Misinformation Persists in Complementary Health: Evaluating the Reliability and Quality of YouTube-Based Information on the Use of Acupuncture for Chronic Pain.

Introduction: Acupuncture is commonly used to treat chronic pain. Patients often access public social media platforms for healthcare information when querying acupuncture. Our study aims to appraise the utility, accuracy, and quality of information available on YouTube, a popular social media platform, on acupuncture for chronic pain treatment. Methods: Using search terms such as "acupuncture for chronic pain" and "acupuncture pain relief", the top 54 videos by view count were selected. Included videos were >1 minute duration, contained audio in English, had >7000 views, and was related to acupuncture. One primary outcome of interest was categorizing each video's usefulness as useful, misleading, or neither. Another primary outcome of interest was the quality and reliability of each video using validated instruments, including the modified DISCERN (mDISCERN) tool and the Global Quality Scale (GQS). The means were calculated for the video production characteristics, production sources, and mDISCERN and GQS scores. Continuous and categorical outcomes were compared using Student's t-test and chi-square test, respectively. Results: Of the 54 videos, 57.4% were categorized as useful, 14.8% were misleading, and 27.8% were neither. Useful videos had a mean GQS and mDISCERN score of 3.77±0.67 and 3.48±0.63, respectively, while misleading videos had mean GQS and mDISCERN score of 2.50±0.53 and 2.38±0.52, respectively. 41.8% of the useful videos were produced by a healthcare institution while none of the misleading videos were produced by a healthcare institution. However, 87.5% of the misleading videos were produced by health media compared to only 25.8% of useful videos from health media. Discussion: As patients increasingly depend on platforms like YouTube for trustworthy information on complementary health practices such as acupuncture, our study emphasizes the critical need for more higher-quality videos from unbiased healthcare institutions and physicians to ensure patients are receiving reliable information regarding this topic.

Vibrational heat-bath configuration interaction with semistochastic perturbation theory using harmonic oscillator or VSCF modals.

Vibrational heat-bath configuration interaction (VHCI)-a selected configuration interaction technique for vibrational structure theory-has recently been developed in two independent works [J. H. Fetherolf and T. C. Berkelbach, J. Chem. Phys. 154, 074104 (2021); A. U. Bhatty and K. R. Brorsen, Mol. Phys. 119, e1936250 (2021)], where it was shown to provide accuracy on par with the most accurate vibrational structure methods with a low computational cost. Here, we eliminate the memory bottleneck of the second-order perturbation theory correction using the same (semi)stochastic approach developed previously for electronic structure theory. This allows us to treat, in an unbiased manner, much larger perturbative spaces, which are necessary for high accuracy in large systems. Stochastic errors are easily controlled to be less than 1 cm-1. We also report two other developments: (i) we propose a new heat-bath criterion and an associated exact implicit sorting algorithm for potential energy surfaces expressible as a sum of products of one-dimensional potentials; (ii) we formulate VHCI to use a vibrational self-consistent field (VSCF) reference, as opposed to the harmonic oscillator reference configuration used in previous reports. Our tests are done with quartic and sextic force fields, for which we find that with VSCF, the minor improvements to accuracy are outweighed by the higher computational cost associated the matrix element evaluations. We expect VSCF-based VHCI to be important for more general potential representations, for which the harmonic oscillator basis function integrals are no longer analytic.

Electrocardiographic Associations of Cardiac Biomarkers and Cardiac Magnetic Resonance Measures of Fibrosis in the Multiethnic Study of Atherosclerosis (MESA).

Abnormalities in myocardial substrate, including diffuse and replacement fibrosis, increase the risk of cardiovascular disease (CVD). Data are sparse on whether electrocardiogram (ECG) measures, coupled with circulating biomarkers, may aid in identifying cardiac fibrosis. This study aimed to determine whether 12-lead ECG and biomarkers together augment the prediction of cardiac fibrosis in participants who are free of known CVD. This is a cross-sectional analysis in the MESA (Multiethnic Study of Atherosclerosis) study at visit 5 (2010 to 2012), with measurements of biomarkers (cardiac troponin T and growth differentiation factor-15), gadolinium-enhanced cardiac magnetic resonance imaging, and ECG. Logistic regression associations of ECG measures with cardiac magnetic resonance surrogates of fibrosis (highest quartile extracellular volume [interstitial fibrosis] and late gadolinium enhancement [replacement fibrosis]) were adjusted for demographics and risk factors. Using the C-statistic, we evaluated whether adding ECG measures and biomarkers to clinical characteristics improved the prediction of either type of fibrosis. There were 1,170 eligible participants (aged 67.1 ± 8.6 years). Among the ECG measures, QRS duration (odds ratio [OR] 1.41 per 10 ms, 95% confidence interval [CI] 1.10 to 1.81), major ST-T abnormalities (OR 3.03, 95%CI 1.20, 7.65), and abnormal QRS-T angle (OR 6.32, 95%CI 3.00, 13.33) were associated with replacement fibrosis, whereas only abnormal QRS-T angle (OR 3.05, 95%CI,1.69, 5.48) was associated with interstitial fibrosis. ECG markers, in addition to clinical characteristics, improved the prediction of replacement fibrosis (p = 0.002) but not interstitial fibrosis. The addition of cardiac troponin T and growth differentiation factor-15 to the ECG findings did not significantly improve the model discrimination for either type of cardiac fibrosis. In CVD free participants, simple ECG measures are associated with replacement fibrosis and interstitial fibrosis. The addition of these measures improves identification of replacement but not interstitial fibrosis. These findings may help refine the identification of myocardial scar in the general population.

Association of cardiac troponin T and growth differentiation factor 15 with replacement and interstitial cardiac fibrosis in community dwelling adults: The multi-ethnic study of atherosclerosis.

Background: Subclinical abnormalities in myocardial structure (stage B heart failure) may be identified by cardiac and non-organ specific biomarkers. The associations of high-sensitivity cardiac troponin T (hs-cTnT) and growth differentiation factor-15 (GDF-15) with cardiac magnetic resonance imaging (CMR) interstitial fibrosis (extracellular volume [ECV]) is unknown and for GDF-15 the association with replacement (late gadolinium enhancement [LGE]) is also unknown. GDF-15 is a systemic biomarker also released by myocytes associated with fibrosis and inflammation. We sought to define the associations of hs-cTnT and GDF-15 with these CMR fibrosis measures in the MESA cohort. Methods: We measured hs-cTnT and GDF-15 in MESA participants free of cardiovascular disease at exam 5. CMR measurements were complete in 1737 for LGE and 1258 for ECV assessment. We estimated the association of each biomarker with LGE and increased ECV (4th quartile) using logistic regression, adjusted for demographics and risk factors. Results: Mean age of the participants was 68 ± 9 years. Unadjusted, both biomarkers were associated with LGE, but after adjustment only hs-cTnT concentrations remained significant (4th vs. 1st quartile OR] 7.5, 95% CI: 2.1, 26.6). For interstitial fibrosis both biomarkers were associated with 4th quartile ECV, but the association was attenuated compared to replacement fibrosis. After adjustment, only hs-cTnT concentrations remained significant (1st to 4th quartile OR 1.7, 95%CI: 1.1, 2.8). Conclusion: Our findings identify that both interstitial and replacement fibrosis are associated with myocyte cell death/injury, but GDF-15 a non-organ specific biomarker prognostic for incident cardiovascular disease is not associated with preclinical evidence of cardiac fibrosis.

Impact of Glucagon-Like Peptide 1 Receptor Agonists in Patients with Hemoglobin A1c of 9% or Greater.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) are effective hemoglobin A1c (HbA1c) and weight-lowering agents. The treatment effect is unknown in patients with HbA1c of 9% or greater. Objective: The purpose of this study was to evaluate glycemic control and weight loss after adding a GLP-1 agonist in patients with a baseline HbA1c of 9% (75 mmol/mol) or greater. Methods: A single-health system retrospective chart review screened adults with type 2 diabetes mellitus with a baseline hemoglobin A1c of 9% (75 mmol/mol) or greater and were prescribed a GLP-1 agonist for eligibility. The primary outcome assessed was the change in HbA1c from baseline to the first HbA1c check. Secondary outcomes included change in weight (kg) from baseline to the first HbA1c check. Results: Three hundred sixty-two patients were screened of which 151 (41.7%) were included in the final analysis. The mean change in HbA1c from baseline to first HbA1c check for all participants was -2.1% (95% CI: -2.3% to -1.8%; P < .001; -23 mmol/mol [95% CI: -25 to -20 mmol/mol]). The mean change in weight from baseline to first HbA1c check was -2.0 kg (95% CI: -2.6 kg to -1.4 kg; P < .001). Conclusion: In patients with type 2 diabetes mellitus with a baseline HbA1c ≥ 9%, GLP-1 agonist initiation resulted in a significant reduction of both HbA1c and weight compared to baseline. Large, prospective, multisite studies are needed to confirm findings of this retrospective study.

Selected ocular dimensions of three penguin species.

Penguins (Spheniscidae) are a diverse clade of flightless, marine birds. Their eyes, likely a primary driver of behaviour, have been noted to have anatomic adaptations to their amphibious lifestyle. In particular, they have a relatively flat cornea, which would make the transition from a subaerial to a submarine environment require less accommodative effort. However, the ocular dimensions are not known for many penguin species, despite the diversity within the family, and their accommodative abilities have been the source of some dispute. In this study we undertook to establish the basic dimensions of the eye of the smallest, a mid-sized penguin and the second largest penguin. The power of the front surface of the cornea was inversely related to the size of both the eye and penguin, being 41.3 D in the little penguin (Eudyptula minor), a power greater than previously measured in any other penguin species, 26.3 D in the gentoo (Pygoscelis papua) and 19.1 D in the king penguin (Aptenodytes patagonicus). All other dimensions increased or decreased in line with the size of the eye. All penguins were able to achieve emmetropia in air. The gentoo appeared to be emmetropic underwater. A finding of central corneal thickening in some penguins may be artefactual. Calculations using the ocular dimensions demonstrated that the mean retinal illumination of an extended source of light in the little penguin eye is less than that of its larger, deeper-diving relatives.

Placental Neutrophil Infiltration Associated with Tobacco Exposure but Not Development of Bronchopulmonary Dysplasia.

Objective: In utero inflammation is associated with bronchopulmonary dysplasia (BPD) in preterm infants. We hypothesized that maternal tobacco exposure (TE) might induce placental neutrophil infiltration, increasing the risk for BPD. Study design: We compared the composite outcome of BPD and death in a prospective pilot study of TE and no-TE mothers and their infants born <32 weeks. Placental neutrophil infiltration was approximated by neutrophil gelatinase-associated lipocalin (NGAL) ELISA, and total RNA expression was analyzed via NanoString© (Seattle, WA, USA). Result: Of 39 enrolled patients, 44% were classified as tobacco exposure. No significant difference was noted in the infant's composite outcome of BPD or death based on maternal tobacco exposure. NGAL was higher in placentas of TE vs. non-TE mothers (p < 0.05). Placental RNA analysis identified the upregulation of key inflammatory genes associated with maternal tobacco exposure. Conclusion: Tobacco exposure during pregnancy was associated with increased placental neutrophil markers and upregulated inflammatory gene expression. These findings were not associated with BPD.

IgG4-related prostatitis manifesting as urinary obstruction in a 28-year-old male.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a systemic lymphoproliferative disorder characterized by elevated serum IgG4 levels and tumefactive lesions that can involve nearly every organ system. Involvement of the prostate is rare but has been reported in limited cases. CASE PRESENTATION: A 28-year-old man of Asian descent with a history of sinusitis and priapism presented to hospital with rigors and voiding symptoms. He was diagnosed with IgG4-RD one month prior to presentation, following pathological analysis of a submandibular mass that demonstrated chronic sclerosing sialadenitis. On presentation, white blood cell count, C-reactive protein, and prostate serum antigen levels were all within normal limits. Examination was notable for a large, firm prostate, and a foley catheter was inserted. Contrast CT of the abdomen was unremarkable. Further workup revealed elevated serum IgG4 levels (9.22 g/L) and he was subsequently started on prednisone 35 mg daily. Imaging to screen for systemic IgG4-RD involvement demonstrated paravertebral soft tissue involvement and he was given rituximab 1000 mg IV × 2 doses. MRI revealed diffuse prostatitis. Five days after starting prednisone and one day after his first dose of rituximab, he successfully passed trial of void and was discharged home. CONCLUSIONS: IgG4-related prostatitis is a rare and underrecognized manifestation of IgG4-RD. Our case highlights the need to consider IgG4-related prostatitis as an etiology of urinary obstruction in young individuals. Resolution of symptoms following treatment with steroids may be diagnostic of IgG4-related prostatitis, and may potentially avoid the need for invasive diagnostic procedures such as prostate biopsy.

Interventions for Frailty Among Older Adults With Cardiovascular Disease: JACC State-of-the-Art Review.

With the aging of the world's population, a large proportion of patients seen in cardiovascular practice are older adults, but many patients also exhibit signs of physical frailty. Cardiovascular disease and frailty are interdependent and have the same physiological underpinning that predisposes to the progression of both disease processes. Frailty can be defined as a phenomenon of increased vulnerability to stressors due to decreased physiological reserves in older patients and thus leads to poor clinical outcomes after cardiovascular insults. There are various pathophysiologic mechanisms for the development of frailty: cognitive decline, physical inactivity, poor nutrition, and lack of social supports; these risk factors provide opportunity for various types of interventions that aim to prevent, improve, or reverse the development of frailty syndrome in the context of cardiovascular disease. There is no compelling study demonstrating a successful intervention to improve a global measure of frailty. Emerging data from patients admitted with heart failure indicate that interventions associated with positive outcomes on frailty and physical function are multidimensional and include tailored cardiac rehabilitation. Contemporary cardiovascular practice should actively identify patients with physical frailty who could benefit from frailty interventions and aim to deliver these therapies in a patient-centered model to optimize quality of life, particularly after cardiovascular interventions.

Serum Biomarkers are Associated With Atherosclerotic Cardiovascular Disease Among Patients With Nonalcoholic Fatty Liver Disease Undergoing Elective Angiography.

BACKGROUND & AIMS: Cardiovascular disease is the most common cause of death among patients with nonalcoholic fatty liver disease (NAFLD). We assessed select cardiac biomarker associations for existing or future coronary artery disease (CAD) risk in patients with NAFLD. METHODS: Patients with/without NAFLD undergoing elective cardiac angiography were prospectively enrolled. Severe CAD was defined as presence of at least 1 proximal artery >70% stenosis; risk of severe CAD as either existing severe CAD or atherosclerotic cardiovascular disease score ≥20; NAFLD was defined as hepatic fat in the absence of other liver diseases. Cardiac biomarkers (high-sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, and high-sensitivity cardiac troponin I [hs-cTnI]) were measured using Atellica Solution assays (Siemens Healthineers). RESULTS: A total of 619 patients were enrolled (mean age, 63 ± 10 years; 80% male; 31% type 2 diabetes; 65% NAFLD); 42% had severe CAD, and 57% had risk of severe CAD. NAFLD prevalence was similar between patients with and without severe CAD (68% vs 62%; P > .05). Patients with NAFLD with severe CAD (44%) or with risk of severe CAD (58%) had higher levels of hs-cTnI than NAFLD controls (both P < .001). Presence of severe CAD or risk of severe CAD in all patients was associated with older age, male, aspects of metabolic syndrome, and elevated hs-cTnI: odds ratio 2.0 (95% confidence interval [CI],1.4-2.9) and 1.8 (95% CI, 1.1-3.0), respectively; 2.3 (95% CI, 1.4-3.8) and 2.2 (95% CI, 1.2-4.2), respectively, in patients with NAFLD (all P < .02). CONCLUSION: CAD is common in patients with NAFLD. High hs-cTnI was associated with an increased risk of CAD. Pending validation, hs-cTnI may be a useful marker for CAD risk prediction in patients with NAFLD.

The influence of heart failure on clinical and economic outcomes among older adults ≥75 years of age with acute myocardial infarction.

BACKGROUND: We aimed to evaluate the influence of heart failure (HF) on clinical and economic outcomes among older adults ≥75 years of age during their acute myocardial infarction (AMI) admission in large population-based study from the United States. We also evaluated the clinical characteristics associated with the presence of HF and the predictors of mortality, healthcare utilization, and cost among older adults with AMI. METHODS: From January 1, 2000, to December 31, 2016, AMI admission was identified using the primary diagnosis and concomitant HF was identified using any non-primary diagnoses in the Premier Healthcare Database. RESULTS: Of the 468,654 patients examined, 42,946 (9%) had concomitant HF during their AMI admission. These patients were older, more often female, and were more likely to be White. Patients with concomitant HF were more likely to be frail than non-HF patients (59% vs 15%, P < .001). The mean (SD) Elixhauser comorbidity index was 2.6 (2.5) vs 0.4 (1.1), P < .001 in the AMI with HF vs AMI only group. The use of percutaneous coronary intervention in those with AMI and HF was lower than those with AMI only (15% vs 31%, P < .001). The overall mortality rate for those with HF was 12%, the median [IQR] hospital length of stay was 5 [3,9] days, and only 25% of patients were discharged home. A higher proportion of patients were discharged to rehabilitation or hospice if they had AMI and HF (Rehabilitation: 33% vs 20%, P < .001; Hospice: 5% vs 3%, P < .001). The mean unadjusted cost of an AMI hospitalization in patients with concomitant HF was lower ($12,411 ± $14,860) than in those without HF ($15,828 ± $19,330). After adjusting for age, gender, race, hypertension, frailty, revascularization strategy, and death, the average cost of hospitalization attributed to concomitant HF was +$1,075 (95% CI +876 to $1,274) when compared to AMI patients without HF. CONCLUSION: In patients ≥75 years of age, AMI with concomitant HF carries higher risk of death, but at ages ≥85 years, the risk difference diminishes due to other competing risks. HF was also associated with longer hospital length of stay and higher likelihood of referral to hospice and rehabilitation facilities when compared to older patients without HF. Care for these older adults is associated with increased hospitalization costs. Measures to identify HF in older adults during their AMI admission are necessary to optimize health outcomes, care delivery, and costs.

Primary pure carcinoid tumor of the testis: Radiology, pathology and molecular correlation.

We describe a case of a primary carcinoid tumor of the testis in a 35-year-old man as an incidental finding. Testicular ultrasound showed a 1.1 cm hypoechoic/isoechoic mass with some calcification in the left testicle. The pathology examination of the radical orchiectomy demonstrated a pure carcinoid tumor, with the adjacent coarse calcification. Fluorescence in situ hybridization showed 35 % of the tumor cells had one additional chromosome 12p11.21 signal. This case adds to the rare reports in the literature of a primary pure carcinoid tumor of the testis, and provides additional insight into the radiological and pathological correlation of this disease.

Accurate Electronic Excitation Energies in Full-Valence Active Space via Bootstrap Embedding.

Fragment embedding has been widely used to circumvent the high computational scaling of using accurate electron correlation methods to describe the electronic ground states of molecules and materials. However, similar applications that utilize fragment embedding to treat electronic excited states are comparably less reported in the literature. The challenge here is twofold. First, most fragment embedding methods are most effective when the property of interest is local, but the change of the wave function upon excitation is nonlocal in general. Second, even for local excitations, an accurate estimate of, for example, the excitation energy can still be challenging owing to the need for a balanced treatment of both the ground and the excited states. In this work, we show that bootstrap embedding (BE), a fragment embedding method developed recently by our group, is promising toward describing general electronic excitations. Numerical simulations show that the excitation energies in full-valence active space (FVAS) can be well-estimated by BE to an error of ∼0.05 eV using relatively small fragments, for both local excitations and the excitations of some large dye molecules that exhibit strong charge-transfer characters. We hence anticipate BE to be a promising solution to accurately describing the excited states of large chemical systems.

Bootstrap embedding with an unrestricted mean-field bath.

A suite of quantum embedding methods have recently been developed where the Schmidt decomposition is applied to the full system wavefunction to derive basis states that preserve the entanglement between the fragment and the bath. The quality of these methods can depend heavily on the quality of the initial full system wavefunction. Most of these methods, including bootstrap embedding (BE) [M. Welborn et al; J. Chem. Phys. 145, 074102 (2016)], start from a spin-restricted mean-field wavefunction [call this restricted BE (RBE)]. Given that spin-unrestricted wavefunctions can capture a significant amount of strong correlation at the mean-field level, we suspect that starting from a spin-unrestricted mean-field wavefunction will improve these embedding methods for strongly correlated systems. In this work, BE is generalized to an unrestricted Hartree-Fock bath [call this unrestricted BE (UBE)], and UBE is applied to model hydrogen ring systems. UBE's improved versatility over RBE is utilized to calculate high spin symmetry states that were previously unattainable with RBE. Ionization potentials, electron affinities, and spin-splittings are computed using UBE with accuracy on par with spin-unrestricted coupled cluster singles and doubles. Even for cases where RBE is viable, UBE converges more reliably. We discuss the limitations or weaknesses of each calculation and how improvements to RBE and density matrix embedding theory these past few years can also improve UBE.

Bootstrap Embedding For Large Molecular Systems.

Recent developments in quantum embedding theories have provided attractive approaches to correlated calculations for large systems. In this work, we extend our previous work [J. Chem. Theory Comput. 2019, 15, 4497-4506; J. Phys. Chem. Lett. 2019, 10, 6368-6374] on bootstrap embedding (BE) to enable correlated ab initio calculations at the coupled cluster with singles and doubles (CCSD) level for large molecules. We introduce several new algorithmic developments that significantly reduce the computational cost of BE, while maintaining its accuracy. The resulting implementation scales as O(N3) for the integral transform and O(N) for the CCSD calculation. Numerical results on a series of conjugated molecules suggest that BE with reasonably sized fragments can recover more than 99.5% of the total correlation energy of a full CCSD calculation, while the required computational resources (time and storage) compare favorably to one popular local correlation scheme: domain localized pair natural orbital (DLPNO). The largest BE calculation in this work involves ∼2900 basis functions and can be performed on a single node with 16 CPU cores and 64 GB of memory in a few days. We anticipate that these developments represent an important step toward the application of BE to solve practical problems.

Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes.

AIMS: To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y12 receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS). METHODS AND RESULTS: In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24 h (VerifyNow assay) and 8 h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y12 reaction units (PRU) <100 at 30 min post-dose and lasting ≥3 h. At 30 min post-dose, 89% of patients were responders to selatogrel 8 mg, 90% to selatogrel 16 mg, and 16% to placebo (P < 0.0001). PRU values (mean ± standard deviation) were 10 ± 25 (8 mg), 4 ± 10 (16 mg), and 163 ± 73 (placebo) at 15 min and remained <100 up to 8 h for both doses, returning to pre-dose or near pre-dose levels by 24 h post-dose. LTA data showed similarly rapid and potent inhibition of platelet aggregation. Selatogrel plasma concentrations peaked ∼30 min post-dose. Selatogrel was safe and well-tolerated with transient dyspnoea occurring overall in 7% (16/229) of patients (95% confidence interval: 4-11%). CONCLUSIONS: Selatogrel was rapidly absorbed following subcutaneous administration in CCS patients, providing prompt, potent, and consistent platelet P2Y12 inhibition sustained for ≥8 h and reversible within 24 h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable.

Effects of vorapaxar on clot characteristics, coagulation, inflammation, and platelet and endothelial function in patients treated with mono- and dual-antiplatelet therapy.

BACKGROUND: Vorapaxar is indicated with standard antiplatelet therapy (APT) in patients with a history of myocardial infarction (MI) or peripheral arterial disease (PAD). OBJECTIVES: To evaluate the comparative effects of vorapaxar on platelet-fibrin clot characteristics (PFCC), coagulation, inflammation, and platelet and endothelial function during treatment with daily 81 mg aspirin (A), 75 mg clopidogrel (C), both (C + A), or neither. METHODS: Thrombelastography, conventional platelet aggregation (PA), ex vivo endothelial function by ENDOPAT, coagulation, platelet activation/inflammation marked by urinary 11-dehydrothromboxane B2 (UTxB2 ) and safety were determined in patients who were APT naïve (n = 21), on C (n = 8), on A (n = 29), and on A + C (n = 23) during 1 month of vorapaxar therapy and 1 month of offset. RESULTS: Vorapaxar had no effect on PFCC, ADP- or collagen-induced PA, thrombin time, fibrinogen, PT, PTT, von Willebrand factor (vWF), D-dimer, or endothelial function (P > .05 in all groups). Inhibition of SFLLRN (PAR-1 activating peptide)-stimulated PA by vorapaxar was accelerated by A + C at 2 hours (P < .05 versus other groups) with nearly complete inhibition by 30 days that persisted through 30 days after discontinuation in all groups (P < .001). SFLLRN-induced PA during offset was lower in APT patients versus APT-naïve patients (P < .05). Inhibition of UTxB2 was observed in APT-naive patients treated with vorapaxar (P < .05). Minor bleeding was only observed in C-treated patients. CONCLUSION: Vorapaxar had no influence on PFCC measured by thrombelastography, coagulation, or endothelial function irrespective of APT. Inhibition of protease activated receptor (PAR)-1 mediated platelet aggregation by vorapaxar was accelerated by A + C and offset was prolonged by concomitant APT. Vorapaxar-induced anti-inflammatory effects were observed in non-aspirin-treated patients.

Using SCF metadynamics to extend density matrix embedding theory to excited states.

A new framework based on density matrix embedding theory (DMET) capable of directly targeting excited electronic states is proposed and implemented. DMET has previously been shown to be an effective method of calculating the ground state energies of systems exhibiting strong static correlation but has never been applied to calculate excited state energies. In this work, the Schmidt decomposition is applied directly on excited states, approximated by higher lying self-consistent field solutions. The DMET prescription is applied following this Schmidt decomposition allowing for a direct embedding of excited states. Initial results are obtained for a system of multiple hydrogen dimers and the lithium hydride dissociation. We analyze the nature of each part of the excited state DMET calculation and identify challenges. These challenges to the implementation of excited state DMET are discussed, and potential suggestions moving forward are recommended.

Bootstrap Embedding for Molecules.

Fragment embedding is one way to circumvent the high computational scaling of accurate electron correlation methods. The challenge of applying fragment embedding to molecular systems primarily lies in the strong entanglement and correlation that prevent accurate fragmentation across chemical bonds. Recently, Schmidt decomposition has been shown effective for embedding fragments that are strongly coupled to a bath in several model systems. In this work, we extend a recently developed quantum embedding scheme, bootstrap embedding (BE), to molecular systems. The resulting method utilizes the matching conditions naturally arising from using overlapping fragments to optimize the embedding. Numerical simulation suggests that the accuracy of the embedding improves rapidly with fragment size for small molecules, whereas larger fragments that include orbitals from different atoms may be needed for larger molecules. BE scales linearly with system size (apart from an integral transform) and hence can potentially be useful for large-scale calculations.