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The central challenge in building a quantum computer is error correction. Unlike classical bits, which are susceptible to only one type of error, quantum bits (qubits) are susceptible to two types of error, corresponding to flips of the qubit state about the X and Z  directions. Although the Heisenberg uncertainty principle precludes simultaneous monitoring of X - and Z -flips on a single qubit, it is possible to encode quantum information in large arrays of entangled qubits that enable accurate monitoring of all errors in the system, provided that the error rate is low 1 . Another crucial requirement is that errors cannot be correlated. Here we characterize a superconducting multiqubit circuit and find that charge noise in the chip is highly correlated on a length scale over 600 micrometres; moreover, discrete charge jumps are accompanied by a strong transient reduction of qubit energy relaxation time across the millimetre-scale chip. The resulting correlated errors are explained in terms of the charging event and phonon-mediated quasiparticle generation associated with absorption of γ-rays and cosmic-ray muons in the qubit substrate. Robust quantum error correction will require the development of mitigation strategies to protect multiqubit arrays from correlated errors due to particle impacts. Cosmic-ray particles and γ-rays striking superconducting circuits can generate qubit errors that are spatially correlated across several millimetres, hampering current error-correction approaches.

Quantum circuits interact with the environment via several temperature-dependent degrees of freedom. Multiple experiments to-date have shown that most properties of superconducting devices appear to plateau out at T ≈ 50 mK – far above the refrigerator base temperature. This is for example reflected in the thermal state population of qubits, in excess numbers of quasiparticles, and polarisation of surface spins – factors contributing to reduced coherence. We demonstrate how to remove this thermal constraint by operating a circuit immersed in liquid 3 He. This allows to efficiently cool the decohering environment of a superconducting resonator, and we see a continuous change in measured physical quantities down to previously unexplored sub-mK temperatures. The 3 He acts as a heat sink which increases the energy relaxation rate of the quantum bath coupled to the circuit a thousand times, yet the suppressed bath does not introduce additional circuit losses or noise. Such quantum bath suppression can reduce decoherence in quantum circuits and opens a route for both thermal and coherence management in quantum processors. Removing excess energy (cooling) and reducing noise in superconducting quantum circuits is central to improved coherence. Lucas et al. demonstrate cooling of a superconducting resonator and its noisy environment to sub-mK temperatures by immersion in liquid 3 He.

Noise and decoherence due to spurious two-level systems located at material interfaces are long-standing issues for solid-state quantum devices. Efforts to mitigate the effects of two-level systems have been hampered by a lack of knowledge about their chemical and physical nature. Here, by combining dielectric loss, frequency noise and on-chip electron spin resonance measurements in superconducting resonators, we demonstrate that desorption of surface spins is accompanied by an almost tenfold reduction in the charge-induced frequency noise in the resonators. These measurements provide experimental evidence that simultaneously reveals the chemical signatures of adsorbed magnetic moments and highlights their role in generating charge noise in solid-state quantum devices. The performance of solid-state quantum devices is often affected by low-frequency noise that appears to arise from the presence of two-level defects. Here the authors show that surface spins that cause magnetic noise are an origin of dielectric noise in superconducting resonators.

The performance of a great variety of electronic devices—ranging from semiconductor transistors to superconducting qubits—is hampered by low-frequency noise with spectra proportional to 1/ f . The ubiquity and negative impact of 1/ f noise has motivated intensive research into its cause, and it is now believed to originate from a bath of fluctuating two-level defect states (TLSs) embedded in the material. This phenomenon is commonly described by the long-established standard tunnelling model (STM) of independent TLS. A key prediction of STM is that the noise should vanish at low temperatures. Here we report measurements on superconducting microresonators over previously unattainable, very long time scales that show an increase in 1/ f noise at low temperatures and low microwave power, contrary to the STM. We propose a new generalised tunnelling model that includes significant interaction between multiple TLSs, which fully describes these observations, as well as recent studies of individual TLS lifetimes in superconducting qubits. The quantum noise generated as multiple two-level systems switch state is usually described by the standard tunnelling model. By studying superconducting resonators, Burnett et al. show that this model fails at low temperatures, and propose a new model to accurately describe the noise in quantum circuits.

Patients with radioiodine-refractory differentiated thyroid cancer (DTC) previously treated with vascular endothelial growth factor receptor (VEGFR)-targeted therapy have aggressive disease and no available standard of care. The aim of this study was to evaluate the tyrosine kinase inhibitor cabozantinib in this patient population. In this global, randomised, double-blind, placebo-controlled, phase 3 trial, patients aged 16 years and older with radioiodine-refractory DTC (papillary or follicular and their variants) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (2:1) to oral cabozantinib (60 mg once daily) or matching placebo, stratified by previous lenvatinib treatment and age. The randomisation scheme used stratified permuted blocks of block size six and an interactive voice–web response system; both patients and investigators were masked to study treatment. Patients must have received previous lenvatinib or sorafenib and progressed during or after treatment with up to two VEGFR tyrosine kinase inhibitors. Patients receiving placebo could cross over to open-label cabozantinib on disease progression confirmed by blinded independent radiology committee (BIRC). The primary endpoints were objective response rate (confirmed response per Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) in the first 100 randomly assigned patients (objective response rate intention-to-treat [OITT] population) and progression-free survival (time to earlier of disease progression per RECIST version 1.1 or death) in all patients (intention-to-treat [ITT] population), both assessed by BIRC. This report presents the primary objective response rate analysis and a concurrent preplanned interim progression-free survival analysis. The study is registered with ClinicalTrials.gov, NCT03690388, and is no longer enrolling patients. Between Feb 27, 2019, and Aug 18, 2020, 227 patients were assessed for eligibility, of whom 187 were enrolled from 164 clinics in 25 countries and randomly assigned to cabozantinib (n=125) or placebo (n=62). At data cutoff (Aug 19, 2020) for the primary objective response rate and interim progression-free survival analyses, median follow-up was 6·2 months (IQR 3·4–9·2) for the ITT population and 8·9 months (7·1–10·5) for the OITT population. An objective response in the OITT population was achieved in ten (15%; 99% CI 5·8–29·3) of 67 patients in the cabozantinib group versus 0 (0%; 0–14·8) of 33 in the placebo (p=0·028) but did not meet the prespecified significance level (α=0·01). At interim analysis, the primary endpoint of progression-free survival was met in the ITT population; cabozantinib showed significant improvement in progression-free survival over placebo: median not reached (96% CI 5·7–not estimable [NE]) versus 1·9 months (1·8–3·6); hazard ratio 0·22 (96% CI 0·13–0·36; p<0·0001). Grade 3 or 4 adverse events occurred in 71 (57%) of 125 patients receiving cabozantinib and 16 (26%) of 62 receiving placebo, the most frequent of which were palmar–plantar erythrodysaesthesia (13 [10%] vs 0), hypertension (11 [9%] vs 2 [3%]), and fatigue (ten [8%] vs 0). Serious treatment-related adverse events occurred in 20 (16%) of 125 patients in the cabozantinib group and one (2%) of 62 in the placebo group. There were no treatment-related deaths. Our results show that cabozantinib significantly prolongs progression-free survival and might provide a new treatment option for patients with radioiodine-refractory DTC who have no available standard of care. Exelixis.

In This report, the central challenge in building a quantum computer is error correction. Unlike classical bits, which are susceptible to only one type of error, quantum bits (“qubits”) are susceptible to two types of error, corresponding to flips of the qubit state about the X- and Z-directions. While the Heisenberg Uncertainty Principle precludes simultaneous monitoring of X- and Z-flips on a single qubit, it is possible to encode quantum information in large arrays of entangled qubits that enable accurate monitoring of all errors in the system, provided the error rate is low. Another crucial requirement is that errors cannot be correlated. Here, we characterize a superconducting multiqubit circuit and find that charge fluctuations are highly correlated on a length scale over 600 µm; moreover, discrete charge jumps are accompanied by a strong transient suppression of qubit energy relaxation time across the millimeter-scale chip. The resulting correlated errors are explained in terms of the charging event and phonon-mediated quasiparticle poisoning associated with absorption of gamma rays and cosmic-ray muons in the qubit substrate. Robust quantum error correction will require the development of mitigation strategies to protect multiqubit arrays from correlated errors due to particle impacts.

PAX5 is a nuclear transcription factor required for B cell development, and its expression was evaluated in upper aerodigestive malignancies and pancreatic cancer by immunoblotting. The PAX5 protein expression was relatively strong in small-cell lung cancer (SCLC, 11/12); however, its expression was not detected in non-SCLC (NSCLC, n=13), mesothelioma (n=7), pancreatic (n=6), esophageal (n=6) and head and neck cancer cell lines (n=12). In comparison, PAX8 and PAX3 expressions were absent or non-detectable in SCLC cell lines; however, PAX8 was expressed in most of the tested NSCLC cell lines (13/13) and also frequently in all the other cell lines. We also detected frequent expressions of PAX2 and PAX9 protein in the various cell lines. Utilizing neuroendocrine tumor samples, we found that the frequency as well as the average intensity of the expression of PAX5 increased from pulmonary carcinoid (9%, moderate and strong PAX5 expression, n=44), to large-cell neuroendocrine carcinoma (LCNC, 27%, n=11) to SCLC (33%, n=76). FISH analysis revealed no translocations of the PAX5 gene, but polyploidy in some SCLC tumor tissues (6/37). We determined that PAX5 could regulate the transcription of c-Met using luciferase-coupled reporter and chromatin immunoprecipitation analysis. In addition, the phospho-c-Met (active form) and PAX5 were both localized to the same intra-nuclear compartment in hepatocyte growth factor treated SCLC cells and interacted with each other. Finally, we determined the therapeutic translational potential of PAX5 using PAX5 knockdown SCLC cells in conjunction with Topoisomerase 1 (SN38) and c-Met (SU11274) inhibitors. Loss of endogenous PAX5 significantly decreased the viability of SCLC cells, especially when combined with SN38 or SU11274, and maximum effect was seen when both inhibitors were used. Therefore, we propose that PAX5 could be an important regulator of c-Met transcription and a potential target for therapy in SCLC.

Background and importanceMany studies support pembrolizumab (a humanised monoclonal antibody directed towards programmed cell death protein-1 (PD-1)) as the firstline treatment of advanced non-small cell lung cancer (NSCLC) without EGFR/ALK alterations.Aim and objectivesThe aim of this observational was to report clinical outcome in terms of overall survival (OS) analysis, as well as in stratified OS, in subgroups of patients.Material and methodsBetween 1 July 2017 and 28 February 2020, 98 patients with NSCLC were eligible to be treated with pembrolizumab (200 mg q3w fixed dose). The last follow-up date was 24 August 2020. Clinical data, such as expression of PD-L1, performance status (ECOG-PS), treatment duration, toxicity (CTCAE V.5.0) and outcome were collected from the local electronic medical records. OS, defined as the time from the start of therapy to death or last follow-up, was compared in subgroups of patients using the log rank test (with R software); p<0.05 was considered statistically significant.ResultsThis investigation provided preliminary results for 98 patients (of whom 64% were male). Median age was 73 years (range 44–89). ECOG-PS was 0 or 1 in 91% of cases and 29.6% of patients had a PD-L1 >90%. Median duration of treatment was seven cycles. At a median follow-up of 14.6 months, the percentage of patients still alive was 51% and median OS was 13.3 months (95% CI 10.5 to 31.4). The analysis revealed that OS was not influenced by sex or PD-L1, but significantly associated with ECOG-PS (p<0.001). Immunorelated adverse events occurred in 75.5% of patients (29.6% cutaneous, 24.5% gastrointestinal and 19.4% endocrinological). Patients with toxicity showed a significantly higher median OS (29.6 months, 95% CI 12.2 to NA) compared with those without significant toxicity (6.5 months, 95% CI 1.3 to 13.1, p=0.002).Conclusion and relevanceThese real life findings in the setting of advanced NSCLC patients with PD-L1 TPS ≥50% demonstrated the effectiveness of pembrolizumab. A median OS of 13.3 months was similar to that estimated in the real world Pembreizh study (15.3 months). The detection rate of AE of 75.5% was comparable with 73.4% in the KEYNOTE-024 study. However, pembrolizumab as mono-immunotherapy represents the standard of care as firstline treatment but results from trials evaluating combinations with chemotherapy (KEYNOTE189) could further change the therapeutic approaches.References and/or acknowledgementsConflict of interestNo conflict of interest

Myofibroblastoma of the breast is a rare benign neoplasm, which has rarely been reported in association with gynecomastia. We report a case of a 25-year-old male patient with an epithelioid myofibroblastoma arising in a context of bilateral gynecomastia. The lesion was composed of nests and cords of epithelioid cells, with round to oval nuclei, granular chrornatin, and distinct nucleoli dispersed in a myxoid to collagenous stroma with marked vascular proliferation. Immunohistocrhemical profile showed diffuse positivity for vimentin and focal immunoreactivity for desmin, whereas cytokeratins (CAM5.2 and AE1/AE3), EMA, alph-a smooth muscle actin, actin HHF35, CEA, S1OO, factor VIII, neuron-specific enolase, CD31, and CD34 were all negative. We emphasize that this diagnosis is difficult to establish, owing to the rarity of this variant and clinical presentation.