deepAFT: A nonlinear accelerated failure time model with artificial neural network.

The Cox regression model or accelerated failure time regression models are often used for describing the relationship between survival outcomes and potential explanatory variables. These models assume the studied covariates are connected to the survival time or its distribution or their transformations through a function of a linear regression form. In this article, we propose nonparametric, nonlinear algorithms (deepAFT methods) based on deep artificial neural networks to model survival outcome data in the broad distribution family of accelerated failure time models. The proposed methods predict survival outcomes directly and tackle the problem of censoring via an imputation algorithm as well as re-weighting and transformation techniques based on the inverse probabilities of censoring. Through extensive simulation studies, we confirm that the proposed deepAFT methods achieve accurate predictions. They outperform the existing regression models in prediction accuracy, while being flexible and robust in modeling covariate effects of various nonlinear forms. Their prediction performance is comparable to other established deep learning methods such as deepSurv and random survival forest methods. Even though the direct output is the expected survival time, the proposed AFT methods also provide predictions for distributional functions such as the cumulative hazard and survival functions without additional learning efforts. For situations where the popular Cox regression model may not be appropriate, the deepAFT methods provide useful and effective alternatives, as shown in simulations, and demonstrated in applications to a lymphoma clinical trial study.

Comparison of Predictive Models for Prevention of Missed Endoscopy Appointments- failure of a Predictive Model to Outperform Overbooking Model.

BACKGROUND: Patient late cancelation and nonattendance for endoscopy appointments is an ongoing problem affecting the productivity and wait times of endoscopy units. Previous research evaluated a model for predictive overbooking and had promising results. STUDY: All endoscopy visits at an outpatient endoscopy unit during 4 nonconsecutive months were included in the data analysis. Patients who did not attend their appointment, or canceled with 48 hours of their appointment were considered nonattendees. Demographic, health, and prior visit behavior data was collected and the groups compared. RESULTS: 1780 patients attended 2331 visits in the study period. Comparing the attendee versus non-attendees, there were significant differences in mean age, prior absenteeism, prior cancelations, and total number of hospital visits. No significant differences were seen between groups in winter versus non-winter months, the day of the week, sex distribution, type of procedure booked, or whether the referral was from specialist clinic or direct to procedure. The visit cancelation proportion (calculated excluding current visit) was substantially higher in the absentee group ( P <0.0001). A predictive model was developed and compared to current booking as well as a straight overbooking of 7%. Both overbooking models performed better than the current practice, but the predictive overbooking model did not outperform straight overbooking. CONCLUSIONS: Developing an endoscopy unit specific predictive model may not be more beneficial than straight overbooking as calculated by missed appointment percentage.

Dynamical Effects of Solvation on Norbornadiene/Quadricyclane Systems.

Molecules that can undergo reversible chemical transformations following the absorption of light, the so-called molecular photoswitches, have attracted increasing attention in technologies, such as solar energy storage. Here, the optical and thermochemical properties of the photoswitch are central to its applicability, and these properties are influenced significantly by solvation. We investigate the effects of solvation on two norbornadiene/quadricyclane photoswitches. Emphasis is put on the energy difference between the two isomers and the optical absorption as these are central to the application of the systems in solar energy storage. Using a combined classical molecular dynamics and quantum mechanical/molecular mechanical computational scheme, we showcase that the dynamic effects of solvation are important. In particular, it is found that standard implicit solvation models generally underestimate the energy difference between the two isomers and overestimate the strength of the absorption, while the explicit solvation spectra are also less red-shifted than those obtained using implicit solvation models. We also find that the absorption spectra of the two systems are strongly correlated with specific dihedral angles. Altogether, this highlights the importance of including the dynamic effects of solvation.

Stacked or Folded? Impact of Chelate Cooperativity on the Self-Assembly Pathway to Helical Nanotubes from Dinucleobase Monomers.

Self-assembled nanotubes exhibit impressive biological functions that have always inspired supramolecular scientists in their efforts to develop strategies to build such structures from small molecules through a bottom-up approach. One of these strategies employs molecules endowed with self-recognizing motifs at the edges, which can undergo either cyclization-stacking or folding-polymerization processes that lead to tubular architectures. Which of these self-assembly pathways is ultimately selected by these molecules is, however, often difficult to predict and even to evaluate experimentally. We show here a unique example of two structurally related molecules substituted with complementary nucleobases at the edges (i.e., G:C and A:U) for which the supramolecular pathway taken is determined by chelate cooperativity, that is, by their propensity to assemble in specific cyclic structures through Watson-Crick pairing. Because of chelate cooperativities that differ in several orders of magnitude, these molecules exhibit distinct supramolecular scenarios prior to their polymerization that generate self-assembled nanotubes with different internal monomer arrangements, either stacked or coiled, which lead at the same time to opposite helicities and chiroptical properties.

Heterocyclic [9]Helicenes Exhibiting Bright Circularly Polarized Luminescence.

We describe a concise synthetic strategy for the preparation of heterocyclic [9]helicenes and a simple preparative-scale protocol for the optical resolution of the resulting M- and P-enantiomers. The helicenes were characterized by single-crystal X-ray diffraction along with a range of spectroscopic and computational techniques. A fluorescence quantum yield of up to 65 % was observed, and the chiroptical properties of both M- and P-helicenes revealed large dissymmetry factors. The circularly polarized luminescence brightness reaches up to 17 M-1 cm-1 , as measured experimentally and verified computationally, which makes this the highest circularly polarized luminescence brightness among heterocyclic helicenes. We describe how chiroptical properties (both circular dichroism and circularly polarized luminescence) can be described and predicted using quantum chemical calculations. The synthetic approach also reveals by-products that originate from internal oxidation reactions, presumably mediated by the close proximity of the π-surfaces in the helicene structure.

Inhibit progression of coronary artery calcification with vitamin K in hemodialysis patients (the iPACK-HD study): a randomized, placebo-controlled multi-center, pilot trial.

BACKGROUND: Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with end-stage kidney disease. METHODS: A parallel randomized placebo-controlled pilot trial was designed to determine whether 10 mg of phylloquinone thrice weekly versus placebo modifies coronary artery calcification progression over 12 months in patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units (ClinicalTrials.gov identifier NCT01528800). The primary outcome was feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol). CAC score was used to assess calcification at baseline and 12 months. Secondary objectives were to explore the impact of phylloquinone on vitamin K-related biomarkers (phylloquinone, dephospho-uncarboxylated MGP and the Gla-osteocalcin to Glu-osteocalcin ratio) and events of clinical interest. RESULTS: A total of 86 patients with a CAC score ≥30 Agatston Units were randomized to either 10 mg of phylloquinone or a matching placebo three times per week. In all, 69 participants (80%) completed the trial. Recruitment rate (4.4 participants/month) and medication compliance (96%) met pre-defined feasibility criteria of ≥4.17 and ≥90%, respectively. Patients randomized to phylloquinone for 12 months had significantly reduced levels of dephospho-uncarboxylated MGP (86% reduction) and increased levels of phylloquinone and Gla-osteocalcin to Glu-osteocalcin ratio compared with placebo. There was no difference in the absolute or relative progression of coronary artery calcification between groups. CONCLUSION: We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible.

Solving response expressions in the ADC/ISR framework.

We present an implementation for the calculation of molecular response properties using the algebraic-diagrammatic construction (ADC)/intermediate state representation approach. For the second-order ADC model [ADC(2)], a memory-efficient ansatz avoiding the storage of double excitation amplitudes is investigated. We compare the performance of different numerical algorithms for the solution of the underlying response equations for ADC(2) and show that our approach also strongly improves the convergence behavior for the investigated algorithms compared with the standard implementation. All routines are implemented in an open-source Python library.

Distinct Heterocyclic Moieties Govern the Selectivity of Thiophene-Vinylene-Based Ligands Towards Aß or Tau Pathology in Alzheime's Disease.

Distinct aggregated proteins are correlated with numerous neurodegenerative diseases and the development of ligands that selectively detect these pathological hallmarks is vital. Recently, the synthesis of thiophene-based optical ligands, denoted bi-thiophene-vinyl-benzothiazoles (bTVBTs), that could be utilized for selective assignment of tau pathology in brain tissue with Alzheime's disease (AD) pathology, was reported. Herein, we investigate the ability of these ligands to selectively distinguish tau deposits from aggregated amyloid-ß (Aß), the second AD associated pathological hallmark, when replacing the terminal thiophene moiety with other heterocyclic motifs. The selectivity for tau pathology was reduced when introducing specific heterocyclic motifs, verifying that specific molecular interactions between the ligands and the aggregates are necessary for selective detection of tau deposits. In addition, ligands having certain heterocyclic moieties attached to the central thiophene-vinylene building block displayed selectivity to aggregated Aß pathology. Our findings provide chemical insights for the development of ligands that can distinguish between aggregated proteinaceous species consisting of different proteins and might also aid in creating novel agents for clinical imaging of tau pathology in AD.

Urgent care-seeking and injury severity for intimate partner violence during COVID-19: a Canadian retrospective chart review.

BACKGROUND: Early reports raised alarms that intimate partner violence (IPV) increased during the COVID-19 pandemic, but initial studies showed that visits to emergency departments (EDs) decreased. This study assessed the impact of the prolonged pandemic and its associated restrictions on both rates of urgent care-seeking and injury severity for IPV. METHODS: Data from the Kingston Health Sciences Centre's (KHSC) ED were utilized to compare IPV presentations during 'Pre-COVID' (December 17, 2018 - March 16, 2020) and 'COVID' (March 17, 2020 - June 16, 2021), as well as three periods of heightened local restrictions: 'Lockdown-1' (March 17 - June 12, 2020), 'Lockdown-2' (December 26, 2020 - February 10, 2021) and 'Lockdown-3' (April 8 - June 2, 2021). The primary outcomes were incidence rate of IPV visits and injury severity, which was assessed using the Clinical Injury Extent Score (CIES) and Injury Severity Score (ISS). RESULTS: A total of 128 individuals were included. This sample had mean age of 34 years, was comprised of mostly women (97%), and represented a variety of intimate relationship types. Some individuals presented multiple times, resulting in a total of 139 acute IPV presentations. The frequency of IPV visits during COVID was similar to the Pre-COVID time period (67 vs. 72; p = 0.67). Incidence rate was 13% higher during COVID, though this difference was non-significant (6.66 vs. 5.90; p = 0.47). IPV visit frequency varied across lockdown periods (11 in Lockdown-1, 12 in Lockdown-2 and 6 in Lockdown-3), with the highest incidence rate during Lockdown-2 (12.71). There were more moderate and severe injuries during COVID compared to Pre-COVID, but mean CIES was not statistically significantly different (1.91 vs. 1.69; p = 0.29), nor was mean ISS (11.88 vs. 12.52; p = 0.73). CONCLUSIONS: During the 15-months following the start of COVID-19, there were small, but non-significant increases in both incidence rate and severity of IPV presentations to the KHSC ED. This may reflect escalation of violence as pandemic restrictions persisted and requires further investigation.

Performance of the 2021 Race-Free CKD-EPI Creatinine- and Cystatin C-Based Estimated GFR Equations Among Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: Race-free estimated glomerular filtration rate (eGFR) equations incorporating creatinine with and without cystatin C were recently developed and recommended for routine use. However, the performance of these equations among kidney transplant recipients (KTRs) remains unknown. STUDY DESIGN: Cross-sectional study to validate the 2021 race-free Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) eGFR equation based on creatinine alone (eGFRcr) or based on creatinine and cystatin C (eGFRcr-cys) among KTRs. SETTING & PARTICIPANTS: KTRs in stable condition (N = 415) from Canada and New Zealand with same-day measurements of creatinine, cystatin C, and glomerular filtration rate (GFR) using radiolabeled diethylenetriaminepentaacetic acid. TESTS COMPARED: The 2009 CKD-EPI eGFRcr, 2021 CKD-EPI eGFRcr, 2012 CKD-EPI eGFRcr-cys, 2021 CKD-EPI eGFRcr-cys, 2012 CKD-EPI eGFRcys, and Modification of Diet in Renal Disease (MDRD) Study eGFR equations were compared with measured GFR. OUTCOMES: Bias, precision, accuracy, and correct classification by CKD stage. Bias was defined as the difference between estimated and measured GFR. Precision was represented by the interquartile range. Accuracy was defined as the percentages of participants with eGFRs within 10%/20%/30% (P10/P20/P30) of measured GFR, root mean square error, and mean absolute error. RESULTS: 87% of patients studied were White, 3% Black, and 10% other races. Mean measured GFR was 53 ± 19 (SD) mL/min/1.73 m2. The 2009 and 2021 CKD-EPI eGFRcr equations demonstrated similar median bias (-2.3 vs -0.2 mL/min/1.73 m2, respectively), precision (14.5 vs 14.9 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/65%/84% vs 33%/63%/84%). The 2012 and 2021 CKD-EPI eGFRcr-cys equations also demonstrated similar median bias (-3.6 vs 0.3 mL/min/1.73 m2, respectively), precision (13.3 vs 14.3 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/63%/80% vs 32%/67%/83%). No clear difference in performance was detected between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations among KTRs. The proportion of correct classification by CKD stage was similar across all eGFR equations. LIMITATIONS: Moderate sample size, few patients had a GFR <30 mL/min/1.73 m2, and the large majority of patients were White. CONCLUSIONS: Among KTRs, the 2021 race-free CKD-EPI eGFR equations perform similarly to the previous CKD-EPI equations that included race correction terms. No significant difference in performance was observed between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations in the kidney transplant population.

Nontrivial spectral band progressions in electronic circular dichroism spectra of carbohelicenes revealed by linear response calculations.

We demonstrate that contemporary computational resources allow for accurate theoretical studies of systems matching recent advances in experimental helicene chemistry. Concerned with first-principles calculations of carbohelicenes, our work surpasses CH[12] as the largest system investigated to date and unravels trends in the electronic structure of the low-lying states of the homologous series. Utilizing a highly efficient implementation of linear response algorithms, we present electronic circular dichroism (CD) spectra of carbohelicenes ranging from CH[5] to CH[30] at the level of Kohn-Sham density-functional theory. Our results for a systematic increase in system size show the emergence of new CD bands that subsequently rise to intensities dominating the spectrum. The spectral band progressions exhibit a periodicity directly linked to the number of overlapping layers of conjugation. While our findings rectify the current understanding of the electronic structure of carbohelicenes, they also serve as a general call for caution regarding the extrapolation of trends from small system ranges.

Modeling Absorption and Emission Spectroscopies of Symmetric and Asymmetric Azaoxahelicenes in Vacuum and Solution.

Helicenes are of general interest due to the significant chiral signals in both absorption- and emission-based spectroscopy. Herein, the spectroscopic properties of four recently synthesized azaoxahelicenes are studied using density functional theory methods. The azaoxahelicenes have 7, 9, 10, and 13 units and one to two complete turns of the structure. UV-vis absorption and electronic circular dichroism spectra are determined both in vacuum and in solution using explicit solvation through a combined molecular dynamics/polarizable embedding framework. Additionally, emission and circularly polarized luminescence spectra are determined based on vibronic calculations. The resulting spectra are in good agreement with the experimentally available data, highlighting that both absorption- and emission-based spectra of the systems can be modeled computationally such that reliable predictions can be made for systems that are yet to be synthesized.

Median sternotomy pain after cardiac surgery: To block, or not? A systematic review and meta-analysis.

BACKGROUND: Inadequate pain control after median sternotomy leads to reduced mobilization, increased respiratory complications, and longer hospital stays. Typically, postoperative pain is controlled by opioid analgesics that may have several adverse effects. Parasternal intercostal block (PSB) has emerged as part of a multimodal strategy to control pain after median sternotomy. However, the effectiveness of this intervention on postoperative pain control and analgesic use has not been fully established. METHODS AND RESULTS: We conducted a meta-analysis to assess the effect of PSB on postoperative pain and analgesic use in adult cardiac surgery patients undergoing median sternotomy. PubMed, Embase, Google Scholar, and the Cochrane database were searched with the following search strategy: ([postoperative pain] or [pain relief] OR [analgesics] or [analgesia] or [nerve block] or [regional block] or [local block] or [regional anesthesia] or [local anesthetic] or [parasternal block] and [sternotomy]) and (humans [filter]). Inclusion criteria were: patients who underwent cardiac surgery via median sternotomy, age >18 and parasternal block (continuous and single dose). Exclusion criteria were: noncardiac surgery, nonparasternal nerve blocks, and the use of NSAIDS in parasternal block. Quality assessment was performed by three independent reviewers via the Cochrane risk of bias assessment tool. Of 1165 total citations, 18 were found to be relevant. Of these 18 citations, 7 citations (N = 2223 patients) reported postoperative pain scores in an extractable format and 11 citations (N = 2155 patients) reported postoperative opioid use in an extractable format. For postoperative opioid use, morphine equivalent doses were calculated for all studies and postoperative pain scores were standardized to a 10-point visual analog scale for comparison between studies; both these were reported as total opioid use or cumulative score ranging from 24 to 72 h postoperative. All data analyses were run using a random effects model, using a restricted maximum likelihood estimator, to obtain summary standardized mean differences with 95% confidence interval (CI's). For studies which only reported median and interquatile range (IQR), the median was standard deviation was estimated by IQR/1.35. Following median sternotomy both postoperative pain (SMD [95% CI] -0.49 [-0.92 to -0.06]) and postoperative morphine equivalent use (SMD [95% CI] -1.68 [-3.11 to -0.25]) were significantly less in the PSB group. CONCLUSION: Our meta-analysis suggests that parasternal nerve block significantly reduces postoperative pain and opioid use.

Semi-Quantitative MALDI Measurements of Blood-Based Samples for Molecular Diagnostics.

Accurate and precise measurement of the relative protein content of blood-based samples using mass spectrometry is challenging due to the large number of circulating proteins and the dynamic range of their abundances. Traditional spectral processing methods often struggle with accurately detecting overlapping peaks that are observed in these samples. In this work, we develop a novel spectral processing algorithm that effectively detects over 1650 peaks with over 3.5 orders of magnitude in intensity in the 3 to 30 kD m/z range. The algorithm utilizes a convolution of the peak shape to enhance peak detection, and accurate peak fitting to provide highly reproducible relative abundance estimates for both isolated peaks and overlapping peaks. We demonstrate a substantial increase in the reproducibility of the measurements of relative protein abundance when comparing this processing method to a traditional processing method for sample sets run on multiple matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) instruments. By utilizing protein set enrichment analysis, we find a sizable increase in the number of features associated with biological processes compared to previously reported results. The new processing method could be very beneficial when developing high-performance molecular diagnostic tests in disease indications.

Simultaneous glomerular filtration rate determination using inulin, iohexol, and 99mTc-DTPA demonstrates the need for customized measurement protocols.

Urinary inulin clearance is considered the gold standard of glomerular filtration rate (GFR) measurement but plasma clearance of less expensive and more accessible tracers is more commonly performed. Many plasma sampling protocols exist but little is known about their accuracy. Here, the study objectives were to compare plasma iohexol and 99mTc-DTPA GFR with varying sampling strategies to the GFR measured by urinary inulin and to identify protocols with the greatest accuracy according to clinical characteristics. GFR was measured simultaneously using urinary inulin, plasma iohexol, and plasma 99mTc DTPA clearance. Blood was sampled from 2 to 10 hours after injection. For each method, bias, precision, and accuracy (P30 and mean absolute error) were calculated for the entire cohort and for eGFR-EPI creatinine subgroups (<30, 30-59, and ≥60 ml/min/1.73m2) and the edema stage using urinary inulin clearance as the gold standard. The mean inulin GFR of the 77 participants was 33 ml/min/1.73m2. Delay of both the initial and the final samples in plasma iohexol protocols yielded the highest accuracy in the setting of low GFR (<30 ml/min/1.73m2). Early initial and final samples yielded the highest accuracy in the setting of high GFRs (≥60 ml/min/1.73m2). No sampling strategy was accurate in edematous patients. Thus, our study demonstrates that customization of GFR protocols according to the anticipated level of GFR are required to optimize protocol accuracy.

Deciphering the Electronic Transitions of Thiophene-Based Donor-Acceptor-Donor Pentameric Ligands Utilized for Multimodal Fluorescence Microscopy of Protein Aggregates.

Anionic pentameric thiophene acetates can be used for fluorescence detection and diagnosis of protein amyloid aggregates. Replacing the central thiophene unit by benzothiadiazole (BTD) or quinoxaline (QX) leads to large emission shifts and basic spectral features have been reported [Chem. Eur. J. 2015, 21, 15133-13137]. Here we present new detailed experimental results of solvent effects, time-resolved fluorescence and examples employing multi-photon microscopy and lifetime imaging. Quantum chemical response calculations elucidate how the introduction of the BTD/QX groups changes the electronic states and emissions. The dramatic red-shift follows an increased conjugation and quinoid character of the π-electrons of the thiophene backbone. An efficient charge transfer in the excited states S1 and S2 compared to the all-thiophene analogue makes these more sensitive to the polarity and quenching by the solvent. Taken together, the results guide in the interpretation of images of stained Alzheimer disease brain sections employing advanced fluorescence microscopy and lifetime imaging, and can aid in optimizing future fluorescent ligand development.

Overview and Diagnostic Accuracy of Near Infrared Spectroscopy in Carotid Endarterectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: Carotid endarterectomy is recommended for the prevention of ischaemic stroke due to carotid stenosis. However, the risk of stroke after carotid endarterectomy has been estimated at 2% - 5%. Monitoring intra-operative cerebral oxygenation with near infrared spectroscopy (NIRS) has been assessed as a strategy to reduce intra- and post-operative complications. The aim was to summarise the diagnostic accuracy of NIRS to detect intra-operative ischaemic events, the values associated with ischaemic events, and the relative contribution of external carotid contamination to the NIRS signal in adults undergoing carotid endarterectomy. DATA SOURCES: EMBASE, MEDLINE, Cochrane Centre Register of Controlled Trials, and reference lists through May 2019 were searched. REVIEW METHODS: Non-randomised and randomised studies assessing NIRS as an intra-operative monitoring tool in carotid endarterectomy were included. Studies using NIRS as the reference were excluded. Risk of bias was assessed using the Newcastle Ottawa Scale, RoB-2, and QUADAS-2. RESULTS: Seventy-six studies were included (n = 8 480), under local (n = 1 864) or general (n = 6 582) anaesthesia. Seven studies were eligible for meta-analysis (n = 524). As a tool for identifying intra-operative ischaemia, specificity increased with more stringent NIRS thresholds, while there was unpredictable variation in sensitivity across studies. A Δ20% threshold under local anaesthesia resulted in pooled estimates for sensitivity and specificity of 70.5% (95% confidence interval, CI, 54.1 - 82.9) and 92.4% (95% CI 85.5 - 96.1) compared with awake neurological monitoring. These studies had low or unclear risk of bias. NIRS signal consistently dropped across clamping and recovered to pre-clamp values upon de-clamp in most studies, and larger decreases were observed in patients with ischaemic events. The contribution of extracranial signal to change in signal across clamp varied from 3% to 50%. CONCLUSION: NIRS has low sensitivity and high specificity to identify intra-operative ischaemia compared with awake monitoring. Extracranial signal contribution was highly variable. Ultimately, data from high quality studies are desperately needed to determine the utility of NIRS.

Electronic circular dichroism spectra using the algebraic diagrammatic construction schemes of the polarization propagator up to third order.

Expressions for the calculation of rotatory strengths using the algebraic diagrammatic construction (ADC) scheme of the polarization propagator in both length and velocity gauges have been implemented. This enables the simulation of electronic circular dichroism (ECD) spectra at the ADC level up to third order of perturbation theory. The ADC(n) methods produce rotatory strengths of comparable accuracy to those obtained with coupled cluster methods of corresponding approximation levels, as evaluated for methyloxirane, methylthiirane, dimethyloxirane, dimethylthiirane, hydrogen peroxide, and dihydrogen disulfide. ECD spectra of (1R)-camphor, (1R)-norcamphor, and (1R)-fenchone computed at the third order ADC(3) level of theory are shown to agree very favorably with experimental gas phase spectra, demonstrating the usefulness of ADC for the calculation of chiro-optical properties of organic molecules. ADC(2) in combination with the polarizable continuum model is shown to successfully reproduce the ECD spectrum of the L-epinephrine enantiomer in water, further demonstrating the applicability of this approach.

Efficient implementation of isotropic cubic response functions for two-photon absorption cross sections within the self-consistent field approximation.

Within the self-consistent field approximation, computationally tractable expressions for the isotropic second-order hyperpolarizability have been derived and implemented for the calculation of two-photon absorption cross sections. The novel tensor average formulation presented in this work allows for the evaluation of isotropic damped cubic response functions using only ∼3.3% (one-photon off-resonance regions) and ∼10% (one-photon resonance regions) of the number of auxiliary Fock matrices required when explicitly calculating all the needed individual tensor components. Numerical examples of the two-photon absorption cross section in the one-photon off-resonance and resonance regions are provided for alanine-tryptophan and 2,5-dibromo-1,4-bis(2-(4-diphenylaminophenyl)vinyl)-benzene. Furthermore, a benchmark set of 22 additional small- and medium-sized organic molecules is considered. In all these calculations, a quantitative assessment is made of the reduced and approximate forms of the cubic response function in the one-photon off-resonance regions and results demonstrate a relative error of less than ∼5% when using the reduced expression as compared to the full form of the isotropic cubic response function.

Analytical gradients for core-excited states in the algebraic diagrammatic construction (ADC) framework.

Expressions for analytical molecular gradients of core-excited states have been derived and implemented for the hierarchy of algebraic diagrammatic construction (ADC) methods up to extended second-order within the core-valence separation (CVS) approximation. We illustrate the use of CVS-ADC gradients by determining relaxed core-excited state potential energy surfaces and optimized geometries for water, formic acid, and benzene. For water, our results show that in the dissociative lowest core-excited state, a linear configuration is preferred. For formic acid, we find that the O K-edge lowest core-excited state is non-planar, a fact that is not captured by the equivalent core approximation where the core-excited atom with its hole is replaced by the "Z + 1" neighboring atom in the periodic table. For benzene, the core-excited state gradients are presented along the Jahn-Teller distorted geometry of the 1s → π* excited state. Our development may pave a new path to studying the dynamics of molecules in their core-excited states.