The Chronus Quantum (ChronusQ) Software Package

The Chronus Quantum (ChronusQ) software package is an open source (under the GNU General Public License v2) software infrastructure which targets the solution of challenging problems that arise in ab initio electronic structure theory. Special emphasis is placed on the consistent treatment of time dependence and spin in the electronic wave function, as well as the inclusion of relativistic effects in said treatments. In addition, ChronusQ provides support for the inclusion of uniform finite magnetic fields as external perturbations through the use of gauge-including atomic orbitals (GIAO). ChronusQ is a parallel electronic structure code written in modern C++ which utilizes both message passing (MPI) and shared memory (OpenMP) parallelism. In addition to the examination of the current state of code base itself, a discussion regarding ongoing developments and developer contributions will also be provided.Comment: 43 pages, 2 figure

Standard carotid endarterectomy versus carotid artery stenting with closed-cell stent design and distal embolic protection: does the age matter?

Carotid artery endarterectomy (CEA) is considered the gold standard for treatment of symptomatic and asymptomatic carotid disease. Carotid artery stenting (CAS) is a less invasive approach and therefore could be considered a viable alternative to CEA, especially in high-risk patients or those with relative contraindications to CEA (i.e. actinic stenosis, post-CEA restenosis, previous neck or tracheostomy surgery, contralateral laryngeal nerve paralysis, etc.). Methods – The aim of this study is to evaluate the short- and medium-term outcomes of CAS performed with a single type of closed-cell stent design and distal filter protection by comparing the procedure with CEA based upon 3 endpoints: overall survival rate, stroke free survival rate and restenosis free survival rate. The same endpoints were also evaluated in 2 different age groups, more and less than 70 years, to show possible age-based differences on outcomes. Among 105 patients (77 males, 28 females), 74 were submitted to CEA and 31 were subject to CAS. In all cases the same self-expanding stent with closed-cell design (XACT Carotid Stent, Abbott Vascular) and the same distal embolic protection device (Emboshield NAV, Abbott Vascular) were employed. Results – At 12 months, no statistically significant difference was observed in overall survival rates (CEA 93.2% vs CAS 93.5%, p=0.967) and restenosis free survival rates (CEA 94.5% vs CAS 96.8%, p=0.662). An increased stroke free survival rate was observed in the CEA group when compared to the CAS group (CEA 100.0% vs CAS 93.5%, p=0.028). The age-based endpoints didn’t show any significant difference. Conclusion - These results suggest that CEA still remains the gold standard of treatment for carotid stenosis given its greater efficacy in the prevention of stroke CAS. However, CAS could be considered as an alternative treatment to CEA to be used in select cases only

Proximal Gamma Ray Spectroscopy for monitoring Soil Water Content in vineyards

Soil Water Content (SWC) is a key information in precision agriculture for obtaining high levels of efficiency and health of crops, while reducing water consumption. In particular, for the case of vineyards, due to the recent extreme temperature fluctuations, the knowledge of the SWC of the entire field becomes crucial to allow a timely intervention with emergency irrigation to preserve plant health and yield. Unlike electromagnetic SWC measurements, that are punctual and gravimetric measurements, that are punctual and also time-consuming, the Proximal Gamma Ray Spectroscopy (PGRS) technique can provide field-scale, non-invasive, and real-time measurements of SWC. This is achievable through an in-situ NaI detector, continuously recording photons resulting from the radioactive decay of 40K in the soil, which are attenuated proportionally based on the amount of stored water. Given the inverse proportionality between soil moisture and photons detected by the gamma ray sensor, the SWC value can be easily obtained. In this study we investigate the performance of PGRS applied to the case of study of a vineyard at the farm “Il Poggione” located in Montalcino (Siena, Italy). The effectiveness of the results obtained is supported by different tests: first the validation allowed to compare the PGRS measurement (5.8 ± 1.5)% with a gravimetric measurement (9.0 ± 2.5)%, highlighting a 1-σ agreement; then by the rainfall recognition capability indeed, in correspondence to the most significant rainfall event (18 mm) the SWC value before and after the rain increased of 7.8%. Moreover, the integration of the in-situ system with an agrometeorological station resulted in a Web App, allowing for real time data storage and thus facilitating data management, spectrum analysis, and display for both gamma ray sensor and agrometeorological station results, enabling comprehensive studies of environmental parameters (e.g., temperature, air humidity). This research underlines the potential of PGRS as a precise, real-time, and field scale SWC monitoring tool not only in vineyards but for cultivated fields in general. Further refinements concerning the gamma ray spectra analysis and broader applications in environmental monitoring are envisaged for improved agricultural practices. This study was supported by the project STELLA (Sistema inTEgrato per Lo studio del contenuto d'acqua in agricoLturA) (CUP: D94E20002180009) funded by the Tuscany region under the program POR FESR 2014/2020

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Theoretical study of time resolved spectroscopy and non-equilibrium processes

We developed new theoretical models and computational tools to explore the dynamical behavior of several systems, mostly in the biological field, undergoing nonequilibrium process or time-resolved spectroscopy. We focused our attention on the cutting edge challenges of the modern theoretical and computational chemistry, without ever neglecting the experimental implications. In fact, we can easily say that our challenges share the same attention in both the theoretical chemistry and the modern and newest experimental and technological applications, such as the newest time-resolved spectroscopies, the solar cell device design, innovative protein-based bio-sensors. The common, and in our opinion intriguing, factors of our work are the following: the molecular dynamics, the characterization of electronic excited states, and the modeling of complex events. Therefore, in each phase of the project we designed our theory and our computational experiments by studying our cases as a dynamic embedded system, surrounded by its environment, describing its excited electronic states and its temporal evolution. Moreover, the time dependence of our results provided an additional trigger to develop also new, or more accurate, tools of analysis. Three different case studies are presented, facing different experimental issues affecting different and shorter and shorter time scales. First, the N-methyl-6-oxyquinolinium betaine time resolved Stokes-Shift experiment in water solution was investigated. Nowadays, thanks to the ultra-fast pulsed laser techniques, we are able to freeze the far-from-equilibrium structures during a molecular vibration or a reaction. We proposed a new computational protocol to study the excited state dynamics ruling the non equilibrium relaxation process affecting a fluorescent probe upon the electronic excitation. In this work, we explained how the whole time dependent signal is influenced in a dynamical way by several collective solvent motions. After we presented several theoretical tools to characterize the behavior of transient excited states within bio-macromolecules. In particular we focused our efforts to study the excited state photo-reactivity and the optical behavior of the Green Fluorescent Protein (GFP). We calculate at the same level of TD-DFT the vertical excitation energy of the anionic GFP chromophore in the protein and in ethanol, dioxane, methanol and water solutions. As result, we reproduced for the first time the experimental trend of the absorption peaks with 0.015 eV as standard deviation of the accuracy. During this work, we also contributed to the tangled debate on the gas-phase GFP chromophore experimental reference absorption value. Moreover, the Excited State Proton Transfer in the GFP is a complex and fascinating event of a paramount importance in many scientific and technological fields. Therefore, we also proposed an innovative computational protocol to face the simulation of a complex non-equilibrium process, such as the photo-reactivity affecting the GFP, going from easier to more accurate modeling approaches, along with showing the nature of the mechanism and the complex role of the protein matrix on it. Finally, we explored the exciton dynamics of bulk hetero-junction (BHJ) based polymer solar cells. Therefore, we exploited a computational method that provides the explicit evolution of the electronic density along the time after the photon absorption, on sub-femto time scale. The innovative real-time non-adiabatic nonperturbative TDDFT electronic dynamics was used to better understand the interplay between the photo-excited electron-hole pair and the charge separated state. This work gave us an useful molecular insight for BHJ based polymer solar cell design, showing the crucial role of theoretical chemistry to investigate how small modifications on molecular scale can influence the properties of the whole device

Understanding Charge Dynamics in Dense Electronic Manifolds in Complex Environments

: Photoinduced charge transfer (CT) excited states and their relaxation mechanisms can be highly interdependent on the environment effects and the consequent changes in the electronic density. Providing a molecular interpretation of the ultrafast (subpicosecond) interplay between initial photoexcited states in such dense electronic manifolds in condensed phase is crucial for improving and understanding such phenomena. Real-time time-dependent density functional theory is here the method of choice to observe the charge density, explicitly propagated in an ultrafast time domain, along with all time-dependent properties that can be easily extracted from it. A designed protocol of analysis for real-time electronic dynamics to be applied to time evolving electronic density related properties to characterize both in time and in space CT dynamics in complex systems is here introduced and validated, proposing easy to be read cross-correlation maps. As case studies to test such tools, we present the photoinduced charge-transfer electronic dynamics of 5-benzyluracil, a mimic of nucleic acid/protein interactions, and the metal-to-ligand charge-transfer electronic dynamics in water solution of [Ru(dcbpy)2(NCS)2]4-, dcbpy = (4,4'-dicarboxy-2,2'-bipyridine), or "N34-", a dye sensitizer for solar cells. Electrostatic and explicit ab initio treatment of solvent molecules have been compared in the latter case, revealing the importance of the accurate modeling of mutual solute-solvent polarization on CT kinetics. We observed that explicit quantum mechanical treatment of solvent slowed down the charge carriers mobilities with respect to the gas-phase. When all water molecules were modeled instead as simpler embedded point charges, the electronic dynamics appeared enhanced, with a reduced hole-electron distance and higher mean velocities due to the close fixed charges and an artificially increased polarization effect. Such analysis tools and the presented case studies can help to unveil the influence of the electronic manifold, as well as of the finite temperature-induced structural distortions and the environment on the ultrafast charge motions

Theoretical and computational tools to understand the spectroscopy and reactivity of bio-molecules

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