CMOS-based cryogenic control of silicon quantum circuits.

The most promising quantum algorithms require quantum processors that host millions of quantum bits when targeting practical applications1. A key challenge towards large-scale quantum computation is the interconnect complexity. In current solid-state qubit implementations, an important interconnect bottleneck appears between the quantum chip in a dilution refrigerator and the room-temperature electronics. Advanced lithography supports the fabrication of both control electronics and qubits in silicon using technology compatible with complementary metal oxide semiconductors (CMOS)2. When the electronics are designed to operate at cryogenic temperatures, they can ultimately be integrated with the qubits on the same die or package, overcoming the 'wiring bottleneck'3-6. Here we report a cryogenic CMOS control chip operating at 3 kelvin, which outputs tailored microwave bursts to drive silicon quantum bits cooled to 20 millikelvin. We first benchmark the control chip and find an electrical performance consistent with qubit operations of 99.99 per cent fidelity, assuming ideal qubits. Next, we use it to coherently control actual qubits encoded in the spin of single electrons confined in silicon quantum dots7-9 and find that the cryogenic control chip achieves the same fidelity as commercial instruments at room temperature. Furthermore, we demonstrate the capabilities of the control chip by programming a number of benchmarking protocols, as well as the Deutsch-Josza algorithm10, on a two-qubit quantum processor. These results open up the way towards a fully integrated, scalable silicon-based quantum computer.

Multifractality in spin glasses.

We unveil the multifractal behavior of Ising spin glasses in their low-temperature phase. Using the Janus II custom-built supercomputer, the spin-glass correlation function is studied locally. Dramatic fluctuations are found when pairs of sites at the same distance are compared. The scaling of these fluctuations, as the spin-glass coherence length grows with time, is characterized through the computation of the singularity spectrum and its corresponding Legendre transform. A comparatively small number of site pairs controls the average correlation that governs the response to a magnetic field. We explain how this scenario of dramatic fluctuations (at length scales smaller than the coherence length) can be reconciled with the smooth, self-averaging behavior that has long been considered to describe spin-glass dynamics.

The Mpemba effect in spin glasses is a persistent memory effect.

The Mpemba effect occurs when a hot system cools faster than an initially colder one, when both are refrigerated in the same thermal reservoir. Using the custom-built supercomputer Janus II, we study the Mpemba effect in spin glasses and show that it is a nonequilibrium process, governed by the coherence length ξ of the system. The effect occurs when the bath temperature lies in the glassy phase, but it is not necessary for the thermal protocol to cross the critical temperature. In fact, the Mpemba effect follows from a strong relationship between the internal energy and ξ that turns out to be a sure-tell sign of being in the glassy phase. Thus, the Mpemba effect presents itself as an intriguing avenue for the experimental study of the coherence length in supercooled liquids and other glass formers.

Reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) as a user-friendly system to detect SARS-CoV-2 infection: a multicentric study.

Although reverse transcriptase quantitative PCR remains the gold standard to perform viral detection, reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) is already used to perform diagnosis of various infections. This work reports the results of a multicentric study performed in Sicily to evaluate the diagnostic power of an RT-LAMP kit for the diagnosis of SARS-CoV-2 infection on a total of 551 samples collected in January and February 2021, revealing sensitivity, specificity, accuracy, positive and negative predictive values ≥95%. Our results suggest the potential employment of this kit as a screening test to be used where fast and reliable results are demanded without the need for expensive instruments and highly-skilled personnel.

A statics-dynamics equivalence through the fluctuation-dissipation ratio provides a window into the spin-glass phase from nonequilibrium measurements.

We have performed a very accurate computation of the nonequilibrium fluctuation-dissipation ratio for the 3D Edwards-Anderson Ising spin glass, by means of large-scale simulations on the special-purpose computers Janus and Janus II. This ratio (computed for finite times on very large, effectively infinite, systems) is compared with the equilibrium probability distribution of the spin overlap for finite sizes. Our main result is a quantitative statics-dynamics dictionary, which could allow the experimental exploration of important features of the spin-glass phase without requiring uncontrollable extrapolations to infinite times or system sizes.

Occupational exposure to fluoro-edenite and prevalence of anti-nuclear autoantibodies.

An environmental contamination due to an asbestiform mineral fiber, fluoro-edenite (FE), caused a significantly increased mortality rate for malignant mesothelioma in Biancavilla, Italy. Exposure to fluoro-edenite has been associated with inflammatory processes as an early response to inhaled fibers. The aim was to explore prevalence of anti-nuclear autoantibodies (ANA) in a group of construction workers residing and working in the contaminated area. Prevalences for samples positive to ANA were 60% (n = 9) and 13% (n = 2), for exposed and nonexposed, respectively (p-value <0.05), the odds ratio was 9.75 (95% CI: 1.59-59.69). The significance of elevated ANAs in subjects exposed to fibers is unknown; additional studies may provide a better opportunity to establish a correlation between autoimmunity and environmental exposure.

Thermodynamic glass transition in a spin glass without time-reversal symmetry.

Spin glasses are a longstanding model for the sluggish dynamics that appear at the glass transition. However, spin glasses differ from structural glasses in a crucial feature: they enjoy a time reversal symmetry. This symmetry can be broken by applying an external magnetic field, but embarrassingly little is known about the critical behavior of a spin glass in a field. In this context, the space dimension is crucial. Simulations are easier to interpret in a large number of dimensions, but one must work below the upper critical dimension (i.e., in d < 6) in order for results to have relevance for experiments. Here we show conclusive evidence for the presence of a phase transition in a four-dimensional spin glass in a field. Two ingredients were crucial for this achievement: massive numerical simulations were carried out on the Janus special-purpose computer, and a new and powerful finite-size scaling method.

Deep-learning survival analysis for patients with calcific aortic valve disease undergoing valve replacement.

Calcification of the aortic valve (CAVDS) is a major cause of aortic stenosis (AS) leading to loss of valve function which requires the substitution by surgical aortic valve replacement (SAVR) or transcatheter aortic valve intervention (TAVI). These procedures are associated with high post-intervention mortality, then the corresponding risk assessment is relevant from a clinical standpoint. This study compares the traditional Cox Proportional Hazard (CPH) against Machine Learning (ML) based methods, such as Deep Learning Survival (DeepSurv) and Random Survival Forest (RSF), to identify variables able to estimate the risk of death one year after the intervention, in patients undergoing either to SAVR or TAVI. We found that with all three approaches the combination of six variables, named albumin, age, BMI, glucose, hypertension, and clonal hemopoiesis of indeterminate potential (CHIP), allows for predicting mortality with a c-index of approximately 80 % . Importantly, we found that the ML models have a better prediction capability, making them as effective for statistical analysis in medicine as most state-of-the-art approaches, with the additional advantage that they may expose non-linear relationships. This study aims to improve the early identification of patients at higher risk of death, who could then benefit from a more appropriate therapeutic intervention.

An energy-efficient in-memory computing architecture for survival data analysis based on resistive switching memories.

One of the objectives fostered in medical science is the so-called precision medicine, which requires the analysis of a large amount of survival data from patients to deeply understand treatment options. Tools like machine learning (ML) and deep neural networks are becoming a de-facto standard. Nowadays, computing facilities based on the Von Neumann architecture are devoted to these tasks, yet rapidly hitting a bottleneck in performance and energy efficiency. The in-memory computing (IMC) architecture emerged as a revolutionary approach to overcome that issue. In this work, we propose an IMC architecture based on resistive switching memory (RRAM) crossbar arrays to provide a convenient primitive for matrix-vector multiplication in a single computational step. This opens massive performance improvement in the acceleration of a neural network that is frequently used in survival analysis of biomedical records, namely the DeepSurv. We explored how the synaptic weights mapping strategy and the programming algorithms developed to counter RRAM non-idealities expose a performance/energy trade-off. Finally, we discussed how this application is tailored for the IMC architecture rather than being executed on commodity systems.

COVID-19 Vaccine and Death: Causality Algorithm According to the WHO Eligibility Diagnosis.

The current challenge worldwide is the administration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Even if rarely, severe vascular adverse reactions temporally related to vaccine administration have induced diffidence in the population at large. In particular, researchers worldwide are focusing on the so-called "thrombosis and thrombocytopenia after COVID-19 vaccination". This study aims to establish a practical workflow to define the relationship between adverse events following immunization (AEFI) and COVID-19 vaccination, following the basic framework of the World Health Organization (WHO). Post-mortem investigation plays a pivotal role to support this causality relationship when death occurs. To demonstrate the usefulness and feasibility of the proposed workflow, we applied it to two exemplificative cases of suspected AEFI following COVID-19 vaccination. Based on the proposed model, we took into consideration any possible causality relationship between COVID-19 vaccine administration and AEFI. This led us to conclude that vaccination with ChAdOx1 nCov-19 may cause the rare development of immune thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4), which clinically mimics heparin-induced autoimmune thrombocytopenia. We suggest the adoption of the proposed methodology in order to confirm or rule out a causal relationship between vaccination and the occurrence of AEFI.

Rare spondylodiscitis due to Mycobacterium mucogenicum.

BACKGROUND: Nontuberculous mycobacteria (NTM) represents an important cause of infection, particularly in immunocompromised patients. Spondylodiscitis is unusual and may be associated with underlying causes such as drug abuse. Timely diagnosis and treatment are critical, as without this, patients will demonstrate progressive neurological deterioration. Here, we present a rare case of Mycobacterium mucogenicum spondylodiscitis in a 36-year-old male, along with a focused literature review. CASE DESCRIPTION: A 36-year-old female with previous drug abuse presented with 3-years of progressive thoracolumbar pain. The MRI of the spine revealed paravertebral abscesses from Th10-L1 with vertebral lesions involving Th11-Th12 levels (e.g., vertebral body collapse/deformity and destruction of the posterior vertebral walls). After a needle CT-guided biopsy of the paravertebral tissues, real time-polymerase chain reaction (RT-PCR) amplification documented NTM; the final identification was M. mucogenicum. The patient then underwent a Th11-Th12 decompressive laminectomy, facetectomy, granulomatous tissue debridement, and posterior pedicle screw fusion from Th8-Th10, and L1-L3. Postoperatively, the patient's pain resolved, and she was left with residual lower extremities dysesthesias; 6-months later, she could walk without assistance. CONCLUSION: Spondylodiscitis caused by M. mucogenicum is rare, and the medical and surgical treatment is comparable to that for other NTM groups.

Hippocampal, amygdala, and neocortical synchronization of theta rhythms is related to an immediate recall during rey auditory verbal learning test.

It is well known that theta rhythms (3-8 Hz) are the fingerprint of hippocampus, and that neural activity accompanying encoding of words differs according to whether the items are later remembered or forgotten ["subsequent memory effect" (SME)]. Here, we tested the hypothesis that temporal synchronization of theta rhythms among hippocampus, amygdala, and neocortex is related to immediate memorization of repeated words. To address this issue, intracerebral electroencephalographic (EEG) activity was recorded in five subjects with drug-resistant temporal lobe epilepsy (TLE), under presurgical monitoring routine. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of Rey auditory verbal learning test (RAVLT), a popular test for the clinical evaluation of the immediate and delayed memory. They heard the same list of 15 common words for five times. Each time, immediately after listening the list, the subjects were required to repeat as many words as they could recall. Spectral coherence of the intracerebral EEG activity was computed in order to assess the temporal synchronization of the theta (about 3-8 Hz) rhythms among hippocampus, amygdala, and temporal-occipital neocortex. We found that theta coherence values between amygdala and hippocampus, and between hippocampus and occipital-temporal cortex, were higher in amplitude during successful than unsuccessful immediate recall. A control analysis showed that this was true also for a gamma band (40-45 Hz). Furthermore, these theta and gamma effects were not observed in an additional (control) subject with drug-resistant TLE and a wide lesion to hippocampus. In conclusion, a successful immediate recall to the RAVLT was associated to the enhancement of temporal synchronization of the theta (gamma) rhythms within a cerebral network including hippocampus, amygdala, and temporal-occipital neocortex.

Vaccine-preventable disease in healthcare workers in Sicily (Italy): seroprevalence against measles.

Aim: Measles is one of the most infectious communicable diseases. The objective of this study was to determine the immunity to measles of healthcare workers (HCWs) operating in three hospitals of Catania. Methods: A total of 549 HCWs underwent measles screening. A 5 ml blood sample was taken from each worker to measure IgG antibody levels. Results: Overall seroprotection was 86%. Unvaccinated HCWs agreed to undergo the vaccination offered by the hospital. Furthermore, it was found that younger workers are less seroprotected than older ones. Conclusion: Model legislation may be helpful to countries wishing to implement immunization requirements in healthcare settings in order to virtually eliminate the risk of acquiring and spreading measles in healthcare settings.

Tuberculosis screening among healthcare workers in Sicily, Italy.

Tuberculosis (TB) is a diffuse communicable disease; and healthcare workers (HCWs) are among the at-risk populations for the disease. This study reports the result of TB surveillance in HCWs operating in three hospitals: one classified as 'low' risk for TB and two as 'medium' risk. A total of 2228 HCWs underwent TB screening using the standard Mantoux technique (also known as the tuberculin sensitivity test [TST]). Interferon-γ release assay (IGRA) was carried out in TST-positive subjects. Results showed an overall positivity of 21% to TST and 2% to IGRA test. TST and IGRA results were statistically associated with HCWs born after 1981. This result is due to university policies that highly recommend TB immunization. Data support the use of IGRA assay in TST-positive HCWs, in order to identify latent TB infection from vaccination.

3T MRI evaluation of the accuracy of atlas-based subthalamic nucleus identification.

Modulation of the activity of the subthalamic nucleus (STN) using deep brain stimulation (DBS) in patients with advanced Parkinson's disease is the most common procedure performed today by functional neurosurgeons. The STN contours cannot be entirely identified on common 1.5 T images; in particular, the ventromedial border of the STN often blends with the substantia nigra. 3 T magnetic resonance imaging (MRI) provides better resolution and can improve the identification of the STN borders. In this work, we have directly identified the STN using 3 T MR imaging to validate the accuracy of a computer-aided atlas-based procedure for automatic STN identification. Coordinates of the STN were obtained from the Talairach and Tournoux atlas and transformed into the coordinates of the Montreal Neurological Institute (MNI) standard brain volume, creating a mask representation of the STN. 3 T volumetric T1 and T2 weighted (T1w and T2w, respectively) acquisitions were obtained for ten patients. The MNI standard brain volume was registered onto each patient MRI, using a new approach based on global affine, region-of-interest affine, and local nonrigid registrations. The estimated deformation field was then applied to the STN atlas-based mask, providing its location on the patient MRI. The entire procedure required on average about 20 min. Because STN is easily identifiable on 3 T T2w-MRIs, it was manually delineated; the coordinates of the center of mass of the manually and automatically identified structures were compared. Additionally, volumetric overlapping indices were calculated and the spatial relationship between the midcommissural point and the STN center of mass was investigated. All indices indicated, on average, good agreement between manually and automatically identified structures; displacement of the centers of mass of the manually and automatically identified structures was less than or equal to 2.35 mm, and more than 80% of the manually identified volume was covered by the automatic localization, on average. Bland-Altman analysis indicated that the automatic STN identification was within the limits of agreement with the manual localization on 3 T MRIs. Automatic atlas-based STN localization provides an accurate and user-friendly tool and can enhance target identification when 1.5 T scanners with limited capability to identify the STN boundaries are used.

Direct validation of atlas-based red nucleus identification for functional radiosurgery.

Treatment targets in functional neurosurgery usually consist of selected structures within the thalamus and basal ganglia, which can be stimulated in order to affect specific brain pathways. Chronic electrical stimulation of these structures is a widely used approach for selected patients with advanced movement disorders. An alternative therapeutic solution consists of producing a lesion in the target nucleus, for example by means of radiosurgery, a noninvasive procedure, and this prevents the use of intraoperative microelectrode recording as a method for accurate target definition. The need to have accurate noninvasive localization of the target motivated our previous work on atlas-based identification; the aim of this present work is to provide additional validation of this approach based on the identification of the red nuclei (RN), which are located near the subthalamic nucleus (STN). Coordinates of RN were obtained from the Talairach and Tournoux (TT) atlas and transformed into the coordinates of the Montreal Neurological Institute (MNI) atlas, creating a mask representation of RN. The MNI atlas volume was nonrigidly registered onto the patient magnetic resonance imaging (MRI). This deformation field was then applied to the RN mask, providing its location on the patient MRI. Because RN are easily identifiable on 1.5 T T2-MRI images, they were manually delineated; the coordinates of the centers of mass of the manually and automatically identified structures were compared. Additionally, volumetric overlapping indices were calculated. Ten patients were examined by this technique. All indices indicated a high level of agreement between manually and automatically identified structures. These results not only confirm the accuracy of the method but also allow fine tuning of the automatic identification method to be performed.

Quantitative evaluation for brain CT/MRI coregistration based on maximization of mutual information in patients with focal epilepsy investigated with subdural electrodes.

Patients with drug-resistant focal epilepsy may require intracranial investigations with subdural electrodes. These must be correctly localized with respect to the brain cortical surface and require appropriate monitoring. For this purpose, coregistration techniques, which fuse preimplantation 3D magnetic resonance imaging scans with postimplantation computed tomography scans, have been implemented. In order to reduce localization errors due to the fusion process, we used a coregistration method based on the maximization of mutual information (MI) in 11 patients with extratemporal epilepsy who were invasively investigated. Our registration method is based on three processing steps: rigid-body transformation for coregistration, computation of MI as a similarity measure and the use of the Downhill Simplex optimization method. After consistency analysis, the shift of the registration method reached 0.14+/-0.27 mm in translation and 0.03+/-0.14 degrees in rotation, and the accuracies assessed on voxels of skull surface and voxels of the center of the brain volume were 1.42+/-0.61 and 1.15+/-0.53 mm, respectively. The accuracy of the fusion process reached submillimeter range, and results were considered reliable for surgical planning in all studied patients.

A reconfigurable cryogenic platform for the classical control of quantum processors.

The implementation of a classical control infrastructure for large-scale quantum computers is challenging due to the need for integration and processing time, which is constrained by coherence time. We propose a cryogenic reconfigurable platform as the heart of the control infrastructure implementing the digital error-correction control loop. The platform is implemented on a field-programmable gate array (FPGA) that supports the functionality required by several qubit technologies and that can operate close to the physical qubits over a temperature range from 4 K to 300 K. This work focuses on the extensive characterization of the electronic platform over this temperature range. All major FPGA building blocks (such as look-up tables (LUTs), carry chains (CARRY4), mixed-mode clock manager (MMCM), phase-locked loop (PLL), block random access memory, and IDELAY2 (programmable delay element)) operate correctly and the logic speed is very stable. The logic speed of LUTs and CARRY4 changes less then 5%, whereas the jitter of MMCM and PLL clock managers is reduced by 20%. The stability is finally demonstrated by operating an integrated 1.2 GSa/s analog-to-digital converter (ADC) with a relatively stable performance over temperature. The ADCs effective number of bits drops from 6 to 4.5 bits when operating at 15 K.

Alpha, beta and gamma electrocorticographic rhythms in somatosensory, motor, premotor and prefrontal cortical areas differ in movement execution and observation in humans.

OBJECTIVE: In the present study, we tested the hypothesis that both movement execution and observation induce parallel modulations of alpha, beta, and gamma electrocorticographic (ECoG) rhythms in primary somatosensory (Brodmann area 1-2, BA1-2), primary motor (BA4), ventral premotor (BA6), and prefrontal (BA44 and BA45, part of putative human mirror neuron system underlying the understanding of actions of other people) areas. METHODS: ECoG activity was recorded in drug-resistant epileptic patients during the execution of actions to reach and grasp common objects according to their affordances, as well as during the observation of the same actions performed by an experimenter. RESULTS: Both action execution and observation induced a desynchronization of alpha and beta rhythms in BA1-2, BA4, BA6, BA44 and BA45, which was generally higher in amplitude during the former than the latter condition. Action execution also induced a major synchronization of gamma rhythms in BA4 and BA6, again more during the execution of an action than during its observation. CONCLUSION: Human primary sensorimotor, premotor, and prefrontal areas do generate alpha, beta, and gamma rhythms and differently modulate them during action execution and observation. Gamma rhythms of motor areas are especially involved in action execution. SIGNIFICANCE: Oscillatory activity of neural populations in sensorimotor, premotor and prefrontal (part of human mirror neuron system) areas represents and distinguishes own actions from those of other people. This methodological approach might be used for a neurophysiological diagnostic imaging of social cognition in epileptic patients.