Feasibility and Utility of Anatomical and Physiological Evaluation of Coronary Disease With Cardiac CT in Severe Aortic Stenosis (FUTURE-AS Registry): Rationale and Design.

Background: Coronary artery disease (CAD) in patients with severe aortic stenosis (AS) is common and may be associated with worse outcomes. Computed tomography coronary angiography (CTCA) and fractional flow reserve derived from computed tomography (FFRCT) are tools for comprehensive coronary assessment. The utility and safety of CTCA and FFRCT in the work-up for transcatheter aortic valve replacement (TAVR) is not established, especially in an evolving landscape that involves younger TAVR patients. The FUTURE-AS Registry will assess the utility and safety of cardiac-optimized CTCA and FFRCT to evaluate CAD and guide referral for downstream invasive coronary angiography (ICA) in patients with severe AS being considered for TAVR. Methods: FUTURE-AS is an international, prospective, multicenter registry of patients with severe AS referred for TAVR being assessed for CAD with CTCA and FFRCT. The primary end point is the per-patient sensitivity and negative predictive value of CTCA and FFRCT for identifying anatomical and physiologically significant CAD compared to ICA and invasive FFR. The safety end point is the incidence of symptomatic hypotension or bradycardia requiring intervention following the administration of nitroglycerin or ß-blocker medications. Feasibility end points include the incidence of noninterpretable CTCA scans and CTCA scans not adequate for FFR analysis. Other utility end points include specificity, positive predictive value, and accuracy of CTCA and FFRCT. Lastly, the potential of a CTCA and FFRCT guided strategy to defer pre-TAVR ICA will be assessed. Conclusions: FUTURE-AS will characterize the utility, safety, and feasibility of CTCA and FFRCT for coronary assessment pre-TAVR.

Novel Magnetic Resonance Imaging Tools for Hypertrophic Cardiomyopathy Risk Stratification.

Hypertrophic cardiomyopathy (HCM) is a common genetic disorder with a well described risk of sudden cardiac death; however, risk stratification has remained a challenge. Recently, novel parameters in cardiac magnetic resonance imaging (CMR) have shown promise in helping to improve upon current risk stratification paradigms. In this manuscript, we have reviewed novel CMR risk markers and their utility in HCM. The results of the review showed that T1, extracellular volume, CMR feature tracking, and other miscellaneous novel CMR variables have the potential to improve sudden death risk stratification and may have additional roles in diagnosis and prognosis. The strengths and weaknesses of these imaging techniques, and their potential utility and implementation in HCM risk stratification are discussed.

Patient enablement and health-related quality of life for patients with chronic back and knee pain: a cross-sectional study in primary care.

BACKGROUND: Chronic back and knee pain impairs health- related quality of life (HRQoL) and patient enablement can improve HRQoL. AIM: To determine whether enablement was a moderator of the effect of chronic back and knee pain on HRQoL. DESIGN AND SETTING: A cross-sectional study of Chinese patients with chronic back and knee problems in public primary care clinics in Hong Kong. METHOD: Each participant completed the Chinese Patient Enablement Instrument-2 (PEI-2), the Chinese Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Pain Rating Scale (PRS). Multivariable regression examined the effects of PRS score and PEI-2 score on WOMAC total score. A moderation regression model and simple slope analysis were used to evaluate whether the interaction between enablement (PEI-2) and pain (PRS) had a significant effect on HRQoL (WOMAC). RESULTS: Valid patient-reported outcome data from 1306 participants were analysed. PRS score was associated with WOMAC total score (ß = 0.326, P<0.001), whereas PEI-2 score was associated inversely with WOMAC total score (ß = -0.260, P<0.001) and PRS score. The effect of the interaction between PRS and PEI-2 (PRS × PEI-2) scores on WOMAC total score was significant (ß = -0.191, P<0.001) suggesting PEI-2 was a moderator. Simple slope analyses showed that the relationship between PRS and WOMAC was stronger for participants with a low level of PEI-2 (gradient 3.056) than for those with a high level of PEI-2 (gradient 1.746). CONCLUSION: Patient enablement moderated the impact of pain on HRQoL. A higher level of enablement can lessen impairment in HRQoL associated with chronic back and knee pain.

ST Elevation Myocardial Infarction Complicated by Cardiogenic Shock: Systematic Review of Survival Predictors.

Background: Cardiogenic shock complicating acute myocardial infarction is associated with reduced survival despite advancements in the treatment of acute coronary syndromes. Characterizing predictors of morbidity and mortality in this setting is crucial to improving risk stratification and management. Notwithstanding, the interplay of factors determining survival in this condition remains poorly studied. Methods: Embase, MEDLINE, and CINAHL databases were searched for original studies evaluating predictors of short-term (30-day or in-hospital) survival in ST elevation myocardial infarction with cardiogenic shock (STEMI-CS). Included studies were analyzed by way of vote counting, identifying variables that predicted mortality or survival. Results: Twenty-four studies, consisting of 14,735 patients (5649 nonsurvivors and 9086 survivors) were included. All studies were observational by design (17 retrospective and 7 prospective) with clinical and statistical heterogeneity. Unsuccessful revascularization, reduced left ventricular ejection fraction, renal impairment, and other variables were identified as key independent predictors of mortality. Conclusion: Several key variables have been shown to independently increase mortality in STEMI-CS populations. Future prospective studies examining the prognostic role of multivariate scoring systems incorporating these domains are required.

Feasibility and acceptability of electronic EQ-5D-5L for routine measurement of HRQOL in patients with chronic musculoskeletal problems in Hong Kong primary care.

BACKGROUND: Information on HRQOL can enhance patient diagnosis and management but it is rarely available in routine clinical practice. This mixed-method study evaluated the feasibility and acceptability of the electronic EQ-5D-5L measurement of HRQOL in patients with chronic musculoskeletal problems in primary care. METHODS: In three primary care clinics, 665 patients with musculoskeletal problems completed the electronic EQ-5D-5L and Visual Analogue Scale (e-EQ-5D-5L/VAS), and a questionnaire on socio-demographics, perceived ease of use (PEOU), and perceived usefulness (PU) at baseline and two follow-ups. Patient completion and response rates, and time to complete the e-EQ-5D-5L/VAS were measured. During the same consultations, 49 doctors reviewed the e-EQ-5D-5L/VAS reports and completed a clinician questionnaire on PEOU, PU, and time spent to address each report. Individual interviews along with focus group discussions were conducted on patients, doctors, and research assistants for further exploration. RESULTS: Mean completion time reduced from baseline to first and second follow-up (120.66, 83.99, and 105.22 s, respectively). Completion and response rates were high at each follow-up visit (> 99.8% and > 91.11%, respectively). Doctors needed less than 2 min to read the report but felt the time required to address the report was a significant barrier. Some patients had difficulties using e-platforms, in understanding or answering questions; but, PEOU improved with time (p < 0.001). Most patients found the e-platforms useful (> 85.3%). Clinicians agreed a great majority of the reports were easy to use (76.0-85.1%) and useful (69.2-72.0%), particularly aiding with a holistic view of the patient's musculoskeletal problem. CONCLUSION: The e-EQ-5D-5L/VAS is a feasible and acceptable measurement of HRQOL of patients with chronic musculoskeletal problems in routine primary care in Hong Kong which can assist real-time management decisions. TRIAL REGISTRATION: NCT03609762.

Unveiling new perspective of phylogeography, genetic diversity, and population dynamics of Southeast Asian and Pacific chickens.

The complex geographic and temporal origins of chicken domestication have attracted wide interest in molecular phylogeny and phylogeographic studies as they continue to be debated up to this day. In particular, the population dynamics and lineage-specific divergence time estimates of chickens in Southeast Asia (SEA) and the Pacific region are not well studied. Here, we analyzed 519 complete mitochondrial DNA control region sequences and identified 133 haplotypes with 70 variable sites. We documented 82.7% geographically unique haplotypes distributed across major haplogroups except for haplogroup C, suggesting high polymorphism among studied individuals. Mainland SEA (MSEA) chickens have higher overall genetic diversity than island SEA (ISEA) chickens. Phylogenetic trees and median-joining network revealed evidence of a new divergent matrilineage (i.e., haplogroup V) as a sister-clade of haplogroup C. The maximum clade credibility tree estimated the earlier coalescence age of ancestral D-lineage (i.e., sub-haplogroup D2) of continental chickens (3.7 kya; 95% HPD 1985-4835 years) while island populations diverged later at 2.1 kya (95% HPD 1467-2815 years). This evidence of earlier coalescence age of haplogroup D ancestral matriline exemplified dispersal patterns to the ISEA, and thereafter the island clade diversified as a distinct group.

Insights on the historical biogeography of Philippine domestic pigs and its relationship with continental domestic pigs and wild boars.

The Philippine archipelago was believed to have never been connected to the Asian continent even during the severe Quaternary sea-level drops. As a result, the history of domestic pig (Sus scrofa) dispersal in the Philippines remains controversial and must have some anthropogenic origin associated with human migration events. In this study, the context of origin, dispersal, and the level of genetic introgression in Philippine domestic pigs were deduced using mitochondrial DNA D-loop analysis altogether with domestic pigs and wild boar corresponding to their geographic origin. The results revealed considerable genetic diversity (0.900±0.016) and widespread Asian pig-ancestry (94.60%) in the phylogenetic analysis, with admixed European pig-origin (5.10%) harboring various fractions of ancestry from Berkshire and Landrace. The close genetic connection between the continental wild boars and domestic pigs present in the Philippine domestic pigs corroborates our hypothesis of a genetic signal that may be associated with the recently reported multiple waves of human migrations to the Philippines. The Haplogroup D7, reported to occur only in Indo-Burma Biodiversity Hotspots, included a high frequency of Philippine domestic pig haplotypes (54.08%), which poses an interesting challenge because its distribution is not consistent with the hypothesized migration route of Neolithic Austronesian-speaking populations. We detected the first Pacific Clade signature and ubiquitously distributed D2 haplotypes (Asian major) on several Philippine islands. The analyses of mismatch distribution and neutrality test were consistent with the Bayesian skyline plot which showed a long stationary period of effective population size. The population decline was consistent with the pronounced population bottleneck in Asian and European pigs during the interglacial periods of the Pleistocene. The results of this study will support the conservation strategies and improvements of economically important genetic resources in the Philippines.

Origin and Demographic History of Philippine Pigs Inferred from Mitochondrial DNA.

The Philippines is a mega-diverse country that lies at the crossroads of past human migrations in the Asia-Pacific region and is believed to have never been connected to the Asian continent, even during the major sea-level subsidence of the Quaternary. As a result, the history of pig dispersal in the Philippines remains controversial, due to limited molecular studies and absence of archaeological evidence of pig domestication. This study provides the first comprehensive analysis of 184 complete mitochondrial DNA D-loop region from Philippine pigs to elucidate their early dispersal history by performing a phylogenetic comparison with wild boars and domestic pigs worldwide. The results showed a demographic signal of the ancestry of Philippine pigs that had a close genetic relationship with those from the mainland Southeast Asia and Northeast Asia, suggesting gene flow that may have resulted from human migration and trade. Here we have suggested two possible dispersal routes. One parallels the Neolithic expansion in Island Southeast Asia and Oceania via Northeast Asia, the other from the mainland Southeast Asia, into Palawan and Sulu Archipelago as early as prehistoric times via the Sundaic Region. Despite geographic barriers to migration, numerous genetic lineages have persisted across the Philippine islands, even justifying the recognition of a Philippine Lanyu subclade. The prehistoric population history suggests a demographic expansion that coincided with the interglacial periods of the Pleistocene and may have spread from the southern regions into the eastern and central regions of the Philippines. The intriguing signal of discrepancy discovered between the ancestral pattern and distribution range of the numerous endemic Philippine wild pigs opens a challenging new approach to illuminate complexity among these animals. Our study has contributed significantly towards completing the sparse molecular studies on Philippine pigs, an essential for creating win-win conservation measures.

Publisher Correction: Demonstration of qubit operations below a rigorous fault tolerance threshold with gate set tomography.

This corrects the article DOI: 10.1038/ncomms14485.

A silicon metal-oxide-semiconductor electron spin-orbit qubit.

The silicon metal-oxide-semiconductor (MOS) material system is a technologically important implementation of spin-based quantum information processing. However, the MOS interface is imperfect leading to concerns about 1/f trap noise and variability in the electron g-factor due to spin-orbit (SO) effects. Here we advantageously use interface-SO coupling for a critical control axis in a double-quantum-dot singlet-triplet qubit. The magnetic field-orientation dependence of the g-factors is consistent with Rashba and Dresselhaus interface-SO contributions. The resulting all-electrical, two-axis control is also used to probe the MOS interface noise. The measured inhomogeneous dephasing time, [Formula: see text], of 1.6 µs is consistent with 99.95% 28Si enrichment. Furthermore, when tuned to be sensitive to exchange fluctuations, a quasi-static charge noise detuning variance of 2 µeV is observed, competitive with low-noise reports in other semiconductor qubits. This work, therefore, demonstrates that the MOS interface inherently provides properties for two-axis qubit control, while not increasing noise relative to other material choices.

Coherent coupling between a quantum dot and a donor in silicon.

Individual donors in silicon chips are used as quantum bits with extremely low error rates. However, physical realizations have been limited to one donor because their atomic size causes fabrication challenges. Quantum dot qubits, in contrast, are highly adjustable using electrical gate voltages. This adjustability could be leveraged to deterministically couple donors to quantum dots in arrays of qubits. In this work, we demonstrate the coherent interaction of a 31P donor electron with the electron of a metal-oxide-semiconductor quantum dot. We form a logical qubit encoded in the spin singlet and triplet states of the two-electron system. We show that the donor nuclear spin drives coherent rotations between the electronic qubit states through the contact hyperfine interaction. This provides every key element for compact two-electron spin qubits requiring only a single dot and no additional magnetic field gradients, as well as a means to interact with the nuclear spin qubit.

Demonstration of qubit operations below a rigorous fault tolerance threshold with gate set tomography.

Quantum information processors promise fast algorithms for problems inaccessible to classical computers. But since qubits are noisy and error-prone, they will depend on fault-tolerant quantum error correction (FTQEC) to compute reliably. Quantum error correction can protect against general noise if-and only if-the error in each physical qubit operation is smaller than a certain threshold. The threshold for general errors is quantified by their diamond norm. Until now, qubits have been assessed primarily by randomized benchmarking, which reports a different error rate that is not sensitive to all errors, and cannot be compared directly to diamond norm thresholds. Here we use gate set tomography to completely characterize operations on a trapped-Yb+-ion qubit and demonstrate with greater than 95% confidence that they satisfy a rigorous threshold for FTQEC (diamond norm ≤6.7 × 10-4).

The Intraoperative Effect of Methadone on Somatosensory Evoked Potentials.

BACKGROUND: Evoked potentials (EP), both somatosensory evoked potentials (SSEP) and transcranial motor evoked potentials (TcMEP), are often used during complex spine surgery to monitor the integrity of spinal pathways during operations in or around the spine. Changes in these monitored EP signals (increased latency and decreased amplitude) may result from ischemia, direct surgical injury, changes in blood pressure, hypoxia, changes in CO2 tension, and anesthetic agents. Typically, a clinically significant change for SSEPs is defined as an increase in latency >10% or a decrease of amplitude >50%. A clinically significant change for TcMEPs is much more complex but is also described in terms of large signal loss or decrease. Opioids have been shown to both increase latency and decrease the amplitude of SSEPs, although this change is usually not clinically significant. There has been a renewed interest in methadone for use in spine and other complex surgeries. However, the effect of methadone on intraoperative monitoring of SSEPs and TcMEPs is unknown. We present the first study to directly look at the effects of methadone on SSEP and TcMEP monitoring during complex spine surgery. METHODS: The goal of this study was to observe the effect of methadone on an unrandomized set of patients. The primary endpoint was methadone's effect on SSEPs, and the secondary endpoint was methadone's effect on TcMEPs. Adult patients undergoing spine surgery requiring intraoperative neuromonitoring were induced with general anesthesia and had a baseline set of SSEPs and TcMEPs recorded. Next, methadone dosed 0.2 mg/kg/lean body weight was given. Repeat SSEPs and TcMEPs were recorded at 5, 10, and 15 minutes, with the timing based on distribution half-life of methadone between 6 and 8 minutes. Postoperatively, adverse events from methadone administration were collected. RESULTS: There was a statistically significant difference found in SSEPs for N20 latency (95% confidence interval [CI], 0.17-0.53; P=0.028), P37 latency (95% CI, 0.65-1.25; P=0.001), and N20 amplitude (95% CI, 0.09-0.32; P=<0.001), but not for P37 amplitude (95% CI, -0.19 to 0.00; P=0.634). There was no significant effect found for TcMEPs, the secondary endpoint of the study, and there were minimal adverse events recorded postoperatively. CONCLUSIONS: The data demonstrate that a single intravenous dose of methadone has a statistically significant difference on the amplitude and latency of SSEPs. However, this statistical difference does not translate into a clinical significance.

Microwave-driven coherent operation of a semiconductor quantum dot charge qubit.

An intuitive realization of a qubit is an electron charge at two well-defined positions of a double quantum dot. This qubit is simple and has the potential for high-speed operation because of its strong coupling to electric fields. However, charge noise also couples strongly to this qubit, resulting in rapid dephasing at all but one special operating point called the 'sweet spot'. In previous studies d.c. voltage pulses have been used to manipulate semiconductor charge qubits but did not achieve high-fidelity control, because d.c. gating requires excursions away from the sweet spot. Here, by using resonant a.c. microwave driving we achieve fast (greater than gigahertz) and universal single qubit rotations of a semiconductor charge qubit. The Z-axis rotations of the qubit are well protected at the sweet spot, and we demonstrate the same protection for rotations about arbitrary axes in the X-Y plane of the qubit Bloch sphere. We characterize the qubit operation using two tomographic approaches: standard process tomography and gate set tomography. Both methods consistently yield process fidelities greater than 86% with respect to a universal set of unitary single-qubit operations.

Two-axis control of a singlet-triplet qubit with an integrated micromagnet.

The qubit is the fundamental building block of a quantum computer. We fabricate a qubit in a silicon double-quantum dot with an integrated micromagnet in which the qubit basis states are the singlet state and the spin-zero triplet state of two electrons. Because of the micromagnet, the magnetic field difference ΔB between the two sides of the double dot is large enough to enable the achievement of coherent rotation of the qubit's Bloch vector around two different axes of the Bloch sphere. By measuring the decay of the quantum oscillations, the inhomogeneous spin coherence time T2* is determined. By measuring T2* at many different values of the exchange coupling J and at two different values of ΔB, we provide evidence that the micromagnet does not limit decoherence, with the dominant limits on T2* arising from charge noise and from coupling to nuclear spins.

Quantum control and process tomography of a semiconductor quantum dot hybrid qubit.

The similarities between gated quantum dots and the transistors in modern microelectronics--in fabrication methods, physical structure and voltage scales for manipulation--have led to great interest in the development of quantum bits (qubits) in semiconductor quantum dots. Although quantum dot spin qubits have demonstrated long coherence times, their manipulation is often slower than desired for important future applications, such as factoring. Furthermore, scalability and manufacturability are enhanced when qubits are as simple as possible. Previous work has increased the speed of spin qubit rotations by making use of integrated micromagnets, dynamic pumping of nuclear spins or the addition of a third quantum dot. Here we demonstrate a qubit that is a hybrid of spin and charge. It is simple, requiring neither nuclear-state preparation nor micromagnets. Unlike previous double-dot qubits, the hybrid qubit enables fast rotations about two axes of the Bloch sphere. We demonstrate full control on the Bloch sphere with π-rotation times of less than 100 picoseconds in two orthogonal directions, which is more than an order of magnitude faster than any other double-dot qubit. The speed arises from the qubit's charge-like characteristics, and its spin-like features result in resistance to decoherence over a wide range of gate voltages. We achieve full process tomography in our electrically controlled semiconductor quantum dot qubit, extracting high fidelities of 85 per cent for X rotations (transitions between qubit states) and 94 per cent for Z rotations (phase accumulation between qubit states).

Fast coherent manipulation of three-electron states in a double quantum dot.

An important goal in the manipulation of quantum systems is the achievement of many coherent oscillations within the characteristic dephasing time T2(*). Most manipulations of electron spins in quantum dots have focused on the construction and control of two-state quantum systems, or qubits, in which each quantum dot is occupied by a single electron. Here we perform quantum manipulations on a system with three electrons per double quantum dot. We demonstrate that tailored pulse sequences can be used to induce coherent rotations between three-electron quantum states. Certain pulse sequences yield coherent oscillations fast enough that more than 100 oscillations are visible within a T2(*) time. The minimum oscillation frequency we observe is faster than 5 GHz. The presence of the third electron enables very fast rotations to all possible states, in contrast to the case when only two electrons are used, in which some rotations are slow.

Fast hybrid silicon double-quantum-dot qubit.

We propose a quantum dot qubit architecture that has an attractive combination of speed and fabrication simplicity. It consists of a double quantum dot with one electron in one dot and two electrons in the other. The qubit itself is a set of two states with total spin quantum numbers S(2)=3/4 (S=1/2) and S(z)=-1/2, with the two different states being singlet and triplet in the doubly occupied dot. Gate operations can be implemented electrically and the qubit is highly tunable, enabling fast implementation of one- and two-qubit gates in a simpler geometry and with fewer operations than in other proposed quantum dot qubit architectures with fast operations. Moreover, the system has potentially long decoherence times. These are all extremely attractive properties for use in quantum information processing devices.

Pulse-gated quantum-dot hybrid qubit.

A quantum-dot hybrid qubit formed from three electrons in a double quantum dot has the potential for great speed, due to the presence of level crossings where the qubit becomes chargelike. Here, we show how to exploit the level crossings to implement fast pulsed gating. We develop one- and two-qubit dc quantum gates that are simpler than the previously proposed ac gates. We obtain closed-form solutions for the control sequences and show that the gates are fast (subnanosecond) and can achieve high fidelities.