Evaluating Energy Differences on a Quantum Computer with Robust Phase Estimation.

We adapt the robust phase estimation algorithm to the evaluation of energy differences between two eigenstates using a quantum computer. This approach does not require controlled unitaries between auxiliary and system registers or even a single auxiliary qubit. As a proof of concept, we calculate the energies of the ground state and low-lying electronic excitations of a hydrogen molecule in a minimal basis on a cloud quantum computer. The denominative robustness of our approach is then quantified in terms of a high tolerance to coherent errors in the state preparation and measurement. Conceptually, we note that all quantum phase estimation algorithms ultimately evaluate eigenvalue differences.

Squeezed light from a nanophotonic molecule.

Delicate engineering of integrated nonlinear structures is required for developing scalable sources of non-classical light to be deployed in quantum information processing systems. In this work, we demonstrate a photonic molecule composed of two coupled microring resonators on an integrated nanophotonic chip, designed to generate strongly squeezed light uncontaminated by noise from unwanted parasitic nonlinear processes. By tuning the photonic molecule to selectively couple and thus hybridize only the modes involved in the unwanted processes, suppression of parasitic parametric fluorescence is accomplished. This strategy enables the use of microring resonators for the efficient generation of degenerate squeezed light: without it, simple single-resonator structures cannot avoid contamination from nonlinear noise without significantly compromising pump power efficiency. We use this device to generate 8(1) dB of broadband degenerate squeezed light on-chip, with 1.65(1) dB directly measured.

Quantum circuits with many photons on a programmable nanophotonic chip.

Growing interest in quantum computing for practical applications has led to a surge in the availability of programmable machines for executing quantum algorithms1,2. Present-day photonic quantum computers3-7 have been limited either to non-deterministic operation, low photon numbers and rates, or fixed random gate sequences. Here we introduce a full-stack hardware-software system for executing many-photon quantum circuit operations using integrated nanophotonics: a programmable chip, operating at room temperature and interfaced with a fully automated control system. The system enables remote users to execute quantum algorithms that require up to eight modes of strongly squeezed vacuum initialized as two-mode squeezed states in single temporal modes, a fully general and programmable four-mode interferometer, and photon number-resolving readout on all outputs. Detection of multi-photon events with photon numbers and rates exceeding any previous programmable quantum optical demonstration is made possible by strong squeezing and high sampling rates. We verify the non-classicality of the device output, and use the platform to carry out proof-of-principle demonstrations of three quantum algorithms: Gaussian boson sampling, molecular vibronic spectra and graph similarity8. These demonstrations validate the platform as a launchpad for scaling photonic technologies for quantum information processing.

What still presents urgently to ENT during a pandemic? Experience of an ENT rapid access clinic during the coronavirus disease 2019 pandemic.

OBJECTIVES: This study sought to determine the conditions that still present to ENT despite government advice to avoid unnecessary travel. It also assessed the impact of social distancing on pathologies presenting to ENT and reviewed the usefulness of telephone consultations in semi-urgent presentations. METHOD: A retrospective review was conducted of 97 instances of patient care carried out in the rapid access ENT clinic at a large district general hospital. RESULTS: Otitis externa and foreign bodies represented 25 per cent and 13 per cent of consultations respectively. Tonsillitis and peritonsillar abscess were uncommon, representing 6 per cent of total consultations. Telephone appointments represented only 28 per cent of total consultations; however, they appeared to reduce the number of physical appointments required. CONCLUSION: Otitis externa and foreign bodies continue to be common during the pandemic. Social distancing measures reduced the number of tonsillitis and quinsy presentations. Telephone consultations are effective for certain urgent presentations to ENT, most noticeably nasal trauma and follow up of non-serious pathologies.

Broadband quadrature-squeezed vacuum and nonclassical photon number correlations from a nanophotonic device.

We report demonstrations of both quadrature-squeezed vacuum and photon number difference squeezing generated in an integrated nanophotonic device. Squeezed light is generated via strongly driven spontaneous four-wave mixing below threshold in silicon nitride microring resonators. The generated light is characterized with both homodyne detection and direct measurements of photon statistics using photon number-resolving transition-edge sensors. We measure 1.0(1) decibels of broadband quadrature squeezing (~4 decibels inferred on-chip) and 1.5(3) decibels of photon number difference squeezing (~7 decibels inferred on-chip). Nearly single temporal mode operation is achieved, with measured raw unheralded second-order correlations g (2) as high as 1.95(1). Multiphoton events of over 10 photons are directly detected with rates exceeding any previous quantum optical demonstration using integrated nanophotonics. These results will have an enabling impact on scaling continuous variable quantum technology.

Precision measurement of the neutral pion lifetime.

The explicit breaking of the axial symmetry by quantum fluctuations gives rise to the so-called axial anomaly. This phenomenon is solely responsible for the decay of the neutral pion π0 into two photons (γγ), leading to its unusually short lifetime. We precisely measured the decay width Γ of the [Formula: see text] process. The differential cross sections for π0 photoproduction at forward angles were measured on two targets, carbon-12 and silicon-28, yielding [Formula: see text], where stat. denotes the statistical uncertainty and syst. the systematic uncertainty. We combined the results of this and an earlier experiment to generate a weighted average of [Formula: see text] Our final result has a total uncertainty of 1.50% and confirms the prediction based on the chiral anomaly in quantum chromodynamics.

Detection of multidrug-resistant Gram-negative bacteria from imported reptile and amphibian meats.

AIMS: The food supply is a potential source of antimicrobial resistance. Current surveillance programmes targeting food are limited to beef, pork and poultry and do not capture niche products. In this study, imported reptile and amphibian products were screened for antimicrobial-resistant bacteria. METHODS AND RESULTS: In all, 53 items including soft shell turtles, frog legs, geckos, snakes and a turtle carapace were purchased from specialty markets in Vancouver and Saskatoon, Canada. Samples were selectively cultured for Salmonella sp., Escherichia coli, extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and meropenem-resistant organisms. Salmonella, all pan-susceptible, were grown from six dried geckos. Escherichia coli were isolated from 19 samples, including ESBL producers from six items. One multidrug-resistant E. coli possessed both the blaCTX-M-55 and mcr-1 genes. An NDM-1-producing Acinetobacter sp. was also isolated from a dried turtle carapace. CONCLUSIONS: Our results suggest that imported reptile and amphibian meats are an underappreciated source of resistant bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The international trade of food may play a role in the dissemination of resistant bacteria. The presence of these bacteria in niche market foods represents a risk of unknown magnitude to public health and a gap in current national resistance surveillance programmes.

Persistent infection with Staphylococcus pseudintermedius in an adult oncology patient with transmission from a family dog.

Staphylococcus pseudintermedius is a well known commensal organism of dogs but also a canine opportunistic pathogen. Reports of this organism being recovered from specimens from humans might suggest an increase prevalence in human infections and/or improved diagnostic leading to more accurate identification. Here we report a case of persistent S. pseudintermedius infection in an adult female oncology patient including colonization of the tip of an indwelling catheter. Diligence by laboratories in correctly isolating and identifying this pathogen (including susceptibility testing) is essential for optimal patient care.

Stimulated four-wave mixing in linearly uncoupled resonators.

We experimentally demonstrate stimulated four-wave mixing in two linearly uncoupled integrated $ {{\rm Si}_3}{{\rm N}_4} $Si3N4 micro-resonators. In our structure, the resonance combs of each resonator can be tuned independently, with the energy transfer from one resonator to the other occurring in the presence of a nonlinear interaction. This method allows flexible and efficient on-chip control of the nonlinear interaction, and is readily applicable to other third-order nonlinear phenomena.

Nonlinear Coupling of Linearly Uncoupled Resonators.

We demonstrate a system composed of two resonators that are coupled solely through a nonlinear interaction, and where the linear properties of each resonator can be controlled locally. We show that this class of dynamical systems has peculiar properties with important consequences for the study of classical and quantum nonlinear optical phenomena. As an example we discuss the case of dual-pump spontaneous four-wave mixing.

Localization of human recombinant adenoviral vectors to the mitochondria following transduction of human cell lines.

Recently, mitochondria have been shown to have a vital role in the innate immune response to viral infection. In response, viruses such as adenovirus, have developed mechanisms to alter mitochondrial function through direct or indirect interaction with the mitochondria. The interaction of human recombinant adenoviral vectors directly with human mitochondria has not previously been shown. We demonstrate that human recombinant adenoviral vectors co-localize to mitochondria. We show that the adenoviral vectors are present within the membranes of the mitochondria and that they cause ultrastructural changes to the cristae. Further, we show that the adenoviral genome is also present in intact mitochondria. We have posited that the interaction between the adenovirus and the mitochondria may act to inhibit mitochondrial function. We have also posited that the transport of the adenoviral genome to the mitochondria may allow the future use of this vector as a tool for gene therapy of mitochondrial diseases. Keywords: mitochondria; human recombinant adenovirus; gene therapy; viral vectors; mitochondrial DNA; electron microscopy.

Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders.

Control of Established Gingivitis and Dental Plaque Using a 1450 ppm Fluoride/Zinc-based Dentifrice: A Randomized Clinical Study.

PURPOSE: To investigate the clinical efficacy in controlling established gingivitis and dental plaque of a 1450 ppm fluoride as sodium monofluorophosphate (SMFP)/zinc-based dentifrice, as compared to a zinc-free dentifrice with 1450 ppm fluoride as SMFP after six months product use. METHODS: A six-month clinical study, with eighty-six (86) subjects, was conducted in Chengdu, China, using a double-blind, randomized, parallel-group treatment design. After a baseline evaluation, study subjects were randomly assigned to one of the two study treatments: 1) 1450 ppm fluoride as SMFP/zinc-based dentifrice (Test) or 2) 1450 ppm fluoride as SMFP/zinc-free dentifrice (Negative Control). Subjects were provided with a soft bristle toothbrush and brushed their teeth twice daily (morning and evening) for one minute with their assigned dentifrice. After three months, and again after six months of product use, subjects returned to the testing facility for their followup gingivitis and plaque examinations. Statistical analyses were performed separately for the gingivitis assessments and dental plaque assessments using the appropriate statistical methods. All statistical tests of hypotheses were two-sided, and employed a level of significance of α = 0.05. RESULTS: After three and six months of product use, subjects assigned to the Test treatment exhibited statistically significant (p < 0.001) reductions in gingival index and plaque index scores as compared to subjects assigned to the Negative Control treatment. CONCLUSION: The results of this single-center, double-blind, parallel-group and randomized clinical study support the conclusion that a 1450 ppm fluoride as SMFP/zinc-based dentifrice provides clinically meaningful and statistically significant reductions in gingivitis (23.8%) and dental plaque (22.5%) as compared to a 1450 ppm fluoride as SMFP/zinc-free dentifrice over a six-month period of twice-daily product use.

Piperazinyl-oxadiazoles as selective sphingosine-1-phosphate receptor agonists.

The discovery of a new series of selective S1P1 agonists is described. This series of piperazinyl-oxadiazole derivatives was rapidly optimized starting from high-throughput screening hit 1 to afford potent and selective lead compound 10d. Further SAR studies showed that 10d was converted to the active phosphate metabolite 29 in vivo. Oral administration of compound 10d to rats was shown to induce lymphopenia at 3 mg/kg.

Ischaemic Priapism and Glucose-6-Phosphate Dehydrogenase Deficiency: A Mechanism of Increased Oxidative Stress?

Ischaemic priapism is a devastating urological condition that has the potential to cause permanent erectile dysfunction. The disorder has been associated with numerous medical conditions and the use of pharmacotherapeutic agents. The aetiology is idiopathic in a number of cases. There are two prior case reports of the association of ischaemic priapism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report on a third case of priapism associated with G6PD deficiency and review recently described molecular mechanisms of increased oxidative stress in the pathophysiology of ischaemic priapism. The case report of a 32-year old Afro-Caribbean male with his first episode of major ischaemic priapism is described. Screening for common causes of ischaemic priapism, including sickle cell disease was negative. Glucose-6-phosphate dehydrogenase deficiency was discovered on evaluation for priapism. Penile aspiration was performed and erectile function was good post treatment.Glucose-6-phosphate dehydrogenase deficiency is a cause for ischaemic priapism and should be a part of the screening process in idiopathic causes of the disorder. Increased oxidative stress occurs in G6PD deficiency and may lead to priapism.

Testosterone replacement therapy does not promote priapism in hypogonadal men with sickle cell disease: 12-month safety report.

Hypogonadism, which is highly prevalent in men with sickle cell disease (SCD), affects quality of life and causes great morbidity. The safety of testosterone replacement therapy (TRT) in SCD in relation to priapism episodes is relatively unknown. Our aim was to monitor the safety of TRT in a cohort of seven hypogonadal men with SCD. Testosterone undecanoate (Nebido) 1 g was administered intramuscularly to adult men with homozygous SCD (Hb SS) having hypogonadism [serum total testosterone ≤12.0 nmol/L (346 ng/dL), reference range 12.5-38.1 nmol/L (360-1098 ng/dL)] for 12 months. Serum total testosterone, haemoglobin, haematocrit, renal and liver function tests, glucose and PSA measurements were done at baseline and 12-month follow-up. Trough serum total testosterone, haemoglobin and haematocrit were measured three monthly. Priapism events and adverse drug events were assessed every 3 months. International Index of Erectile Function (IIEF), Androgen Deficiency in the Ageing Male (ADAM) and World Health Organization Quality of Life (WHOQOL) questionnaires were administered at baseline, 6 and 12 months. Seven men with a mean age of 34.4 years were treated. Median total testosterone increased from 10.6 to 11.2 nmol/L (p = 0.46). Median serum lactate dehydrogenase levels decreased from 1445 to 1143.5 IU/L (p < 0.05), while all other laboratory indices remained stable. Injection site pain was the most frequently reported adverse event, with no increases in painful crises, hypersensitivity or oedema. After TRT, there was no significant increase in priapism frequency. Median questionnaire scores were increased for the IIEF (46-68, p = 0.018), reduced for ADAM (5.0-2.0, p = 0.016) and unchanged for WHOQOL (98-103, p = 0.086). TRT using testosterone undecanoate with eugonadal intent for hypogonadism appears to be safe in men with SCD. This treatment does not appear to promote priapism occurrences and rather it possibly improves sexual function. Future prospective evaluations in larger groups of hypogonadal men with SCD are necessary to confirm these findings.