Virtual patients designed for training against medical error: Exploring the impact of decision-making on learner motivation.

OBJECTIVES: Medical error is a significant cause of patient harms in clinical practice, but education and training are recognised as having a key role in minimising their incidence. The use of virtual patient (VP) activities targeting training in medical error allows learners to practice patient management in a safe environment. The inclusion of branched decision-making elements in the activities has the potential to drive additional generative cognitive processing and improved learning outcomes, but the increased cognitive load on learning risks negatively affecting learner motivation. The aim of this study is to better understand the impact that the inclusion of decision-making and inducing errors within the VP activities has on learner motivation. METHODS: Using a repeated study design, over a period of six weeks we provided undergraduate medical students at six institutions in three countries with a series of six VPs written around errors in paediatric practice. Participants were divided into two groups and received either linearly structured VPs or ones that incorporated branched decision-making elements. Having completed all the VPs, each participant was asked to complete a survey designed to assess their motivation and learning strategies. RESULTS: Our analysis showed that in general, there was no significant difference in learner motivation between those receiving the linear VPs and those who received branched decision-making VPs. The same results were generally reflected across all six institutions. CONCLUSIONS: The findings demonstrated that the inclusion of decision-making elements did not make a significant difference to undergraduate medical students' motivation, perceived self-efficacy or adopted learning strategies. The length of the intervention was sufficient for learners to overcome any increased cognitive load associated with branched decision-making elements being included in VPs. Further work is required to establish any immediate impact within periods shorter than the length of our study or upon achieved learning outcomes

High-frequency homogenization for periodic media

This article is available open access through the publisher’s website at the link below. Copyright @ 2010 The Royal Society.An asymptotic procedure based upon a two-scale approach is developed for wave propagation in a doubly periodic inhomogeneous medium with a characteristic length scale of microstructure far less than that of the macrostructure. In periodic media, there are frequencies for which standing waves, periodic with the period or double period of the cell, on the microscale emerge. These frequencies do not belong to the low-frequency range of validity covered by the classical homogenization theory, which motivates our use of the term ‘high-frequency homogenization’ when perturbing about these standing waves. The resulting long-wave equations are deduced only explicitly dependent upon the macroscale, with the microscale represented by integral quantities. These equations accurately reproduce the behaviour of the Bloch mode spectrum near the edges of the Brillouin zone, hence yielding an explicit way for homogenizing periodic media in the vicinity of ‘cell resonances’. The similarity of such model equations to high-frequency long wavelength asymptotics, for homogeneous acoustic and elastic waveguides, valid in the vicinities of thickness resonances is emphasized. Several illustrative examples are considered and show the efficacy of the developed techniques.NSERC (Canada) and the EPSRC

The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

<p>Abstract</p> <p>Background</p> <p>The mitochondrial DNA (mtDNA) T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV).</p> <p>Methods</p> <p>A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection) were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer.</p> <p>Results</p> <p>The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93), gender (males 60% vs 53%, P = 0.54), and stage of HIV disease (mean CD4 T cell count 260.7/μL vs. 176/μL, P = 0.21). The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30) in the HIV-associated cardiomyopathy cases and 13.5% (5/37) in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11).</p> <p>Conclusion</p> <p>The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.</p

Transmission of Mitochondrial DNA Diseases and Ways to Prevent Them

Recent reports of strong selection of mitochondrial DNA (mtDNA) during transmission in animal models of mtDNA disease, and of nuclear transfer in both animal models and humans, have important scientific implications. These are directly applicable to the genetic management of mtDNA disease. The risk that a mitochondrial disorder will be transmitted is difficult to estimate due to heteroplasmy—the existence of normal and mutant mtDNA in the same individual, tissue, or cell. In addition, the mtDNA bottleneck during oogenesis frequently results in dramatic and unpredictable inter-generational fluctuations in the proportions of mutant and wild-type mtDNA. Pre-implantation genetic diagnosis (PGD) for mtDNA disease enables embryos produced by in vitro fertilization (IVF) to be screened for mtDNA mutations. Embryos determined to be at low risk (i.e., those having low mutant mtDNA load) can be preferentially transferred to the uterus with the aim of initiating unaffected pregnancies. New evidence that some types of deleterious mtDNA mutations are eliminated within a few generations suggests that women undergoing PGD have a reasonable chance of generating embryos with a lower mutant load than their own. While nuclear transfer may become an alternative approach in future, there might be more difficulties, ethical as well as technical. This Review outlines the implications of recent advances for genetic management of these potentially devastating disorders

Radiometric approach for the detection of picophytoplankton assemblages across oceanic fronts

Cell abundances of Prochlorococcus, Synechococcus, and autotrophic picoeukaryotes were estimated in surface waters using principal component analysis (PCA) of hyperspectral and multispectral remote-sensing reflectance data. This involved the development of models that employed multilinear correlations between cell abundances across the Atlantic Ocean and a combination of PCA scores and sea surface temperatures. The models retrieve high Prochlorococcus abundances in the Equatorial Convergence Zone and show their numerical dominance in oceanic gyres, with decreases in Prochlorococcus abundances towards temperate waters where Synechococcus flourishes, and an emergence of picoeukaryotes in temperate waters. Fine-scale in-situ sampling across ocean fronts provided a large dynamic range of measurements for the training dataset, which resulted in the successful detection of fine-scale Synechococcus patches. Satellite implementation of the models showed good performance (R2 > 0.50) when validated against in-situ data from six Atlantic Meridional Transect cruises. The improved relative performance of the hyperspectral models highlights the importance of future high spectral resolution satellite instruments, such as the NASA PACE mission’s Ocean Color Instrument, to extend our spatiotemporal knowledge about ecologically relevant phytoplankton assemblages

Nitrogen deposition and its contribution to nitrogen cycling and associated soil processes

Human activity has greatly perturbed the nitrogen cycle through increased fixation by legumes, by energy and fertilizer production, and by the mobilization of N from long-term storage pools. This extra reactive N is readily transported through the environment, and there is increasing evidence that it is changing ecosystems through eutrophication and acidification. Rothamsted Experimental Station, UK has been involved in research on N cycling in ecosystems since its inception in 1843. Measurements of precipitation composition at Rothamsted, made since 1853, show an increase of nitrate and ammonium N in precipitation from 1 and 3 kg N ha(-1) yr(-1) respectively, in 1855 to a maximum of 8 and 10 kg N ha(-1) yr(-1) in 1980, decreasing to 4 and 5 kg N ha(-1) y(-1) today. Nitrogen inputs via dry deposition do, however, remain high. Recent measurements with diffusion tubes and filter packs show large concentrations of nitrogen dioxide of c. 20 mu g m(-3) in winter and c. 10 mu g m(-3) in summer; the difference is linked to the use of central heating, and with variations in wind direction and pollutant source. Concentrations of nitric acid and particulate N exhibit maxima of 1.5 and 2 mu g m(-3) in summer and winter, respectively. Concentrations of ammonia are small, barely rising above 1 mu g m(-3). Taking deposition velocities from the literature gives a total deposition of all measured N species to winter cereals of 43.3 kg N ha(-1) yr(-1), 84 % as oxidized species, 79 % dry deposited. The fate of this N deposited to the very long-term Broadbalk Continuous Wheat Experiment at Rothamsted has been simulated using the SUNDIAL N-cycling model: at equilibrium, after 154 yr of the experiment and with N deposition increasing from c. 10 kg ha(-1) yr(-1) in 1843 to 45 kg ha(-1) yr(-1) today, c. 5 % is leached, 12% is denitrified, 30% immobilized in the soil organic matter and 53 % taken off in the crop. The 'efficiency of use' of the deposited N decreases, and losses and immobilization increase as the amount of fertilizer N increases. The deposited N itself, and the acidification that is associated with it (from the nitric acid, ammonia and ammonium), has reduced the number of plant species on the 140-yr-old Park Grass hay meadow. It has also reduced methane oxidation rates in soil by c. 15 % under arable land and 30 % under woodland, and has caused N saturation of local woodland ecosystems: nitrous oxide emission rates of up to 1.4 kg ha(-1) yr(-1) are equivalent to those from arable land receiving > 200 kg N ha(-1) yr(-1), and in proportion to the excess N deposited; measurements of N cycling processes and pools using N-15 pool dilution techniques show a large nitrate pool and enhanced rates of nitrification relative to immobilization. Ratios of gross nitrification:gross immobilization might prove to be good indices of N saturation

Credit bureaus between risk-management, creditworthiness assessment and prudential supervision

"This text may be downloaded for personal research purposes only. Any additional reproduction for other purposes, whether in hard copy or electronically, requires the consent of the author. If cited or quoted, reference should be made to the full name of the author, the title, the working paper or other series, the year, and the publisher."This paper discusses the role and operations of consumer Credit Bureaus in the European Union in the context of the economic theories, policies and law within which they work. Across Europe there is no common practice of sharing the credit data of consumers which can be used for several purposes. Mostly, they are used by the lending industry as a practice of creditworthiness assessment or as a risk-management tool to underwrite borrowing decisions or price risk. However, the type, breath, and depth of information differ greatly from country to country. In some Member States, consumer data are part of a broader information centralisation system for the prudential supervision of banks and the financial system as a whole. Despite EU rules on credit to consumers for the creation of the internal market, the underlying consumer data infrastructure remains fragmented at national level, failing to achieve univocal, common, or defined policy objectives under a harmonised legal framework. Likewise, the establishment of the Banking Union and the prudential supervision of the Euro area demand standardisation and convergence of the data used to measure debt levels, arrears, and delinquencies. The many functions and usages of credit data suggest that the policy goals to be achieved should inform the legal and institutional framework of Credit Bureaus, as well as the design and use of the databases. This is also because fundamental rights and consumer protection concerns arise from the sharing of credit data and their expanding use

High frequency of mitochondrial genome instability in human endometrial carcinomas

To investigate the occurrence of somatic mitochondrial DNA (mtDNA) mutations in human primary endometrial carcinomas, we sequenced the D-loop region, the 12S and 16S rRNA genes of mtDNA of cancer tissues and their matched normal controls. About 56% (28 out of 50) of cases carry one or more somatic changes in mtDNA including deletion, point mutation and mitochondrial microsatellite instability (mtMSI), namely the change in length of short base-repetitive sequences of mtDNA. In particular, mtMSI was frequently detected in 89% (25 out of 28) of all the cases carrying somatic changes followed by point mutations (25%; seven out of 28) and deletion (3.5%; one out of 28). The CCCCCTCCCC sequences located in the Hypervariable Regions I and II of the D-loop and 12S rRNA gene are instability hot spot regions in endometrial carcinomas. It is suggested that errors in replication may account for the high frequency of mtMSI in human endometrial carcinomas. The relatively high prevalence of mtMSI may be a potential new tool for detection of endometrial cancer. © 2003 Cancer Research UK.link_to_subscribed_fulltex

Onset of the aerobic nitrogen cycle during the Great Oxidation Event

The rise of oxygen on the early Earth (about 2.4 billion years ago)1 caused a reorganization of marine nutrient cycles2, 3, including that of nitrogen, which is important for controlling global primary productivity. However, current geochemical records4 lack the temporal resolution to address the nature and timing of the biogeochemical response to oxygenation directly. Here we couple records of ocean redox chemistry with nitrogen isotope (15N/14N) values from approximately 2.31-billion-year-old shales5 of the Rooihoogte and Timeball Hill formations in South Africa, deposited during the early stages of the first rise in atmospheric oxygen on the Earth (the Great Oxidation Event)6. Our data fill a gap of about 400 million years in the temporal 15N/14N record4 and provide evidence for the emergence of a pervasive aerobic marine nitrogen cycle. The interpretation of our nitrogen isotope data in the context of iron speciation and carbon isotope data suggests biogeochemical cycling across a dynamic redox boundary, with primary productivity fuelled by chemoautotrophic production and a nitrogen cycle dominated by nitrogen loss processes using newly available marine oxidants. This chemostratigraphic trend constrains the onset of widespread nitrate availability associated with ocean oxygenation. The rise of marine nitrate could have allowed for the rapid diversification and proliferation of nitrate-using cyanobacteria and, potentially, eukaryotic phytoplankton

Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency

Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6-months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only ~ 1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt-tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomic and proteomic analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress response associated with increased FGF21 and GDF15 expression enhances the metabolism modulated by serine biosynthesis, one carbon metabolism, TCA lipid oxidation and amino acid availability, while in the second step mTOR activation leads to increased mitochondrial biogenesis. Our data suggest that the spontaneous recovery in infants with digenic mutations may be modulated by the above described changes. Similar mechanisms may explain the variable penetrance and tissue specificity of other mtDNA mutations and highlight the potential role of amino acids in improving mitochondrial disease