This paper presents a comparison of a graph-based genetic algorithm (GB-GA) and machine learning (ML) results for the optimization of log
values with a constraint for synthetic accessibility and ...shows that the GA is as good as or better than the ML approaches for this particular property. The molecules found by the GB-GA bear little resemblance to the molecules used to construct the initial mating pool, indicating that the GB-GA approach can traverse a relatively large distance in chemical space using relatively few (50) generations. The paper also introduces a new non-ML graph-based generative model (GB-GM) that can be parameterized using very small data sets and combined with a Monte Carlo tree search (MCTS) algorithm. The results are comparable to previously published results (
, 2017,
, 972-976) using a recurrent neural network (RNN) generative model, and the GB-GM-based method is several orders of magnitude faster. The MCTS results seem more dependent on the composition of the training set than the GA approach for this particular property. Our results suggest that the performance of new ML-based generative models should be compared to that of more traditional, and often simpler, approaches such a GA.
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Recent predictions of absolute binding free energies of host-guest complexes in aqueous solution using electronic structure theory have been encouraging for some systems, while other systems remain ...problematic. In this paper I summarize some of the many factors that could easily contribute 1-3 kcal mol
−1
errors at 298 K: three-body dispersion effects, molecular symmetry, anharmonicity, spurious imaginary frequencies, insufficient conformational sampling, wrong or changing ionization states, errors in the solvation free energy of ions, and explicit solvent (and ion) effects that are not well-represented by continuum models. While I focus on binding free energies in aqueous solution the approach also applies (with minor adjustments) to any free energy difference such as conformational or reaction free energy differences or activation free energies in any solvent.
Binding free energies: a holy grail of computational chemistry.
The new empirical rules for protein pKa predictions implemented in the PROPKA3.0 software package (Olsson et al. J. Chem. Theory Comput.2010, 7, 525-537) have been extended to the prediction of pKa ...shifts of active site residues and ionizable ligand groups in protein-ligand complexes. We present new algorithms that allow pKa shifts due to inductive (i.e., covalently coupled) intraligand interactions, as well as noncovalently coupled interligand interactions in multiligand complexes, to be included in the prediction. The number of different ligand chemical groups that are automatically recognized has been increased to 18, and the general implementation has been changed so that new functional groups can be added easily by the user, aided by a new and more general protonation scheme. Except for a few cases, the new algorithms in PROPKA3.1 are found to yield results similar to or better than those obtained with PROPKA2.0 (Bas et al. Proteins: Struct., Funct., Bioinf.2008, 73, 765-783). Finally, we present a novel algorithm that identifies noncovalently coupled ionizable groups, where pKa prediction may be especially difficult. This is a general improvement to PROPKA and is applied to proteins with and without ligands.
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Purpose - This paper seeks to investigate shopping orientation and online clothing purchases across four different gender-related purchasing contexts. A conceptual model for understanding the impact ...of shopping orientation on consumer online clothing purchase is proposed and tested both in a general setting and across purchasing contexts.Design methodology approach - Questionnaires were distributed to 1,150 Danish household addresses by use of the "drop-off-call-back" survey method. A total of 441 households returned usable responses from either one or both adults in the household. Most adults provided responses with respect to purchasing clothing for themselves and for their partner, making a total of 906 cases distributed across the four purchasing contexts. T-tests and linear structural equation modelling were utilised to investigate expectations and hypotheses.Findings - The results support the expected differences in men's and women's shopping orientations and willingness to purchase clothing online. On average, consumers indicate that reduced difficulty in selecting items is sorely needed when purchasing clothing online. However, when evaluated across different purchasing situations, perceived difficulty in selecting items is an important action barrier only for women. Less fun significantly affected online clothing purchases for men purchasing clothing for themselves, but not for women doing the same.Research limitations implications - Future research may seek to verify the proposed conceptual model using a range of specific clothing items across different purchasing situations. Future research may also expand the model by suggesting other influencing factors on consumers' online clothing purchasing.Practical implications - In order to attract more men, online clothing retailers should improve perceived online fun, whereas difficulty in selecting items should be reduced in order to attract more women.Originality value - The study is unique in the sense that it investigates online clothing behaviour across four different gender-related purchasing contexts.
Background
Colorectal cancer is the third most frequent cancer in the world. As the sojourn time for this cancer is several years and a good prognosis is associated with early stage diagnosis, ...screening has been implemented in a number of countries. Both screening with faecal occult blood test and flexible sigmoidoscopy have been shown to reduce mortality from colorectal cancer in randomised controlled trials. The comparative effectiveness of these tests on colorectal cancer mortality has, however, never been evaluated, and controversies exist over which test to choose.
Objectives
To compare the effectiveness of screening for colorectal cancer with flexible sigmoidoscopy to faecal occult blood testing.
Search methods
We searched MEDLINE and EMBASE (November 16, 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11) and reference lists for eligible studies.
Selection criteria
Randomised controlled trials comparing screening with flexible sigmoidoscopy or faecal occult blood testing to each other or to no screening. Only studies reporting mortality from colorectal cancer were included. Faecal occult blood testing had to be repeated (annually or biennially).
Data collection and analysis
Data retrieval and assessment of risk of bias were performed independently by two review authors. Standard meta‐analyses using a random‐effects model were conducted for flexible sigmoidoscopy and faecal occult blood testing (FOBT) separately and we calculated relative risks with 95% confidence intervals (CI). We used a Bayesian approach (a contrast‐based network meta‐analysis method) for indirect analyses and presented the results as posterior median relative risk with 95% credibility intervals. We assessed the quality of evidence using GRADE.
Main results
We identified nine studies comprising 338,467 individuals randomised to screening and 405,919 individuals to the control groups. Five studies compared flexible sigmoidoscopy to no screening and four studies compared repetitive guaiac‐based FOBT (annually and biennially) to no screening. We did not consider that study risk of bias reduced our confidence in our results. We did not identify any studies comparing the two screening methods directly. When compared with no screening, colorectal cancer mortality was lower with flexible sigmoidoscopy (relative risk 0.72; 95% CI 0.65 to 0.79, high quality evidence) and FOBT (relative risk 0.86; 95% CI 0.80 to 0.92, high quality evidence). In the analyses based on indirect comparison of the two screening methods, the relative risk of dying from colorectal cancer was 0.85 (95% credibility interval 0.72 to 1.01, low quality evidence) for flexible sigmoidoscopy screening compared to FOBT. No complications occurred after the FOBT test itself, but 0.03% of participants suffered a major complication after follow‐up. Among more than 60,000 flexible sigmoidoscopy screening procedures and almost 6000 work‐up colonoscopies, a major complication was recorded in 0.08% of participants. Adverse event data should be interpreted with caution as the reporting of adverse effects was incomplete.
Authors' conclusions
There is high quality evidence that both flexible sigmoidoscopy and faecal occult blood testing reduce colorectal cancer mortality when applied as screening tools. There is low quality indirect evidence that screening with either approach reduces colorectal cancer deaths more than the other. Major complications associated with screening require validation from studies with more complete reporting of harms.
Computational discovery of organometallic catalysts that effectively catalyze nitrogen fixation is a difficult task. The complexity of the chemical reactions involved and the lack of understanding of ...natures enzyme catalysts raises the need for intricate computational models. In this study, we use a dataset of 91 experimentally verified ligands as starting population for a Genetic Algorithm (GA) and use this to discover molybdenum based nitrogen fixation catalyst in trigonal bipyramidal and octahedral configurations. Through evolutionary discovery with a semi-empirical quantum method driven GA and a density functional theory (DFT) based screening process, we find 3 promising catalyst candidates that are shown to effectively catalyze the first protonation step of the Schrock cycle. Synthetic accessibility (SA) scores are used to guide the GA towards reasonable ligands and the work features a description of the GA framework, including pre-screening of catalyst candidates that involves assignment of metal coordination atoms and catalyst stereoisomers. This research thus not only offers insights into the specific field of molybdenum-based catalysts for nitrogen fixation but also demonstrates the broader applicability and potential of genetic algorithms in the field of catalyst discovery and materials science.
Using genetic algorithms and semiempirical quantum mechanical methods for discovery of nitrogen fixation catalysts.
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Background
Audit and feedback is widely used as a strategy to improve professional practice either on its own or as a component of multifaceted quality improvement interventions. This is based on the ...belief that healthcare professionals are prompted to modify their practice when given performance feedback showing that their clinical practice is inconsistent with a desirable target. Despite its prevalence as a quality improvement strategy, there remains uncertainty regarding both the effectiveness of audit and feedback in improving healthcare practice and the characteristics of audit and feedback that lead to greater impact.
Objectives
To assess the effects of audit and feedback on the practice of healthcare professionals and patient outcomes and to examine factors that may explain variation in the effectiveness of audit and feedback.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2010, Issue 4, part of The Cochrane Library. www.thecochranelibrary.com, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (searched 10 December 2010); MEDLINE, Ovid (1950 to November Week 3 2010) (searched 09 December 2010); EMBASE, Ovid (1980 to 2010 Week 48) (searched 09 December 2010); CINAHL, Ebsco (1981 to present) (searched 10 December 2010); Science Citation Index and Social Sciences Citation Index, ISI Web of Science (1975 to present) (searched 12‐15 September 2011).
Selection criteria
Randomised trials of audit and feedback (defined as a summary of clinical performance over a specified period of time) that reported objectively measured health professional practice or patient outcomes. In the case of multifaceted interventions, only trials in which audit and feedback was considered the core, essential aspect of at least one intervention arm were included.
Data collection and analysis
All data were ed by two independent review authors. For the primary outcome(s) in each study, we calculated the median absolute risk difference (RD) (adjusted for baseline performance) of compliance with desired practice compliance for dichotomous outcomes and the median percent change relative to the control group for continuous outcomes. Across studies the median effect size was weighted by number of health professionals involved in each study. We investigated the following factors as possible explanations for the variation in the effectiveness of interventions across comparisons: format of feedback, source of feedback, frequency of feedback, instructions for improvement, direction of change required, baseline performance, profession of recipient, and risk of bias within the trial itself. We also conducted exploratory analyses to assess the role of context and the targeted clinical behaviour. Quantitative (meta‐regression), visual, and qualitative analyses were undertaken to examine variation in effect size related to these factors.
Main results
We included and analysed 140 studies for this review. In the main analyses, a total of 108 comparisons from 70 studies compared any intervention in which audit and feedback was a core, essential component to usual care and evaluated effects on professional practice. After excluding studies at high risk of bias, there were 82 comparisons from 49 studies featuring dichotomous outcomes, and the weighted median adjusted RD was a 4.3% (interquartile range (IQR) 0.5% to 16%) absolute increase in healthcare professionals' compliance with desired practice. Across 26 comparisons from 21 studies with continuous outcomes, the weighted median adjusted percent change relative to control was 1.3% (IQR = 1.3% to 28.9%). For patient outcomes, the weighted median RD was ‐0.4% (IQR ‐1.3% to 1.6%) for 12 comparisons from six studies reporting dichotomous outcomes and the weighted median percentage change was 17% (IQR 1.5% to 17%) for eight comparisons from five studies reporting continuous outcomes. Multivariable meta‐regression indicated that feedback may be more effective when baseline performance is low, the source is a supervisor or colleague, it is provided more than once, it is delivered in both verbal and written formats, and when it includes both explicit targets and an action plan. In addition, the effect size varied based on the clinical behaviour targeted by the intervention.
Authors' conclusions
Audit and feedback generally leads to small but potentially important improvements in professional practice. The effectiveness of audit and feedback seems to depend on baseline performance and how the feedback is provided. Future studies of audit and feedback should directly compare different ways of providing feedback.
In this study, we have revised the rules and parameters for one of the most commonly used empirical pK a predictors, PROPKA, based on better physical description of the desolvation and dielectric ...response for the protein. We have introduced a new and consistent approach to interpolate the description between the previously distinct classifications into internal and surface residues, which otherwise is found to give rise to an erratic and discontinuous behavior. Since the goal of this study is to lay out the framework and validate the concept, it focuses on Asp and Glu residues where the protein pK a values and structures are assumed to be more reliable. The new and improved implementation is evaluated and discussed; it is found to agree better with experiment than the previous implementation (in parentheses): rmsd = 0.79 (0.91) for Asp and Glu, 0.75 (0.97) for Tyr, 0.65 (0.72) for Lys, and 1.00 (1.37) for His residues. The most significant advance, however, is in reducing the number of outliers and removing unreasonable sensitivity to small structural changes that arise from classifying residues as either internal or surface.
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