Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolism.

Background: In haemodynamically stable patients with acute symptomatic pulmonary embolism (PE), studies have not evaluated the usefulness of combining the measurement of cardiac troponin, transthoracic echocardiogram (TTE), and lower extremity complete compression ultrasound (CCUS) testing for predicting the risk of PE-related death. Methods: The study assessed the ability of three diagnostic tests (cardiac troponin I (cTnI), echocardiogram, and CCUS) to prognosticate the primary outcome of PE-related mortality during 30 days of follow-up after a diagnosis of PE by objective testing. Results: Of 591 normotensive patients diagnosed with PE, the primary outcome occurred in 37 patients (6.3%; 95% CI 4.3% to 8.2%). Patients with right ventricular dysfunction (RVD) by TTE and concomitant deep vein thrombosis (DVT) by CCUS had a PE-related mortality of 19.6%, compared with 17.1% of patients with elevated cTnI and concomitant DVT and 15.2% of patients with elevated cTnI and RVD. The use of any two-test strategy had a higher specificity and positive predictive value compared with the use of any test by itself. A combined three-test strategy did not further improve prognostication. For a subgroup analysis of high-risk patients, according to the pulmonary embolism severity index (classes IV and V), positive predictive values of the two-test strategies for PE-related mortality were 25.0%, 24.4% and 20.7%, respectively. Conclusions: In haemodynamically stable patients with acute symptomatic PE, a combination of echocardiography (or troponin testing) and CCUS improved prognostication compared with the use of any test by itself for the identification of those at high risk of PE-related death.

Multiple Geotechnological Tools Applied to Digital Mapping of Tropical Soils

ABSTRACT In recent years, geotechnologies as remote and proximal sensing and attributes derived from digital terrain elevation models indicated to be very useful for the description of soil variability. However, these information sources are rarely used together. Therefore, a methodology for assessing and specialize soil classes using the information obtained from remote/proximal sensing, GIS and technical knowledge has been applied and evaluated. Two areas of study, in the State of São Paulo, Brazil, totaling approximately 28.000 ha were used for this work. First, in an area (area 1), conventional pedological mapping was done and from the soil classes found patterns were obtained with the following information: a) spectral information (forms of features and absorption intensity of spectral curves with 350 wavelengths -2,500 nm) of soil samples collected at specific points in the area (according to each soil type); b) obtaining equations for determining chemical and physical properties of the soil from the relationship between the results obtained in the laboratory by the conventional method, the levels of chemical and physical attributes with the spectral data; c) supervised classification of Landsat TM 5 images, in order to detect changes in the size of the soil particles (soil texture); d) relationship between classes relief soils and attributes. Subsequently, the obtained patterns were applied in area 2 obtain pedological classification of soils, but in GIS (ArcGIS). Finally, we developed a conventional pedological mapping in area 2 to which was compared with a digital map, ie the one obtained only with pre certain standards. The proposed methodology had a 79 % accuracy in the first categorical level of Soil Classification System, 60 % accuracy in the second category level and became less useful in the categorical level 3 (37 % accuracy).

GIS - Based Decision and Outreach Tools for Aggregate Source Management, September 2008

This research project combined various datasets, existing and created for this project, into an Interactive Mapping Service (IMS) for use by Iowa DOT personnel, county planning and zoning departments and the public in order to make more informed decisions regarding aggregate sources and future access to them. Iowa DOT Technical Advisory Committee meetings were held, along with public forum presentations, in order to understand better the social, ecological and economic limitations to extracting aggregate. The information needed by potential users was conveyed and integrated into a single informational source, the Aggregate Planning IMS.

European guidelines for the development of mechanisms/tools supporting the individual demand for training through use of training Vouchers

El projecte de TAV es basa en la transferència d'un sistema de vals de capacitació, i en com aquest sistema de vals és adaptable a altres països o regions. En el document s'analitzen diferents conceptes teòrics sobre la conveniència o no de la implantació d'aquest sistema. A més a més, aquest document és una guia per a les organitzacions interessades en l'adaptació del sistema de vals formatius al seu territori, mostrant els passos a seguir i oferint eines útils per aconseguir-ho.

Bioavailability of repeated oral administration of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase in healthy volunteers.

BACKGROUND: MDL 100,240 (pyrido[2,1-a] [2]benzazepine-4-carboxylic acid,7-[[2-(acetylthio)-1-oxo-3-phenylpropyl]amino]-1,2,3,4,6,7,8, 12b-octahydro-6-oxo, [4S-[4alpha,7alpha(R(*)),12bbeta]]-) is a molecule possessing an inhibiting ability on both angiotensin converting enzyme (ACE) and neutral endopeptidase, the enzyme responsible for atrial natriuretic peptide (ANP) degradation. Such a dual mechanism of action presents a potential clinical interest for the treatment of hypertension and congestive heart failure. OBJECTIVES: To evaluate the bioavailability of MDL 100,240 and its accumulation over repeated oral administration, using ACE inhibition as a surrogate for plasma drug level and determining its profile after oral and i.v. administration. METHODS: First, in an open, one-period, single-dose study, the ACE inhibition profile was characterised following a 12.5 mg MDL 100,240 i.v. infusion. Second, in a three-group, parallel, randomised, double-blind study, each group of four subjects received q.d., over 8 days, 2.5, 10 or 20 mg of MDL 100,240 orally. The ACE inhibition profile was determined on day 1 and day 8. Trough plasma ACE was measured on days 2, 3 and 4. The recovery of ACE activity was monitored up to 72 h after the last dose of MDL 100,240. RESULTS: ACE inhibition profile was similar on day 1 and day 8, and trough inhibition remained unchanged after the 8 days of treatment with 10 mg or 20 mg. Following repeated 2.5-mg ingestion, trough inhibition increased from 33% to 44% after the eighth dose. The oral bioavailability of MDL 100,240 was estimated at 85%, not statistically different from 100%. The accumulation ratio at steady state was estimated at 112%. Expressing the accumulation ratio in terms of half-life, a t(1/2) of 0.31 days or 7. 5 h was estimated. CONCLUSION: MDL 100,240 (oral solution) has a good bioavailability, as estimated by ACE inhibition, and no drug accumulation seems to occur over 8 days with the 10-mg and 20-mg doses, but a slight rise in the trough level is observed with the 2. 5-mg dose.

E-tools for civic education : experiences from the election campaign in Switzerland 2007

Political participation is often very low in Switzerland especially among students and young citizens. In the run-up to the Swiss parliamentary election in October 2007 several online tools and campaigns were developed with the aim to increase not only the level of information about the political programs of parties and candidates, but also the electoral participation of younger citizens. From a practical point of view this paper will describe the development, marketing efforts and the distribution as well as the use of two of these tools : the so-called "Parteienkompass" (party compass) and the "myVote"-tool - an online voting assistance tool based on an issue-matching system comparing policy preferences between voters and candidates on an individual level. We also havea look at similar tools stemming from Voting Advice Applications (VAA) in other countries in Western Europe. The paper closes with the results of an evaluation and an outlook to further developments and on-going projects in the near future in Switzerland.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Introduction: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on measurement of blood concentrations. Maintaining concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. In the last decades computer programs have been developed to assist clinicians in this assignment. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Method: Literature and Internet search was performed to identify software. All programs were tested on common personal computer. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software's characteristics. Numbers of drugs handled vary widely and 8 programs offer the ability to the user to add its own drug model. 10 computer programs are able to compute Bayesian dosage adaptation based on a blood concentration (a posteriori adjustment) while 9 are also able to suggest a priori dosage regimen (prior to any blood concentration measurement), based on individual patient covariates, such as age, gender, weight. Among those applying Bayesian analysis, one uses the non-parametric approach. The top 2 software emerging from this benchmark are MwPharm and TCIWorks. Other programs evaluated have also a good potential but are less sophisticated (e.g. in terms of storage or report generation) or less user-friendly.¦Conclusion: Whereas 2 integrated programs are at the top of the ranked listed, such complex tools would possibly not fit all institutions, and each software tool must be regarded with respect to individual needs of hospitals or clinicians. Interest in computing tool to support therapeutic monitoring is still growing. Although developers put efforts into it the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capacity of data storage and report generation.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Objectives: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on blood concentrations measurement. Maintaining concentrations within a target range requires pharmacokinetic (PK) and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Methods: Literature and Internet were searched to identify software. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software characteristics. Numbers of drugs handled vary from 2 to more than 180, and integration of different population types is available for some programs. Nevertheless, 8 programs offer the ability to add new drug models based on population PK data. 10 computer tools incorporate Bayesian computation to predict dosage regimen (individual parameters are calculated based on population PK models). All of them are able to compute Bayesian a posteriori dosage adaptation based on a blood concentration while 9 are also able to suggest a priori dosage regimen, only based on individual patient covariates. Among those applying Bayesian analysis, MM-USC*PACK uses a non-parametric approach. The top 2 programs emerging from this benchmark are MwPharm and TCIWorks. Others programs evaluated have also a good potential but are less sophisticated or less user-friendly.¦Conclusions: Whereas 2 software packages are ranked at the top of the list, such complex tools would possibly not fit all institutions, and each program must be regarded with respect to individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Although interest in TDM tools is growing and efforts were put into it in the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capability of data storage and automated report generation.

Diagnostic Tools for Identifying Sleepy Drivers in the Field, RB21-012, 2013

The overarching goal of this project was to identify and evaluate cognitive and behavioral indices that are sensitive to sleep deprivation and may help identify commercial motor vehicle drivers (CMV) who are at-risk for driving in a sleep deprived state and may prove useful in field tests administered by officers. To that end, we evaluated indices of driver physiognomy (e.g., yawning, droopy eyelids, etc.) and driver behavioral/cognitive state (e.g. distracted driving) and the sensitivity of these indices to objective measures of sleep deprivation. The measures of sleep deprivation were sampled on repeated occasions over a period of 3.5-months in each of 44 drivers diagnosed with Obstructive Sleep Apnea (OSA) and 22 controls (matched for gender, age within 5 years, education within 2 years, and county of residence for rural vs. urban driving). Comprehensive analyses showed that specific dimensions of driver physiognomy associated with sleepiness in previous research and face-valid composite scores of sleepiness did not: 1) distinguish participants with OSA from matched controls; 2) distinguish participants before and after PAP treatment including those who were compliant with their treatment; 3) predict levels of sleep deprivation acquired objectively from actigraphy watches, not even among those chronically sleep deprived. Those findings are consistent with large individual differences in driver physiognomy. In other words, when individuals were sleep deprived as confirmed by actigraphy watch output they did not show consistently reliable behavioral markers of being sleep deprived. This finding held whether each driver was compared to him/herself with adequate and inadequate sleep, and even among chronically sleep deprived drivers. The scientific evidence from this research study does not support the use of driver physiognomy as a valid measure of sleep deprivation or as a basis to judge whether a CMV driver is too fatigued to drive, as on the current Fatigued Driving Evaluation Checklist.. Fair and accurate determinations of CMV driver sleepiness in the field will likely require further research on alternative strategies that make use of a combination of information sources besides driver physiognomy, including work logs, actigraphy, in vehicle data recordings, GPS data on vehicle use, and performance tests.

Traitement chronique de l'hypertension arterielle par un inhibiteur de l'enzyme de conversion de l'angiotensine. [Chronic treatment of hypertension by an inhibitor of angiotensin converting enzyme]

Captopril, or SQ 14,225 an orally active inhibitor of angiotensin-converting enzyme, produced a significant blood pressure reduction in 26 hypertensives. This new drug, alone or combined with a diuretic, has normalized the blood pressure of the 22 patients on long-term treatment.

A next step in adeno-associated virus-mediated gene therapy for neurological diseases: regulation and targeting.

Recombinant adeno-associated virus (rAAV) vectors mediating long term transgene expression are excellent gene therapy tools for chronic neurological diseases. While rAAV2 was the first serotype tested in the clinics, more efficient vectors derived from the rh10 serotype are currently being evaluated and other serotypes are likely to be tested in the near future. In addition, aside from the currently used stereotaxy-guided intraparenchymal delivery, new techniques for global brain transduction (by intravenous or intra-cerebrospinal injections) are very promising. Various strategies for therapeutic gene delivery to the central nervous system have been explored in human clinical trials in the past decade. Canavan disease, a genetic disease caused by an enzymatic deficiency, was the first to be approved. Three gene transfer paradigms for Parkinson's disease have been explored: converting L-dopa into dopamine through AADC gene delivery in the putamen; synthesizing GABA through GAD gene delivery in the overactive subthalamic nucleus and providing neurotrophic support through neurturin gene delivery in the nigro-striatal pathway. These pioneer clinical trials demonstrated the safety and tolerability of rAAV delivery in the human brain at moderate doses. Therapeutic effects however, were modest, emphasizing the need for higher doses of the therapeutic transgene product which could be achieved using more efficient vectors or expression cassettes. This will require re-addressing pharmacological aspects, with attention to which cases require either localized and cell-type specific expression or efficient brain-wide transgene expression, and when it is necessary to modulate or terminate the administration of transgene product. The ongoing development of targeted and regulated rAAV vectors is described.