From NWChem to NWChemEx: Evolving with the Computational Chemistry Landscape.

Since the advent of the first computers, chemists have been at the forefront of using computers to understand and solve complex chemical problems. As the hardware and software have evolved, so have the theoretical and computational chemistry methods and algorithms. Parallel computers clearly changed the common computing paradigm in the late 1970s and 80s, and the field has again seen a paradigm shift with the advent of graphical processing units. This review explores the challenges and some of the solutions in transforming software from the terascale to the petascale and now to the upcoming exascale computers. While discussing the field in general, NWChem and its redesign, NWChemEx, will be highlighted as one of the early codesign projects to take advantage of massively parallel computers and emerging software standards to enable large scientific challenges to be tackled.

A parallel, distributed memory implementation of the adaptive sampling configuration interaction method.

The many-body simulation of quantum systems is an active field of research that involves several different methods targeting various computing platforms. Many methods commonly employed, particularly coupled cluster methods, have been adapted to leverage the latest advances in modern high-performance computing. Selected configuration interaction (sCI) methods have seen extensive usage and development in recent years. However, the development of sCI methods targeting massively parallel resources has been explored only in a few research works. Here, we present a parallel, distributed memory implementation of the adaptive sampling configuration interaction approach (ASCI) for sCI. In particular, we will address the key concerns pertaining to the parallelization of the determinant search and selection, Hamiltonian formation, and the variational eigenvalue calculation for the ASCI method. Load balancing in the search step is achieved through the application of memory-efficient determinant constraints originally developed for the ASCI-PT2 method. The presented benchmarks demonstrate near optimal speedup for ASCI calculations of Cr2 (24e, 30o) with 106, 107, and 3 × 108 variational determinants on up to 16 384 CPUs. To the best of the authors' knowledge, this is the largest variational ASCI calculation to date.

Distributed memory, GPU accelerated Fock construction for hybrid, Gaussian basis density functional theory.

With the growing reliance of modern supercomputers on accelerator-based architecture such a graphics processing units (GPUs), the development and optimization of electronic structure methods to exploit these massively parallel resources has become a recent priority. While significant strides have been made in the development GPU accelerated, distributed memory algorithms for many modern electronic structure methods, the primary focus of GPU development for Gaussian basis atomic orbital methods has been for shared memory systems with only a handful of examples pursing massive parallelism. In the present work, we present a set of distributed memory algorithms for the evaluation of the Coulomb and exact exchange matrices for hybrid Kohn-Sham DFT with Gaussian basis sets via direct density-fitted (DF-J-Engine) and seminumerical (sn-K) methods, respectively. The absolute performance and strong scalability of the developed methods are demonstrated on systems ranging from a few hundred to over one thousand atoms using up to 128 NVIDIA A100 GPUs on the Perlmutter supercomputer.

PluginPlay: Enabling exascale scientific software one module at a time.

For many computational chemistry packages, being able to efficiently and effectively scale across an exascale cluster is a heroic feat. Collective experience from the Department of Energy's Exascale Computing Project suggests that achieving exascale performance requires far more planning, design, and optimization than scaling to petascale. In many cases, entire rewrites of software are necessary to address fundamental algorithmic bottlenecks. This in turn requires a tremendous amount of resources and development time, resources that cannot reasonably be afforded by every computational science project. It thus becomes imperative that computational science transition to a more sustainable paradigm. Key to such a paradigm is modular software. While the importance of modular software is widely recognized, what is perhaps not so widely appreciated is the effort still required to leverage modular software in a sustainable manner. The present manuscript introduces PluginPlay, https://github.com/NWChemEx-Project/PluginPlay, an inversion-of-control framework designed to facilitate developing, maintaining, and sustaining modular scientific software packages. This manuscript focuses on the design aspects of PluginPlay and how they specifically influence the performance of the resulting package. Although, PluginPlay serves as the framework for the NWChemEx package, PluginPlay is not tied to NWChemEx or even computational chemistry. We thus anticipate PluginPlay to prove to be a generally useful tool for a number of computational science packages looking to transition to the exascale.

Computing Free Energies with Fluctuation Relations on Quantum Computers.

As a central thermodynamic property, free energy enables the calculation of virtually any equilibrium property of a physical system, allowing for the construction of phase diagrams and predictions about transport, chemical reactions, and biological processes. Thus, methods for efficiently computing free energies, which in general is a difficult problem, are of great interest to broad areas of physics and the natural sciences. The majority of techniques for computing free energies target classical systems, leaving the computation of free energies in quantum systems less explored. Recently developed fluctuation relations enable the computation of free energy differences in quantum systems from an ensemble of dynamic simulations. While performing such simulations is exponentially hard on classical computers, quantum computers can efficiently simulate the dynamics of quantum systems. Here, we present an algorithm utilizing a fluctuation relation known as the Jarzynski equality to approximate free energy differences of quantum systems on a quantum computer. We discuss under which conditions our approximation becomes exact, and under which conditions it serves as a strict upper bound. Furthermore, we successfully demonstrate a proof of concept of our algorithm using the transverse field Ising model on a real quantum processor. As quantum hardware continues to improve, we anticipate that our algorithm will enable computation of free energy differences for a wide range of quantum systems useful across the natural sciences.

Implementation of transanal minimally invasive surgery (TAMIS) for rectal neoplasms: results from a single centre.

BACKGROUND: Local excisions are important in a tailored approach to treatment of rectal neoplasms. In cases of low risk T1 local excision facilitates rectal-preserving treatment. Transanal minimally invasive surgery (TAMIS) is the most recent alternative developed for local excision. In this study we evaluate the results after implementing TAMIS as the routine procedure for local excision of rectal neoplasms. METHODS: All patients who underwent TAMIS from January 2016 to January 2020 at St. Olav's University Hospital were included, and clinical, pathological and oncological data were prospectively registered. The primary endpoint was local recurrence, and the secondary endpoint was complications. RESULTS: There were 76 patients (42 men, mean age was 69 years [range 26-88 years]), The mean tumour level was 82 mm (range 20-140 mm) from the anal verge measured on rigid proctoscopy, and mean tumour size was 32 mm (range 8-73 mm). Three patients experienced complications needing intervention (Clavien-Dindo > 3A). Seventeen patients had rectal adenocarcinoma, 9 of whom underwent R0 completion total mesorectal excision (cTME). Fifty-five patients had an adenoma, 3 of whom developed recurrence (5.4%) within 12 months. All recurrences were treated successfully with a new TAMIS procedure. In addition, TAMIS was used in treatment of 2 patients with a neuroendocrine tumour, 1 patient with a haemangioma and 1 patient with a solitary rectal ulcer. CONCLUSIONS: TAMIS surgery is associated with a low risk of complications and a low recurrence rate in rectal neoplasms. In cases of adenocarcinoma, R0 cTME surgery is feasible in the sub-group with high risk T1 and T2 tumours.

Quantum Algorithm for High Energy Physics Simulations.

Simulating quantum field theories is a flagship application of quantum computing. However, calculating experimentally relevant high energy scattering amplitudes entirely on a quantum computer is prohibitively difficult. It is well known that such high energy scattering processes can be factored into pieces that can be computed using well established perturbative techniques, and pieces which currently have to be simulated using classical Markov chain algorithms. These classical Markov chain simulation approaches work well to capture many of the salient features, but cannot capture all quantum effects. To exploit quantum resources in the most efficient way, we introduce a new paradigm for quantum algorithms in field theories. This approach uses quantum computers only for those parts of the problem which are not computable using existing techniques. In particular, we develop a polynomial time quantum final state shower that accurately models the effects of intermediate spin states similar to those present in high energy electroweak showers with a global evolution variable. The algorithm is explicitly demonstrated for a simplified quantum field theory on a quantum computer.

Mitigating Depolarizing Noise on Quantum Computers with Noise-Estimation Circuits.

A significant problem for current quantum computers is noise. While there are many distinct noise channels, the depolarizing noise model often appropriately describes average noise for large circuits involving many qubits and gates. We present a method to mitigate the depolarizing noise by first estimating its rate with a noise-estimation circuit and then correcting the output of the target circuit using the estimated rate. The method is experimentally validated on a simulation of the Heisenberg model. We find that our approach in combination with readout-error correction, randomized compiling, and zero-noise extrapolation produces close to exact results even for circuits containing hundreds of CNOT gates. We also show analytically that zero-noise extrapolation is improved when it is applied to the output of our method.

Reactions of U+ with H2, D2, and HD Studied by Guided Ion Beam Tandem Mass Spectrometry and Theory.

The kinetic energy-dependent reactions of the atomic actinide uranium cation (U+) with H2, D2, and HD were examined by guided ion beam tandem mass spectrometry. An average 0 K bond dissociation energy of D0(U+ - H) = 2.48 ± 0.06 eV is obtained by analysis of the endothermic product ion cross sections. Quantum chemistry calculations were performed for comparison with experimental thermochemistry, including high-level CASSCF-CASPT2-RASSI calculations of the spin-orbit corrections. CCSD(T) and the CASSCF levels show excellent agreement with experiment, whereas B3LYP and PBE0 slightly overestimate and the M06 approach badly underestimates the bond energy for UH+. Theory was also used to investigate the electronic structures of the reaction intermediates and potential energy surfaces. The experimental product branching ratio for the reaction of U+ with HD indicates that these reactions occur primarily via a direct reaction mechanism, despite the presence of a deep-well for UH2+ formation according to theory. The reactivity and hydride bond energy for U+ are compared with those for transition metal, lanthanide, and actinide cations, and periodic trends are discussed. These comparisons suggest that the 5f electrons on uranium are largely core and uninvolved in the reactive chemistry.

Physical exercise during adjuvant chemotherapy for colorectal cancer-a non-randomized feasibility study.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide, and a large proportion of the patients receive adjuvant oxaliplatin-based chemotherapy. Most of these experience chemotherapy-induced peripheral neuropathy (CIPN), affecting quality of life. Evidence to advise exercise to reduce CIPN is limited. The primary aim of this study was to investigate the feasibility of an exercise intervention and data collection among CRC patients during adjuvant chemotherapy. MATERIAL AND METHODS: This non-randomized feasibility study included CRC patients admitted to adjuvant chemotherapy to an intervention consisting of supervised aerobic endurance, resistance, and balance exercises twice a week at the hospital in addition to home-based exercise once a week. A physiotherapist supervised the patients, and the intervention lasted throughout the period of adjuvant chemotherapy (12-24 weeks). Participants performed physical tests and filled in questionnaires at baseline, 3, 6, 9, and 12 months. RESULTS AND CONCLUSION: Nineteen (63%) of 30 invited patients consented. A major barrier to recruit or consent to participation was long travel distance to the hospital. The completion rate of questionnaires and physical tests were near 100%. Seven participants dropped out, five before the intervention started. Median attendance to supervised exercise was 85%. There were no serious adverse events related to the intervention. Except for a planned higher intensity of endurance exercise, we found the intervention feasible and safe. Based on experiences in this study, some adjustments have been made for an upcoming randomized trial, including the supervised exercise taking place close to participants' homes. TRIAL REGISTRATION: NCT03885817, March 22, 2019, retrospectively registered.

Evolution and risk factors of anal incontinence during the first 6 years after first delivery: a prospective cohort study.

OBJECTIVE: To explore changes in prevalence of anal incontinence (AI) from late first pregnancy to 6 years postpartum, and to evaluate possible risk factors for changes in AI during the 6-year period. DESIGN: Prospective longitudinal cohort study. SETTING: Two Norwegian health regions. POPULATION OR SAMPLE: Women with first deliveries between May 2009 and December 2010. METHODS: Participants reported AI in late pregnancy, 6 months, 1 and 6 years after first delivery using postal or digital questionnaires. AI prevalence was calculated, and mixed effects Poisson regression analyses with robust variance were applied. MAIN OUTCOME MEASURES: AI from late pregnancy to 6 years postpartum. RESULTS: Among 1571 participants, 65% had normal vaginal first deliveries, 20% had vaginal deliveries complicated by instrumental intervention and/or obstetric anal sphincter injury (IVD ± OASIS). Nearly 1 in 10 women reported persistent incontinence during the 6 years. The overall AI prevalence was reduced from late pregnancy to 1 year postpartum for all modes of delivery. At 6 years postpartum, women with IVD ± OASIS had a higher AI prevalence (23%; 95% CI 16-30%) compared with women with caesarean section (8%; 95% CI 2-13%) or normal vaginal delivery (12%; 95% CI 9-16%). Moreover, women who were <23 years, ≥34 years, unemployed during first pregnancy, who had active bowel disease (PR: 2.4; 95% CI 2.0-2.7), or bowel evacuation problems during the 6-year period had higher AI prevalence. CONCLUSIONS: Mode of first delivery modified AI prevalence during the 6-year period, whereas age, bowel disease and bowel evacuation problems were associated with higher prevalence of AI from late first pregnancy to 6 years postpartum. TWEETABLE ABSTRACT: Complicated vaginal delivery, age and bowel emptying problems increase the risk of long-term anal incontinence.

Caesarean section performed by medical doctors and associate clinicians in Sierra Leone.

BACKGROUND: Many countries lack sufficient medical doctors to provide safe and affordable surgical and emergency obstetric care. Task-sharing with associate clinicians (ACs) has been suggested to fill this gap. The aim of this study was to assess maternal and neonatal outcomes of caesarean sections performed by ACs and doctors. METHODS: All nine hospitals in Sierra Leone where both ACs and doctors performed caesarean sections were included in this prospective observational multicentre non-inferiority study. Patients undergoing caesarean section were followed for 30 days. The primary outcome was maternal mortality, and secondary outcomes were perinatal events and maternal morbidity. RESULTS: Between October 2016 and May 2017, 1282 patients were enrolled in the study. In total, 1161 patients (90·6 per cent) were followed up with a home visit at 30 days. Data for 1274 caesarean sections were analysed, 443 performed by ACs and 831 by doctors. Twin pregnancies were more frequently treated by ACs, whereas doctors performed a higher proportion of operations outside office hours. There was one maternal death in the AC group and 15 in the doctor group (crude odds ratio (OR) 0·12, 90 per cent confidence interval 0·01 to 0·67). There were fewer stillbirths in the AC group (OR 0·74, 0·56 to 0·98), but patients were readmitted twice as often (OR 2·17, 1·08 to 4·42). CONCLUSION: Caesarean sections performed by ACs are not inferior to those undertaken by doctors. Task-sharing can be a safe strategy to improve access to emergency surgical care in areas where there is a shortage of doctors.

Prediction of atomization energy using graph kernel and active learning.

Data-driven prediction of molecular properties presents unique challenges to the design of machine learning methods concerning data structure/dimensionality, symmetry adaption, and confidence management. In this paper, we present a kernel-based pipeline that can learn and predict the atomization energy of molecules with high accuracy. The framework employs Gaussian process regression to perform predictions based on the similarity between molecules, which is computed using the marginalized graph kernel. To apply the marginalized graph kernel, a spatial adjacency rule is first employed to convert molecules into graphs whose vertices and edges are labeled by elements and interatomic distances, respectively. We then derive formulas for the efficient evaluation of the kernel. Specific functional components for the marginalized graph kernel are proposed, while the effects of the associated hyperparameters on accuracy and predictive confidence are examined. We show that the graph kernel is particularly suitable for predicting extensive properties because its convolutional structure coincides with that of the covariance formula between sums of random variables. Using an active learning procedure, we demonstrate that the proposed method can achieve a mean absolute error of 0.62 ± 0.01 kcal/mol using as few as 2000 training samples on the QM7 dataset.

Stochastic resolution of identity second-order Matsubara Green's function theory.

We develop a stochastic resolution of identity representation to the second-order Matsubara Green's function (sRI-GF2) theory. Using a stochastic resolution of the Coulomb integrals, the second order Born self-energy in GF2 is decoupled and reduced to matrix products/contractions, which reduces the computational cost from O(N5) to O(N3) (with N being the number of atomic orbitals). The current approach can be viewed as an extension to our previous work on stochastic resolution of identity second order Møller-Plesset perturbation theory [T. Y. Takeshita et al., J. Chem. Theory Comput. 13, 4605 (2017)] and offers an alternative to previous stochastic GF2 formulations [D. Neuhauser et al., J. Chem. Theory Comput. 13, 5396 (2017)]. We show that sRI-GF2 recovers the deterministic GF2 results for small systems, is computationally faster than deterministic GF2 for N > 80, and is a practical approach to describe weak correlations in systems with 103 electrons and more.

Safety, productivity and predicted contribution of a surgical task-sharing programme in Sierra Leone.

BACKGROUND: Surgical task-sharing may be central to expanding the provision of surgical care in low-resource settings. The aims of this paper were to describe the set-up of a new surgical task-sharing training programme for associate clinicians and junior doctors in Sierra Leone, assess its productivity and safety, and estimate its future role in contributing to surgical volume. METHODS: This prospective observational study from a consortium of 16 hospitals evaluated crude in-hospital mortality over 5 years and productivity of operations performed during and after completion of a 3-year surgical training programme. RESULTS: Some 48 trainees and nine graduated surgical assistant community health officers (SACHOs) participated in 27 216 supervised operations between January 2011 and July 2016. During training, trainees attended a median of 822 operations. SACHOs performed a median of 173 operations annually. Caesarean section, hernia repair and laparotomy were the most common procedures during and after training. Crude in-hospital mortality rates after caesarean sections and laparotomies were 0·7 per cent (13 of 1915) and 4·3 per cent (7 of 164) respectively for operations performed by trainees, and 0·4 per cent (5 of 1169) and 8·0 per cent (11 of 137) for those carried out by SACHOs. Adjusted for patient sex, surgical procedure, urgency and hospital, mortality was lower for operations performed by trainees (OR 0·47, 95 per cent c.i. 0·32 to 0·71; P < 0·001) and SACHOs (OR 0·16, 0·07 to 0·41; P < 0·001) compared with those conducted by trainers and supervisors. CONCLUSION: SACHOs rapidly and safely achieved substantial increases in surgical volume in Sierra Leone.

Revealing Disparate Chemistries of Protactinium and Uranium. Synthesis of the Molecular Uranium Tetroxide Anion, UO4.

The synthesis, reactivity, structures, and bonding in gas-phase binary and complex oxide anion molecules of protactinium and uranium have been studied by experiment and theory. The oxalate ions, AnVO2(C2O4)-, where An = Pa or U, are essentially actinyl ions, AnVO2+, coordinated by an oxalate dianion. Both react with water to yield the pentavalent hydroxides, AnVO(OH)2(C2O4)-. The chemistry of Pa and U becomes divergent for reactions that result in oxidation: whereas PaVI is inaccessible, UVI is very stable. The UVO2(C2O4)- complex exhibits a remarkable spontaneous exothermic replacement of the oxalate ligand by O2 to yield UO4- and two CO2 molecules. The structure of the uranium tetroxide anion is computed to correspond to distorted uranyl, UVIO22+, coordinated in the equatorial plane by two equivalent O atoms each having formal charges of -1.5 and U-O bond orders intermediate between single and double. The unreactive nature of PaVO2(C2O4)- toward O2 is a manifestation of the resistance toward oxidation of PaV, and clearly reveals the disparate chemistries of Pa and U. The uranium tetroxide anion, UO4-, reacts with water to yield UO5H2-. Infrared spectra obtained for UO5H2- confirm the computed lowest-energy structure, UO3(OH)2-.

Cleaving Off Uranyl Oxygens through Chelation: A Mechanistic Study in the Gas Phase.

Recent efforts to activate the strong uranium-oxygen bonds in the dioxo uranyl cation have been limited to single oxo-group activation through either uranyl reduction and functionalization in solution, or by collision induced dissociation (CID) in the gas-phase, using mass spectrometry (MS). Here, we report and investigate the surprising double activation of uranyl by an organic ligand, 3,4,3-LI(CAM), leading to the formation of a formal U6+ chelate in the gas-phase. The cleavage of both uranyl oxo bonds was experimentally evidenced by CID, using deuterium and 18O isotopic substitutions, and by infrared multiple photon dissociation (IRMPD) spectroscopy. Density functional theory (DFT) computations predict that the overall reaction requires only 132 kJ/mol, with the first oxygen activation entailing about 107 kJ/mol. Combined with analysis of similar, but unreactive ligands, these results shed light on the chelation-driven mechanism of uranyl oxo bond cleavage, demonstrating its dependence on the presence of ligand hydroxyl protons available for direct interactions with the uranyl oxygens.

Do pelvic floor muscle exercises reduce postpartum anal incontinence? A randomised controlled trial.

OBJECTIVE: To evaluate the effect of pelvic floor muscle exercises (PFME) for postpartum anal incontinence (AI). DESIGN: A parallel two-armed randomised controlled trial stratified on obstetrical anal sphincter injury with primary sphincter repair and hospital affinity. SETTING: Ano-rectal specialist out-patient clinics at two hospitals in Norway. POPULATION: One hundred and nine postpartum women with AI at baseline. METHODS: The intervention group received 6 months of individual physiotherapy-led PFME and the control group written information on PFME. Changes in St. Mark's scores and predictors of post-intervention AI were assessed by independent samples t-tests and multiple linear regression analyses, respectively. The study was not blind. MAIN OUTCOME MEASURES: The primary outcome measure was change in AI symptoms on the St. Mark's score from baseline to post-intervention. Secondary outcome measures were manometry measures of anal sphincter length and strength, endoanal ultrasound (EAUS) defect score and voluntary pelvic floor muscle contraction. RESULTS: There was a significant difference in the reduction of St. Mark's scores from baseline to post-intervention in favour of the PFME group (-2.1 versus -0.8 points, P = 0.040). No differences in secondary outcome measures were found between groups. Baseline St. Mark's, PFME group affinity and EAUS defect score predicted post-intervention St. Mark's score in the imputed intention-to-treat analyses. The analysis on un-imputed data showed that women performing weekly PFME improved their AI scores more than women in the control group did. CONCLUSIONS: Our results indicate that individually adapted PFME reduces postpartum AI symptoms. TWEETABLE ABSTRACT: Performing regular pelvic floor muscle exercises may be an effective treatment for postpartum anal incontinence.

Heptavalent Actinide Tetroxides NpO4- and PuO4-: Oxidation of Pu(V) to Pu(VII) by Adding an Electron to PuO4.

The highest known actinide oxidation states are Np(VII) and Pu(VII), both of which have been identified in solution and solid compounds. Recently a molecular Np(VII) complex, NpO3(NO3)2-, was prepared and characterized in the gas phase. In accord with the lower stability of heptavalent Pu, no Pu(VII) molecular species has been identified. Reported here are the gas-phase syntheses and characterizations of NpO4- and PuO4-. Reactivity studies and density functional theory computations indicate the heptavalent metal oxidation state in both. This is the first instance of Pu(VII) in the absence of stabilizing effects due to condensed phase solvation or crystal fields. The results indicate that addition of an electron to neutral PuO4, which has a computed electron affinity of 2.56 eV, counterintuitively results in oxidation of Pu(V) to Pu(VII), concomitant with superoxide reduction.

Open Abdomen Treated with Negative Pressure Wound Therapy: Indications, Management and Survival.

BACKGROUND: Open abdomen treatment (OAT) is a significant burden for patients and is associated with considerable mortality. The primary aim of this study was to report survival and cause of mortality after OAT. Secondary aims were to evaluate length of stay (LOS) in intensive care unit (ICU) and in hospital, time to abdominal closure and major complications. METHODS: Retrospective review of prospectively registered patients undergoing OAT between October 2006 and June 2014 at Trondheim University Hospital, Norway. RESULTS: The 118 patients with OAT had a median age of 63 (20-88) years. OAT indications were abdominal compartment syndrome (ACS) (n = 53), prophylactic (n = 29), abdominal contamination/second look laparotomy (n = 22), necrotizing fasciitis (n = 7), hemorrhage packing (n = 4) and full-thickness wound dehiscence (n = 3). Eight percent were trauma patients. Vacuum-assisted wound closure (VAWC) with mesh-mediated traction (VAWCM) was used in 92 (78 %) patients, the remaining 26 (22 %) had VAWC only. Per-protocol primary fascial closure rate was 84 %. Median time to abdominal closure was 12 days (1-143). LOS in the ICU was 15 (1-89), and in hospital 29 (1-246) days. Eighty-one (68 %) patients survived the hospital stay. Renal failure requiring renal replacement therapy (RRT) (OR 3.9, 95 % CI 1.37-11.11), ACS (OR 3.1, 95 % CI 1.19-8.29) and advanced age (OR 1.045, 95 % CI 1.004-1.088) were independent predictors of mortality in multivariate analysis. The nine patients with an entero-atmospheric fistula (EAF) survived. CONCLUSION: Two-thirds of the patients treated with OAT survived. Renal failure with RRT, ACS and advanced age were predictors of mortality, whereas EAF was not associated with increased mortality.