Cytochrome P450 CYP1B1 interacts with 8-<i>methoxypsoralen</i> (8-MOP) and influences psoralen-Ultraviolet A (PUVA) sensitivity

Background: There are unpredictable inter-individual differences in sensitivity to psoralen-UVA (PUVA) photochemotherapy, used to treat skin diseases including psoriasis. Psoralens are metabolised by cytochrome P450 enzymes (P450), and we hypothesised that variability in cutaneous P450 expression may influence PUVA sensitivity. We previously showed that P450 CYP1B1 was abundantly expressed in human skin and regulated by PUVA, and described marked inter-individual differences in cutaneous CYP1B1 expression.Objectives: We investigated whether CYP1B1 made a significant contribution to 8-methoxypsoralen (8-MOP) metabolism, and whether individuality in CYP1B1 activity influenced PUVA sensitivity.Methods: We used E. coli membranes co-expressing various P450s and cytochrome P450 reductase (CPR) to study 8-MOP metabolism and cytotoxicity assays in CYP1B1-expressing mammalian cells to assess PUVA sensitivity.Results: We showed that P450s CYP1A1, CYP1A2, CYP1B1, CYP2A6 and CYP2E1 influence 8-MOP metabolism. As CYP1B1 is the most abundant P450 in human skin, we further demonstrated that: (i) CYP1B1 interacts with 8-MOP (ii) metabolism of the CYP1B1 substrates 7-ethoxyresorufin and 17-b-estradiol showed concentration-dependent inhibition by 8-MOP and (iii) inhibition of 7-ethoxyresorufin metabolism by 8-MOP was influenced by CYP1B1 genotype. The influence of CYP1B1 on PUVA cytotoxicity was further investigated in a Chinese hamster ovary cell line, stably expressing CYP1B1 and CPR, which was more sensitive to PUVA than control cells, suggesting that CYP1B1 metabolises 8-MOP to a more phototoxicmetabolite(s).Conclusion: Our data therefore suggest that CYP1B1 significantly contributes to cutaneous 8-MOP metabolism, and that individuality in CYP1B1 expression may influence PUVA sensitivity

Fusing Information in a 3D Chart-of-the-Future Display

The Data Visualization Research Lab at the Center for Coastal and Ocean Mapping is investigating how three-dimensional navigational displays can most effectively be constructed. This effort is progressing along multiple paths and is implemented in the GeoNav3D system, a 3D chart-of-the-future research prototype. We present two lines of investigation here. First, we explore how tide, depth, and planning information can be combined (fused) into a single view, in order to give the user a more realistic picture of effective water depths. In the GeoNav3D system, 3D shaded bathymetry, coded for color depth, is used to display navigable areas. As in ENC displays, different colors are used to easily identify areas that are safe, areas where under-keel clearance is minimal, and areas where depths are too shallow. Real-time or model-generated tide information is taken into account in dynamically color-coding the depths. One advantage to using a continuous bathymetric model, versus discrete depth areas, is that the model can be continuously adjusted for water level. This concept is also extended for planning purposes by displaying the color-coded depths along a proposed corridor at the expected time of reaching each point. In our second line of investigation, we explore mechanisms for linking information from multiple 3D views into a coherent whole. In GeoNav3D, it is possible to create a variety of plan and perspective views, and these views can be attached to moving reference frames. This provides not only semi-static views such as from-the-bridge and under-keel along-track profile views, but also more dynamic, interactive views. These views are linked through visual devices that allow the fusion of information from among the views. We present several such devices and show how they highlight relevant details and help to minimize user confusion. Investigation into the utility of various linked views for aiding realsituation decision-making is ongoin

GeoZui3D: Data Fusion for Interpreting Oceanographic Data

GeoZui3D stands for Geographic Zooming User Interface. It is a new visualization software system designed for interpreting multiple sources of 3D data. The system supports gridded terrain models, triangular meshes, curtain plots, and a number of other display objects. A novel center of workspace interaction method unifies a number of aspects of the interface. It creates a simple viewpoint control method, it helps link multiple views, and is ideal for stereoscopic viewing. GeoZui3D has a number of features to support real-time input. Through a CORBA interface external entities can influence the position and state of objects in the display. Extra windows can be attached to moving objects allowing for their position and data to be monitored. We describe the application of this system for heterogeneous data fusion, for multibeam QC and for ROV/AUV monitoring

Economics knowledge, attitudes and experience of student teachers in Scotland

There is a move away from teaching economics as a separate subject in Scotland. It is now mainly taught within Business Management courses in upper secondary school and is embedded within several subject areas in both primary and early secondary curricula, a move that is in step with broader curricular aims to break down barriers among subjects. This writing discusses the need for clearly situated teaching and learning of economics, provided by teachers provided by teachers who have sufficient background knowledge to devise effective contexts for learning, whether or not it is taught as a discrete subject. The results of a survey of student teachers' levels of economic literacy are analysed and recommendations made for the preparation of teachers to deal effectively with embedded approaches to teaching about economics

The link between practice nurse training and asthma outcomes

This article details the results of a study undertaken to establish whether or not there is a link between the level of practice nurse training and clinical outcomes in asthma management. General practices within one health district voluntarily &lsquo;opted in' to an asthma management initiative which involved clinical audit of 30 asthma patients. Thirty two (41%) practices submitted details on 954 asthma patients. Positive patient outcomes were associated with practices that had clinics organized by a specially trained asthma nurse (n=11). Fewer patients in this group suffered from asthma symptoms, they had fewer acute attacks, were given more aggressive short course systemic steroids and fewer patients lost days as a result of asthma, when compared with practices where the clinics were run by nurses who did not have the diploma qualification (n=14). The authors conclude that there is a strong case for recommending that all general practices should employ a nurse who has undertaken specialized training in asthma in order to improve patient management

School Bond Success: An Exploratory Case Study

Following two-failed school bond issues in 1995 and 1998, one mid-sized rural school district organized an effort that led to two successful school bond elections in 2001 and 2003. The school district’s strategic plan mirrored many of the recommendations for successful bond referendums published in School Bond Success: A Strategy for Building America’s Schools. Findings from this case study, utilizing a Rapid Assessment Process, illustrate many of the reasons why the school district passed two consecutive bond issues with unprecedented community support. Although the findings from this school district may not match the concerns of all communities, it provides readers with a perspective of voters’ beliefs in one rural school district

The UK quality and outcomes framework pay-for-performance scheme and spirometry: rewarding quality or just quantity? A cross-sectional study in Rotherham, UK

Background: Accurate spirometry is important in the management of COPD. The UK Quality and Outcomes Framework pay-for-performance scheme for general practitioners includes spirometry related indicators within its COPD domain. It is not known whether high achievement against QOF spirometry indicators is associated with spirometry to BTS standards. Methods: Data were obtained from the records of 3,217 patients randomly sampled from 5,649 patients with COPD in 38 general practices in Rotherham, UK. Severity of airflow obstruction was categorised by FEV1 (% predicted) according to NICE guidelines. This was compared with clinician recorded COPD severity. The proportion of patients whose spirometry met BTS standards was calculated in each practice using a random sub-sample of 761 patients. The Spearman rank correlation between practice level QOF spirometry achievement and performance against BTS spirometry standards was calculated. Results: Spirometry as assessed by clinical records was to BTS standards in 31% of cases (range at practice level 0% to 74%). The categorisation of airflow obstruction according to the most recent spirometry results did not agree well with the clinical categorisation of COPD recorded in the notes (Cohen's kappa = 0.34, 0.30 - 0.38). 12% of patients on COPD registers had FEV1 (% predicted) results recorded that did not support the diagnosis of COPD. There was no association between quality, as measured by adherence to BTS spirometry standards, and either QOF COPD9 achievement (Spearman's rho = -0.11), or QOF COPD10 achievement (rho = 0.01). Conclusion: The UK Quality and Outcomes Framework currently assesses the quantity, but not the quality of spirometry

Electronic Chart of the Future: The Hampton Roads Project

ECDIS is evolving from a two-dimensional static display of chart-related data to a decision support system capable of providing real-time or forecast information. While there may not be consensus on how this will occur, it is clear that to do this, ENC data and the shipboard display environment must incorporate both depth and time in an intuitively understandable way. Currently, we have the ability to conduct high-density hydrographic surveys capable of producing ENCs with decimeter contour intervals or depth areas. Yet, our existing systems and specifications do not provide for a full utilization of this capability. Ideally, a mariner should be able to benefit from detailed hydrographic data, coupled with both forecast and real-time water levels, and presented in a variety of perspectives. With this information mariners will be able to plan and carry out transits with the benefit of precisely determined and easily perceived underkeel, overhead, and lateral clearances. This paper describes a Hampton Roads Demonstration Project to investigate the challenges and opportunities of developing the “Electronic Chart of the Future.” In particular, a three-phase demonstration project is being planned: 1. Compile test datasets from existing and new hydrographic surveys using advanced data processing and compilation procedures developed at the University of New Hampshire’s Center for Coastal and Ocean Mapping/Joint Hydrographic Center (CCOM/JHC); 2. Investigate innovative approaches being developed at the CCOM/JHC to produce an interactive time- and tide-aware navigation display, and to evaluate such a display on commercial and/or government vessels; 3. Integrate real-time/forecast water depth information and port information services transmitted via an AIS communications broadcast

Shadowing the rotating annulus. Part II: Gradient descent in the perfect model scenario

Shadowing trajectories are model trajectories consistent with a sequence of observations of a system, given a distribution of observational noise. The existence of such trajectories is a desirable property of any forecast model. Gradient descent of indeterminism is a well-established technique for finding shadowing trajectories in low-dimensional analytical systems. Here we apply it to the thermally-driven rotating annulus, a laboratory experiment intermediate in model complexity and physical idealisation between analytical systems and global, comprehensive atmospheric models. We work in the perfect model scenario using the MORALS model to generate a sequence of noisy observations in a chaotic flow regime. We demonstrate that the gradient descent technique recovers a pseudo-orbit of model states significantly closer to a model trajectory than the initial sequence. Gradient-free descent is used, where the adjoint model is set to $\lambda$I in the absence of a full adjoint model. The indeterminism of the pseudo-orbit falls by two orders of magnitude during the descent, but we find that the distance between the pseudo-orbit and the initial, true, model trajectory reaches a minimum and then diverges from truth. We attribute this to the use of the $\lambda$-adjoint, which is well suited to noise reduction but not to finely-tuned convergence towards a model trajectory. We find that $\lambda=0.25$ gives optimal results, and that candidate model trajectories begun from this pseudo-orbit shadow the observations for up to 80 s, about the length of the longest timescale of the system, and similar to expected shadowing times based on the distance between the pseudo-orbit and the truth. There is great potential for using this method with real laboratory data.Comment: This paper was originally prepared for submission in 2011; but, after Part I was not accepted, it was not submitted. It has not been peer-reviewed. We no longer have the time or resources to work on this topic, but would like this record of our work to be available for others to read, cite, and follow up. 22 pages, 11 figure