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Multi-configurational electronic structure theory delivers the most versatile approximations to many-electron wavefunctions, flexible enough to deal with all sorts of transformations, ranging from electronic excitations, to open-shell molecules and chemical reactions. Multi-configurational models are therefore essential to establish universally applicable, predictive ab initio methods for chemistry. Here, we present a discussion of explicit correlation approaches which address the nagging problem of dealing with static and dynamic electron correlation in multi-configurational active-space approaches. We review the latest developments and then point to their key obstacles. Our discussion is supported by new data obtained with tensor network methods. We argue in favor of simple electron-only correlator expressions that may allow one to define transcorrelated models in which the correlator does not bear a dependence on molecular structure.

Automated and high-throughput quantum chemical investigations into chemical processes have become feasible in great detail and broad scope. This results in an increase in complexity of the tasks and in the amount of generated data. An efficient and intuitive way for an operator to interact with these data and to steer virtual experiments is required. Here, we introduce Heron, a graphical user interface that allows for advanced human-machine interactions with quantum chemical exploration campaigns into molecular structure and reactivity. Heron offers access to interactive and automated explorations of chemical reactions with standard electronic structure modules, haptic force feedback, microkinetic modeling, and refinement of data by automated correlated calculations including black-box complete active space calculations. It is tailored to the exploration and analysis of vast chemical reaction networks. We show how interoperable modules enable advanced workflows and pave the way for routine low-entrance-barrier access to advanced modeling techniques.

In this work, we investigate the possibility of improving multireference-driven coupled cluster (CC) approaches with an algorithm that iteratively combines complete active space (CAS) calculations with tailored CC and externally corrected CC. This is accomplished by establishing a feedback loop between the CC and CAS parts of a calculation through a similarity transformation of the Hamiltonian with those CC amplitudes that are not encompassed by the active space. We denote this approach as the complete active space iterative coupled cluster (CASiCC) ansatz. We investigate its efficiency and accuracy in the singles and doubles approximation by studying the prototypical molecules H 4 , H 8 , H 2 O, and N 2 . Our results demonstrate that CASiCC systematically improves on the single-reference CCSD and the externally corrected CCSD methods across entire potential energy curves while retaining modest computational costs. However, the tailored coupled cluster method shows superior performance in the strong correlation regime, suggesting that its accuracy is based on error compensation. We find that the iterative versions of externally corrected and tailored coupled cluster methods converge to the same results.

The software for chemical interaction networks (SCINE) project aims at pushing the frontier of quantum chemical calculations on molecular structures to a new level. While calculations on individual structures as well as on simple relations between them have become routine in chemistry, new developments have pushed the frontier in the field to high-throughput calculations. Chemical relations may be created by a search for specific molecular properties in a molecular design attempt, or they can be defined by a set of elementary reaction steps that form a chemical reaction network. The software modules of SCINE have been designed to facilitate such studies. The features of the modules are (i) general applicability of the applied methodologies ranging from electronic structure (no restriction to specific elements of the periodic table) to microkinetic modeling (with little restrictions on molecularity), full modularity so that SCINE modules can also be applied as stand-alone programs or be exchanged for external software packages that fulfill a similar purpose (to increase options for computational campaigns and to provide alternatives in case of tasks that are hard or impossible to accomplish with certain programs), (ii) high stability and autonomous operations so that control and steering by an operator are as easy as possible, and (iii) easy embedding into complex heterogeneous environments for molecular structures taken individually or in the context of a reaction network. A graphical user interface unites all modules and ensures interoperability. All components of the software have been made available as open source and free of charge., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND) license (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.

Quantum chemical calculations on atomistic systems have evolved into a standard approach to studying molecular matter. These calculations often involve a significant amount of manual input and expertise, although most of this effort could be automated, which would alleviate the need for expertise in software and hardware accessibility. Here, we present the AutoRXN workflow, an automated workflow for exploratory high-throughput electronic structure calculations of molecular systems, in which (i) density functional theory methods are exploited to deliver minimum and transition-state structures and corresponding energies and properties, (ii) coupled cluster calculations are then launched for optimized structures to provide more accurate energy and property estimates, and (iii) multi-reference diagnostics are evaluated to back check the coupled cluster results and subject them to automated multi-configurational calculations for potential multi-configurational cases. All calculations are carried out in a cloud environment and support massive computational campaigns. Key features of all components of the AutoRXN workflow are autonomy, stability, and minimum operator interference. We highlight the AutoRXN workflow with the example of an autonomous reaction mechanism exploration of the mode of action of a homogeneous catalyst for the asymmetric reduction of ketones.

The tailored coupled cluster (TCC) approach is a promising ansatz that preserves the simplicity of single-reference coupled cluster theory while incorporating a multi-reference wave function through amplitudes obtained from a preceding multi-configurational calculation. Here, we present a detailed analysis of the TCC wave function based on model systems, which require an accurate description of both static and dynamic correlation. We investigate the reliability of the TCC approach with respect to the exact wave function. In addition to the error in the electronic energy and standard coupled cluster diagnostics, we exploit the overlap of TCC and full configuration interaction wave functions as a quality measure. We critically review issues, such as the required size of the active space, size-consistency, symmetry breaking in the wave function, and the dependence of TCC on the reference wave function. We observe that possible errors caused by symmetry breaking can be mitigated by employing the determinant with the largest weight in the active space as reference for the TCC calculation. We find the TCC model to be promising in calculations with active orbital spaces which include all orbitals with a large single-orbital entropy, even if the active spaces become very large and then may require modern active-space approaches that are not restricted to comparatively small numbers of orbitals. Furthermore, utilizing large active spaces can improve on the TCC wave function approximation and reduce the size-consistency error because the presence of highly excited determinants affects the accuracy of the coefficients of low-excited determinants in the active space.

Disability-disaggregated data are increasingly considered important to monitor progress in Universal Eye Health Care. Hospital-based data are still elusive because of the cultural ambiguities of the term disability, especially in under-resourced Health Information Systems in low-and middle-income countries. The aim of this study was to estimate the hospital-based rate of disability in patients presenting at an eye department of a rural hospital in Paraguay and to discuss implications for the management of access barriers. Therefore, we introduced two standardized sets of the Washington Group (WG) Questions as a pilot project. In total, 999 patients answered the self-report WG short set (WG-SS) questionnaire with six functional domains, and 501 of these patients answered an extended set, which included additional domains for "anxiety" and "depression" (WG-ES3). Overall, 27.7% (95% Confidence Interval (CI) 24.9-30.3) were categorized as having a disability. A total of 9.6% (95% CI 7.9-11.6) were categorized as having a disability because of communication difficulties, which was second only to visual difficulties. The odds ratio for disability for patients aged 70 years and older was 8.5 (95% CI 5.0-14.4) and for male patients, it was 0.83 (95% CI 0.62-1.1). Of those patients who answered the WG-ES3, 3.4% were categorized as having a disability because of being worried, nervous or anxious and 1.4% because of feeling depressed. An analysis of the questions of the "depression" domain was impeded by a high rate of measurement errors. The results of the different domains can now be used to inform the identification and mitigation of potential access barriers to eye health services for different types of impairments.

Background: Universal access and equity are salient principles of the World Health Organization global action plan 'Towards Universal Eye Health'. However, collection of disability-disaggregated data to measure access to eye hospitals in low- and middle income countries, including referral to rehabilitative services, are not routinely integrated into Health Management Information Systems., Objective: This report presents secondary-data analysis of disability-disaggregated data collection that was introduced at a tertiary eye hospital in a rural province in Cambodia., Methods: A modified version of the Washington Group Short Set of Questions was used to count the number of eye patients with self-reported difficulties. The number of referrals of patients with unavoidable visual impairment to low vision services as well as referral to rehabilitative services was also counted., Results: From 2011 to 2016, out of 182,327 patients overall 4981 (2.7%; 95% CI 2.66-2.81) reported difficulties with hearing, moving or communicating in addition to visual or other eye-related problems. Most of the difficulties were reported in the age group of patients aged 50 years and older (89.8% [95% CI 88.9-90.6]). All together 901 (0.5%; 95% CI 0.46-0.53) patients were treated at the low vision unit and 652 (0.36%; 95% CI 0.33-0.39) patients were referred to rehabilitation services. The number of referrals to rehabilitation declined annually from the year 2013-2016., Conclusions: Patients with self-reported impairments constitute a significant proportion of the eye hospital's population. A modified version of the Washington Group Short Set of Questions enabled routine disability-disaggregated data collection but resulted also in possible under-reporting of difficulties., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To assess the impact of inclusive eye health programs for people with disabilities., Design: A synthesis evaluation study., Methods: A cross-disciplinary team of ophthalmologists, evaluation, and disability-inclusive development advisors purposively selected evaluation reports of CBM-supported inclusive eye health programs in low- and middle-income countries. Employing a change-promoting paradigm, salient achievements and challenges were narratively analyzed and recommendations suggested based on a previously developed framework for strengthening disability inclusion in eye health programs., Results: Evaluations from 10 programs implemented in 6 countries (Cambodia, Egypt, Ethiopia, Indonesia, Pakistan, Vietnam) from 2011 to 2016 were identified. Training of medical staff and government officials resulted in increased awareness about disability rights and improved physical accessibility of eye health facilities. Relevant information about inclusion in eye health was incorporated in national eye health training curricula in some countries. Information, education, and communication material about eye health neglected patients with hearing and learning impairments. An overly narrow focus on disability inclusion confounded intersectoral barriers to eye health services. Collaboration of eye health staff with disability peoples organizations improved significantly but evidence of its impact was elusive. Collection of disability-disaggregated data posed significant challenges and made it difficult to demonstrate increased access to eye health programs by people with disabilities., Conclusions: Introduction of disability inclusion in eye health systems of countries with limited resources poses significant challenges. Future programs striving to improve access to eye health services for marginalized populations including people with disabilities might consider more flexible and contextualized approaches., (Copyright 2018 Asia-Pacific Academy of Ophthalmology.)

Aim: To identify the current roles of eye and health care workers in eye care delivery and investigate their potential roles in screening and detection for management of diabetic retinopathy (DR) through task sharing., Methods: Purposive sampling of 24 participants including health administrators, members from non-government organizations and all available eye care workers in Takeo province were recruited. This cross sectional mixed method study comprised a survey and in-depth interviews. Data were collected from medical records at Caritas Takeo Eye Hospital (CTEH) and Kiri Vong District Referral Hospital Vision Centre, and a survey and interviews with participants were done to explore the potential roles for task sharing in DR management. Qualitative data were transcribed into a text program and then entered into N-Vivo (version 10) software for data management and analysis., Results: From 2009 to 2012, a total of 105 178 patients were examined and 14 030 eye surgeries were performed in CTEH by three ophthalmologists supported by ophthalmic nurses in operating and eye examination for patients. Between January 2011 and September 2012, 151 patients (72 males) with retinal pathology including 125 (83%) with DR visited CTEH. In addition 170 patients with diabetes were referred to CTEH for eye examinations from Mo Po Tsyo screening programs for people with diabetes. Factors favouring task sharing included high demand for eye care services and scarcity of ophthalmologists., Conclusion: Task sharing and team work for eye care services is functional. Participants favor the potential role of ophthalmic nurses in screening for DR through task sharing.

Purpose: To assess the barriers influencing eye healthcare seeking behavior after community outreach screening., Design: A concurrent mixed methods study., Methods: A total of 469 patients screened during the previous 12 months were followed up, of which 354 (75%) from 5 districts were interviewed in person, using a semi-structured questionnaire, in-depth interviews (n = 11), and 16 focus groups (n = 71). SPSS and NVivo were used to analyze response frequency and identify themes., Results: Of the respondents, 98% (350/354) reported they were told they had an eye problem, with 295 individuals (83%) told to attend CARITAS Takeo Eye Hospital (CTEH) and 55 to have their eyes checked at Kiri Vong Vision Centre. Of those 68.9% (244/354) who reported seeking treatment, only 7.4% (18/244) reported they attended CTEH, 54% (n = 132) attended a "local pharmacy," 31.6% (n = 77) "self-treated at home," 11% (n = 27) reported "using steam from boiling rice," and 10.7% (n = 26) attended a "traditional healer." Of those who reported reasons for "not attending," responses included "no time" (47.8%, 86/180), "no one to accompany" (21.7%, n = 39), "fear of losing sight" (17.8%, n = 32), "cannot afford to travel" (16.1%, n = 29), and "eye problem is not serious enough" (15.6%, n = 28). Follow-up of patient records identified that 128 individuals (79 females) attended eye care services., Conclusions: Socioeconomic factors, personal concerns, and the use of local cultural remedies were reasons for not seeking eye hospital treatment. An integrated community approach to improve awareness and uptake of appropriate treatment is recommended., (Copyright 2017 Asia-Pacific Academy of Ophthalmology.)

Chicory (Cichorium intybus) accumulates caffeic acid esters with important significance for human health. In this study, we aim at a better understanding of the biochemical pathway of these bioactive compounds. Detailed metabolic analysis reveals that C. intybus predominantly accumulates caftaric and chicoric acids in leaves, whereas isochlorogenic acid (3,5-diCQA) was almost exclusively accumulated in roots. Chlorogenic acid (3-CQA) was equally distributed in all organs. Interestingly, distribution of the four compounds was related to leaf age. Induction with methyljasmonate (MeJA) of root cell suspension cultures results in an increase of 3-CQA and 3,5-diCQA contents. Expressed sequence tag libraries were screened using members of the BAHD family identified in Arabidopsis and tobacco as baits. The full-length cDNAs of five genes were isolated. Predicted amino acid sequence analyses revealed typical features of BAHD family members. Biochemical characterization of the recombinant proteins expressed in Escherichia coli showed that two genes encode HCTs (hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyltransferases, HCT1 and HCT2) whereas, three genes encode HQTs (hydroxycinnamoyl-CoA:quinate hydroxycinnamoyltransferases, HQT1, HQT2, and HQT3). These results totally agreed with the phylogenetic analysis done with the predicted amino acid sequences. Quantitative real-time polymerase chain reaction analysis of gene expression indicated that HQT3, HCT1, and HCT2 might be more directly associated with CQA accumulation in cell culture in response to MeJA elicitation. Transient expression of HCT1 and HQT1 in tobacco resulted in a higher production of 3-CQA. All together these data confirm the involvement of functionally redundant genes in 3-CQA and related compound synthesis in the Asteraceae family.

Purpose: To estimate the prevalence of blindness and cataract surgical outcomes in persons 50 years or older above in Takeo Province, Cambodia., Design: A population based survey., Methods: A total of 93 villages were selected through probability proportionate to size using the Rapid Assessment of Avoidable Blindness methodology. Households from 93 villages were selected using compact segment sampling. Visual acuity (VA) of 4650 people 50 years or older was tested and lens status and cause of visual impairment were assessed., Results: The response rate was 96.2%. The age- and sex-adjusted prevalence of bilateral blindness [presenting visual acuity (PVA) <3/60 in the better eye] was 3.4% (95% confidence interval, 2.8%-4.0%), resulting in an estimated 4187 people blind in Takeo Province. The age- and sex-adjusted prevalence of low vision (PVA <6/18 to 3/60) was 21.1%, an estimated 25,900 people. Cataract surgical coverage in the bilaterally blind was 64.7% (female 59.5%, male 78.1%). Cataract surgical outcome was poor (best-corrected visual acuity <6/60) in only 7.7% and good in 88.7% (best-corrected visual acuity ≥6/18) of eyes operated in the last 5 years before the survey., Conclusions: The cataract surgical coverage for women is less than that for men. The increased life expectancy in Cambodia and the fact that women constitute 60.6% of the population (aged ≥50 years) at Takeo Province could have had an impact on cataract workload and high prevalence of blindness. A repeated survey using the same methodology after 8-12 years might be helpful in proving genuine change over time.

High-density genetic maps were constructed for loci involved in nuclear male sterility (NMS1-locus) and sporophytic self-incompatibility (S-locus) in chicory (Cichorium intybus L.). The mapping population consisted of 389 F1' individuals derived from a cross between two plants, K28 (male-sterile) and K59 (pollen-fertile), both heterozygous at the S-locus. This F1' mapping population segregated for both male sterility (MS) and strong self-incompatibility (SI) phenotypes. Phenotyping F1' individuals for MS allowed us to map the NMS1-locus to linkage group (LG) 5, while controlled diallel and factorial crosses to identify compatible/incompatible phenotypes mapped the S-locus to LG2. To increase the density of markers around these loci, bulked segregant analysis was used. Bulks and parental plants K28 and K59 were screened using amplified fragment length polymorphism (AFLP) analysis, with a complete set of 256 primer combinations of EcoRI-ANN and MseI-CNN. A total of 31,000 fragments were generated, of which 2,350 showed polymorphism between K59 and K28. Thirteen AFLP markers were identified close to the NMS1-locus and six in the vicinity of the S-locus. From these AFLP markers, eight were transformed into sequence-characterized amplified region (SCAR) markers and of these five showed co-dominant polymorphism. The chromosomal regions containing the NMS1-locus and the S-locus were each confined to a region of 0.8 cM. In addition, we mapped genes encoding proteins similar to S-receptor kinase, the female determinant of sporophytic SI in the Brasicaceae, and also markers in the vicinity of the putative S-locus of sunflower, but none of these genes or markers mapped close to the chicory S-locus.

Purpose: To evaluate outcome and monitoring of cataract surgical services at Takeo Eye Hospital, Cambodia, Design: A prospective, hospital-based report using a cataract surgical record form from the International Center for Eye Health, London., Methods: Data including preoperative and postoperative visual acuity (VA), proportion of ocular pathology, intraoperative and postoperative complications, type of surgery, and causes of poor outcome of all patients with cataract were collected. Exclusion criteria were age of patients being younger than 20 years, combined cataract-glaucoma surgeries, and having traumatic cataract., Results: A total of 8211 cataract surgeries were performed from January 2007 to December 2011. Preoperatively, the presenting VA was less than 6/60 in 65.8%. At discharge, 51.8% had a presenting VA of 6/18 or better.Outcome was poor (VA < 6/60) in 10.6%. Over 5 years, the percentage of patients with poor outcome decreased from 12.6% to 8.5%. Total operative complications decreased from 18.2% in 2007 to 3.3% in 2011, with a reduction of vitreous loss from 6.5% to 1.8%. Of all surgeries, 21.2% were performed by resident physicians. At the first follow-up 1 to 3 weeks postoperatively, 62.6% of the patients presented, whereas 23.9% presented for a second follow-up after 4 to 6 weeks., Conclusions: Monitoring of cataract surgical services indicated an increase in quantity and quality. Hospital-based data collection as recommended by the World Health Organization action plan for the prevention of avoidable blindness is possible, but biased data collection has to be considered in the interpretation of the data.

Purpose: To investigate how knowledge and attitudes influence the access to eye-care services in Takeo Province, Cambodia., Design: A cross-sectional survey (n=600)., Methods: 30 villages were randomly selected. Groups included: >50 years, 30-49 years, and parents with children <5 years. A newly developed Knowledge, Attitude and Practice in Eye Health (KAP-EH) questionnaire about knowledge and treatment of eye diseases, practices and attitudes to accessing services was used to interview respondents. Descriptive analysis, including Chi square and logistic regression tested for associations with sub-groups of gender, age group, education and self-reported type of disability., Results: The proportion of respondents who reported having knowledge of specific eye conditions ranged from 97% for eye injury, to 8% for diabetic eye disease. While 509 (85%) people reported knowledge of cataract, 47% did not know how cataract was treated and only 19% listed surgery. The older group (66.5%) were least informed about cataract (p= 0.001) compared to other groups, and were least likely to believe that some blindness could be prevented (p < 0.001). Women (55%) were more likely than men (46%) (p=0 .003) to report that a child with blindness could attend school, as did people without a disability compared to those with a disability (58% vs 34%) (p < 0.001)., Conclusions: The knowledge about cataract and refractive error and what to do to resolve the problems was low among this population and this study suggests that poor knowledge of eye diseases might contribute to the occurrence of un-operated cataract and uncorrected refractive error.

Simple sequence repeats (SSRs) are known to exhibit high degrees of variability even among closely related individuals. Their usage as nuclear genetic markers requires their conversion into sequence-tagged sites (STSs). In this paper we present the development of simple sequences as STSs for Beta vulgaris. This species comprises wild, cultivated, and weedy forms; the latter are thought to originate from accidental hybridisation between the other two. Two partial genomic libraries were screened with simple sequence motifs (AT, CA, CT, ATT, GTG, and CA, CT, respectively). Clones of 22 CA, nine CT, eight ATT, and one GTG sequence were obtained. AT micro satellites were present in compound motifs, not recognised by the probe. Sequence comparisons revealed that 20 CA clones containing short motifs (<16 bp) were variants of a previously described approximately 320-bp satellite DNA (Schmidt et al. 1991), and hence did not correspond to unique loci. Polymorphism of one (ATT)15 and three (CT)n, with n=15, 17 and 26, was detected by PCR on a sample of 64 plants from the different forms of B. vulgaris. 13 (ATT), 13 (CT), nine (CT) alleles and one (CT) allele were detected. One of the ATT alleles was much larger than the others (>800 bp). Genetic variability was high among wild beets, lower among cultivated beets, and intermediate among weed beets. One allele of each locus was found at high frequencies in cultivated beets and, to a lower extent, in weed beets. The combination of three polymorphic loci allowed the individual identification of 17/17 wild and 15/15 weed beets, and 21/32, mostly homozygous, cultivated beets.

Populations of weed beets have expanded into European sugar beet production areas since the 1970s, thereby forming a serious new weed problem for this crop. We sampled seeds in different French populations and studied mitochondrial DNA, chloroplast DNA and life-cycle variability. Given the maternal inheritance of the mitochondrial and chloroplastic genomes and the nuclear determinism of the annual habit, we were able to determine the maternal origin and evolution of these weed beet populations. Our study shows that they carry the dominant allele "B" for annual habit at high frequency. The main cytoplasmic DNA type found in northern weed beet populations is the cytoplasmic male-sterile type characteristic of sugar beets. We were able to determine that these populations arise from seeds originating from the accidental pollinations of cultivated beets by adventitious beets in the seed production area, which have been transported to the regions where sugar beets are cultivated. These seeds are supposedly the origin of the weed forms and a frequently disturbed cultivated environment has selected for annual habit and early flowering genotypes. We discuss the consequences of the weed beet populations for the breeding, seed production and release of herbicide-resistant transgenic sugar beets.

Viroids are replicated via a rolling circle-like mechanism in which (+) strand oligomeric intermediates have to be cleaved enzymatically to unit-length molecules followed by ligation to mature circles. A transcript of potato spindle tuber viroid, which is still infectious, consists of a monomeric molecule with only 22 additional nucleotides, thus doubling part of the central conserved region of viroids. It was shown that this transcript can be cleaved and ligated in vitro to circles by RNase T1. To elucidate the site and mechanism of processing, 16 different site-specific mutants of this longer-than-unit-length transcript were constructed and analyzed by in vitro processing with RNase T1, infectivity studies, temperature-gradient gel electrophoresis, and structure calculations. The wild-type sequence and several mutated transcripts are able to adopt a particular secondary structure which is the prerequisite for enzymatic cleavage and ligation by RNase T1. This "processing structure" exposes both potential cleavage sites in the nearest spatial neighborhood, thus favoring the subsequent ligation to circles. Those mutated sequences for which the formation of the processing structure is impossible or thermodynamically highly unfavored are not processed. The results demonstrate that the particular structural features of viroids enable them to be cleaved and ligated by one and the same enzyme, RNase T1. The in vitro mechanism may serve as a mechanistic model for cellular processing of viroids.