Predictors of 30-day and 12-month mortality in left main stem percutaneous coronary intervention 2016-2020: A study from two UK centers.

INTRODUCTION: Left main stem percutaneous coronary intervention (LMS-PCI) is a complex high-risk procedure which can be performed as an alternative to coronary artery bypass graft (CABG) procedure in surgical turn-down patients or where there is equipoise in percutaneous versus surgical strategies. Current guidelines suggest that PCI is an appropriate alternative to CABG in patients with unprotected LMS disease and low SYNTAX score. However, "real world" data on outcomes of LMS-PCI remain limited. This study aims to quantify and determine predictors of mortality following LMS-PCI. METHODS: Using local coronary angioplasty registries from two UK centers, all LMS-PCI cases were identified from 2016 to 2020. Descriptive statistics and multivariate logistic regressions were used to examine the association between baseline and procedural characteristics with 30-day and 12-month mortality. RESULTS: We identified 484 cases of LMS-PCI between 2016 and 2020. There was a year-on-year increase in the number of LMS-PCI, the highest being in 2020. Covariates associated with higher 30-day mortality were age (OR 1.07, 95% CI: 1.02-1.12) and shock preprocedure (OR 23.88, 95% CI: 7.90-72.20). Covariates associated with higher 12-month mortality were age (OR 1.04, 95% CI: 1.01-1.08), acute coronary syndrome (ACS) (OR 2.50, 95% CI: 1.08-5.80), renal disease (OR 5.24, 95% CI: 1.47-18.68), and shock preprocedure (OR 7.93, 95% CI: 3.30-19.05). Overall, 30-day and 12-month mortality in this contemporary data set were 9.5% and 16.7%, respectively, with significantly lower rates in elective cases (p < 0.01). CONCLUSIONS: Older age and cardiogenic shock preprocedure were associated with increased 30-day mortality after LMS-PCI. Twelve-month mortality was associated with older age, ACS presentation, preexisting renal disease, and cardiogenic shock preprocedure.

Repeated echocardiographic imaging of aortic stenosis: Real-life lessons.

BACKGROUND: Timing of aortic valve intervention is dependent on the accuracy and reproducibility of echocardiographic (ECHO) parameters. We aimed to assess haemodynamic subsets of aortic stenosis (AS), their change over time, and variability of ECHO parameters. METHOD: This retrospective, longitudinal study compared sequential ECHO over 15 months to identify concordant or discordant aortic valve area (AVA) and mean pressure gradient (MPG) in order to determine the real world variability of echocardiographic indices. RESULTS: We included 143 patients with a mean age of 76.0 years. The median length of time between studies was 112 days (IQR 38-208). Initially, participants were classified as 9 (6.4%) mild, 47 (33.6%) moderate, and 84 (60.0%%) severe AS. In 80 (55.9%) AVA and MPG were concordant; stroke volume index (SVi) was < 35 mL/m2 in 53 (74.6%). AS severity was downgraded in 29 (20.7%) patients. MPG was most consistent and AVA was the least consistent between successive investigations (intraclass correlation coefficients R = .86 and R = .76, respectively). Even small variations in left ventricular outflow tract (LVOT) measurement of 1 standard deviation reclassified up to 67% of participants from severe to non-severe. CONCLUSION: Almost half of patients with AS have valve area/gradient discordance. Variations in LVOT diameter measurement commensurate with clinical practice reclassified AS severity in up to two-third of cases. Change in AS severity should only be accepted following careful scrutiny of all available ECHO data.

Sensitivity, Noise and Resolution in a BEOL-Modified Foundry-Made ISFET with Miniaturized Reference Electrode for Wearable Point-of-Care Applications.

Ion-sensitive field-effect transistors (ISFETs) form a high sensitivity and scalable class of sensors, compatible with advanced complementary metal-oxide semiconductor (CMOS) processes. Despite many previous demonstrations about their merits as low-power integrated sensors, very little is known about their noise characterization when being operated in a liquid gate configuration. The noise characteristics in various regimes of their operation are important to select the most suitable conditions for signal-to-noise ratio (SNR) and power consumption. This work reports systematic DC, transient, and noise characterizations and models of a back-end of line (BEOL)-modified foundry-made ISFET used as pH sensor. The aim is to determine the sensor sensitivity and resolution to pH changes and to calibrate numerical and lumped element models, capable of supporting the interpretation of the experimental findings. The experimental sensitivity is approximately 40 mV/pH with a normalized resolution of 5 mpH per µm2, in agreement with the literature state of the art. Differences in the drain current noise spectra between the ISFET and MOSFET configurations of the same device at low currents (weak inversion) suggest that the chemical noise produced by the random binding/unbinding of the H+ ions on the sensor surface is likely the dominant noise contribution in this regime. In contrast, at high currents (strong inversion), the two configurations provide similar drain noise levels suggesting that the noise originates in the underlying FET rather than in the sensing region.

Crowdsensing IoT Architecture for Pervasive Air Quality and Exposome Monitoring: Design, Development, Calibration, and Long-Term Validation.

A pervasive assessment of air quality in an urban or mobile scenario is paramount for personal or city-wide exposure reduction action design and implementation. The capability to deploy a high-resolution hybrid network of regulatory grade and low-cost fixed and mobile devices is a primary enabler for the development of such knowledge, both as a primary source of information and for validating high-resolution air quality predictive models. The capability of real-time and cumulative personal exposure monitoring is also considered a primary driver for exposome monitoring and future predictive medicine approaches. Leveraging on chemical sensing, machine learning, and Internet of Things (IoT) expertise, we developed an integrated architecture capable of meeting the demanding requirements of this challenging problem. A detailed account of the design, development, and validation procedures is reported here, along with the results of a two-year field validation effort.

A Wearable Low-Power Sensing Platform for Environmental and Health Monitoring: The Convergence Project.

The low-power sensing platform proposed by the Convergence project is foreseen as a wireless, low-power and multifunctional wearable system empowered by energy-efficient technologies. This will allow meeting the strict demands of life-style and healthcare applications in terms of autonomy for quasi-continuous collection of data for early-detection strategies. The system is compatible with different kinds of sensors, able to monitor not only health indicators of individual person (physical activity, core body temperature and biomarkers) but also the environment with chemical composition of the ambient air (NOx, COx, NHx particles) returning meaningful information on his/her exposure to dangerous (safety) or pollutant agents. In this article, we introduce the specifications and the design of the low-power sensing platform and the different sensors developed in the project, with a particular focus on pollutant sensing capabilities and specifically on NO2 sensor based on graphene and CO sensor based on polyaniline ink.

Nanowire Tunnel FET with Simultaneously Reduced Subthermionic Subthreshold Swing and Off-Current due to Negative Capacitance and Voltage Pinning Effects.

Nanowire tunnel field-effect transistors (TFETs) have been proposed as the most advanced one-dimensional (1D) devices that break the thermionic 60 mV/decade of the subthreshold swing (SS) of metal oxide semiconductor field-effect transistors (MOSFETs) by using quantum mechanical band-to-band tunneling and excellent electrostatic control. Meanwhile, negative capacitance (NC) of ferroelectrics has been proposed as a promising performance booster of MOSFETs to bypass the aforementioned fundamental limit by exploiting the differential amplification of the gate voltage under certain conditions. We combine these two principles into a single structure, a negative capacitance heterostructure TFET, and experimentally demonstrate a double beneficial effect: (i) a super-steep SS value down to 10 mV/decade and an extended low slope region that is due to the NC effect and, (ii) a remarkable off-current reduction that is experimentally observed and explained for the first time by the effect of the ferroelectric dipoles, which set the surface potential in a slightly negative value and further blocks the source tunneling current in the off-state. State-of-the-art InAs/InGaAsSb/GaSb nanowire TFETs are employed as the baseline transistor and PZT and silicon-doped HfO2 as ferroelectric materials.

Exchange Bias in Magnetic Topological Insulator Superlattices.

Magnetic doping and proximity coupling can open a band gap in a topological insulator (TI) and give rise to dissipationless quantum conduction phenomena. Here, by combining these two approaches, we demonstrate a novel TI superlattice structure that is alternately doped with transition and rare earth elements. An unexpected exchange bias effect is unambiguously confirmed in the superlattice with a large exchange bias field using magneto-transport and magneto-optical techniques. Further, the Curie temperature of the Cr-doped layers in the superlattice is found to increase by 60 K compared to a Cr-doped single-layer film. This result is supported by density-functional-theory calculations, which indicate the presence of antiferromagnetic ordering in Dy:Bi2Te3 induced by proximity coupling to Cr:Sb2Te3 at the interface. This work provides a new pathway to realizing the quantum anomalous Hall effect at elevated temperatures and axion insulator state at zero magnetic field by interface engineering in TI heterostructures.

Detection of ultra-low protein concentrations with the simplest possible field effect transistor.

Silicon nanowire (Si NW) sensors have attracted great attention due to their ability to provide fast, low-cost, label-free, real-time detection of chemical and biological species. Usually configured as field effect transistors (FETs), they have already demonstrated remarkable sensitivity with high selectivity (through appropriate functionalisation) towards a large number of analytes in both liquid and gas phases. Despite these excellent results, Si NW FET sensors have not yet been successfully employed to detect single molecules of either a chemical or biological target species. Here we show that sensors based on silicon junctionless nanowire transistors (JNTs), the simplest possible transistors, are capable of detecting the protein streptavidin at a concentration as low as 580 zM closely approaching the single molecule level. This ultrahigh detection sensitivity is due to the intrinsic advantages of junctionless devices over conventional FETs. Apart from their superior functionality, JNTs are much easier to fabricate by standard microelectronic processes than transistors containing p-n junctions. The ability of JNT sensors to detect ultra-low concentrations (in the zeptomolar range) of target species, and their potential for low-cost mass production, will permit their deployment in numerous environments, including life sciences, biotechnology, medicine, pharmacology, product safety, environmental monitoring and security.

Paramagnetism in Bacillus spores: Opportunities for novel biotechnological applications.

Spores of Bacillus megaterium, Bacillus cereus, and Bacillus subtilis were found to exhibit intrinsic paramagnetic properties as a result of the accumulation of manganese ions. All three Bacillus species displayed strong yet distinctive magnetic properties arising from differences in manganese quantity and valency. Manganese ions were found to accumulate both within the spore core as well as being associated with the surface of the spore. Bacillus megaterium spores accumulated up to 1 wt.% manganese (II) within, with a further 0.6 wt.% adsorbed onto the surface. At room temperature, Bacillus spores possess average magnetic susceptibilities in the range of 10-6 to 10-5 . Three spore-related biotechnological applications-magnetic sensing, magnetic separation and metal ion adsorption-were assessed subsequently, with the latter two considered as having the most potential for development.

Effect of hysteretic and non-hysteretic negative capacitance on tunnel FETs DC performance.

This work experimentally demonstrates that the negative capacitance effect can be used to significantly improve the key figures of merit of tunnel field effect transistor (FET) switches. In the proposed approach, a matching condition is fulfilled between a trained-polycrystalline PZT capacitor and the tunnel FET (TFET) gate capacitance fabricated on a strained silicon-nanowire technology. We report a non-hysteretic switch configuration by combining a homojunction TFET and a negative capacitance effect booster, suitable for logic applications, for which the on-current is increased by a factor of 100, the transconductance by 2 orders of magnitude, and the low swing region is extended. The operation of a hysteretic negative capacitance TFET, when the matching condition for the negative capacitance is fulfilled only in a limited region of operation, is also reported and discussed. In this late case, a limited improvement in the device performance is observed. Overall, the paper demonstrates the main beneficial effects of negative capacitance on TFETs are the overdrive and transconductance amplification, which exactly address the most limiting performances of current TFETs.

Tunnel field-effect transistors as energy-efficient electronic switches.

Power dissipation is a fundamental problem for nanoelectronic circuits. Scaling the supply voltage reduces the energy needed for switching, but the field-effect transistors (FETs) in today's integrated circuits require at least 60 mV of gate voltage to increase the current by one order of magnitude at room temperature. Tunnel FETs avoid this limit by using quantum-mechanical band-to-band tunnelling, rather than thermal injection, to inject charge carriers into the device channel. Tunnel FETs based on ultrathin semiconducting films or nanowires could achieve a 100-fold power reduction over complementary metal-oxide-semiconductor (CMOS) transistors, so integrating tunnel FETs with CMOS technology could improve low-power integrated circuits.

Graphene Quantum Capacitors for High Frequency Tunable Analog Applications.

Graphene quantum capacitors (GQC) are demonstrated to be enablers of radio-frequency (RF) functions through voltage-tuning of their capacitance. We show that GQC complements MEMS and MOSFETs in terms of performance for high frequency analog applications and tunability. We propose a CMOS compatible fabrication process and report the first experimental assessment of their performance at microwaves frequencies (up to 10 GHz), demonstrating experimental GQCs in the pF range with a tuning ratio of 1.34:1 within 1.25 V, and Q-factors up to 12 at 1 GHz. The figures of merit of graphene variable capacitors are studied in detail from 150 to 350 K. Furthermore, we describe a systematic, graphene specific approach to optimize their performance and predict the figures of merit achieved if such a methodology is applied.

An animal homolog of plant Mep/Amt transporters promotes ammonia excretion by the anal papillae of the disease vector mosquito Aedes aegypti.

The transcripts of three putative ammonia (NH3/NH4 (+)) transporters, Rhesus-like glycoproteins AeRh50-1, AeRh50-2 and Amt/Mep-like AeAmt1 were detected in the anal papillae of larval Aedes aegypti Quantitative PCR studies revealed 12-fold higher transcript levels of AeAmt1 in anal papillae relative to AeRh50-1, and levels of AeRh50-2 were even lower. Immunoblotting revealed AeAmt1 in anal papillae as a pre-protein with putative monomeric and trimeric forms. AeAmt1 was immunolocalized to the basal side of the anal papillae epithelium where it co-localized with Na(+)/K(+)-ATPase. Ammonium concentration gradients were measured adjacent to anal papillae using the scanning ion-selective electrode technique (SIET) and used to calculate ammonia efflux by the anal papillae. dsRNA-mediated reductions in AeAmt1 decreased ammonia efflux at larval anal papillae and significantly increased ammonia levels in hemolymph, indicating a principal role for AeAmt1 in ammonia excretion. Pharmacological characterization of ammonia transport mechanisms in the anal papillae suggests that, in addition to AeAmt1, the ionomotive pumps V-type H(+)-ATPase and Na(+)/K(+)-ATPase as well as NHE3 are involved in ammonia excretion at the anal papillae.

Condition for the negative capacitance effect in metal-ferroelectric-insulator-semiconductor devices.

In this paper, we report a detailed study of the negative capacitance field effect transistor (NCFET). We present the condition for the stabilization of the negative capacitance to achieve the voltage amplification across the active layer. The theory is based on Landau's theory of ferroelectrics combined with the surface potential model in all regimes of operation. We demonstrate the validity of the presented theory on experimental NCFETs using a gate stack made of P(VDF-TrFE) and SiO2. The proposed analytical modeling shows good agreement with experimental data.

Accessory mitral valve--an unexpected intra-operative TEE finding causing left ventricular outflow tract obstruction in an adult.

There is a long-standing debate between proponents of routine intra-operative echo and those who want it restricted to selected groups of patients (such as those undergoing valve repair or correction of congenital abnormalities). We present a case where routine transesophageal echocardiography (TEE) identified completely unexpected pathology, with implications for the postoperative follow-up and for patient outcomes. A 64-year-old male, with a history of surgical repair of coarctation of the aorta in childhood, was admitted for elective valve replacement for severe aortic stenosis (AS). Previous transthoracic echocardiography had not identified any other pathology apart from AS, but routine intra-operative TEE picked up severe turbulence in the left ventricular outflow tract (LVOT). On further analysis this was due to 2 mechanisms: a localized subaortic membrane and a "cystic" mass attached to the anterior mitral leaflet, protruding into the LVOT in systole. Multiplane imaging of the mass disclosed an accessory mitral valve (MV), a rare congenital abnormality. The patient had excision of the stenosed aortic valve and of the subaortic membrane, while the accessory MV was spared, as the surgeon judged its removal might distort the mitral apparatus. Postoperative recovery was unremarkable and the patient went home with symptomatic improvement. This case illustrates the fact that even "standard" cardiac procedures can benefit from intra-operative TEE which, in our view, should be available for all patients who undergo heart surgery.

Sudden Cardiac Arrest in a Youth with Multiple Arrhythmic Substrates.

Background: Mitral valve prolapse (MVP) is a common condition with an estimated prevalence of 1-3%, in which there is systolic displacement of a morphologically redundant mitral valve towards the left atrium. Mitral annular disjunction (MAD) is a separation of the MV attachment with the left ventricle, with hypermobility of the leaflets, and with systolic "curling" of the basal LV (left ventricle) myocardium. It is frequently associated with MVP and may confer an increased arrhythmic risk. Case Description. A 28-year-old male had ventricular fibrillation leading to out-of-hospital cardiac arrest, which was successfully resuscitated. His coronary arteries were unobstructed on invasive coronary angiography. Transthoracic echocardiogram (TTE) demonstrated MAD, confirmed by cardiac magnetic resonance (CMR) imaging and transoesophageal echocardiogram (TOE). The LV was severely dilated with reduced EF (ejection fraction), and the QTc interval was also prolonged. His father had died suddenly aged 50 years. Conclusions: This report describes the clinical dilemma of identifying and treating a patient with multiple potential causes of cardiac arrest. Despite being relatively common, the clinical significance of MAD is still uncertain and the extent to which it may be linked with complications such as ventricular arrhythmias and sudden cardiac death. MAD appears to confer an increased risk of ventricular arrhythmias, particularly when associated with MVP, particularly nonsustained VT.

Effects of the selective AMPA modulator NBI-1065845 on the pharmacokinetics of midazolam or ethinyl estradiol-levonorgestrel in healthy adults.

This parallel-arm, phase I study investigated the potential cytochrome P450 (CYP)3A induction effect of NBI-1065845 (TAK-653), an investigational α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiator in phase II development for major depressive disorder. The midazolam treatment arm received the sensitive CYP3A substrate midazolam on Day 1, followed by NBI-1065845 alone on Days 5-13; on Day 14, NBI-1065845 was administered with midazolam, then NBI-1065845 alone on Day 15. The oral contraceptive treatment arm received ethinyl estradiol-levonorgestrel on Day 1, then NBI-1065845 alone on Days 5-13; on Day 14, NBI-1065845 was administered with ethinyl estradiol-levonorgestrel, then NBI-1065845 alone on Days 15-17. Blood samples were collected for pharmacokinetic analyses. The midazolam treatment arm comprised 14 men and 4 women, of whom 16 completed the study. Sixteen of the 17 healthy women completed the oral contraceptive treatment arm. After multiple daily doses of NBI-1065845, the geometric mean ratios (GMRs) (90% confidence interval) for maximum observed concentration were: midazolam, 0.94 (0.79-1.13); ethinyl estradiol, 1.00 (0.87-1.15); and levonorgestrel, 0.99 (0.87-1.13). For area under the plasma concentration-time curve (AUC) from time 0 to infinity, the GMRs were as follows: midazolam, 0.88 (0.78-0.98); and ethinyl estradiol, 1.01 (0.88-1.15). For levonorgestrel, the GMR for AUC from time 0 to the last quantifiable concentration was 0.87 (0.78-0.96). These findings indicate that NBI-1065845 is not a CYP3A inducer and support its administration with CYP3A substrates. NBI-1065845 was generally well tolerated, with no new safety signals observed after coadministration of midazolam, ethinyl estradiol, or levonorgestrel.

Spatially homogeneous ferromagnetism below the enhanced Curie temperature in EuO(1-x) thin films.

We have used low-energy implanted muons as a volume sensitive probe of the magnetic properties of EuO(1-x) thin films. We find that static and homogeneous magnetic order persists up to the elevated T(C) in the doped samples, and the muon signal displays the double dome feature also observed in the sample magnetization. Our results appear incompatible with either the magnetic phase separation or bound magnetic polaron descriptions previously suggested to explain the elevated T(C), but are compatible with an RKKY-like interaction mediating magnetic interactions above 69 K.

Stress cardiomyopathy: case series and the review of literature.

BACKGROUND: Apical ballooning syndrome (ABS) or stress cardiomyopathy is increasingly recognized as a cause of acute coronary syndrome with unobstructed coronaries, but remains underdiagnosed. OBJECTIVES: Retrospective review of the angiographic database (between January 2006 and December 2010) to obtain incidence and clinical presentation of ABS at our center. ABS was defined according to the modified Mayo Clinic criteria. CASE RESULTS: Normal or unobstructed coronaries on angiography were observed in 1780 (25.4%) of a total of 6983 patients who underwent urgent or emergency coronary angiography. Twelve patients (0.17%) fulfilled the modified Mayo Clinic criteria for ABS. Eleven patients (92%) were aged ≥ 50 years (median 68 years, range 27-86 years), and 10 were female (83%). Four patients (31%) presented with ST-elevation myocardial infarction, and 1 patient presented with cardiogenic shock and acute coronary syndrome. Emotional stress was the precipitant in 4 patients (33%). Unusual precipitants like cold-water immersion and intravenous chemotherapy were observed. All 12 patients had the typical appearance of ABS on left ventriculogram (75%) or echocardiography (25%). Follow-up imaging with either echocardiography or magnetic resonance imaging (done in all 12 patients) up to 16 weeks after discharge showed that left ventricular function had normalized. CONCLUSIONS: The incidence and clinical features of ABS in our tertiary center are similar to those reported in other settings. Unusual precipitants were observed, but left ventriculograms were performed less frequently and could be contributory to the under-diagnosis of ABS.