An atomic boson sampler.

A boson sampler implements a restricted model of quantum computing. It is defined by the ability to sample from the distribution resulting from the interference of identical bosons propagating according to programmable, non-interacting dynamics1. An efficient exact classical simulation of boson sampling is not believed to exist, which has motivated ground-breaking boson sampling experiments in photonics with increasingly many photons2-12. However, it is difficult to generate and reliably evolve specific numbers of photons with low loss, and thus probabilistic techniques for postselection7 or marked changes to standard boson sampling10-12 are generally used. Here, we address the above challenges by implementing boson sampling using ultracold atoms13,14 in a two-dimensional, tunnel-coupled optical lattice. This demonstration is enabled by a previously unrealized combination of tools involving high-fidelity optical cooling and imaging of atoms in a lattice, as well as programmable control of those atoms using optical tweezers. When extended to interacting systems, our work demonstrates the core abilities required to directly assemble ground and excited states in simulations of various Hubbard models15,16.

Realizing spin squeezing with Rydberg interactions in an optical clock.

Neutral-atom arrays trapped in optical potentials are a powerful platform for studying quantum physics, combining precise single-particle control and detection with a range of tunable entangling interactions1-3. For example, these capabilities have been leveraged for state-of-the-art frequency metrology4,5 as well as microscopic studies of entangled many-particle states6-11. Here we combine these applications to realize spin squeezing-a widely studied operation for producing metrologically useful entanglement-in an optical atomic clock based on a programmable array of interacting optical qubits. In this demonstration of Rydberg-mediated squeezing with a neutral-atom optical clock, we generate states that have almost four decibels of metrological gain. In addition, we perform a synchronous frequency comparison between independent squeezed states and observe a fractional-frequency stability of 1.087(1) × 10-15 at one-second averaging time, which is 1.94(1) decibels below the standard quantum limit and reaches a fractional precision at the 10-17 level during a half-hour measurement. We further leverage the programmable control afforded by optical tweezer arrays to apply local phase shifts to explore spin squeezing in measurements that operate beyond the relative coherence time with the optical local oscillator. The realization of this spin-squeezing protocol in a programmable atom-array clock will enable a wide range of quantum-information-inspired techniques for optimal phase estimation and Heisenberg-limited optical atomic clocks12-16.

Half-minute-scale atomic coherence and high relative stability in a tweezer clock.

The preparation of large, low-entropy, highly coherent ensembles of identical quantum systems is fundamental for many studies in quantum metrology1, simulation2 and information3. However, the simultaneous realization of these properties remains a central challenge in quantum science across atomic and condensed-matter systems2,4-7. Here we leverage the favourable properties of tweezer-trapped alkaline-earth (strontium-88) atoms8-10, and introduce a hybrid approach to tailoring optical potentials that balances scalability, high-fidelity state preparation, site-resolved readout and preservation of atomic coherence. With this approach, we achieve trapping and optical-clock excited-state lifetimes exceeding 40 seconds in ensembles of approximately 150 atoms. This leads to half-minute-scale atomic coherence on an optical-clock transition, corresponding to quality factors well in excess of 1016. These coherence times and atom numbers reduce the effect of quantum projection noise to a level that is comparable with that of leading atomic systems, which use optical lattices to interrogate many thousands of atoms in parallel11,12. The result is a relative fractional frequency stability of 5.2(3) × 10-17τ-1/2 (where τ is the averaging time in seconds) for synchronous clock comparisons between sub-ensembles within the tweezer array. When further combined with the microscopic control and readout that are available in this system, these results pave the way towards long-lived engineered entanglement on an optical-clock transition13 in tailored atom arrays.

Microscopy of the interacting Harper-Hofstadter model in the two-body limit.

The interplay between magnetic fields and interacting particles can lead to exotic phases of matter that exhibit topological order and high degrees of spatial entanglement. Although these phases were discovered in a solid-state setting, recent innovations in systems of ultracold neutral atoms-uncharged atoms that do not naturally experience a Lorentz force-allow the synthesis of artificial magnetic, or gauge, fields. This experimental platform holds promise for exploring exotic physics in fractional quantum Hall systems, owing to the microscopic control and precision that is achievable in cold-atom systems. However, so far these experiments have mostly explored the regime of weak interactions, which precludes access to correlated many-body states. Here, through microscopic atomic control and detection, we demonstrate the controlled incorporation of strong interactions into a two-body system with a chiral band structure. We observe and explain the way in which interparticle interactions induce chirality in the propagation dynamics of particles in a ladder-like, real-space lattice governed by the interacting Harper-Hofstadter model, which describes lattice-confined, coherently mobile particles in the presence of a magnetic field. We use a bottom-up strategy to prepare interacting chiral quantum states, thus circumventing the challenges of a top-down approach that begins with a many-body system, the size of which can hinder the preparation of controlled states. Our experimental platform combines all of the necessary components for investigating highly entangled topological states, and our observations provide a benchmark for future experiments in the fractional quantum Hall regime.

High-risk ankle fractures in high-risk older patients: to fix or nail?

INTRODUCTION: Optimal treatment of high-risk ankle fractures in older, comorbid patients is unknown. Results of open reduction internal fixation (ORIF) versus tibiotalocalcaneal (TTC) fusion nailing for the treatment of high-risk geriatric ankle fractures were investigated. MATERIALS AND METHODS: Results of ORIF versus TTC fusion nailing were evaluated via retrospective case-control cohort study of 60 patients over age 50 with an open ankle fracture or one with at least 50% talar subluxation and at least 1 high-risk comorbidity: diabetes mellitus (DM), peripheral vascular disease, immunosuppression, active smoking, or a BMI > 35. The primary outcome was reoperation rate within 1-year post-surgery. Secondary outcomes include infection, peri-implant fracture, malunion/nonunion, mortality, length of stay, disposition, and hospital acquired complications. RESULTS: Mean age was 71 (ORIF) and 68 (TTC). 12/47 (25.5%) ORIF cases were open fractures versus 4/14 (28.6%) with TTC. There were no significant differences between ORIF and TTC in 1-year reoperation rates (17% vs 21.4%), infection rates (12.8% vs 14.3%), or union rates (76.% vs 85.7%), respectively. One TTC patient sustained a peri-implant fracture treated nonoperatively. There were no significant differences in medical risk factors between groups other than a higher rate of DM in the TTC group, 42.6% vs 78.6%, p = 0.02. Incomplete functional outcome data in this challenging patient cohort precluded drawing conclusions. CONCLUSION: ORIF and TTC fusion nailing result in comparable and acceptable reoperation, infection, and union rates in treating high-risk ankle fractures in patients over 50 with at least 1 major comorbidity for increased complications; further study is warranted.

Preparation of Low Entropy Correlated Many-Body States via Conformal Cooling Quenches.

We propose and analyze a method for preparing low entropy many-body states in isolated quantum optical systems of atoms, ions, and molecules. Our approach is based upon shifting entropy between different regions of a system by spatially modulating the magnitude of the effective Hamiltonian. We conduct two case studies, on a topological spin chain and the spinful fermionic Hubbard model, focusing on the key question: can a "conformal cooling quench" remove sufficient entropy within experimentally accessible timescales? Finite-temperature, time-dependent matrix product state calculations reveal that even moderately sized bath regions can remove enough energy and entropy density to expose coherent low-temperature physics. The protocol is particularly natural in systems with long-range interactions, such as lattice-trapped polar molecules and Rydberg-excited atoms, where the magnitude of the Hamiltonian scales directly with the interparticle spacing. To this end, we propose simple, near-term implementations of conformal cooling quenches in systems of atoms or molecules, where signatures of low-temperature phases may be observed.

Asymmetric Blockade and Multiqubit Gates via Dipole-Dipole Interactions.

Because of their strong and tunable interactions, Rydberg atoms can be used to realize fast two-qubit entangling gates. We propose a generalization of a generic two-qubit Rydberg-blockade gate to multiqubit Rydberg-blockade gates that involve both many control qubits and many target qubits simultaneously. This is achieved by using strong microwave fields to dress nearby Rydberg states, leading to asymmetric blockade in which control-target interactions are much stronger than control-control and target-target interactions. The implementation of these multiqubit gates can drastically simplify both quantum algorithms and state preparation. To illustrate this, we show that a 25-atom Greenberger-Horne-Zeilinger state can be created using only three gates with an error of 5.8%.

Management of a Unique Sinonasal Undifferentiated Carcinoma Subtype in the Era of SARS-CoV-2.

The novel coronavirus (SARS-CoV-2) pandemic has influenced the timeliness of care for patients with both common and rare conditions, particularly those affecting high-risk operative sites such as the upper aerodigestive tract. Sinonasal undifferentiated carcinoma (SNUC) represents a rare malignancy of the sinonasal tract, a unique subset of which has never been previously reported in the otolaryngology literature and is characterized by inactivation of the SMARCB (INI-1) tumor suppressor gene. This subtype exhibits a particularly poor prognosis and is characterized pathologically by its rhabdoid appearance. Here we present the case of an individual who was diagnosed with a sinonasal mass during the SARS-CoV-2 pandemic, which was ultimately found to be SMARCB (INI-1)-deficient sinonasal carcinoma. Advanced imaging was deferred in the interest of limiting the patient's exposure to the virus, and expedited operative management was performed which facilitated prompt referral for adjuvant chemoradiation. The SARS-CoV-2 pandemic presents unique challenges, but the work-up of high-risk lesions must be prioritized; this continues to be paramount as SARS-CoV-2 resurges in many cities across the USA.

A Rare Case of Temporal Bone Pneumocephalus Tracking through the Internal Auditory Canal.

A 39-year-old male with chronic hydrocephalus requiring biventricular shunts presented with progressive pneumocephalus over several years. He showed no improvement following ventriculoperitoneal (VP) shunt revision and anterior skull base repair for a sphenoid dehiscence. Imaging continued to show worsening pneumocephalus with air tracking along the right facial nerve from the geniculate ganglion to the internal auditory canal (IAC). The patient then underwent tympanomastoidectomy and skull base reconstruction. Based on a search of published literature, this appears to be the first reported case of temporal bone pneumocephalus coursing through the IAC, unlike most cases associated with tegmen defects and middle fossa pneumocephalus.

Predictors of Nodal Metastasis in Mucoepidermoid Carcinoma of the Oral Cavity and Oropharynx.

INTRODUCTION: Mucoepidermoid carcinoma (MEC) of the upper aerodigestive tract (UADT) is an uncommon malignancy, with limited literature available on its clinical and pathologic characteristics. Here, we describe the behavior of MEC of the UADT including pathologic characteristics and predictors of nodal metastasis. METHODS: Retrospective cohort study of patients with MEC of the UADT treated at an academic medical center from January 2008 to May 2018. Data was collected about demographics and tumor characteristics including clinical and histological data. The two-tailed Student t test and χ2 analysis were performed to assess for predictors of nodal metastasis. RESULTS: We identified 44 patients with minor salivary gland MEC of the oral cavity (OC) and oropharynx (OP). All patients were treated with primary site surgery. The primary site was the OC in 25 patients (57%) and OP in 19 (43%). Low-grade histology was seen in 27 specimens (61.4%), intermediate histology in 9 specimens (20.5%), and high-grade histology in 8 specimens (18.2%). Perineural invasion was noted in 10 specimens (22.7%). Neck dissection was performed in 17 patients (39%), with pathologically positive nodes found in 9 (20.5%). Notably, 5 of the 9 positive nodal specimens were found in clinically node-negative necks. Pathologically positive cervical lymph nodes were significantly associated with the OP as the primary site (p = 0.0005), perineural invasion (p = 0.012), lymphovascular invasion (p < 0.001), and high-grade histology (p = 0.004) in the primary specimen. DISCUSSION: MEC of the UADT is an uncommon malignancy. Our findings suggest elective neck dissection should be considered with perineural and lymphovascular invasion, high-grade tumor, and the OP as the primary site.

Nondestructive Cooling of an Atomic Quantum Register via State-Insensitive Rydberg Interactions.

We propose a protocol for sympathetically cooling neutral atoms without destroying the quantum information stored in their internal states. This is achieved by designing state-insensitive Rydberg interactions between the data-carrying atoms and cold auxiliary atoms. The resulting interactions give rise to an effective phonon coupling, which leads to the transfer of heat from the data atoms to the auxiliary atoms, where the latter can be cooled by conventional methods. This can be used to extend the lifetime of quantum storage based on neutral atoms and can have applications for long quantum computations. The protocol can also be modified to realize state-insensitive interactions between the data and the auxiliary atoms but tunable and nontrivial interactions among the data atoms, allowing one to simultaneously cool and simulate a quantum spin model.

Variational Spin-Squeezing Algorithms on Programmable Quantum Sensors.

Arrays of atoms trapped in optical tweezers combine features of programmable analog quantum simulators with atomic quantum sensors. Here we propose variational quantum algorithms, tailored for tweezer arrays as programmable quantum sensors, capable of generating entangled states on demand for precision metrology. The scheme is designed to generate metrological enhancement by optimizing it in a feedback loop on the quantum device itself, thus preparing the best entangled states given the available quantum resources. We apply our ideas to the generation of spin-squeezed states on Sr atom tweezer arrays, where finite-range interactions are generated through Rydberg dressing. The complexity of experimental variational optimization of our quantum circuits is expected to scale favorably with system size. We numerically show our approach to be robust to noise, and surpassing known protocols.

Screening for poverty and intervening in a primary care setting: an acceptability and feasibility study.

BACKGROUND: A movement is emerging to encourage health providers and health organizations to take action on the social determinants of health. However, few evidence-based interventions exist. Digital tools have not been examined in depth. OBJECTIVE: To assess the acceptability and feasibility of integrating, within routine primary care, screening for poverty and an online tool that helps identify financial benefits. METHODS: The setting was a Community Health Centre serving a large number of low-income individuals in Toronto, Canada. Physicians were encouraged to use the tool at every possible encounter during a 1-month period. A link to the tool was easily accessible, and reminder emails were circulated regularly. This mixed-methods study used a combination of pre-intervention and post-intervention surveys, focus groups and interviews. RESULTS: Thirteen physicians participated (81.25% of all) and represented a range of genders and years in practice. Physicians reported a strong awareness of the importance of identifying poverty as a health concern, but low confidence in their ability to address poverty. The tool was used with 63 patients over a 1-month period. Although screening and intervening on poverty is logistically challenging in regular workflows, online tools could assist patients and health providers identify financial benefits quickly. Future interventions should include more robust follow-up. CONCLUSIONS: Our study contributes to the evidence based on addressing the social determinants of health in clinical settings. Future approaches could involve routine screening, engaging other members of the team in intervening and following up, and better integration with the electronic health record.

Vestibulotoxicity in a patient without renal failure after inhaled tobramycin.

Aminoglycoside antibiotics have a long history of use in the control of gram-negative bacterial infections, but their systemic use has been complicated by known ototoxicity and nephrotoxicity. Because of the utility of these medications in patients with frequent pulmonary infections, there has been a move towards the use of inhaled agents, in particular tobramycin, due to a lower rate of systemic complications. Inhaled tobramycin is generally consider to be safe from otologic complications, with only two previous reports of ototoxicity, both in patients who had underlying chronic renal disease. Here we present the first case of a patient developing isolated vestibular toxicity, without associated hearing loss or evidence of renal insufficiency, in a patient receiving inhaled tobramycin. This is an extremely rare complication of an inhaled aminoglycoside and underscores the importance of careful monitoring despite perceived safety.

Pigmented Villonodular Synovitis Presenting as Unilateral Hearing Loss: Review of the Literature and Case Report.

BACKGROUND/AIMS: To review the existing literature on pigmented villonodular synovitis (PVNS) of the temporomandibular joint (TMJ) and report a rare case of PVNS of the TMJ presenting with unilateral hearing loss. METHODS: Review of the existing literature and a description of personal experience with PVNS of the TMJ presenting with unilateral hearing loss. RESULTS: Review of the existing literature revealed 76 reported cases of PVNS of the TMJ. The most common presenting symptom was of a slowly enlarging mass or swelling of the preauricular area, with dysfunctional TMJ also frequently reported. All patients underwent surgical excision with some pursuing radiation as adjuvant therapy. Presented Patient: A 46-year-old man presented with several months of unilateral subjective hearing loss and aural fullness. Imaging revealed a mass centered along the superior TMJ with expansion through the squamous temporal bone and extra-axial intracranial extension into the middle cranial fossa. Imaging characteristics and fine-needle aspiration biopsy were consistent with PVNS. INTERVENTION: The patient underwent near-total excision of the mass via frontotemporal craniectomy and lateral temporal bone resection. FOLLOW-UP: At the 16-month follow-up there was no evidence of disease recurrence. CONCLUSION: PVNS of the TMJ represents a rare entity that can present with a variety of symptoms including unilateral hearing loss.

Conditional Deletion of Prnp Rescues Behavioral and Synaptic Deficits after Disease Onset in Transgenic Alzheimer's Disease.

Biochemical and genetic evidence implicate soluble oligomeric amyloid-ß (Aßo) in triggering Alzheimer's disease (AD) pathophysiology. Moreover, constitutive deletion of the Aßo-binding cellular prion protein (PrPC) prevents development of memory deficits in APPswe/PS1ΔE9 mice, a model of familial AD. Here, we define the role of PrPC to rescue or halt established AD endophenotypes in a therapeutic disease-modifying time window after symptom onset. Deletion of Prnp at either 12 or 16 months of age fully reverses hippocampal synapse loss and completely rescues preexisting behavioral deficits by 17 months. In contrast, but consistent with a neuronal function for Aßo/PrPC signaling, plaque density, microgliosis, and astrocytosis are not altered. Degeneration of catecholaminergic neurons remains unchanged by PrPC reduction after disease onset. These results define the potential of targeting PrPC as a disease-modifying therapy for certain AD-related phenotypes after disease onset.SIGNIFICANCE STATEMENT The study presented here further elucidates our understanding of the soluble oligomeric amyloid-ß-Aßo-binding cellular prion protein (PrPC) signaling pathway in a familial form of Alzheimer's disease (AD) by implicating PrPC as a potential therapeutic target for AD. In particular, genetic deletion of Prnp rescued several familial AD (FAD)-associated phenotypes after disease onset in a mouse model of FAD. This study underscores the therapeutic potential of PrPC deletion given that patients already present symptoms at the time of diagnosis.

Measurement-Based Entanglement of Noninteracting Bosonic Atoms.

We demonstrate the ability to extract a spin-entangled state of two neutral atoms via postselection based on a measurement of their spatial configuration. Typically, entangled states of neutral atoms are engineered via atom-atom interactions. In contrast, in our Letter, we use Hong-Ou-Mandel interference to postselect a spin-singlet state after overlapping two atoms in distinct spin states on an effective beam splitter. We verify the presence of entanglement and determine a bound on the postselected fidelity of a spin-singlet state of (0.62±0.03). The experiment has direct analogy to creating polarization entanglement with single photons and hence demonstrates the potential to use protocols developed for photons to create complex quantum states with noninteracting atoms.

Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network.

Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aß levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies. Consistent with the human data, subsequent analyses using the APPswe/PS1ΔE9 (APP/PS1) mouse model of cerebral amyloidosis show that PGRN deficiency has no exacerbating effects on Aß pathology. In contrast and unexpectedly, PGRN deficiency significantly reduces diffuse Aß plaque growth in these APP/PS1 mice. This protective effect is due, at least in part, to enhanced microglial Aß phagocytosis caused by PGRN deficiency-induced expression of TYROBP network genes (TNG) including an AD risk factor Trem2. PGRN-deficient APP/PS1 mice also exhibit less severe axonal dystrophy and partially improved behavior phenotypes. While PGRN deficiency reduces these amyloidosis-related phenotypes, other neuronal injury mechanisms are increased by loss of PGRN, revealing a multidimensional interaction of GRN with AD. For example, C1q complement deposition at synapses is enhanced in APP/PS1 mice lacking PGRN. Moreover, PGRN deficiency increases tau AT8 and AT180 pathologies in human P301L tau-expressing mice. These human and rodent data suggest that global PGRN reduction induces microglial TNG expression and increases AD risk by exacerbating neuronal injury and tau pathology, rather than by accelerating Aß pathology.

Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer's disease.

Alzheimer's disease-related phenotypes in mice can be rescued by blockade of either cellular prion protein or metabotropic glutamate receptor 5. We sought genetic and biochemical evidence that these proteins function cooperatively as an obligate complex in the brain. We show that cellular prion protein associates via transmembrane metabotropic glutamate receptor 5 with the intracellular protein mediators Homer1b/c, calcium/calmodulin-dependent protein kinase II, and the Alzheimer's disease risk gene product protein tyrosine kinase 2 beta. Coupling of cellular prion protein to these intracellular proteins is modified by soluble amyloid-ß oligomers, by mouse brain Alzheimer's disease transgenes or by human Alzheimer's disease pathology. Amyloid-ß oligomer-triggered phosphorylation of intracellular protein mediators and impairment of synaptic plasticity in vitro requires Prnp-Grm5 genetic interaction, being absent in transheterozygous loss-of-function, but present in either single heterozygote. Importantly, genetic coupling between Prnp and Grm5 is also responsible for signalling, for survival and for synapse loss in Alzheimer's disease transgenic model mice. Thus, the interaction between metabotropic glutamate receptor 5 and cellular prion protein has a central role in Alzheimer's disease pathogenesis, and the complex is a potential target for disease-modifying intervention.

Prion-Protein-interacting Amyloid-ß Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models.

Alzheimer disease (AD) is characterized by amyloid-ß accumulation, with soluble oligomers (Aßo) being the most synaptotoxic. However, the multivalent and unstable nature of Aßo limits molecular characterization and hinders research reproducibility. Here, we characterized multiple Aßo forms throughout the life span of various AD mice and in post-mortem human brain. Aßo exists in several populations, where prion protein (PrP(C))-interacting Aßo is a high molecular weight Aß assembly present in multiple mice and humans with AD. Levels of PrP(C)-interacting Aßo match closely with mouse memory and are equal or superior to other Aß measures in predicting behavioral impairment. However, Aßo metrics vary considerably between mouse strains. Deleting PrP(C) expression in mice with relatively low PrP(C)-interacting Aßo (Tg2576) results in partial rescue of cognitive performance as opposed to complete recovery in animals with a high percentage of PrP(C)-interacting Aßo (APP/PSEN1). These findings highlight the relative contributions and interplay of Aßo forms in AD.