COSMOS next generation - A public knowledge base leveraging chemical and biological data to support the regulatory assessment of chemicals.

The COSMOS Database (DB) was originally established to provide reliable data for cosmetics-related chemicals within the COSMOS Project funded as part of the SEURAT-1 Research Initiative. The database has subsequently been maintained and developed further into COSMOS Next Generation (NG), a combination of database and in silico tools, essential components of a knowledge base. COSMOS DB provided a cosmetics inventory as well as other regulatory inventories, accompanied by assessment results and in vitro and in vivo toxicity data. In addition to data content curation, much effort was dedicated to data governance - data authorisation, characterisation of quality, documentation of meta information, and control of data use. Through this effort, COSMOS DB was able to merge and fuse data of various types from different sources. Building on the previous effort, the COSMOS Minimum Inclusion (MINIS) criteria for a toxicity database were further expanded to quantify the reliability of studies. COSMOS NG features multiple fingerprints for analysing structure similarity, and new tools to calculate molecular properties and screen chemicals with endpoint-related public profilers, such as DNA and protein binders, liver alerts and genotoxic alerts. The publicly available COSMOS NG enables users to compile information and execute analyses such as category formation and read-across. This paper provides a step-by-step guided workflow for a simple read-across case, starting from a target structure and culminating in an estimation of a NOAEL confidence interval. Given its strong technical foundation, inclusion of quality-reviewed data, and provision of tools designed to facilitate communication between users, COSMOS NG is a first step towards building a toxicological knowledge hub leveraging many public data systems for chemical safety evaluation. We continue to monitor the feedback from the user community at support@mn-am.com.

Improving disease knowledge in 6- to 10-year-olds with sickle cell disease: A quasi-experimental study.

BACKGROUND: Increasing knowledge and understanding of disease is known to improve outcomes in persons living with a chronic illness. In this paper, we aim to compare the disease knowledge of children with sickle cell disease (SCD), age 6-10 years, who received an intervention (an educational colouring book on SCD) geared towards improving disease knowledge, to those who did not received the colouring book. METHODS: A quasi-experimental study was conducted where disease knowledge was determined in 56 children who had received the colouring book and compared to 60 children who did not receive this intervention. RESULTS: The mean knowledge score was significantly higher in the intervention group (mean difference = 2.65; 95% CI [1.43, 3.86]), as well as in older children and in those in higher grades but there was no difference between sexes. In a multiple regression model (adjusted R2 : 0.39; p value < .001), knowledge score was significantly higher in those who received the intervention (ß: 2.62; 95% CI [1.48, 3.76]) while adjusting for age, gender, persons living at home, and the father's employment status. CONCLUSION: The study highlights that a simple, inexpensive (cost: US$1/book) child-friendly intervention can significantly improve knowledge about SCD even in young children. It also underlines various social factors that are associated with children's understanding of their disease.

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules-the SPUtNIk study.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. METHODS AND ANALYSIS: The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) (18FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for 18FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. ETHICS AND DISSEMINATION: Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN30784948; Pre-results.

Database of published retention factors for immobilized artificial membrane HPLC and an assessment of the effect of experimental variability.

A database was collated of published experimental logarithmic values for the relative retention factors (log k(IAM)) measured using an immobilized artificial membrane column and high-performance liquid chromatography (IAM HPLC). Log k(IAM) is an alternative measure of hydrophobicity to the octanol/water partition coefficient (log K(OW)). While there are several accepted methods to measure log K(OW), no standardized method exists to determine log k(IAM). The database of collated log k(IAM) values includes 13 key experimental parameters and contains 1,686 values for 555 compounds, which are predominantly polar organic compounds and include drug molecules and surfactants. These compounds are acidic, basic, and neutral and both ionized and un-ionized under the conditions of analysis. The data compiled demonstrated experimental variability for each experimental parameter considered, including column stationary phase, pH, temperature, and mobile phase. Reducing the experimental variability allowed for greater consistency in the datasets.

Assessment of methods to define the applicability domain of structural alert models.

It is important that in silico models for use in chemical safety legislation, such as REACH, are compliant with the OECD Principles for the Validation of (Q)SARs. Structural alert models can be useful under these circumstances but lack an adequately defined applicability domain. This paper examines several methods of domain definition for structural alert models with the aim of assessing which were the most useful. Specifically, these methods were the use of fragments, chemical descriptor ranges, structural similarity, and specific applicability domain definition software. Structural alerts for mutagenicity in Derek for Windows (DfW) were used as examples, and Ames test data were used to define and test the domain of chemical space where the alerts produce reliable results. The usefulness of each domain was assessed on the criterion that confidence in the correctness of predictions should be greater inside the domain than outside it. By using a combination of structural similarity and chemical fragments a domain was produced where the majority of correct positive predictions for mutagenicity were within the domain and a large proportion of the incorrect positive predictions outside it. However this was not found for the negative predictions; there was little difference between the percentage of true and false predictions for inactivity which were found as either within or outside the applicability domain. A hypothesis for the occurrence of this difference between positive and negative predictions is that differences in structure between training and test compounds are more likely to remove the toxic potential of a compound containing a structural alert than to add an unknown mechanism of action (structural alert) to a molecule which does not already contain an alert. This could be especially true for well studied end points such as the Ames assay where the majority of mechanisms of action are likely to be known.

Decrease in the rate of ruptured ectopic pregnancies: a successful team approach.

Noting the increasing frequency of ectopic pregnancy and desiring to reduce both morbidity and mortality, OB/GYN physicians at a large midwestern HMO systematically monitored all ectopic pregnancies in their clinical practice as the first step in a quality improvement project. Data were collected on several components of care including access, risk assessment, diagnosis of ectopic pregnancy, and intervention. To ensure the system was able to coordinate new diagnostic and therapeutic modalities, several key initiatives were instituted to improve patient outcomes. These included application of comprehensive guidelines, increased ultrasound availability, and increased staff and patient awareness. Following the implementation of the initiatives, there was a decrease in rupture rates from 32% in 1988 to 5% in 1992. This paper discusses the development and integration of the initiatives into the staff model HMO.

Dynamic contrast-enhanced MR imaging assessment of vascularized free fibular grafts.

Magnetic resonance (MR) imaging may be a noninvasive method for assessing perfusion of vascularized bone grafts placed for treatment of avascular necrosis. One proximal femur of seven beagles was devascularized, with insertion of a vascularized fibular graft. MR imaging at 1 week (seven dogs) and 6 weeks (five dogs) after surgery included pre- and postcontrast spin-echo sequences, unenhanced two-dimensional time-of-flight (TOF) vascular imaging, and dynamic gradient-echo imaging during infusion of gadolinium. Relative signal intensity values of selected regions obtained from the dynamic gradient-echo images were plotted as percent enhancement versus time. In the operated hip, MR imaging did not show enhancement in six of seven femoral heads and greater trochanters at 1 week after surgery, with similar results after 6 weeks. MR imaging of fibular grafts 6 weeks after surgery showed an initial rapid increase in enhancement and a subsequent slower increase in five of five dogs, although no enhancement was seen in six of seven dogs at 1 week. These findings contrasted with a rapid initial increase in enhancement followed by slow decline in non-operated hips. Two-dimensional TOF imaging did not show the vascular pedicle of the graft in any dog. Findings of radionuclide bone scanning performed 1 week after surgery were consistent with devascularization of the operated femur and fibular graft. However, tetracycline distribution and histologic findings confirmed the viability of five of five grafts within the devascularized femurs 6 weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Automating materials management via the computer grey market.

For all but the top 10% of major national corporations who need leading edge computer technology, the "grey market" is an excellent source of first rate equipment at bargain basement prices. But to tap this market profitably, shoppers have to understand how and why it works.

Use of noninvasive electromagnetic flowmetry in the assessment of peripheral arterial disease.

The need for noninvasive techniques capable of quantitating peripheral arterial insufficiency is becoming increasingly obvious. We have shown the technique of noninvasive elctromagnetic flowmetry to be capable of distinguishing three relatively discrete clinical zones by quantitating the peak pulsatile flow of blood through the thigh and calf. The obtained peak pulsatile flow values were in close agreement with ischemic index values previously reported as grading the degree of ischemia in a patient. In certain patients, the noninvasive electromagnetic flowmeter has yielded information not readily available from Doppler systolic pressure measurements. With the noninvasive technique of electromagnetic flowmetry and Doppler ultrasound, it is possible to confirm and quantitate patient complaints, follow disease progression and document improvement following arterial reconstructive operations. The noninvasive electromagnetic flowmeter has also been shown to be invaluable in the selection of the operative procedure by providing information about arterial run-on, run-in and run-off.

Assessment of the healing potentials of ulcers of the skin by photoplethysmography.

An objective method of assessing the healing potentials of skin ulcers would eliminate the long waiting period necessary for visual evidence of healing or nonhealing to appear. This would permit the continued conservative treatment for healing ulcers and prompt surgical interventions for those ulcers which are nonhealing. In this preliminary study, the cutaneous blood flow immediately around the ulcer site was studied using the photoplethysmograph. Vigorous cutaneous blood flow shown by good pulsatile wave forms on the photoplethysmograph is shown to be indicative of an ongoing healing process in which spontaneous healing of the ulcer can be predicted. Ulcers with nonpulsatile wave forms fail to heal with conservative management. One patient with nonpulsatile wave forms at the ulcer site showed improvement and eventual healing of the ulcer after undergoing a lumbar sympathectomy. Thus, nonpulsatile blood flow shown by poor wave forms on the photoplethysmograph would suggest early surgical intervention. This method may also aid in determining the extent of surgical excision of the ischemic scar tissue surrounding the chronic skin ulcer.

Certificated incapacity and unemployment in alcoholics.

Seventy-three male alcoholics permitted information to be obtained from official sources about time recorded as lost from work in receipt of sickness or unemployment benefits and about their weekly state insurance contributions. The average yearly time loss was 121-7 working days per person, comprising an average yearly loss through sickness of 86-1 and through unemployment of 35-6 working days respectively. By contrast the recorded national sickness loss for men in a comparable twelve months period averaged 15-9 working days per person. Thirteen alcoholics showed over five years, prolonged deficiency in work attendance. State benefits to the subjects, over twelve months during the early 1970s, totalled pounds 18,434.80. Diagnoses on their medical certificates underestimated incapacity from alcoholism.