Mining unexpected temporal associations: Applications in detecting adverse drug reactions

Copyright © 2008 IEEEIn various real-world applications, it is very useful mining unanticipated episodes where certain event patterns unexpectedly lead to outcomes, e.g., taking two medicines together sometimes causing an adverse reaction. These unanticipated episodes are usually unexpected and infrequent, which makes existing data mining techniques, mainly designed to find frequent patterns, ineffective. In this paper, we propose unexpected temporal association rules (UTARs) to describe them. To handle the unexpectedness, we introduce a new interestingness measure, residual-leverage, and develop a novel case-based exclusion technique for its calculation. Combining it with an event-oriented data preparation technique to handle the infrequency, we develop a new algorithm MUTARC to find pairwise UTARs. The MUTARC is applied to generate adverse drug reaction (ADR) signals from real-world healthcare administrative databases. It reliably shortlists not only six known ADRs, but also another ADR, flucloxacillin possibly causing hepatitis, which our algorithm designers and experiment runners have not known before the experiments. TheMUTARC performs much more effectively than existing techniques. This paper clearly illustrates the great potential along the new direction of ADR signal generation from healthcare administrative databases.Huidong (Warren) Jin, Jie Chen, Member, Hongxing He, Graham J. Williams, Chris Kelman and Christine M. O’Keef

Bog plant/lichen tissue nitrogen and sulfur concentrations as indicators of emissions from oil sands development in Alberta, Canada

Increasing gaseous emissions of nitrogen (N) and sulfur (S) associated with oil sands development in northern Alberta (Canada) has led to changing regional wet and dry N and S deposition regimes. We assessed the potential for using bog plant/lichen tissue chemistry (N and S concentrations, C:N and C:S ratios, in 10 plant/lichen species) to monitor changing atmospheric N and S deposition through sampling at five bog sites, 3-6 times per growing season from 2009 to 2016. During this 8-year period, oil sands N emissions steadily increased, while S emissions steadily decreased. We examined the following: (1) whether each species showed changes in tissue chemistry with increasing distance from the Syncrude and Suncor upgrader stacks (the two largest point sources of N and S emissions); (2) whether tissue chemistry changed over the 8 year period in ways that were consistent with increasing N and decreasing S emissions from oil sands facilities; and (3) whether tissue chemistry was correlated with growing season wet deposition of NH4+-N, NO3--N, or SO42--S. Based on these criteria, the best biomonitors of a changing N deposition regime were Evernia mesomorpha, Sphagnum fuscum, and Vaccinium oxycoccos. The best biomonitors of a changing S deposition regime were Evernia mesomorpha, Cladonia mitis, Sphagnum fuscum, Sphagnum capillifolium, Vaccinium oxycoccos, and Picea mariana. Changing N and S deposition regimes in the oil sands region appear to be influencing N and S cycling in what once were pristine ombrotrophic bogs, to the extent that these bogs may effectively monitor future spatial and temporal patterns of deposition

Experimental nitrogen addition alters structure and function of a boreal bog: critical load and thresholds revealed

Bogs and fens cover 6% and 21%, respectively, of the 140,329 km2 Oil Sands Administrative Area in northern Alberta. Development of the oil sands has led to increasing atmospheric N deposition, with values as high as 17 kg N.ha-1yr-1; regional background deposition is N.ha-1yr-1. Bogs, being ombrotrophic, may be especially susceptible to increasing N deposition. To examine responses to N deposition, over five years, we experimentally applied N (as NH4NO3) to a bog near Mariana Lake, Alberta, unaffected by oil sands activities, at rates of 0, 5, 10, 15, 20, and 25 kg N.ha-1yr-1, plus controls (no water or N addition). Increasing N addition: (1) stimulated N2 fixation at deposition .ha-1yr-1, and progressively inhibited N2 fixation as N deposition increased above this level; (2) had no effect on Sphagnum fuscum net primary production (NPP) in years 1, 2, and 4, but inhibited S. fuscum NPP in years 3 and 5; (3) stimulated dominant shrub and Picea mariana NPP; (4) led to increased root biomass and production; (5) changed Sphagnum species relative abundance (decrease in S. fuscum, increase in S. magellanicum, no effect on S. angustifolium); (6) led to increasing abundance of Rhododendron groenlandicum and Andromeda polifolia, and to vascular plants in general; (7) led to increasing shrub leaf N concentrations in Andromeda polifolia, Chamaedaphne calyculata, Vaccinium oxycoccos, V. vitis-idaea, and Picea mariana; (8) stimulated cellulose decomposition, with no effect on S. fuscum peat or mixed vascular plant litter decomposition; (9) had no effect on net N mineralization rates or on porewater NH4+-N, NO3--N, or DON concentrations; and (10) had minimal effects on peat microbial community composition. Increasing experimental N addition led to a switch from new N being taken up primarily by Sphagnum to being taken up primarily by shrubs. As shrub growth and cover increase, Sphagnum abundance and NPP decrease. Because inhibition of N2 fixation by increasing N deposition plays a key role in bog structural and functional responses, we recommend a N deposition critical load of 3 kg N.ha-1yr-1 for northern Alberta bogs

Malignancy risk analysis in patients with inadequate fine needle aspiration cytology (FNAC) of the thyroid

Background Thyroid fine needle aspiration cytology (FNAC) is the standard diagnostic modality for thyroid nodules. However, it has limitations among which is the incidence of non-diagnostic results (Thy1). Management of cases with repeatedly non-diagnostic FNAC ranges from simple observation to surgical intervention. We aim to evaluate the incidence of malignancy in non-diagnostic FNAC, and the success rate of repeated FNAC. We also aim to evaluate risk factors for malignancy in patients with non-diagnostic FNAC. Materials and Methods Retrospective analyses of consecutive cases with thyroid non diagnostic FNAC results were included. Results Out of total 1657 thyroid FNAC done during the study period, there were 264 (15.9%) non-diagnostic FNAC on the first attempt. On repeating those, the rate of a non-diagnostic result on second FNAC was 61.8% and on third FNAC was 47.2%. The overall malignancy rate in Thy1 FNAC was 4.5% (42% papillary, 42% follicular and 8% anaplastic), and the yield of malignancy decreased considerably with successive non-diagnostic FNAC. Ultrasound guidance by an experienced head neck radiologist produced the lowest non-diagnostic rate (38%) on repetition compared to US guidance by a generalist radiologist (65%) and by non US guidance (90%). Conclusions There is a low risk of malignancy in patients with a non-diagnostic FNAC result, commensurate to the risk of any nodule. The yield of malignancy decreased considerably with successive non-diagnostic FNAC

Structure of an archaeal PCNA1-PCNA2-FEN1 complex: elucidating PCNA subunit and client enzyme specificity.

The archaeal/eukaryotic proliferating cell nuclear antigen (PCNA) toroidal clamp interacts with a host of DNA modifying enzymes, providing a stable anchorage and enhancing their respective processivities. Given the broad range of enzymes with which PCNA has been shown to interact, relatively little is known about the mode of assembly of functionally meaningful combinations of enzymes on the PCNA clamp. We have determined the X-ray crystal structure of the Sulfolobus solfataricus PCNA1-PCNA2 heterodimer, bound to a single copy of the flap endonuclease FEN1 at 2.9 A resolution. We demonstrate the specificity of interaction of the PCNA subunits to form the PCNA1-PCNA2-PCNA3 heterotrimer, as well as providing a rationale for the specific interaction of the C-terminal PIP-box motif of FEN1 for the PCNA1 subunit. The structure explains the specificity of the individual archaeal PCNA subunits for selected repair enzyme 'clients', and provides insights into the co-ordinated assembly of sequential enzymatic steps in PCNA-scaffolded DNA repair cascades

Precautionary Regulation in Europe and the United States: A Quantitative Comparison

Much attention has been addressed to the question of whether Europe or the United States adopts a more precautionary stance to the regulation of potential environmental, health, and safety risks. Some commentators suggest that Europe is more risk-averse and precautionary, whereas the US is seen as more risk-taking and optimistic about the prospects for new technology. Others suggest that the US is more precautionary because its regulatory process is more legalistic and adversarial, while Europe is more lax and corporatist in its regulations. The flip-flop hypothesis claims that the US was more precautionary than Europe in the 1970s and early 1980s, and that Europe has become more precautionary since then. We examine the levels and trends in regulation of environmental, health, and safety risks since 1970. Unlike previous research, which has studied only a small set of prominent cases selected non-randomly, we develop a comprehensive list of almost 3,000 risks and code the relative stringency of regulation in Europe and the US for each of 100 risks randomly selected from that list for each year from 1970 through 2004. Our results suggest that: (a) averaging over risks, there is no significant difference in relative precaution over the period, (b) weakly consistent with the flip-flop hypothesis, there is some evidence of a modest shift toward greater relative precaution of European regulation since about 1990, although (c) there is a diversity of trends across risks, of which the most common is no change in relative precaution (including cases where Europe and the US are equally precautionary and where Europe or the US has been consistently more precautionary). The overall finding is of a mixed and diverse pattern of relative transatlantic precaution over the period

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.