leads for new drugs which are difficult to obtain using conventional organic chemical methods. This review, covering up to the end of 2012, reports on the application of Mucor species as catalysts in terpenoid biotransformation to obtain new drug targets, enhance pharmacological activity or decrease the unwanted effects of starting material