A reinvestigation of the deceptively simple reaction of toluene with OH, and the fate of the benzyl radical : a combined thermodynamic and kinetic study on the competition between OH-addition and H-abstraction reactions

This work reports density functional and composite model chemistry calculations performed on the reactions of toluene with the hydroxyl radical. Both the experimentally observed H-abstraction from the methyl group and possible OH additions to the phenyl ring were investigated. Reaction enthalpies and barrier heights suggest that H-abstraction is more favorable than OH-addition to the ring. The calculated reaction rates at room temperature and the radical intermediate product fractions support this view. At first sight, this might seem to disagree with the fact that, under most experimental conditions, cresols are observed in a larger concentration than benzaldehyde. Since the accepted mechanism for benzaldehyde formation involves H-abstraction, a contradiction arises that calls for a more elaborate explanation. In this first exploratory study, we provide evidence that support the preference of H-abstraction over OH addition and present an alternative mechanism which shows that cresols can be actually produced also through H-abstraction and not only from OH-addition, thus justifying the larger proportion of cresols than benzaldehyde among the products

Antimicrobials: A Global Alliance For Optimizing Their Rational Use In Intra-abdominal Infections (agora)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.11NIAID NIH HHS [R01 AI117211

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs

ECLAPTE: Effective Closure of LAParoTomy in Emergency-2023 World Society of Emergency Surgery guidelines for the closure of laparotomy in emergency settings

Laparotomy incisions provide easy and rapid access to the peritoneal cavity in case of emergency surgery. Incisional hernia (IH) is a late manifestation of the failure of abdominal wall closure and represents frequent complication of any abdominal incision: IHs can cause pain and discomfort to the patients but also clinical serious sequelae like bowel obstruction, incarceration, strangulation, and necessity of reoperation. Previous guidelines and indications in the literature consider elective settings and evidence about laparotomy closure in emergency settings is lacking. This paper aims to present the World Society of Emergency Surgery (WSES) project called ECLAPTE (Effective Closure of LAParoTomy in Emergency): the final manuscript includes guidelines on the closure of emergency laparotomy

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Diffusion and Reptation Quantum Monte Carlo Study of the NaK Molecule

<p>Diffusion Monte Carlo (DMC) and Reptation Monte Carlo (RMC) methods, have been applied to study some properties of the NaK molecule. Hartree-Fock (HF), Density Functional (DFT) and single and double configuration interaction (SDCI) wavefunctions with a valence quadruple zeta atomic natural orbital (VQZ/ANO) basis set were used as trial wavefunctions. Values for the potential energy curve, dissociation energy and dipole moment were calculated for all methods and compared with experimental results and previous theoretical derivations. Quantum Monte Carlo (QMC) calculations were shown to be useful methods to recover correlation in NaK, essential to obtain a reasonable description of the molecule. The equilibrium distance—interpolated from the potential energy curves—yield a value of 3.5 Å, in agreement with the experimental value. The dissociation energy, however, is not as good. In this case, a conventional CCSD(T) calculation with an extended aug-pc-4 basis set gives a much better agreement to experiment. On the contrary, the CCSD(T), other MO and DFT methods are not able to reproduce correctly the large dipole moment of this molecule. Even DMC methods with a simple HF trial wavefunction are able to give a better agreement to experiment. RMC methods are even better, and the value obtained with a B3LYP trial wavefunction is very close to the experimental one.</p

Isomerization and Fragmentation Reactions on the [C2SH4] Potential Energy Surface. The Metastable Thione-S-Methylide Isomer

Thione S-methylide (TSM), the parent species of the thiocarbonyl ylide family, is a 1,3-dipolar, planar species on the [C2SH4] potential energy surface (PES), which has not shared the richness of studies dedicated to its isomers, the cyclic thiirane (THI), and the keto-enol pair vinyl thiol (VTH)/thioacetaldehyde (THA). While the conrotatory ring closure reaction toward THI was studied in the ‘90s, no complete analysis of the PES is available in the literature. In the present paper, we report a computational study of the reaction scheme linking all species on that PES. We employ several levels of calculation, ranging from density functional theory (DFT), through CCSD(T) based composite schemes, to CASSCF/CASPT2 multi-reference procedures, to find the best description of TSM, its isomers, and the transition states (TSs) ruling their interconversion. Fragmentation of TSM, THA and THI were investigated and compared to the available experimental information. We found that the B2PLYP-D3 functional, contrary to M06-2XD3 or B97X-D, describes well the geometry of both TSM and the transition state connecting it to THI. The reverse barrier, from THI to TSM, amounts to 52.2 kcal mol-1 (to be compared to 17.6 kcal mol-1 for the direct one), thus explaining why, in general, thiocarbonyl ylides cannot be prepared from thiiranes. Conversion of THI to VTH implies also a large barrier, explaining why the reaction has been observed only at high temperatures. The fragmentation of THI to S(3P) or S(1D) and ethylene was also explored, together with the decomposition to H2S plus acetylene. Open species, both in triplet and singlet states, were identified as intermediates in the fragmentations, and their energies were found to be lower than the transition state for the isomerization of THI to VTH, thus explaining the preference for fragmentation over isomerization at relatively low temperatures

SVECV-f12: benchmark of a composite scheme for accurate and cost effective evaluation of reaction barriers.

A simple composite scheme is presented, based on a combination of density functional geometry and frequencies evaluation, valence energies obtained using the CCSD(T)-f12 method extrapolated to the complete basis set limit, and core-valence correlation corrections employing the MP2 method. The procedure was applied to the 38 reactions in Truhlar’s HTBH38/08 and NHTBH38/08 databases and the errors in the barriers with respect to their best values are presented. Mean unsigned deviation (MUD) for the complete set of 68 independent barriers is 0.40 kcal mol-1 , compared to 1.31 kcal/mol for G4 and 1.62 kcal/mol for the dispersion-corrected M06- 2X method. The accuracy of the procedure is also better that that of other calculations using composite methods of similar cost. The MUD of the new scheme on the barriers in the DBH24/08 subset (12 out of the 38 reactions in the other two sets) is 0.27 kcal mol-1 , better than that obtained at the expensive CCSD(T,full)/aug-cc-pCV(T+d)Z level (0.46 kcal mol-1 ) and comparable to the 2 most exact (and costly) Wn calculations (MUD=0.14 kcal mol-1 ). The maximum unsigned deviation (MaxUD) for all the reactions studied is 0.99 kcal/mol. G4 and M06-2X, on the other side, exhibit MaxUDs of 6.7 and 8.0 kcal/mol respectively. The method was further tested against a subset of the reactions in the databases, for which the geometry and energies of all species were determined at the much more demanding CCSD(T)-F12//pVQZ-F12 level. These results showed that Truhlar’s calculations in this subset are off the best values by a considerable amount, with an rmse of 0.56 kcal/mol. As a consequence, a new dataset of barrier heights, SV20, is presented. The SVECV-F12 procedure on this SV20 database results in rmse and MUD values of only 0.21 and 0.16 kcal/mol. The possible residual errors introduced by the approximations used for each component of the method are tested against more sophisticated calculations and shown to be accurate enough to obtain barriers well under the chemical precision limit at a reasonable cost for molecules of interest in atmospheric chemistry