Automated analysis and validation of open chemical data

Methods to automatically extract Open Data from the chemical literature, validate it, and use it to validate theory are examined. Chemical identifiers which assist the automatic location of chemical structures using commercial Web search engines are investigated. The IUPAC International Chemical Idenfitifer (InChI) gives almost 100% recall and precision, though is shown to be too long for present search engines. A combination of InChI and InChIKey, a shorter, fixed-length hash of the InChI string, is concluded to be the best current method of identifying structures. The proportion of published, Open Crystallographic Information Files (CIFs) that are valid with respect to the specification is shown to be improving, and is around 99% in 2007. The error rate in the conversion of valid CIFs to Chemical Markup Language (CML) is less than 0.2%. The machine generation of connection tables from CIFs requires many heuristics, and in some cases it is impossible to deduce the exact connection table. CrystalEye, a fully-automated system for the reformulation of the fragmented crystallographic Web into a structured XML-based repository is described. Published, Open CIFs can be located and aggregated programmatically with almost 100% recall. It is shown that, by converting CIF data to CML, software can be created to use the latest Web standards and technologies to enhance the ability of Web users to browse, find, keep updated, download and reuse the latest published crystallography. A workflow for the high-throughput calculation of solid-state geometry using a semi-empirical method is described. A wide-range of organic and inorganic systems provided by CrystalEye are used to test both the data and the method. Several errors in the method are discovered, many of which can be attributed to the parameterization process. An Open NMR experiment to perform high-throughput prediction of 13C chemical shifts using a GIAO protocol is described. The data and analysis were provided on publicly-available webpages to enable crowdsourcing, which assisted in discovering an error rate of 6.1% in the starting data. The protocol was refined during the work and shown to have an average unsigned error of 2.24ppm for 13C nuclei of small, rigid molecules; comparable to the errors observed elsewhere for general structures using HOSE and Neural Network methods

Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Original article can be found at: http://journals.cambridge.org/action/displayJournal?jid=PHN Copyright The Authors. DOI: 10.1079/PHN2002439Peer reviewe

Canonical explorations of 'Tel' environments for computer programming

This paper applies a novel technique of canonical gradient analysis, pioneered in ecological sciences, with the aim of exploring student performance and behaviours (such as communication and collaboration) while undertaking formative and summative tasks in technology enhanced learning (TEL) environments for computer programming. The research emphasis is, therefore, on revealing complex patterns, trends, tacit communications and technology interactions associated with a particular type of learning environment, rather than the testing of discrete hypotheses. The study is based on observations of first year programming modules in BSc Computing and closely related joint-honours with software engineering, web and game development courses. This research extends earlier work, and evaluates the suitability of canonical approaches for exploring complex dimensional gradients represented by multivariate and technology-enhanced learning environments. The advancements represented here are: (1) an extended context, beyond the use of the ‘Ceebot’ learning platform, to include learning-achievement following advanced instruction using an industrystandard integrated development environment, or IDE, for engineering software; and (2) longitudinal comparison of consistency of findings across cohort years. Direct findings (from analyses based on code tests, module assessment and questionnaire surveys) reveal overall engagement with and high acceptance of collaborative working and of the TEL environments used, but an inconsistent relationship between deeply learned programming skills and module performance. The paper also discusses research findings in the contexts of established and emerging teaching practices for computer programming, as well as government policies and commercial requirements for improved capacity in computer-science related industries

Urinary antibiotic activity in paediatric patients attending an outpatient department in north-western Cambodia.

OBJECTIVE: Antibiotic resistance is a prominent public and global health concern. We investigated antibiotic use in children by determining the proportion of unselected children with antibacterial activity in their urine attending a paediatric outpatient department in Siem Reap, Cambodia. METHODS: Caregiver reports of medication history and presence of possible infection symptoms were collected in addition to urine samples. Urine antibiotic activity was estimated by exposing bacteria to urine specimens, including assessment against multiresistant bacteria previously isolated from patients in the hospital (a methicillin-resistant Staphylococcus aureus (MRSA), a multiresistant Salmonella typhi and an extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolate). RESULTS: Medication information and urine were collected from 775 children. Caregivers reported medication use in 69.0% of children in the preceding 48 h. 31.7% samples showed antibacterial activity; 16.3% showed activity against a local multiresistant organism. No specimens demonstrated activity against an ESBL-producing E. coli. CONCLUSIONS: Antibiotics are widely used in the community setting in Cambodia. Parents are often ill-informed about drugs given to treat their children. Increasing the regulation and training of private pharmacies in Cambodia may be necessary. Regional surveillance of antibiotic use and resistance is also essential in devising preventive strategies against further development of antibiotic resistance, which would have both local and global consequences

Diagnosing Severe Falciparum Malaria in Parasitaemic African Children: A Prospective Evaluation of Plasma PfHRP2 Measurement.

In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria. Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo) aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH)-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054). In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209), acidosis (p<0.0001), and severe anaemia (p<0.0001). Admission geometric mean (95%CI) plasma PfHRP2 was 1,611 (1,350-1,922) ng/mL in fatal cases (n = 381) versus 1,046 (991-1,104) ng/mL in survivors (n = 3,445, p<0.0001), without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log(10) plasma PfHRP2 and risk of death. Mortality increased 20% per log(10) increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05-1.39, p = 0.009). A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR) for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44-0.83, p = 0.0018) in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69-1.61; p = 0.82). A limitation of the study is that some conclusions are drawn from a mechanistic model, which is inherently dependent on certain assumptions. However, a sensitivity analysis of the model indicated that the results were robust to a plausible range of parameter estimates. Further studies are needed to validate our findings. Plasma PfHRP2 has prognostic significance in African children with severe falciparum malaria and provides a tool to stratify the risk of "true" severe malaria-attributable disease as opposed to other severe illnesses in parasitaemic African children

An Expanded Stratigraphic Record of the Devonian-Carboniferous Boundary Hangenberg Biogeochemical Event from Southeast Iowa (U.S.A.)

The Devonian-Carboniferous boundary in the type area of the Mississippian subsystem (tri-state area of Iowa, Illinois, and Missouri) has been historically difficult to identify. Many of the localities contain similar lithologies and stratigraphic successions, but chronostratigraphic correlation of seemingly identical lithologies can vary greatly in this interval and frequently this has led to miscorrelation. In particular, the similar lithofacies that comprise the McCraney Formation and Louisiana Formation have been a source of stratigraphic confusion for over 100 years. To investigate the Devonian-Carboniferous boundary interval in the Mississippian type area we selected two localities in southeastern Iowa, the H-28 core from Lee County outside of Keokuk, Iowa, and the Starr’s Cave outcrop located near Burlington, Iowa. In total, 62 conodont samples and 299 carbonate carbon isotope samples were processed for this study and recorded the Hangenberg positive carbon isotope excursion and 25 conodont species, including a diverse assemblage of siphonodellids. The Hangenberg excursion is recorded in over 20 m of strata in southeast Iowa, making this one of the thickest stratigraphic records of this important biogeochemical event yet recovered, and helps to define more clearly the position of the base of the Carboniferous System in the region. These results show that the “McCraney” Fm. at the Starr’s Cave outcrop and the coeval carbonate unit in the H-28 core are both the Louisiana Formation, and calls into question the use of the name McCraney throughout the State of Iowa

Two nonrecombining sympatric forms of the human malaria parasite Plasmodium ovale occur globally.

BACKGROUND: Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P. ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. METHODS: Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. RESULTS: Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. CONCLUSIONS: We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated

The First Plasmodium vivax Relapses of Life Are Usually Genetically Homologous

In a prospective infant cohort, 21 infants developed Plasmodium vivax malaria during their first year. Twelve of their mothers also had vivax malaria in the corresponding pregnancies or postpartum period. The genotypes of the maternal and infant infections were all different. Eight of the 12 mothers and 9 of the 21 infants had recurrent infections. Relapse parasite genotypes were different to the initial infection in 13 of 20 (65%) mothers compared with 5 of 24 (21%) infants (P = .02). The first P. vivax relapses of life are usually genetically homologous, whereas relapse in adults may result from activation of heterologous latent hypnozoites acquired from previous inoculations