Time-crystalline eigenstate order on a quantum processor.

Quantum many-body systems display rich phase structure in their low-temperature equilibrium states1. However, much of nature is not in thermal equilibrium. Remarkably, it was recently predicted that out-of-equilibrium systems can exhibit novel dynamical phases2-8 that may otherwise be forbidden by equilibrium thermodynamics, a paradigmatic example being the discrete time crystal (DTC)7,9-15. Concretely, dynamical phases can be defined in periodically driven many-body-localized (MBL) systems via the concept of eigenstate order7,16,17. In eigenstate-ordered MBL phases, the entire many-body spectrum exhibits quantum correlations and long-range order, with characteristic signatures in late-time dynamics from all initial states. It is, however, challenging to experimentally distinguish such stable phases from transient phenomena, or from regimes in which the dynamics of a few select states can mask typical behaviour. Here we implement tunable controlled-phase (CPHASE) gates on an array of superconducting qubits to experimentally observe an MBL-DTC and demonstrate its characteristic spatiotemporal response for generic initial states7,9,10. Our work employs a time-reversal protocol to quantify the impact of external decoherence, and leverages quantum typicality to circumvent the exponential cost of densely sampling the eigenspectrum. Furthermore, we locate the phase transition out of the DTC with an experimental finite-size analysis. These results establish a scalable approach to studying non-equilibrium phases of matter on quantum processors.

Selective iliofemoral stent placement for complex pediatric cases: a decade of institutional experience.

BACKGROUND: Pediatric iliofemoral venous thromboembolism that is resistant to conventional treatments poses significant management challenges. Stent placement represents a potentially underutilized strategy in children when stenosis or thrombosis persists intraprocedurally or recurs postoperatively, despite treatments such as venoplasty, lysis, and thrombectomy. OBJECTIVE: This study aims to report our institutional experience with iliofemoral stenting in 17 pediatric patients with recurrent iliofemoral venous thromboembolism or stenosis. MATERIALS AND METHODS: We performed an IRB-approved retrospective review of pediatric patients (<18 years of age) who underwent iliofemoral venous stenting for recurrent stenosis or thrombosis between January 2012 and December 2022 at a single tertiary care institution. Patient demographics, risk factors for venous thromboembolism, presenting symptoms, and procedural characteristics were recorded. The primary outcome was stent patency rates at interval imaging follow-up. RESULTS: Seventeen patients with mean age of 14.6 years (range 7-17) and mean BMI of 27.7 were stented during the study period. Sixteen of 17 patients presented with evidence of May-Thurner anatomy. 14/17 patients presented with acute iliofemoral venous thromboembolism, 2/17 with chronic venous thromboembolism, and 1/17 with left lower extremity swelling without thrombosis. Seventy-three total angiographic procedures were performed, which included angioplasty, lysis, and thrombectomy, and 23 stent placements. Patients underwent an average of 3 procedures (range 1-9) over a mean of 2.8 months (range 0-17 months) prior to undergoing stent placement. Stents were deployed successfully in all patients. The median follow-up was 18 months (range, 1-77 months). Primary and secondary patency rates were 13/17 (76%) and 14/14 (100%) at 12 months and 12/17 (71%) and 14/14 (100%) at 24 months, respectively. CONCLUSION: In our experience of 17 patients, stent placement appears to be a durable option for children with iliofemoral venous thromboembolism following failure to establish vessel patency or development of recurrent thrombosis/stenosis postoperatively.

Shots fired: evaluation of vascular injury, compartment syndrome, and transfusion rates among civilian ballistic orthopaedic fracture patients presenting to two Level I trauma centres.

PURPOSE: This study investigates baseline patient demographics and predictors of vascular injury, blood transfusion, and compartment syndrome in patients with orthopaedic fractures secondary to GSWs at two high-volume Level I trauma centres. METHODS: A retrospective chart review of all GSW-related trauma patients at two Level I trauma centres between July 2019 and September 2021 was conducted. Chi-squared and two-tailed independent t tests were used for data analysis, and logistic regression with odds ratios (OR) determined predictors of primary outcomes. RESULTS: Among 478 GSW patients, 94 (19.7%) sustained 130 orthopaedic fractures, most commonly at the lower extremity (77.7%). Orthopaedic fracture patients showed significantly higher rates of vascular injury (29.8 vs. 4.7%, p < 0.001), transfusion (27.7 vs. 12.8%, p = 0.006), and compartment syndrome (3.2 vs. 0.3%, p = 0.011) compared to non-orthopaedic injury patients. Univariable analysis identified ankle (OR = 47.50, p < 0.001) and hip/femur fractures (OR = 5.31, p < 0.001) as predictors of vascular injury. Multivariable logistic regression revealed lower extremity vascular injury (OR = 54.69, p = 0.006) and anatomic fracture sites of the humerus (OR = 15.17, p = 0.008), clavicle/scapula (OR = 11.30, p = 0.009), and acetabulum/pelvis (OR = 7.17, p = 0.025) as predictors of blood transfusion. Univariable analysis showed lower extremity vascular injury (OR = 30.14, p = 0.007) as a predictor of compartment syndrome. CONCLUSION: These findings underscore the importance of diagnosing and managing vascular injuries and compartment syndrome in GSW-related orthopaedic fractures, emphasizing the necessity for targeted transfusion strategies in such cases.

Climate Change and Radiology: Impetus for Change and a Toolkit for Action.

This special report discusses the importance of climate change for health care and radiology. The impact of climate change on human health and health equity, the contribution of health care and medical imaging to the climate crisis, and the impetus for change within radiology to create a more sustainable future are covered. The authors focus on actions and opportunities to address climate change in our role as radiologists. A toolkit highlights actions we can take toward a more sustainable future, linking each action with the expected impact and outcome. This toolkit includes a hierarchy of actions from first steps to advocating for system-level change. This includes actions we can take in our daily lives, in radiology departments and professional organizations, and in our relationships with vendors and industry partners. As radiologists, we are adept at managing rapid technological change, which makes us ideally suited to lead these initiatives. Alignment of incentives and synergies with health systems are highlighted given that many of the proposed strategies also result in cost savings.

Stress-Induced (Not Diabetic) Hyperglycemia Is Associated With Mortality in Geriatric Trauma Patients.

INTRODUCTION: Stress-induced hyperglycemia (SIH) is associated with worse outcomes among trauma patients. It is also known that injured geriatric patients have higher mortality when compared to younger patients. We sought to investigate the association of all levels of SIH with mortality among geriatric trauma patients at a level 1 academic trauma center. We hypothesized that SIH in the geriatric trauma population would be associated with increased mortality. METHODS: A retrospective review of all geriatric patients admitted to our level 1 trauma center over a 3-year period (January 2018-December 2020) was performed using the institutional trauma database. Data collected included demographics, injury severity score (ISS), emergency department (ED) blood glucose level, ED systolic blood pressure (SBP), and mortality. Patients were divided into 4 groups based on emergency room blood glucose level, as follows: normoglycemic (<120 mg/dL), mild hyperglycemia (120-150 mg/dL), moderate hyperglycemia (151-199 mg/dL), and severe hyperglycemia (≥200 mg/dL). Multivariable logistic regression analysis was performed to evaluate the association of SIH and in-hospital mortality adjusting for ISS, age, comorbidities, and ED SBP. RESULTS: A total of 4432 geriatric trauma patients were admitted during the study period, of which 3358 patients (75.8%) were not diabetic. There were 2206 females (65.7%), 2993 were White (89.2%), with a mean age of 81.5 y. There were 114 deaths (3.4%). Univariate results showed that there was a statistically significant association between mortality and glucose groups (P < 0.01). The number of deaths in the four glucose groups were, as follows: 30 (2.0%), 32 (3.8%), 20 (6.2%), and 10 (12.2%), respectively. Multivariable logistic regression analysis results showed that compared to the normoglycemic group, the risk of death was higher in the mild, moderate, and severe glucose groups, as follows: mild group (OR 1.80, 95% confidence interval [CI] 1.04-3.13, P 0.04), moderate group (OR 2.53, 95% CI 1.34-4.80, P < 0.01), and severe group (OR 5.04, 95% CI 2.18-11.67, P < 0.01). CONCLUSIONS: Mild, moderate, and severe SIH are statistically significant predictors of death among geriatric trauma patients independently of ISS, age, comorbidities, and SBP.

Complementary mechanochemical and biphasic approaches for the synthesis of organic thiocyanates using hexacyanoferrates as non-toxic cyanide sources.

Herein, we describe two complementary approaches towards various organic thiocyanates that are affordable, reliable and follow the principles of sustainable chemistry, starting from commercially available thiols or disulfides. Additionally, the application of this mild method to the first total synthesis of psammaplin B is demonstrated. Non-toxic and inexpensive ferricyanide is used as the cyanide source, which can be activated either in a mechanochemical, solvent-free approach, or in a biphasic solvent system allowing easier work-up. A total of 27 examples is demonstrated, with up to quantitative yields.

Total Synthesis and Biological Evaluation of the Anti-Inflammatory (13R,14S,15R)-13-Hydroxy-14-deoxyoxacyclododecindione.

The first total synthesis of the natural product (13R,14S,15R)-13-hydroxy-14-deoxyoxacyclododecindione, which was isolated in 2018 as a member of the oxacyclododecindione family, is reported. A synthetic strategy through intramolecular Friedel-Crafts acylation combined with the stereoselective synthesis of a new triol key fragment allowed the preparation of the macrolactone. Due to mismatching physical data of the synthetic product, a revision of the configuration of the natural product isolated in 2018 is required. Light-induced E/Z-isomerism of the macrolactone backbone is described for the first time in the class of oxacyclododecindione-type macrolactones. The hydroxylated macrolactone prepared herein was found to show highly promising IC50 values in biological assays addressing the inhibition of inflammatory responses.

Comparison of different density functional theory methods for the calculation of vibrational circular dichroism spectra.

The determination of the absolute configuration (AC) of an organic molecule is still a challenging task for which the combination of spectroscopic with quantum-mechanical methods has become a promising approach. In this study, we investigated the accuracy of DFT methods (480 overall combinations of 15 functionals, 16 basis sets, and 2 solvation models) to calculate the VCD spectra of six chiral organic molecules in order to benchmark their capability to facilitate the determination of the AC.

Oxygen-Releasing Hyaluronic Acid-Based Dispersion with Controlled Oxygen Delivery for Enhanced Periodontal Tissue Engineering.

Periodontitis is a chronic biofilm-associated inflammatory disease of the tooth-supporting tissues that causes tooth loss. It is strongly associated with anaerobic bacterial colonization and represents a substantial global health burden. Due to a local hypoxic environment, tissue regeneration is impaired. Oxygen therapy has shown promising results as a potential treatment of periodontitis, but so far, local oxygen delivery remains a key technical challenge. An oxygen (O2)-releasing hyaluronic acid (HA)-based dispersion with a controlled oxygen delivery was developed. Cell viability of primary human fibroblasts, osteoblasts, and HUVECs was demonstrated, and biocompatibility was tested using a chorioallantoic membrane assay (CAM assay). Suppression of anaerobic growth of Porphyromonas gingivalis was shown using the broth microdilution assay. In vitro assays showed that the O2-releasing HA was not cytotoxic towards human primary fibroblasts, osteoblasts, and HUVECs. In vivo, angiogenesis was enhanced in a CAM assay, although not to a statistically significant degree. Growth of P. gingivalis was inhibited by CaO2 concentrations higher than 256 mg/L. Taken together, the results of this study demonstrate the biocompatibility and selective antimicrobial activity against P. gingivalis for the developed O2-releasing HA-based dispersion and the potential of O2-releasing biomaterials for periodontal tissue regeneration.

Dynamics of Adaptation During Three Years of Evolution Under Long-Term Stationary Phase.

Many bacterial species that cannot sporulate, such as the model bacterium Escherichia coli, can nevertheless survive for years, following exhaustion of external resources, in a state termed long-term stationary phase (LTSP). Here we describe the dynamics of E. coli adaptation during the first three years spent under LTSP. We show that during this time, E. coli continuously adapts genetically through the accumulation of mutations. For nonmutator clones, the majority of mutations accumulated appear to be adaptive under LTSP, reflected in an extremely convergent pattern of mutation accumulation. Despite the rapid and convergent manner in which populations adapt under LTSP, they continue to harbor extensive genetic variation. The dynamics of evolution of mutation rates under LTSP are particularly interesting. The emergence of mutators affects overall mutation accumulation rates as well as the mutational spectra and the ultimate spectrum of adaptive alleles acquired under LTSP. With time, mutators can evolve even higher mutation rates through the acquisition of additional mutation rate-enhancing mutations. Different mutator and nonmutator clones within a single population and time point can display extreme variation in their mutation rates, resulting in differences in both the dynamics of adaptation and their associated deleterious burdens. Despite these differences, clones that vary greatly in their mutation rates tend to coexist within their populations for many years, under LTSP.

Anti-inflammatory dihydroxanthones from a Diaporthe species.

In a search for anti-inflammatory compounds from fungi inhibiting the promoter activity of the small chemokine CXCL10 (Interferon-inducible protein 10, IP-10) as a pro-inflammatory marker gene, the new dihydroxanthone methyl (1R, 2R)-1,2,8-trihydroxy-6-(hydroxymethyl)-9-oxo-2,9-dihydro-1H-xanthene-1-carboxylate (2) and the previously described dihydroxanthone AGI-B4 (1) were isolated from fermentations of a Diaporthe species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy, mass spectrometry, and calculations using density functional theory (DFT). Compounds 1 and 2 inhibited the LPS/IFNγ induced CXCL10 promoter activity in transiently transfected human MonoMac6 cells in a dose-dependent manner with IC50 values of 4.1 µM (±0.2 µM) and 1.0 µM (±0.06 µM) respectively. Moreover, compounds 1 and 2 reduced mRNA levels and synthesis of pro-inflammatory mediators such as cytokines and chemokines in LPS/IFNγ stimulated MonoMac6 cells by interfering with the Stat1 and NFκB pathway.

Vinylcyclopropane [3+2] Cycloaddition with Acetylenic Sulfones Based on Visible Light Photocatalysis.

The first intermolecular visible light [3+2] cycloaddition reaction performed on a meta photocycloadduct employing acetylenic sulfones is described. The developed methodology exploits the advantages of combining UV and visible-light in a two-step sequence that provides a photogenerated cyclopropane which, through a strain-release process, generates a new cyclopentane ring while significantly increasing the molecular complexity. Mechanistic studies and DFT calculations indicate an energy transfer pathway for the visible light-driven reaction step. This strategy could be extended to simpler vinylcyclopropanes.

Sesquiterpene Lactones from Vernonia tufnelliae: Structural Characterization and Biological Evaluation.

The genus Vernonia is an extremely rich source of biologically active sesquiterpene lactones. The present report describes the spectroscopic structure elucidation and the cytotoxic and antimicrobial properties of five hitherto unknown germacranolide-like sesquiterpenoids and several known compounds. These new derivatives include a compound (1) with an unprecedented 10/5/5/6 tetracyclic framework featuring a hexahydro-1H,3H,7H-furo[3',4':3,4]furo[3,2-c]pyridin-1-one core resulting from an intramolecular cyclization cascade involving a methacrylate substituent and a low molecular weight amine. Furthermore, an elemane-germacranolide hybrid (2) and three amino acid-derived lactones (3-5) were characterized. A plausible biosynthetic pathway to the key alkaloid is presented, while shielding tensor calculations using DFT in combination with the DP4+ method were applied to elucidate its stereostructure. The newly characterized compounds along with ten known sesquiterpene lactones and phenolic compounds have been isolated from Vernonia tufnelliae, a medicinal plant from the western region of Cameroon. Their structures were consistent with spectroscopic and spectrometric data recorded. The present report is the first investigation of the chemistry and biology of V. tufnelliae.

Ethyl Hydroxyethyl Cellulose-A Biocompatible Polymer Carrier in Blood.

The biocompatibility of carrier nanomaterials in blood is largely hampered by their activating or inhibiting role on the clotting system, which in many cases prevents safe intravascular application. Here, we characterized an aqueous colloidal ethyl hydroxyethyl cellulose (EHEC) solution and tested its effect on ex vivo clot formation, platelet aggregation, and activation by thromboelastometry, aggregometry, and flow cytometry. We compared the impact of EHEC solution on platelet aggregation with biocompatible materials used in transfusion medicine (the plasma expanders gelatin polysuccinate and hydroxyethyl starch). We demonstrate that the EHEC solution, in contrast to commercial products exhibiting Newtonian flow behavior, resembles the shear-thinning behavior of human blood. Similar to established nanomaterials that are considered biocompatible when added to blood, the EHEC exposure of resting platelets in platelet-rich plasma does not enhance tissue thromboplastin- or ellagic acid-induced blood clotting, or platelet aggregation or activation, as measured by integrin αIIbß3 activation and P-selectin exposure. Furthermore, the addition of EHEC solution to adenosine diphosphate (ADP)-stimulated platelet-rich plasma does not affect the platelet aggregation induced by this agonist. Overall, our results suggest that EHEC may be suitable as a biocompatible carrier material in blood circulation and for applications in flow-dependent diagnostics.

Designing Codes around Interactions: The Case of a Spin.

I present a new approach for designing quantum error-correcting codes guaranteeing a physically natural implementation of Clifford operations. Inspired by the scheme put forward by Gottesman, Kitaev, and Preskill for encoding a qubit in an oscillator in which Clifford operations may be performed via Gaussian unitaries, this approach yields new schemes for encoding a qubit in a large spin in which single-qubit Clifford operations may be performed via spatial rotations. I construct all possible examples of such codes, provide universal-gate-set implementations using quadratic angular-momentum Hamiltonians, and derive criteria for when these codes exactly correct physically relevant errors.

The Environmental Impact of Interventional Radiology: An Evaluation of Greenhouse Gas Emissions from an Academic Interventional Radiology Practice.

PURPOSE: To calculate the volume of greenhouse gases (GHGs) generated by a hospital-based interventional radiology (IR) department. MATERIALS AND METHODS: Life cycle assessment (LCA) was used to calculate GHGs emitted by an IR department at a tertiary care academic medical center. The volume of waste generated, amount of disposable supplies and linens used, and the operating times of electrical equipment were recorded for procedures performed between 7:00 AM and 7:00 PM on 5 consecutive weekdays. LCA was then performed using purchasing data, plug loads for electrical hardware, data from temperature control units, and estimates of emissions related to travel in the area surrounding the medical center. RESULTS: Ninety-eight procedures were performed on 97 patients. The most commonly performed procedures were drainages (30), placement and removal of venous access (21), and computed tomography-guided biopsies (13). Approximately 23,500 kg CO2e were emitted during the study. Sources of CO2 emissions in descending order were related to indoor climate control (11,600 kg CO2e), production and transportation of disposable surgical items (9,640 kg CO2e), electricity plug load for equipment and lighting (1,060 kg CO2e), staff transportation (524 kg CO2e), waste disposal (426 kg CO2e), production, laundering, and disposal of linens (279 kg CO2e), and gas anesthetics (19.3 kg CO2e). CONCLUSIONS: The practice of IR generates substantial GHG volumes, a majority of which come from energy used to maintain climate control, followed by emissions related to single-use surgical supplies. Efforts to reduce the environmental impact of IR may be focused accordingly.

Diels-Alder reaction of ß-fluoro-ß-nitrostyrenes with cyclic dienes.

The Diels-Alder reaction of ß-fluoro-ß-nitrostyrenes with cyclic 1,3-dienes was investigated. A series of novel monofluorinated norbornenes was prepared in up to 97% yield. The reaction with 1,3-cyclohexadiene permits the preparation of monofluorinated bicyclo[2.2.2]oct-2-enes. The kinetic data of the reactions with 1,3-cyclopentadiene and 1,3-cyclohexadiene were used to calculate activation parameters. Furthermore, the synthetic utility of the cycloadducts obtained was demonstrated.

Making natural products from renewable feedstocks: back to the roots?

Covering: up to mid-2019 This review highlights the utilization of biomass-derived building blocks in the total synthesis of natural products. An overview over several renewable feedstock classes, namely wood/lignin, cellulose, chitin and chitosan, fats and oils, as well as terpenes, is given, covering the time span from the initial beginning of natural product synthesis until today. The focus is put on the origin of the employed carbon atoms and on the nature of the complex structures that were assembled therefrom. The emerging trend of turning away from petrochemically derived starting materials back to bio-based resources, just as seen in the early days of total synthesis, shall be demonstrated.

Persistent Basal Cell Hyperplasia Is Associated With Clinical and Endoscopic Findings in Patients With Histologically Inactive Eosinophilic Esophagitis.

BACKGROUND & AIMS: Although eosinophil count is the standard used to monitor disease activity in patients with eosinophilic esophagitis (EoE), there are often disparities between patient-reported symptoms and eosinophil counts. We examined the prevalence of epithelial alterations, namely basal cell hyperplasia (BCH) and spongiosis, among patients with inactive EoE (eosinophil counts below 15 following therapy) and aimed to determine whether maintenance of these changes in epithelial morphology are associated with persistent clinical findings. METHODS: Esophageal biopsies of 243 patients (mean age, 16.9 years) undergoing routine endoscopy at the University of Pennsylvania were evaluated for epithelial BCH and spongiosis. Univariable analysis was used to calculate the association between epithelial changes and symptoms as well as endoscopic findings and peak eosinophil count. We validated our findings using data from a cohort of patients at the University of North Carolina. RESULTS: The discovery and validation cohorts each included patients with inactive EoE, based on histologic factors, but ongoing BCH and spongiosis. Ongoing BCH, but not spongiosis, in patients with inactive EoE was associated with symptoms (odds ratio, 2.14; 95% CI, 1.03-4.42; P = .041) and endoscopic findings (odds ratio, 7.10; 95% CI, 3.12-16.18; P < .001). CONCLUSIONS: In patients with EoE, the presence of BCH might indicate ongoing disease activity, independent of eosinophil count. This might account for the persistent symptoms in patients who are considered to be in remission based on histologic factors.

Yttrium-90 Radioembolization in the Office-Based Lab.

PURPOSE: To evaluate the feasibility and benefits of performing yttrium-90 radioembolization in an office-based lab (OBL) compared to a hospital setting. MATERIALS AND METHODS: A radioembolization program was established in March 2019 in an OBL that is managed by the radiology department of a tertiary care center. Mapping and treatment angiograms performed in the OBL from March 2019 through January 2020 were compared to mapping and treatment angiograms performed in the hospital during the same time period. RESULTS: One hundred seventy-six mapping and treatment angiograms were evaluated. There was no difference in the proportion of mapping versus treatment angiograms performed at each site, the proportion of lobar versus selective dose vial administrations, or the mean number of dose vials administered per treatment procedure. Procedure start delays were longer in the hospital than in the OBL (28.6 minutes vs 0.8 minutes; P < .0001), particularly for procedures that were not scheduled as the first case of the day (hospital later case delay, 38.8 minutes vs OBL later case delay, 0.5 minutes; P < .0001). Procedures performed in the hospital took longer on average than procedures performed in the OBL (2 hours, 1.8 minutes vs 1 hour, 44.4 minutes; P = .0004), particularly for procedures that were not scheduled as the first case of the day (hospital later case duration, 2 hours, 7.4 minutes vs OBL later case duration, 1 hour, 43 minutes; P = .0006). CONCLUSIONS: Establishing a radioembolization program within an OBL is feasible and might provide more efficient procedure scheduling than the hospital setting.