Formation of robust bound states of interacting microwave photons.

Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles1. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states2-9. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.

Whole-genome sequencing in prenatally detected congenital malformations: prospective cohort study in clinical setting.

OBJECTIVE: To investigate the diagnostic yield of trio whole-genome sequencing (WGS) in fetuses with various congenital malformations referred to a tertiary center for prenatal diagnosis. METHODS: In this prospective study, 50 pregnancies with different congenital malformations, negative for trisomies and causative copy-number variants, were analyzed further with fetal-parental trio WGS analysis. Parents were eligible for inclusion if they accepted further investigation following the detection of isolated or multiple malformations on prenatal ultrasound. Cases with isolated increased nuchal translucency, gamete donation or multiple pregnancy were excluded. WGS with the Illumina Inc. 30× polymerase-chain-reaction-free short-read sequencing included analysis of single-nucleotide variants, insertions and deletions, structural variants, short tandem repeats and copy-number identification of SMN1 and SMN2 genes. RESULTS: A molecular diagnosis was achieved in 13/50 (26%) cases. Causative sequence variants were identified in 12 genes: FGFR3 (n = 2), ACTA1 (n = 1), CDH2 (n = 1), COL1A2 (n = 1), DHCR7 (n = 1), EYA1 (n = 1), FBXO11 (n = 1), FRAS1 (n = 1), L1CAM (n = 1), OFD1 (n = 1), PDHA1 (n = 1) and SOX9 (n = 1). The phenotypes of the cases were divided into different groups, with the following diagnostic yields: skeletal malformation (4/9 (44%)), multisystem malformation (3/7 (43%)), central nervous system malformation (5/15 (33%)) and thoracic malformation (1/10 (10%)). Additionally, two cases carried variants that were considered potentially clinically relevant, even though they were assessed as variants of uncertain significance, according to the guidelines provided by the American College of Medical Genetics and Genomics. Overall, we identified a causative or potentially clinically relevant variant in 15/50 (30%) cases. CONCLUSIONS: We demonstrate a diagnostic yield of 26% with clinical WGS in prenatally detected congenital malformations. This study emphasizes the benefits that WGS can bring to the diagnosis of fetal structural anomalies. It is important to note that causative chromosomal aberrations were excluded from our cohort before WGS. As chromosomal aberrations are a well-known cause of prenatally detected congenital malformations, future studies using WGS as a primary diagnostic test, including assessment of chromosomal aberrations, may show that the detection rate exceeds the diagnostic yield of this study. WGS can add clinically relevant information, explaining the underlying cause of the fetal anomaly, which will provide information concerning the specific prognosis of the condition, as well as estimate the risk of recurrence. A genetic diagnosis can also provide more reproductive choice for future pregnancies. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Inconsistent Return to Sport Despite Improved Outcomes After Re-revision Anterior Cruciate Ligament Reconstruction: An Updated Systematic Review.

PURPOSE: The primary objective was to systematically review the literature evaluating patient-reported outcomes and return to sport after re-revision anterior cruciate ligament reconstruction (ACLR) procedures. The secondary objectives were 2-fold: to identify the risk factors that lead to revision ACLR failure and to assess the secondary knee structure injuries after the initial revision ACLR. METHODS: A systematic review of the literature was performed using the MEDLINE/PubMed and Cochrane databases. The inclusion criteria were outcomes of re-revision ACLR, minimum of 2 years' follow-up, human studies, and English language. Basic science articles, epidemiologic studies, editorials, surgical technique articles, surveys, cadaveric studies, and animal studies were excluded. RESULTS: Fifteen studies met the inclusion criteria and were considered for review. There were 6 Level III and 9 Level IV studies that included 399 patients undergoing re-revision ACLR. The rate of concomitant meniscal lesions at the time of re-revision ranged from 35% to 90%. The prevalence of concomitant cartilaginous lesions at the time of re-revision ranged from 13.6% to 90%. Compared with preoperative scores, patient-reported outcomes overall improved after re-revision ACLR, with mean preoperative Lysholm scores ranging from 38.4 to 73.15 that improved to postoperative scores ranging from 68 to 87.8. However, return to sport at preinjury levels was inconsistent, with rates ranging from 12.5% to 80%. CONCLUSIONS: Re-revision ACLR was found to restore knee stability and improve functional outcomes. Despite this improvement, there was a low rate of return to sport at the preinjury level. Functional outcomes were also inferior when compared with primary ACLR. In addition, concomitant knee pathologies were found to rise in prevalence compared with revision and primary ACLR cases. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV studies.

Reference standards for stress radiography measurements in knee ligament injury and instability: a systematic review.

PURPOSE: Stress radiographs are an easily accessible, cost-effective tool in the evaluation of acute and chronic ligament knee injuries. Stress radiographs provide an objective, quantifiable, and functional assessment of the injured ligament and can be a useful adjunct when planning surgical management and to objectively assess postoperative outcomes. This study aimed to review the literature reporting on stress radiographic techniques in evaluating knee ligament injury and instability and propose thresholds for interpreting stress radiography techniques. METHODS: The following three databases, OVID MEDLINE, the EMBASE library, and the Cochrane Controlled Trials Register, were systematically searched on January 23, 2023, for studies published from January 1970 to January 2023. The search extended to the reference lists of all relevant studies and orthopedic journals. Included studies were those that described a stress technique for the diagnosis of knee ligament injury; studies that reported a description or comparison of the accuracy and/or reliability of one or several stress radiography techniques, or studies that reported a comparison with alternative diagnostic modalities. RESULTS: Sixteen stress radiography techniques were reported for assessing the ACL with stress applied in the anterior plane, 10 techniques for assessing the PCL with stress applied in the posterior plane, 3 techniques for valgus stress, and 4 techniques for varus stress. The Telos device was the most commonly used stress device in the ACL and PCL studies. There was no consensus on the accuracy and reliability of stress radiography techniques for the diagnosis of any knee ligament injury. Stress radiography techniques were compared with alternative diagnostic techniques including instrumented arthrometry, MRI, and physical examination in 18 studies, with variability in the advantages and disadvantages of stress radiography techniques and alternatives. Analysis of results pooled from different studies demonstrated average delta gapping in knees with a completely injured ligament compared to the normal contralateral knee as per the following: for the ACL 4.9 ± 1.4 mm; PCL 8.1 ± 2.5 mm; MCL 2.3 ± 0.05 mm; and the FCL 3.4 ± 0.2 mm. CONCLUSION: Despite heterogeneity in the available literature with regard to stress examination techniques and device utilization, the data support that stress radiography techniques were accurate and reliable when compared to numerous alternatives in the diagnosis of acute and chronic knee ligament injuries. The present study also provides average increased ipsilateral compartment gapping/translation for specific knee ligament injuries based on the best available data. These values provide a reference standard for the interpretation of stress radiography techniques, help to guide surgical decision-making, and provide benchmark values for future investigations. LEVEL OF EVIDENCE: III.

Diagnostic yield using whole-genome sequencing and in-silico panel of 281 genes associated with non-immune hydrops fetalis in clinical setting.

OBJECTIVE: To investigate the diagnostic yield of clinical whole-genome sequencing (WGS) in prenatally diagnosed non-immune hydrops fetalis (NIHF). METHODS: This was a retrospective study of 23 fetuses with prenatally diagnosed NIHF, negative for trisomies and copy-number variants, referred for analysis by WGS with an in-silico panel of 281 genes associated with hydrops fetalis. Due to identification of a high proportion of causative variants in the HRAS gene in the main cohort, Sanger sequencing of HRAS was performed in a replication cohort, consisting of 24 additional fetuses with NIHF that were negative for trisomies and copy-number variants and had not undergone WGS. RESULTS: Of the 23 fetuses in the main cohort, a molecular diagnosis was achieved in 12 (52.2%). Pathogenic or likely pathogenic variants were identified in seven genes: HRAS (n = 5), RIT1 (n = 2), FOXP3 (n = 1), GLB1 (n = 1), MAP2K1 (n = 1), PTPN11 (n = 1) and RASA1 (n = 1). The inheritance pattern of the 12 causative variants was autosomal dominant in 10 cases (HRAS, MAP2K1, PTPN11, RASA1, RIT1), autosomal recessive in one (GLB1) and X-linked recessive in one (FOXP3). Of the 24 fetuses in the replication cohort, a pathogenic variant in HRAS was identified in one, resulting in an overall frequency of causative HRAS variants of 12.8% (6/47) in our two cohorts. CONCLUSIONS: We demonstrate a diagnostic yield of 52% with clinical WGS in NIHF using an in-silico panel of 281 genes. However, the high diagnostic yield may be attributed to the small sample size and possible over-representation of severe phenotypes in the included fetuses. Bearing in mind that chromosomal abnormalities were excluded in our cohorts, a detection rate of up to 75% is possible in prenatally diagnosed NIHF when WGS analysis includes calling of chromosomal aberrations. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Charge Carrier Screening in Photoexcited Epitaxial Semiconductor Nanorods Revealed by Transient X-ray Absorption Linear Dichroism.

Understanding the electronic structure and dynamics of semiconducting nanomaterials at the atomic level is crucial for the realization and optimization of devices in solar energy, catalysis, and optoelectronic applications. We report here on the use of ultrafast X-ray linear dichroism spectroscopy to monitor the carrier dynamics in epitaxial ZnO nanorods after band gap photoexcitation. By rigorously subtracting out thermal contributions and conducting ab initio calculations, we reveal an overall depletion of absorption cross sections in the transient X-ray spectra caused by photogenerated charge carriers screening the core-hole potential of the X-ray absorbing atom. At low laser excitation densities, we observe phase-space filling by excited electrons and holes separately. These results pave the way for carrier- and element-specific probing of charge transfer dynamics across heterostructured interfaces with ultrafast table-top and fourth-generation X-ray sources.

Doppler echocardiographic isovolumetric time intervals in diagnosis of fetal blocked atrial bigeminy and 2:1 atrioventricular block.

OBJECTIVE: To distinguish between blocked atrial bigeminy (BB) and incomplete atrioventricular block with 2:1 conduction (2:1 AVB) can be very difficult, especially in the mid-term fetus. Making a correct diagnosis has important clinical implications, as their prognosis and management differ markedly. Our objective was to investigate whether analysis of isovolumetric time intervals could improve Doppler echocardiography in differentiating these conditions. METHODS: Sixteen fetuses with sustained BB or isolated 2:1 AVB, diagnosed at our tertiary center from 2002 to 2012, were reviewed retrospectively. Doppler recordings of left ventricular in- and outflow, including mitral and aortic valve movements, were used to measure isovolumetric contraction (ICT) and relaxation (IRT) time intervals. ICT reference values obtained from 104 normal pregnancies were used for comparison. RESULTS: Ten fetuses had BB and six 2:1 AVB. Five of the AVB cases were anti-Ro antibody positive and one had long QT syndrome (LQTS). ICT was systematically shorter in BB than in antibody-mediated 2:1 AVB. Nine of 10 cases with BB had an ICT below -2 SD and the five with antibody-mediated 2:1 AVB had values at or above +2 SD. All 15 fetuses with either BB or antibody-mediated AVB had an IRT of < 70 ms, as opposed to a markedly prolonged IRT (105 ms) in the LQTS case. CONCLUSION: Measurement of ICT can improve the differential diagnosis between BB and antibody-mediated 2:1 AVB. Fetuses with BB or antibody-mediated AVB are unlikely to have IRT measurements exceeding 70 ms and, when this is observed, LQTS should be considered a more likely diagnosis.

Effect of anti-inflammatory treatments on patient outcomes and concentrations of inflammatory modulators in the post-surgical and post-traumatic tibiofemoral joint setting: a narrative review.

Background and Objective: There are several anti-inflammatory therapeutic options that can be used in the context of post-surgical and post-traumatic knee settings. Each of these options carries with it certain benefits, as well as potential issues depending on the duration and administration of each therapy. An understanding of how these anti-inflammatory drugs modulate various biomarkers of inflammation is also necessary in understanding how they can affect patient and objective outcomes following acute knee injury or surgery. This review covers the many traditional therapeutic options that have been used in treating knee injuries, as well as some natural therapeutics that have shown anti-inflammatory properties. Methods: A current review of the literature was conducted and synthesized into this narrative review. Key Content and Findings: Many traditional anti-inflammatory therapeutics have been shown to be beneficial in both post-traumatic and post-surgical tibiofemoral joint settings at reducing inflammation and improving patient outcomes. However, many of these treatments have risks associated with them, which becomes problematic with prolonged, repeated administration. Natural anti-inflammatory compounds may also have some benefit as adjunctive treatment options in these settings. Conclusions: There are multiple different therapeutic options that can be used in acute knee settings, but the specific mechanism of injury or surgical context should be weighed when determining the best clinical approach.

Dynamics of magnetization at infinite temperature in a Heisenberg spin chain.

Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.

Stable quantum-correlated many-body states through engineered dissipation.

Engineered dissipative reservoirs have the potential to steer many-body quantum systems toward correlated steady states useful for quantum simulation of high-temperature superconductivity or quantum magnetism. Using up to 49 superconducting qubits, we prepared low-energy states of the transverse-field Ising model through coupling to dissipative auxiliary qubits. In one dimension, we observed long-range quantum correlations and a ground-state fidelity of 0.86 for 18 qubits at the critical point. In two dimensions, we found mutual information that extends beyond nearest neighbors. Lastly, by coupling the system to auxiliaries emulating reservoirs with different chemical potentials, we explored transport in the quantum Heisenberg model. Our results establish engineered dissipation as a scalable alternative to unitary evolution for preparing entangled many-body states on noisy quantum processors.

Extracorporeal Membrane Oxygenation Patient Outcomes Following Restrictive Blood Transfusion Protocol.

OBJECTIVES: To investigate the effect of a restrictive blood product utilization protocol on blood product utilization and clinical outcomes. DESIGN: We retrospectively reviewed all adult extracorporeal membrane oxygenation (ECMO) patients from January 2019 to December 2021. The restrictive protocol, implemented in March 2020, was defined as transfusion of blood products for a hemoglobin level less than 7, platelet levels less than 50, and/or fibrinogen levels less than 100. Subgroup analysis was performed based on the mode of ECMO received: venoarterial ECMO, venovenous ECMO, and ECMO support following extracorporeal cardiopulmonary resuscitation (ECPR). SETTING: M Health Fairview University of Minnesota Medical Center. PATIENTS: The study included 507 patients. INTERVENTIONS: One hundred fifty-one patients (29.9%) were placed on venoarterial ECMO, 70 (13.8%) on venovenous ECMO, and 286 (56.4%) on ECPR. MEASUREMENTS AND MAIN RESULTS: For patients on venoarterial ECMO (48 [71.6%] vs. 52 [63.4%]; p = 0.374), venovenous ECMO (23 [63.9%] vs. 15 [45.5%]; p = 0.195), and ECPR (54 [50.0%] vs. 69 [39.2%]; p = 0.097), there were no significant differences in survival on ECMO. The last recorded mean hemoglobin value was also significantly decreased for venoarterial ECMO (8.10 [7.80-8.50] vs. 7.50 [7.15-8.25]; p = 0.001) and ECPR (8.20 [7.90-8.60] vs. 7.55 [7.10-8.88]; p < 0.001) following implementation of the restrictive transfusion protocol. CONCLUSIONS: These data suggest that a restrictive transfusion protocol is noninferior to ECMO patient survival. Additional, prospective randomized trials are required for further investigation of the safety of a restrictive transfusion protocol.

Noise-resilient edge modes on a chain of superconducting qubits.

Inherent symmetry of a quantum system may protect its otherwise fragile states. Leveraging such protection requires testing its robustness against uncontrolled environmental interactions. Using 47 superconducting qubits, we implement the one-dimensional kicked Ising model, which exhibits nonlocal Majorana edge modes (MEMs) with [Formula: see text] parity symmetry. We find that any multiqubit Pauli operator overlapping with the MEMs exhibits a uniform late-time decay rate comparable to single-qubit relaxation rates, irrespective of its size or composition. This characteristic allows us to accurately reconstruct the exponentially localized spatial profiles of the MEMs. Furthermore, the MEMs are found to be resilient against certain symmetry-breaking noise owing to a prethermalization mechanism. Our work elucidates the complex interplay between noise and symmetry-protected edge modes in a solid-state environment.

Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling.

Although microRNA-7 (miRNA-7) is known to regulate proliferation of cancer cells by targeting Epidermal growth factor receptor (EGFR/ERBB) family, less is known about its role in cardiac physiology. Transgenic (Tg) mouse with cardiomyocyte-specific overexpression of miRNA-7 was generated to determine its role in cardiac physiology and pathology. Echocardiography on the miRNA-7 Tg mice showed cardiac dilation instead of age-associated physiological cardiac hypertrophy observed in non-Tg control mice. Subjecting miRNA-7 Tg mice to transverse aortic constriction (TAC) resulted in cardiac dilation associated with increased fibrosis bypassing the adaptive cardiac hypertrophic response to TAC. miRNA-7 expression in cardiomyocytes resulted in significant loss of ERBB2 expression with no changes in ERBB1 (EGFR). Cardiac proteomics in the miRNA-7 Tg mice showed significant reduction in mitochondrial membrane structural proteins compared to NTg reflecting role of miRNA-7 beyond the regulation of EGFR/ERRB in mediating cardiac dilation. Consistently, electron microscopy showed that miRNA-7 Tg hearts had disorganized rounded mitochondria that was associated with mitochondrial dysfunction. These findings show that expression of miRNA-7 in the cardiomyocytes results in cardiac dilation instead of adaptive hypertrophic response during aging or to TAC providing insights on yet to be understood role of miRNA-7 in cardiac function.

Controlling Listeria monocytogenes in Cottage cheese through heterologous production of enterocin A by Lactococcus lactis.

AIMS: Enterocin A is an example of a class IIa bacteriocin with potent anti-listerial activity. This study was initiated with a view to harnessing this activity, through heterologous production by a lactococcal starter strain, to limit levels of Listeria monocytogenes in a food (Cottage cheese). METHODS AND RESULTS: Plasmid pEnt02 (containing entA, I, T and D genes under the control of a constitutive promoter) was introduced into a Lactococcus lactis strain capable of fermenting lactose. When this bacteriocin-producing starter was used in combination with a non-enterocin A producer, thereby compensating for an associated reduction in acid production, during a Cottage cheese fermentation, a decrease in L. monocytogenes (tagged with lux genes for convenience) levels was evident. CONCLUSIONS: Enterocin A, heterologously produced by a food grade lactic acid bacteria (LAB), was therefore shown to have potential for use as a biocontrol agent in food. SIGNIFICANCE AND IMPACT OF THE STUDY: Many of the most active anti-listerial compounds identified to date are enterocins. However, because of Enterococcus-associated concerns, the use of these antimicrobials in a food setting has been curtailed. Although enterocins have been heterologously produced in LAB to overcome this problem, this study represents the first occasion upon which the benefits of such heterologous production have been demonstrated in a food context.

A deficiency screen for zygotic loci required for establishment and patterning of the epidermis in Caenorhabditis elegans.

To identify genomic regions required for establishment and patterning of the epidermis, we screened 58 deficiencies that collectively delete at least approximately 67% of the Caenorhabditis elegans genome. The epidermal pattern of deficiency homozygous embryos was analyzed by examining expression of a marker specific for one of the three major epidermal cell types, the seam cells. The organization of the epidermis and internal organs was also analyzed using a monoclonal antibody specific for epithelial adherens junctions. While seven deficiencies had no apparent effect on seam cell production, 21 were found to result in subnormal, and five in excess numbers of these cells. An additional 23 deficiencies blocked expression of the seam cell marker, in some cases without preventing cell proliferation. Two deficiencies result in multinucleate seam cells. Deficiencies were also identified that result in subnormal numbers of epidermal cells, hyperfusion of epidermal cells into a large syncytium, or aberrant epidermal differentiation. Finally, analysis of internal epithelia revealed deficiencies that cause defects in formation of internal organs, including circularization of the intestine and bifurcation of the pharynx lumen. This study reveals that many regions of the C. elegans genome are required zygotically for patterning of the epidermis and other epithelia.

Neuropathy in Navajo children: clinical and epidemiologic features.

We describe a rare and apparently unique neuropathic syndrome among Navajo children living on the Navajo Reservation. Clinical features include sensorimotor neuropathy, corneal ulcerations, acral mutilation, poor weight gain, short stature, sexual infantilism, serious systemic infections, and liver derangement including Reye's syndrome-like episodes. Progressive CNS white matter lesions were diagnosed through magnetic resonance imaging. We identified 20 definite and 4 probable cases occurring between 1959 and 1986. Mean age at the time of 1st recognized symptom was 13 months (range, 1 month to 4 years 6 months). Ten individuals have died; 6 of the deaths occurred before 5 years of age. The incidence of this syndrome on the western Navajo reservation is 5 times higher than that on the eastern reservation (38 compared with 7 cases per 100,000 births). Although the etiology is unknown, this syndrome is consistent with an inborn error of metabolism, inherited in an autosomal recessive manner.