An optical tweezer array of ultracold polyatomic molecules.

Polyatomic molecules have rich structural features that make them uniquely suited to applications in quantum information science1-3, quantum simulation4-6, ultracold chemistry7 and searches for physics beyond the standard model8-10. However, a key challenge is fully controlling both the internal quantum state and the motional degrees of freedom of the molecules. Here we demonstrate the creation of an optical tweezer array of individual polyatomic molecules, CaOH, with quantum control of their internal quantum state. The complex quantum structure of CaOH results in a non-trivial dependence of the molecules' behaviour on the tweezer light wavelength. We control this interaction and directly and non-destructively image individual molecules in the tweezer array with a fidelity greater than 90%. The molecules are manipulated at the single internal quantum state level, thus demonstrating coherent state control in a tweezer array. The platform demonstrated here will enable a variety of experiments using individual polyatomic molecules with arbitrary spatial arrangement.

Dipolar spin-exchange and entanglement between molecules in an optical tweezer array.

Ultracold polar molecules are promising candidate qubits for quantum computing and quantum simulations. Their long-lived molecular rotational states form robust qubits, and the long-range dipolar interaction between molecules provides quantum entanglement. In this work, we demonstrate dipolar spin-exchange interactions between single calcium monofluoride (CaF) molecules trapped in an optical tweezer array. We realized the spin-[Formula: see text] quantum XY model by encoding an effective spin-[Formula: see text] system into the rotational states of the molecules and used it to generate a Bell state through an iSWAP operation. Conditioned on the verified existence of molecules in both tweezers at the end of the measurement, we obtained a Bell state fidelity of 0.89(6). Using interleaved tweezer arrays, we demonstrate single-site molecular addressability.

Quantum control of trapped polyatomic molecules for eEDM searches.

Ultracold polyatomic molecules are promising candidates for experiments in quantum science and precision searches for physics beyond the Standard Model. A key requirement is the ability to achieve full quantum control over the internal structure of the molecules. In this work, we established coherent control of individual quantum states in calcium monohydroxide (CaOH) and demonstrated a method for searching for the electron electric dipole moment (eEDM). Optically trapped, ultracold CaOH molecules were prepared in a single quantum state, polarized in an electric field, and coherently transferred into an eEDM-sensitive state where an electron spin precession measurement was performed. To extend the coherence time, we used eEDM-sensitive states with tunable, near-zero magnetic field sensitivity. Our results establish a path for eEDM searches with trapped polyatomic molecules.

Comparison of circulating and excreted metals and of autoimmunity between two Great Plains Tribal communities.

Metals contaminants of the environment from mine waste have been implicated as contributing agents in autoimmune disease. The current study compares metals and autoimmunity in two Tribal communities residing in the Black Hills and the Bighorn Mountains geographical regions that are scattered with extant hard rock mines. With documented drinking water contamination in both communities, in vivo levels of more than half of the measured serum and urine metals differed between the two communities and were substantially different from their national median values. Serum autoantibodies associated with systemic autoimmune disease were rare or at low-level, but antibodies to denatured (single-stranded) DNA and thyroid-specific autoantibodies were commonly elevated, especially in women. A three-tier statistical modeling process was carried out to examine individual metals exposure as predictors of autoantibody levels. For the most part only weak positive associations between individual metals and systemic autoantibodies were found, although univariate quantile regression analysis showed positive statistical associations of serum lead and antimony with anti-chromatin and anti-histone autoantibodies. Using age and gender-adjusted multivariable statistical models, metals did not predict anti-thyroglobulin or -thyroid peroxidase significantly and metals were generally negative predictors of the other autoantibodies. Overall these results suggest that elevated levels of environmental metals and metalloids in these communities may result in suppression of autoantibodies associated with systemic autoimmune disease.

Internal feedback in the cortical perception-action loop enables fast and accurate behavior.

Animals move smoothly and reliably in unpredictable environments. Models of sensorimotor control, drawing on control theory, have assumed that sensory information from the environment leads to actions, which then act back on the environment, creating a single, unidirectional perception-action loop. However, the sensorimotor loop contains internal delays in sensory and motor pathways, which can lead to unstable control. We show here that these delays can be compensated by internal feedback signals that flow backward, from motor toward sensory areas. This internal feedback is ubiquitous in neural sensorimotor systems, and we show how internal feedback compensates internal delays. This is accomplished by filtering out self-generated and other predictable changes so that unpredicted, actionable information can be rapidly transmitted toward action by the fastest components, effectively compressing the sensory input to more efficiently use feedforward pathways: Tracts of fast, giant neurons necessarily convey less accurate signals than tracts with many smaller neurons, but they are crucial for fast and accurate behavior. We use a mathematically tractable control model to show that internal feedback has an indispensable role in achieving state estimation, localization of function (how different parts of the cortex control different parts of the body), and attention, all of which are crucial for effective sensorimotor control. This control model can explain anatomical, physiological, and behavioral observations, including motor signals in the visual cortex, heterogeneous kinetics of sensory receptors, and the presence of giant cells in the cortex of humans as well as internal feedback patterns and unexplained heterogeneity in neural systems.

Endoscopic Ultrasound-Guided Biliary Drainage.

Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD) are currently first- and second-line therapeutic options, respectively, for the relief of biliary obstruction. In recent years, however, endoscopic ultrasound-guided biliary drainage (EUS-BD) has become an established alternative therapy for biliary obstruction. There are multiple different techniques for EUS-BD, which can be distinguished based on the access point within the biliary tree (intrahepatic versus extrahepatic) and the location of stent placement (transenteric versus transpapillary). The clinical and technical success rates of biliary drainage for EUS-BD are similar to both ERCP and PTBD, and complication rates are favorable for EUS-BD relative to PTBD. As EUS-BD becomes more widely practiced and endoscopic tools continue to advance, the outcomes will likely improve, and the breadth of indications for EUS-BD will continue to expand.

Optical Trapping of a Polyatomic Molecule in an ℓ-Type Parity Doublet State.

We report optical trapping of a polyatomic molecule, calcium monohydroxide (CaOH). CaOH molecules from a magneto-optical trap are sub-Doppler laser cooled to 20(3) µK in free space and loaded into an optical dipole trap. We attain an in-trap molecule number density of 3(1)×10^{9} cm^{-3} at a temperature of 57(8) µK. Trapped CaOH molecules are optically pumped into an excited vibrational bending mode, whose ℓ-type parity doublet structure is a potential resource for a wide range of proposed quantum science applications with polyatomic molecules. We measure the spontaneous, radiative lifetime of this bending mode state to be ∼0.7 s.

High-sensitivity low-noise photodetector using a large-area silicon photomultiplier.

The application of silicon photomultiplier (SiPM) technology for weak-light detection at a single photon level has expanded thanks to its better photon detection efficiency in comparison to a conventional photomultiplier tube (PMT). SiPMs with large detection area have recently become commercially available, enabling applications where the photon flux is low both temporarily and spatially. On the other hand, several drawbacks exist in the usage of SiPMs such as a higher dark count rate, many readout channels, slow response time, and optical crosstalk; therefore, users need to carefully consider the trade-offs. This work presents a SiPM-embedded compact large-area photon detection module. Various techniques are adopted to overcome the disadvantages of SiPMs so that it can be generally utilized as an upgrade from a PMT. A simple cooling component and recently developed optical crosstalk suppression method are adopted to reduce the noise which is more serious for larger-area SiPMs. A dedicated readout circuit increases the response frequency and reduces the number of readout channels. We favorably compare this design with a conventional PMT and obtain both higher photon detection efficiency and larger-area acceptance.

Analysis of risk factors for nonunion in pediatric lateral column lengthening.

The lateral column lengthening procedure is a commonly used osteotomy for correction of pes planus performed by inserting a graft in the anterior aspect of the calcaneus through a transverse osteotomy. Though nonunion and calcaneo-cuboid subluxation have been previously reported, these complications have not been extensively studied in pediatric patients. After IRB approval, 111 patients (151 feet) who underwent lateral column lengthening at a single institution were identified. Fifty-three females (70 feet) and 58 males (81 feet) with an average age of 11.4 years (2.6 SD; range 5-17) were analyzed. The primary outcome was nonunion defined as a lack of radiographic evidence of osteotomy healing by 9 months. Underlying diagnosis, pre and postoperative radiographic measurements, age, operative technique, fixation, calcaneo-cuboid subluxation, graft material and concomitant procedures were analyzed for their relationship to nonunion. Nonunion occurred in 7 of 151 feet (4.6%). Patient age at the time of surgery and calcaneo-cuboid subluxation trended toward a significant association with nonunion ( P = 0.053, 0.054, respectively). The degree of surgical correction, as determined by radiographic analysis, and the use of calcaneo-cuboid fixation were not significantly associated with nonunion. None of the other factors evaluated were significantly associated with nonunion. There were three cases of postoperative infections (2.0%), two were superficial and 1 (0.7%) was deep. Thirty-five of 151 feet disclosed radiographic evidence of subluxation. Excluding subluxation, the overall complication rate was 8.6%. Nonunion occurred in 4.6% of pediatric feet undergoing lateral column lengthening. Fixation type was not significantly associated with nonunion. Older age at the time of surgery and calcaneocuboid subluxation trended towards significance. The placement of a calcaneo-cuboid pin was not found to be a significant factor in preventing calcaneo-cuboid subluxation or nonunion.

High-Resolution Laser Spectroscopy of a Functionalized Aromatic Molecule.

We present a high-resolution laser spectroscopic study of the Ã2B2-X̃2A1 and B̃2B1-X̃2A1 transitions of calcium(I) phenoxide, CaOPh (CaOC6H5). The rotationally resolved band systems are analyzed using an effective Hamiltonian model and are accurately modeled as independent perpendicular (b- or c-type) transitions. The structure of calcium monophenoxide is compared to previously observed Ca-containing radicals, and implications for direct laser cooling are discussed. This work demonstrates that functionalization of aromatic molecules with optical cycling centers can preserve many of the properties needed for laser-based control.

Body mass index and additional risk factors for cancer in adults with cystic fibrosis.

BACKGROUND: Adults with cystic fibrosis (CF) have an increased risk of a variety of cancers, notably gastrointestinal cancers. In CF higher body mass index (BMI) is associated with improved long-term outcomes, yet in the general population high BMI is associated with increased cancer risk. We aimed to delineate associations between BMI and other factors with cancer risk in adults with CF. METHODS: This was a retrospective cohort study using CF Foundation Patient Registry data from 1992 to 2015. Data were collected on age, sex, CFTR mutation class, pancreatic insufficiency, and annualized data on BMI and FEV1. The primary analysis was the association between BMI and cancer, with secondary analyses focused on BMI trajectory. Multivariable logistic regression was performed, with analyses stratified by history of transplant. RESULTS: Of 26,199 adults with CF, 446 (1.7%) had cancer diagnosed by histology at a mean age of 40.0 years (SD 12.2), with a higher proportion of transplanted patients developing cancer (137 (3.8%) v 309(1.4%), p < 0.001). Among non-transplanted patients, there was no association between BMI and cancer (p for trend = 0.43). Pancreatic insufficiency (p < 0.01) and higher FEV1 (p < 0.01) were associated with increased cancer risk. In transplanted patients, higher BMI was associated with reduced risk of cancer (p for trend = 0.04). Older age was associated with increased risk in both groups (p < 0.001). BMI trajectories were not associated with cancer risk in either group. CONCLUSION: Higher BMI is associated with a reduced risk of cancer in transplanted adults with CF. Pancreatic insufficiency is a risk factor for cancer in non-transplanted CF patients.

Risk of Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in Patients With Celiac Disease: A Population-Based Cohort Study.

INTRODUCTION: Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort. METHODS: We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged <18 and of RA in individuals with CD aged ≥18. RESULTS: We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years. DISCUSSION: Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA.

Pathway toward Optical Cycling and Laser Cooling of Functionalized Arenes.

Rapid and repeated photon cycling has enabled precision metrology and the development of quantum information systems using atoms and simple molecules. Extending optical cycling to structurally complex molecules would provide new capabilities in these areas, as well as in ultracold chemistry. Increased molecular complexity, however, makes realizing closed optical transitions more difficult. Building on already established strong optical cycling of diatomic, linear triatomic, and symmetric top molecules, recent work has pointed the way to cycling of larger molecules, including phenoxides. The paradigm for these systems is an optical cycling center bonded to a molecular ligand. Theory has suggested that cycling may be extended to even larger ligands, like naphthalene, pyrene, and coronene. Herein, we study optical excitation and fluorescent vibrational branching of CaO-[Formula: see text], SrO-[Formula: see text], and CaO-[Formula: see text] and find only weak decay to excited vibrational states, indicating a promising path to full quantum control and laser cooling of large arene-based molecules.

Functionalizing aromatic compounds with optical cycling centres.

Molecular design principles provide guidelines for augmenting a molecule with a smaller group of atoms to realize a desired property or function. We demonstrate that these concepts can be used to create an optical cycling centre, the Ca(I)-O unit, that can be attached to a number of aromatic ligands, enabling the scattering of many photons from the resulting molecules without changing the molecular vibrational state. Such capability plays a central role in quantum state preparation and measurement, as well as laser cooling and trapping, and is therefore a prerequisite for many quantum science and technology applications. We provide further molecular design principles that indicate the ability to optimize and expand this work to an even broader class of molecules. This represents a great step towards a quantum functional group, which may serve as a generic qubit moiety that can be attached to a wide range of molecular structures and surfaces.

Atypical Climacteric and Functional Ethylene Metabolism and Signaling During Fruit Ripening in Blueberry (Vaccinium sp.).

Climacteric fruits display an increase in respiration and ethylene production during the onset of ripening, while such changes are minimal in non-climacteric fruits. Ethylene is a primary regulator of ripening in climacteric fruits. The ripening behavior and role of ethylene in blueberry (Vaccinium sp.) ripening is controversial. This work aimed to clarify the fruit ripening behavior and the associated role of ethylene in blueberry. Southern highbush (Vaccinium corymbosum hybrids) and rabbiteye (Vaccinium ashei) blueberry displayed an increase in the rate of respiration and ethylene evolution, both reaching a maxima around the Pink and Ripe stages of fruit development, consistent with climacteric fruit ripening behavior. Increase in ethylene evolution was associated with increases in transcript abundance of its biosynthesis genes, AMINOCYCLOPROPANE CARBOXYLATE (ACC) SYNTHASE1 (ACS1) and ACC OXIDASE2 (ACO2), implicating them in developmental ethylene production during ripening. Blueberry fruit did not display autocatalytic system 2 ethylene during ripening as ACS transcript abundance and ACC concentration were not enhanced upon treatment with an ethylene-releasing compound (ethephon). However, ACO transcript abundance was enhanced in response to ethephon, suggesting that ACO was not rate-limiting. Transcript abundance of multiple genes associated with ethylene signal transduction was upregulated concomitant with developmental increase in ethylene evolution, and in response to exogenous ethylene. As these changes require ethylene signal transduction, fruit ripening in blueberry appears to involve functional ethylene signaling. Together, these data indicate that blueberry fruit display atypical climacteric ripening, characterized by a respiratory climacteric, developmentally regulated but non-autocatalytic increase in ethylene evolution, and functional ethylene signaling.

Magneto-optical trapping and sub-Doppler cooling of a polyatomic molecule.

Laser cooling and trapping1,2, and magneto-optical trapping methods in particular2, have enabled groundbreaking advances in science, including Bose-Einstein condensation3-5, quantum computation with neutral atoms6,7 and high-precision optical clocks8. Recently, magneto-optical traps (MOTs) of diatomic molecules have been demonstrated9-12, providing access to research in quantum simulation13 and searches for physics beyond the standard model14. Compared with diatomic molecules, polyatomic molecules have distinct rotational and vibrational degrees of freedom that promise a variety of transformational possibilities. For example, ultracold polyatomic molecules would be uniquely suited to applications in quantum computation and simulation15-17, ultracold collisions18, quantum chemistry19 and beyond-the-standard-model searches20,21. However, the complexity of these molecules has so far precluded the realization of MOTs for polyatomic species. Here we demonstrate magneto-optical trapping of a polyatomic molecule, calcium monohydroxide (CaOH). After trapping, the molecules are laser cooled in a blue-detuned optical molasses to a temperature of 110 µK, which is below the Doppler cooling limit. The temperatures and densities achieved here make CaOH a viable candidate for a wide variety of quantum science applications, including quantum simulation and computation using optical tweezer arrays15,17,22,23. This work also suggests that laser cooling and magneto-optical trapping of many other polyatomic species24-27 will be both feasible and practical.

The Structural and Functional Correlates of Frailty in Persons With Human Immunodeficiency Virus.

BACKGROUND: Persons with HIV (PWH) are at increased risk of frailty, a clinically recognizable state of increased vulnerability resulting from aging-associated decline in multiple physiologic systems. Frailty is often defined by the Fried criteria, which includes subjective and objective standards concerning health resiliency. However, these frailty metrics do not incorporate cognitive performance or neuroimaging measures. METHODS: We compared structural (diffusion tensor imaging [DTI]) and functional (cerebral blood flow [CBF]) neuroimaging markers in PWH with frailty and cognitive performance. Virologically controlled PWH were dichotomized as either frail (≥3) or nonfrail (<3) using the Fried criteria. Cognitive Z-scores, both domain (executive, psychomotor speed, language, and memory) and global, were derived from a battery of tests. We identified three regions of reduced CBF, based on a voxel-wise comparison of frail PWH compared with nonfrail PWH. These clusters (bilateral frontal and posterior cingulate) were subsequently used as seed regions of interest (ROIs) for DTI probabilistic white matter tractography. RESULTS: White matter integrity connecting the ROIs was significantly decreased in frail compared with nonfrail PWH. No differences in cognition were observed between frail and nonfrail PWH. However, reductions in white matter integrity among these ROIs was significantly associated with worse psychomotor speed and executive function across the entire cohort. CONCLUSIONS: We conclude that frailty in PWH can lead to structural and functional brain changes, including subtle changes that are not detectable by standard neuropsychological tests. Multimodal neuroimaging in conjunction with frailty assessment could identify pathological brain changes observed in PWH.

Prevalence of Adenomas on Surveillance Colonoscopies for Patients with a History of Colonic Polyps of Unknown Histology.

BACKGROUND: Guidelines for surveillance colonoscopy depend on polyp histology. When patients present to a new healthcare system and report a personal history of "colon polyps," however, information on polyp histology is frequently unavailable. AIMS: To assess adenoma prevalence in patients with a history of colonic polyps of unknown histology and to compare it to patients undergoing either screening colonoscopy or surveillance colonoscopy for known adenomatous polyps. METHODS: This cohort study evaluated colonoscopies of patients ≥ 50 years of age over a 14-year period at a single institution. The exposure of interest was colonoscopy indication, categorized into three groups: screening colonoscopy, surveillance colonoscopy for history of colonic polyp(s) of unknown histology, and surveillance colonoscopy for history of adenoma(s). The primary outcome was adenoma detection rate. Multivariable logistic regression was used to assess the association between colonoscopy indication and adenoma detection rate. RESULTS: Of 31,856 colonoscopies, the adenoma prevalence was 26.1% for patients undergoing screening colonoscopy, 32.9% for patients with a history of polyps of unknown histology, and 41.9% for patients with a history of known adenomatous polyps. Relative to screening colonoscopies, there were higher odds of adenoma detection in surveillance colonoscopies for polyps of unknown histology (aOR compared to screening 1.42, 95% CI 1.30-1.55) and even higher odds among surveillance colonoscopies for a history of adenoma (aOR compared to screening 1.89, 95% CI 1.75-2.05). CONCLUSION: The adenoma prevalence on surveillance colonoscopy for patients with polyps of unknown histology was higher than that of screening colonoscopies but lower than that of surveillance colonoscopies for patients with adenomatous polyps.

Co-occurrence of Blount's disease and Legg-Calvé-Perthes disease: is obesity a factor?

Legg-Calvé-Perthes disease (LCPD) and Blount's disease share a similar presenting age in addition to similar symptoms such as limp or knee pain. A little overlap is mentioned about both diseases. We sought to present cases of children having both conditions to discuss the implications of this co-occurrence on diagnosis and management. After institutional review board approval, we retrospectively reviewed records of four children who developed both Blount's disease and LCPD. Patient details and outcomes were analyzed. Radiographs were evaluated for the lateral pillar classification, Stulberg classification, tibial metaphyseal-diaphyseal angle and tibiofemoral angle. Two of the cases were initially diagnosed with Blount's disease and subsequently developed Perthes, one case presented initially with both disorders and the final case had Perthes followed by Blount's. Three children were obese and one was overweight. The common symptom to all patients was an abnormal gait, which was painless in two children and painful in two. Blount's disease required surgery in three children. Radiographs showed Lateral Pillar B, B/C border and C hips, and the final Stulberg was stage II (n = 2) or stage IV (n = 2). Obesity is associated with Blount's disease and LCPD, so obese children can be at an increased risk of developing both disorders. Therefore, a child with Blount's disease who has persistent, recurrent or worsening symptoms such as gait disturbance or thigh or knee pain might benefit from a careful physical exam of the hips to prevent a delayed or even missed LCPD diagnosis.

Tunable VUV frequency comb for 229mTh nuclear spectroscopy.

Laser spectroscopy of the 229mTh nuclear clock transition is necessary for the future construction of a nuclear-based optical clock. Precision laser sources with broad spectral coverage in the vacuum ultraviolet are needed for this task. Here, we present a tunable vacuum-ultraviolet frequency comb based on cavity-enhanced seventh-harmonic generation. Its tunable spectrum covers the current uncertainty range of the 229mTh nuclear clock transition.