Ontological theory for ontological engineering: Biomedical systems information integration

Software application ontologies have the potential to become the keystone in state-of-the-art information management techniques. It is expected that these ontologies will support the sort of reasoning power required to navigate large and complex terminologies correctly and efficiently. Yet, there is one problem in particular that continues to stand in our way. As these terminological structures increase in size and complexity, and the drive to integrate them inevitably swells, it is clear that the level of consistency required for such navigation will become correspondingly difficult to maintain. While descriptive semantic representations are certainly a necessary component to any adequate ontology-based system, so long as ontology engineers rely solely on semantic information, without a sound ontological theory informing their modeling decisions, this goal will surely remain out of reach. In this paper we describe how Language and Computing nv (L&C), along with The Institute for Formal Ontology and Medical Information Sciences (IFOMIS), are working towards developing and implementing just such a theory, combining the open software architecture of L&C’s LinkSuiteTM with the philosophical rigor of IFOMIS’s Basic Formal Ontology. In this way we aim to move beyond the more or less simple controlled vocabularies that have dominated the industry to date

Slow fatigue and highly delayed yielding via shear banding in oscillatory shear

We study theoretically the dynamical process of yielding in cyclically sheared amorphous materials, within a thermal elastoplastic model and the soft glassy rheology model. Within both models we find an initially slow accumulation, over many cycles after the inception of shear, of low levels of damage in the form strain heterogeneity across the sample. This slow fatigue then suddenly gives way to catastrophic yielding and material failure. Strong strain localisation in the form of shear banding is key to the failure mechanism. We characterise in detail the dependence of the number of cycles before failure on the amplitude of imposed strain, the working temperature, and the degree to which the sample is annealed prior to shear. We discuss our finding with reference to existing experiments and particle simulations, and suggest new ones to test our predictions.Comment: 4 pages, 5 figure

Constitutive model for the rheology of biological tissue

The rheology of biological tissue is key to processes such as embryo development, wound healing and cancer metastasis. Vertex models of confluent tissue monolayers have uncovered a spontaneous liquid-solid transition tuned by cell shape; and a shear-induced solidification transition of an initially liquid-like tissue. Alongside this jamming/unjamming behaviour, biological tissue also displays an inherent viscoelasticity, with a slow time and rate dependent mechanics. With this motivation, we combine simulations and continuum theory to examine the rheology of the vertex model in nonlinear shear across a full range of shear rates from quastistatic to fast, elucidating its nonlinear stress-strain curves after the inception of shear of finite rate, and its steady state flow curves of stress as a function of strain rate. We formulate a rheological constitutive model that couples cell shape to flow and captures both the tissue solid-liquid transition and its rich linear and nonlinear rheology.Comment: 5 pages, 3 figures; plus supplemental materia

Prevalence and causes of prescribing errors: the prescribing outcomes for trainee doctors engaged in clinical training (PROTECT) study

Objectives Study objectives were to investigate the prevalence and causes of prescribing errors amongst foundation doctors (i.e. junior doctors in their first (F1) or second (F2) year of post-graduate training), describe their knowledge and experience of prescribing errors, and explore their self-efficacy (i.e. confidence) in prescribing. Method A three-part mixed-methods design was used, comprising: prospective observational study; semi-structured interviews and cross-sectional survey. All doctors prescribing in eight purposively selected hospitals in Scotland participated. All foundation doctors throughout Scotland participated in the survey. The number of prescribing errors per patient, doctor, ward and hospital, perceived causes of errors and a measure of doctors' self-efficacy were established. Results 4710 patient charts and 44,726 prescribed medicines were reviewed. There were 3364 errors, affecting 1700 (36.1%) charts (overall error rate: 7.5%; F1:7.4%; F2:8.6%; consultants:6.3%). Higher error rates were associated with : teaching hospitals (p&#60;0.001), surgical (p = &#60;0.001) or mixed wards (0.008) rather thanmedical ward, higher patient turnover wards (p&#60;0.001), a greater number of prescribed medicines (p&#60;0.001) and the months December and June (p&#60;0.001). One hundred errors were discussed in 40 interviews. Error causation was multi-factorial; work environment and team factors were particularly noted. Of 548 completed questionnaires (national response rate of 35.4%), 508 (92.7% of respondents) reported errors, most of which (328 (64.6%) did not reach the patient. Pressure from other staff, workload and interruptions were cited as the main causes of errors. Foundation year 2 doctors reported greater confidence than year 1 doctors in deciding the most appropriate medication regimen. Conclusions Prescribing errors are frequent and of complex causation. Foundation doctors made more errors than other doctors, but undertook the majority of prescribing, making them a key target for intervention. Contributing causes included work environment, team, task, individual and patient factors. Further work is needed to develop and assess interventions that address these.</p

The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study

BackgroundThe durability of isoniazid preventive therapy (IPT) in preventing tuberculosis (TB) is limited in high-prevalence settings. The underlying mechanism (reactivation of persistent latent TB or reinfection) is not known. We aimed to investigate the timing of TB incidence during and after IPT and associated risk factors in a very high TB and HIV-prevalence setting, and to compare the observed rate with a modelled estimate of TB incidence rate after IPT due to reinfection.MethodsIn a post-hoc analysis of a cluster-randomized trial of community-wide IPT among South African gold miners, all intervention arm participants that were dispensed IPT for at least one of the intended 9months were included. An incident TB case was defined as any participant with a positive sputum smear or culture, or with a clinical TB diagnosis assigned by a senior study clinician. Crude TB incidence rates were calculated during and after IPT, overall and by follow-up time. HIV status was not available. Multivariable Cox regression was used to analyse risk factors by follow-up time after IPT. Estimates from a published mathematical model of trial data were used to calculate the average reinfection TB incidence in the first year after IPT.ResultsAmong 18,520 participants (96% male, mean age 41years, median follow-up 2.1years), 708 developed TB. The TB incidence rate during the intended IPT period was 1.3/100 person-years (pyrs; 95% confidence interval (CI), 1.0–1.6) and afterwards 2.3/100 pyrs (95% CI, 1.9–2.7). TB incidence increased within 6months followed by a stable rate over time. There was no evidence for changing risk factors for TB disease over time after miners stopped IPT. The average TB incidence rate attributable to reinfection in the first year was estimated at 1.3/100 pyrs, compared to an observed rate of 2.2/100 pyrs (95% CI, 1.8–2.7).ConclusionsThe durability of protection by IPT was lost within 6–12 months in this setting with a high HIV prevalence and a high annual risk of M. tuberculosis infection. The observed rate was higher than the modelled rate, suggesting that reactivation of persistent latent infection played a role in the rapid return to baseline TB incidence.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0589-3) contains supplementary material, which is available to authorized users

Intramolecular thiomaleimide [2+2] photocycloadditions: stereoselective control for disulfide stapling and observation of excited state intermediates by transient absorption spectroscopy

Thiomaleimides undergo efficient intermolecular [2 + 2] photocycloaddition reactions and offer applications from photochemical peptide stapling to polymer crosslinking; however, the reactions are limited to the formation of the exo head-to-head isomers. Herein, we present an intramolecular variation which completely reverses the stereochemical outcome of this photoreaction, quantitatively generating endo adducts which minimise the structural disturbance of the disulfide staple and afford a 10-fold increase in quantum yield. We demonstrate the application of this reaction on a protein scaffold, using light to confer thiol stability to an antibody fragment conjugate. To understand more about this intriguing class of [2 + 2] photocycloadditions, we have used transient absorption spectroscopy (electronic and vibrational) to study the excited states involved. The initially formed S2 (π1π*) excited state is observed to decay to the S1 (n1π*) state before intersystem crossing to a triplet state. An accelerated intramolecular C–C bond formation provides evidence to explain the increased efficiency of the reaction, and the impact of the various excited states on the carbonyl vibrational modes is discussed

A new Holocene record of geomagnetic secular variation from Windermere, UK

Paleomagnetic secular variation (PSV) records serve as valuable independent stratigraphic correlation and dating tools for marine and terrestrial sediment sequences, and enhance knowledge of geomagnetic field dynamics. We present a new radiocarbon-dated record (WINPSV-12K) of Holocene geomagnetic secular variation from Windermere, updating the existing 1981 UK master PSV curve. Our analyses used continuous U-channel samples taken from the center of four sediment cores retrieved from Windermere in 2012. The natural remanent magnetization (NRM) of each U-channel was measured before and after stepwise alternating field (AF) demagnetization on a superconducting rock magnetometer at intervals of 0.5-cm or 1-cm. The NRM data reveal a stable and well-defined primary magnetization. Component declinations and inclinations estimated using Principal Component Analysis (PCA) of NRM data from the four Windermere cores correlate well on their independent radiocarbon age models. The four records were stacked using a sliding window bootstrap method, resulting in a composite Holocene PSV record (WINPSV-12K). On millennial timescales WINPSV-12K correlates well with other records from Western Europe and the northern North Atlantic to a resolution of ∼ 1 kyr, given age uncertainties and spatial variability between records. WINPSV-12K also compares well to the CALS10k.2 and pfm9k.1a model predictions for Windermere. Key regionally-significant PSV inclination features of WINPSV-12K which correlate with other North Atlantic records include peaks at 5–6, 8.5, and 10 cal ka BP, and a trough at 7calkaBP. Key PSV declination features include the eastward swing from 5.5–2.3 cal ka BP followed by a major westward excursion at 2.3 cal ka BP, peaks at 1.1 and 7calkaBP, and troughs at 5.4 and 8.2 cal ka BP, with the caveat that an estimated magnetic lock-in delay of at least 100–200 yr is present. PSV variations on 1–3 kyr timescales are interpreted to represent strengthening and weakening of the North American versus the Siberian and European–Mediterranean high-latitude flux lobes, based on the close similarities between the North Atlantic regional records and the antiphase existing in the East Asian Stack record and the North East Pacific inclination stack. WINPSV-12K provides a regionally-important new PSV reference curve whose prominent features may serve as stratigraphic markers for North Atlantic paleo-records

Surface Sensing of Quantum Dots by Electron Spins

The nanoscale design of quantum dots (QDs) requires advanced analytical techniques. However, those that are commonly used do not have sufficient sensitivity or spatial resolution. Here, we use magnetic resonance techniques combined with paramagnetic Mn impurities in PbS QDs for sensitive probing of the QD surface and environment. In particular, we reveal inequivalent proton spin relaxations of the capping ligands and solvent molecules, strengths and anisotropies of the Mn nuclear spin interactions, and Mn nuclei distances with ∼1 Å sensitivity. These findings demonstrate the potential of magnetically doped QDs as sensitive magnetic nanoprobes and the use of electron spins for surface sensing

Sources, perceived usefulness and understanding of information disseminated to families who entered home quarantine during the H1N1 pandemic in Victoria, Australia: a cross-sectional study

Background Voluntary home quarantine of cases and close contacts was the main non-pharmaceutical intervention used to limit transmission of pandemic (H1N1) 2009 influenza (pH1N1) in the initial response to the outbreak of the disease in Australia. The effectiveness of voluntary quarantine logically depends on affected families having a clear understanding of what they are being asked to do. Information may come from many sources, including the media, health officials, family and friends, schools, and health professionals. We report the extent to which families who entered home quarantine received and used information on what they were supposed to do. Specifically, we outline their sources of information; the perceived usefulness of each source; and associations between understanding of recommendations and compliance. Methods Cross-sectional survey administered via the internet and computer assisted telephone interview to families whose school children were recommended to go into home quarantine because they were diagnosed with H1N1 or were a close contact of a case. The sample included 314 of 1157 potentially eligible households (27% response rate) from 33 schools in metropolitan Melbourne. Adjusting for clustering within schools, we describe self-reported \u27understanding of what they were meant to do during the quarantine period\u27; source of information (e.g. health department) and usefulness of information. Using logistic regression we examine whether compliance with quarantine recommendations was associated with understanding and the type of information source used. Results Ninety per cent understood what they were meant to do during the quarantine period with levels of understanding higher in households with cases (98%, 95% CI 93%-99% vs 88%, 95% CI 84%-91%, P = 0.006). Over 87% of parents received information about quarantine from the school, 63% from the health department and 44% from the media. 53% of households were fully compliant and there was increased compliance in households that reported that they understood what they were meant to do (Odds Ratio 2.27, 95% CI 1.35-3.80). Conclusions It is critical that public health officials work closely with other government departments and media to provide clear, consistent and simple information about what to do during quarantine as high levels of understanding will maximise compliance in the quarantined population