Consensus scoring for enriching near-native structures from protein-protein docking decoys

The identification of near native protein-protein complexes among a set of decoys remains highly challenging. A stategy for improving the success rate of near native detection is to enrich near native docking decoys in a small number of top ranked decoys. Recently, we found that a combination of three scoring functions (energy, conservation, and interface propensity) can predict the location of binding interface regions with reasonable accuracy. Here, these three scoring functions are modified and combined into a consensus scoring function called ENDES for enriching near native docking decoys. We found that all individual scores result in enrichment for the majority of 28 targets in ZDOCK2.3 decoy set and the 22 targets in Benchmark 2.0. Among the three scores, the interface propensity score yields the highest enrichment in both sets of protein complexes. When these scores are combined into the ENDES consensus score, a significant increase in enrichment of near-native structures is found. For example, when 2000 dock decoys are reduced to 200 decoys by ENDES, the fraction of near-native structures in docking decoys increases by a factor of about six in average. ENDES was implemented into a computer program that is available for download at http://sparks.informatics.iupui.edu.

P2Y(1) antagonists: Combining receptor-based modeling and QSAR for a quantitative prediction of the biological activity based on consensus scoring

P2Y(1) is an ADP-activated G protein-coupled receptor (GPCR). Its antagonists impede platelet aggregation in vivo and are potential antithrombotic agents. Combining ligand and structure-based modeling we generated a consensus model (LIST-CM) correlating antagonist structures with their potencies. We docked 45 antagonists into our rhodopsin-based human P2Y(1) homology model and calculated docking scores and free binding energies with the Linear Interaction Energy (LIE) method in continuum-solvent. The resulting alignment was also used to build QSAR based on CoMFA, CoMSIA, and molecular descriptors. To benefit from the strength of each technique and compensate for their limitations, we generated our LIST-CM with a PLS regression based on the predictions of each methodology. A test set featuring untested substituents was synthesized and assayed in inhibition of 2-MeSADP-stimulated PLC activity and in radioligand binding. LIST-CM outperformed internal and external predictivity of any individual model to predict accurately the potency of 75% of the test set.

Consensus scoring, correct responses and reliability of the MSCEIT V2

The scoring protocol adopted by the MSCEIT V2 has been criticised since its development. The present study raises questions regarding the value of consensus scoring by analysing responses within the categorical subscales of Changes and Blends using the Optimal Scaling technique within the Categorical Principal Components Analysis (CATPCA) via Statistical Package for the Social Sciences (SPSS), (n = 206). On a number of occasions, there was no clear agreement as to the ‘‘correct” response to items within these categorical subscales. Such an issue seems integral to the application of the MSCEIT V2 and one which deserves more attention. On a more positive note, improvements were made to the reliabilities of the subscales of Changes and Blends, using Optimal Scaling, but less so for Changes. Nevertheless, this raises the possibility of improving the reliabilities of other subscales in the MSCEIT V2 and in turn improving the power of subsequent statistical tests.

Integration of Ligand- and Target-Based Virtual Screening for the Discovery of Cruzain Inhibitors

A myriad of methods are available for virtual screening of small organic compound databases. In this study we have successfully applied a quantitative model of consensus measurements, using a combination of 3D similarity searches (ROCS and EON), Hologram Quantitative Structure Activity Relationships (HQSAR) and docking (FRED, FlexX, Glide and AutoDock Vina), to retrieve cruzain inhibitors from collected databases. All methods were assessed individually and then combined in a Ligand-Based Virtual Screening (LBVS) and Target-Based Virtual Screening (TBVS) consensus scoring, using Receiving Operating Characteristic (ROC) curves to evaluate their performance. Three consensus strategies were used: scaled-rank-by-number, rank-by-rank and rank-by-vote, with the most thriving the scaled-rank-by-number strategy, considering that the stiff ROC curve appeared to be satisfactory in every way to indicate a higher enrichment power at early retrieval of active compounds from the database. The ligand-based method provided access to a robust and predictive HQSAR model that was developed to show superior discrimination between active and inactive compounds, which was also better than ROCS and EON procedures. Overall, the integration of fast computational techniques based on ligand and target structures resulted in a more efficient retrieval of cruzain inhibitors with desired pharmacological profiles that may be useful to advance the discovery of new trypanocidal agents.

Post-anaesthetic discharge scoring criteria: key findings from a systematic review

Background
Patient safety depends on nurses' clinical judgment. In post-anaesthetic care, objective scoring systems are commonly used to help nurses assess when a patient is ready to go back to the ward or be discharged home after day surgery. Although there are several criteria used to assess patient readiness for discharge from the post-anaesthetic care unit, evaluation of the validity and reliability of these criteria is scarce.

Aims
This article presents key findings from a systematic review conducted to identify the essential components of an effective and feasible scoring system to assess patients following surgical anaesthesia for discharge from the post-anaesthetic care unit.

Methods
The protocol for the systematic review of quantitative studies investigating assessment criteria for discharge of adult patients from the post-anaesthetic care unit was approved by the Joanna Briggs Institute and conducted consistent with the methodology of the Institute. Twelve databases and grey literature, such as conference proceedings, were searched for published studies between 1970 and 2010. Two reviewers independently assessed study eligibility for inclusion. Reference lists of included studies were appraised.

Results
Eight studies met the inclusion criteria; only one was a randomised controlled trial. Variables identified as essential when assessing a patient's readiness for discharge from the post-anaesthetic care unit were conscious state, blood pressure, nausea and vomiting, and pain. Assessment of psychomotor and cognitive recovery and other vital signs were also identified as relevant variables to consider.

Conclusions
There was limited high-quality research regarding criteria to assess patient readiness for discharge from the post-anaesthetic unit. The key recommendations, with moderate to high risk of bias, include that assessment of specific variables (pain, conscious state, blood pressure, and nausea and vomiting) should be made before patient discharge. These key findings have informed a subsequent study to reach international consensus on effective assessment criteria and a project to test the clinical reliability of a tool for use by nurses in assessing patient readiness for discharge from post-anaesthetic care.

An epidemiological scoring system for tooth wear and dental erosive wear

Background: The prevalence and severity of tooth wear and dental erosion is rising in children and there is no consensus about an index to be employed. Aim: To assess the reliability of an epidemiological scoring system dental wear index (DWI) to measure tooth wear and dental erosive wear. Design: An epidemiological cross-sectional survey was conducted to evaluate and compare tooth wear and dental erosion using the dental wear index and erosion wear index (EWI). The study was conducted with randomised samples of 2,371 children aged between 4 years and 12 years selected from the State of São Paulo, Brazil. Records were used for calculating tooth wear and dental erosion; the incisal edge and canine cusp were excluded. Results: As the schoolchildren's ages increased the severity of primary tooth wear increased in canines (P = 0.0001, OR = 0.34) and molars (P = 0.0001, OR = 2.47) and erosion wear increased in incisal/occlusal (P = 0.0001, OR = 5.18) and molars (P = 0.0001, OR = 2.47). There was an increased prevalence of wear in the permanent teeth of older schoolchildren, particularly on the incisal/occlusal surfaces (P = 0.0001, OR = 7.03). Conclusion: The prevalence of tooth wear and dental erosion increased as age increased in children. The epidemiological scoring system Dental Wear Index is able to measure both tooth wear and dental erosive wear. This index should be used to monitor the progression of non-carious lesions and to evaluate the levels of disease in the population.

Basic Erosive Wear Examination (BEWE): a new scoring system for scientific and clinical needs

A new scoring system, the Basic Erosive Wear Examination (BEWE), has been designed to provide a simple tool for use in general practice and to allow comparison to other more discriminative indices. The most severely affected surface in each sextant is recorded with a four level score and the cumulative score classified and matched to risk levels which guide the management of the condition. The BEWE allows re-analysis and integration of results from existing studies and, in time, should initiate a consensus within the scientific community and so avoid continued proliferation of indices. Finally, this process should lead to the development of an internationally accepted, standardised and validated index. The BEWE further aims to increase the awareness of tooth erosion amongst clinicians and general dental practitioners and to provide a guide as to its management.

Psoriasis beyond the skin: an expert group consensus on the management of psoriatic arthritis and common co-morbidities in patients with moderate-to-severe psoriasis

BACKGROUND Psoriatic arthritis (PsA) and co-morbidities of psoriasis represent a significant clinical and economic burden for patients with moderate-to-severe psoriasis. Often these co-morbidities may go unrecognized or undertreated. While published data are available on the incidence and impact of some of them, practical guidance for dermatologists on detection and management of these co-morbidities is lacking. OBJECTIVE To prepare expert recommendations to improve the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis. METHODS A systematic literature review was conducted on some common co-morbidities of psoriasis-cardiovascular (CV) diseases (including obesity, hypertension, hyperglycaemia and dyslipidaemia), psychological co-morbidities (including depression, alcohol abuse and smoking) and PsA-to establish the incidence and impact of each. Data gaps were identified and a Delphi survey was carried out to obtain consensus on the detection and management of each co-morbidity. The expert panel members for the Delphi survey comprised 10 dermatologists with substantial clinical expertise in managing moderate-to-severe psoriasis patients, as well as a cardiologist and a psychologist (see appendix) with an interest in dermatology. Agreement was defined using a Likert scale of 1-7. Consensus regarding agreement for each statement was defined as ≥75% of respondents scoring either 1 (strongly agree) or 2 (agree). RESULTS The expert panel members addressed several topics including screening, intervention, monitoring frequency, and the effects of anti-psoriatic treatment on each co-morbidity. Consensus was achieved on 12 statements out of 22 (3 relating to PsA, 4 relating to psychological factors, 5 relating to CV factors). The panel members felt that dermatologists have an important role in screening their psoriasis patients for PsA and in assessing them for psychological and CV co-morbidities. In most cases, however, patients should be referred for specialist management if other co-morbidities are detected. CONCLUSION This article provides useful and practical guidance for the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis.

Nation & internation practices in decision support tools in road asset management

This document provides a review of international and national practices in investment decision support tools in road asset management. Efforts were concentrated on identifying analytic frameworks, evaluation methodologies and criteria adopted by current tools. Emphasis was also given to how current approaches support Triple Bottom Line decision-making. Benefit Cost Analysis and Multiple Criteria Analysis are principle methodologies in supporting decision-making in Road Asset Management. The complexity of the applications shows significant differences in international practices. There is continuing discussion amongst practitioners and researchers regarding to which one is more appropriate in supporting decision-making. It is suggested that the two approaches should be regarded as complementary instead of competitive means. Multiple Criteria Analysis may be particularly helpful in early stages of project development, say strategic planning. Benefit Cost Analysis is used most widely for project prioritisation and selecting the final project from amongst a set of alternatives. Benefit Cost Analysis approach is useful tool for investment decision-making from an economic perspective. An extension of the approach, which includes social and environmental externalities, is currently used in supporting Triple Bottom Line decision-making in the road sector. However, efforts should be given to several issues in the applications. First of all, there is a need to reach a degree of commonality on considering social and environmental externalities, which may be achieved by aggregating the best practices. At different decision-making level, the detail of consideration of the externalities should be different. It is intended to develop a generic framework to coordinate the range of existing practices. The standard framework will also be helpful in reducing double counting, which appears in some current practices. Cautions should also be given to the methods of determining the value of social and environmental externalities. A number of methods, such as market price, resource costs and Willingness to Pay, are found in the review. The use of unreasonable monetisation methods in some cases has discredited Benefit Cost Analysis in the eyes of decision makers and the public. Some social externalities, such as employment and regional economic impacts, are generally omitted in current practices. This is due to the lack of information and credible models. It may be appropriate to consider these externalities in qualitative forms in a Multiple Criteria Analysis. Consensus has been reached in considering noise and air pollution in international practices. However, Australia practices generally omitted these externalities. Equity is an important consideration in Road Asset Management. The considerations are either between regions, or social groups, such as income, age, gender, disable, etc. In current practice, there is not a well developed quantitative measure for equity issues. More research is needed to target this issue. Although Multiple Criteria Analysis has been used for decades, there is not a generally accepted framework in the choice of modelling methods and various externalities. The result is that different analysts are unlikely to reach consistent conclusions about a policy measure. In current practices, some favour using methods which are able to prioritise alternatives, such as Goal Programming, Goal Achievement Matrix, Analytic Hierarchy Process. The others just present various impacts to decision-makers to characterise the projects. Weighting and scoring system are critical in most Multiple Criteria Analysis. However, the processes of assessing weights and scores were criticised as highly arbitrary and subjective. It is essential that the process should be as transparent as possible. Obtaining weights and scores by consulting local communities is a common practice, but is likely to result in bias towards local interests. Interactive approach has the advantage in helping decision-makers elaborating their preferences. However, computation burden may result in lose of interests of decision-makers during the solution process of a large-scale problem, say a large state road network. Current practices tend to use cardinal or ordinal scales in measure in non-monetised externalities. Distorted valuations can occur where variables measured in physical units, are converted to scales. For example, decibels of noise converts to a scale of -4 to +4 with a linear transformation, the difference between 3 and 4 represents a far greater increase in discomfort to people than the increase from 0 to 1. It is suggested to assign different weights to individual score. Due to overlapped goals, the problem of double counting also appears in some of Multiple Criteria Analysis. The situation can be improved by carefully selecting and defining investment goals and criteria. Other issues, such as the treatment of time effect, incorporating risk and uncertainty, have been given scant attention in current practices. This report suggested establishing a common analytic framework to deal with these issues.

Comparison of scoring systems for invasive pests using ROC analysis and Monte Carlo simulation

Different international plant protection organisations advocate different schemes for conducting pest risk assessments. Most of these schemes use structured questionnaire in which experts are asked to score several items using an ordinal scale. The scores are then combined using a range of procedures, such as simple arithmetic mean, weighted averages, multiplication of scores, and cumulative sums. The most useful schemes will correctly identify harmful pests and identify ones that are not. As the quality of a pest risk assessment can depend on the characteristics of the scoring system used by the risk assessors (i.e., on the number of points of the scale and on the method used for combining the component scores), it is important to assess and compare the performance of different scoring systems. In this article, we proposed a new method for assessing scoring systems. Its principle is to simulate virtual data using a stochastic model and, then, to estimate sensitivity and specificity values from these data for different scoring systems. The interest of our approach was illustrated in a case study where several scoring systems were compared. Data for this analysis were generated using a probabilistic model describing the pest introduction process. The generated data were then used to simulate the outcome of scoring systems and to assess the accuracy of the decisions about positive and negative introduction. The results showed that ordinal scales with at most 5 or 6 points were sufficient and that the multiplication-based scoring systems performed better than their sum-based counterparts. The proposed method could be used in the future to assess a great diversity of scoring systems.

Clinical education for nephrology nurse practitioner candidates in Australia : a consensus statement

Objectives: To develop recommendations for the clinical education required to prepare Australian Nurse Practitioner candidates for advanced and extended practice in nephrology settings. Methods: Using the Delphi research technique a consensus statement was developed over a nine month period. All endorsed and candidate Nephrology Nurse Practitioners (NNP) were invited to participate as the expert panel. The Delphi research technique uses a systematic and iterative process. The expert panel were asked to generate a list of items which were then circulated to all NNPs. They were asked to determine their degree of agreement or disagreement with each statement using a 5-point Likert scale There was opportunity for free-text comments to be provided if desired. Results from each round were collated; the document was refined and circulated to the experts for a subsequent round. Consensus was demonstrated after three Delphi rounds. Results: The consensus statement comprises four components explaining the role and membership of the mentorship team, the setting and location of NNP clinical education, learning strategies to support the NNP, and outcomes of NNP clinical education. Demographic questions in the final survey revealed information about the qualifications, years of experience, and practice location of Australian NNPs. Conclusions: The consensus statement is not prescriptive but it will inform NNP candidates, university course providers and mentors about the expected extended nephrology specific clinical education that will enable the NNP to provide advanced nursing care for patients regardless of the stage of chronic kidney disease (CKD) and the practice setting.