Diversity of Odonata (Insecta) in lotic systems from Serra da Bodoquena, Mato Grosso do Sul State, Brazil

Diversity of Odonata (Insecta) in lotic systems from Serra da Bodoquena, Mato Grosso do Sul State, Brazil. A systematic survey was carried out in four lotic systems from Serra da Bodoquena, the largest natural forests of the State, from August 2007 to November 2008. 548 specimens belonging to 33 species, distributed in 5 families were sampled. Libellulidae was dominant, with 13 species, followed by Gomphidae, Coenagrionidae, Protoneuridae and Calopterygidae.

El Misterio de la biblioteca Mil.lènium o cómo promover relaciones colaborativas desde la participación del alumnado = The Mystery of the Mil.lènium Library: How to Promote Collaborative Relationships Through Student Participation

La pedagogía crítica acentúa la falta de neutralidad de la escuela respecto a las relaciones de poder que existen en la sociedad. Su propuesta consiste en modificar las relaciones de poder en el aula en el sentido de transformar las relaciones coercitivas –las que reproducen las relaciones existentes– en relaciones colaborativas partiendo del reconocimiento y la participación de los alumnos en las actividades escolares. Desde esta perspectiva, uno de los objetivos de las actividades es que los niños produzcan «textos identitarios», entendidos como artefactos que los alumnos se pueden apropiar para promover su desarrollo cognitivo. El artículo muestra el trabajo educativo integrado desde Educación Infantil hasta 6.º de Primaria de una escuela de la provincia de Girona en la que el 97% de los alumnos es de origen extranjero y cuyo propósito es incrementar las habilidades lingüísticas orales y escritas en la lengua escolar, así como la utilización de otros lenguajes multimedia. La unidad didáctica consiste en la elaboración de un cuento a lo largo de un curso escolar por parte de todo el alumnado con la ayuda de los profesores, de dos autores y de tres ilustradores. Cada ciclo escolar decide los personajes y el escenario y explicita textualmente el transcurso de la acción. Los ilustradores producen las imágenes y los autores posibilitan la transición de aquello que ha elaborado un ciclo al producto del siguiente. La actividad basada en la participación y la utilización de procedimientos democráticos de decisión se inserta en la propuesta educativa y lingüística de la escuela, así como en sus concreciones curriculares. Los resultados muestran que los textos construidos por los niños se apoyan en sus «fondos de conocimiento» sociales y familiares y constituyen una fuente de progreso en la consecución de las competencias básicas y en la construcción de valores democráticos

Applicability of a distributed watershed pollution model in a data-poor environment in Santa Catarina State, Brazil

Intensification of agricultural production without a sound management and regulations can lead to severe environmental problems, as in Western Santa Catarina State, Brazil, where intensive swine production has caused large accumulations of manure and consequently water pollution. Natural resource scientists are asked by decision-makers for advice on management and regulatory decisions. Distributed environmental models are useful tools, since they can be used to explore consequences of various management practices. However, in many areas of the world, quantitative data for model calibration and validation are lacking. The data-intensive distributed environmental model AgNPS was applied in a data-poor environment, the upper catchment (2,520 ha) of the Ariranhazinho River, near the city of Seara, in Santa Catarina State. Steps included data preparation, cell size selection, sensitivity analysis, model calibration and application to different management scenarios. The model was calibrated based on a best guess for model parameters and on a pragmatic sensitivity analysis. The parameters were adjusted to match model outputs (runoff volume, peak runoff rate and sediment concentration) closely with the sparse observed data. A modelling grid cell resolution of 150 m adduced appropriate and computer-fit results. The rainfall runoff response of the AgNPS model was calibrated using three separate rainfall ranges (< 25, 25-60, > 60 mm). Predicted sediment concentrations were consistently six to ten times higher than observed, probably due to sediment trapping along vegetated channel banks. Predicted N and P concentrations in stream water ranged from just below to well above regulatory norms. Expert knowledge of the area, in addition to experience reported in the literature, was able to compensate in part for limited calibration data. Several scenarios (actual, recommended and excessive manure applications, and point source pollution from swine operations) could be compared by the model, using a relative ranking rather than quantitative predictions.

Land-use systems affect Archaeal community structure and functional diversity in western Amazon soils

The study of the ecology of soil microbial communities at relevant spatial scales is primordial in the wide Amazon region due to the current land use changes. In this study, the diversity of the Archaea domain (community structure) and ammonia-oxidizing Archaea (richness and community composition) were investigated using molecular biology-based techniques in different land-use systems in western Amazonia, Brazil. Soil samples were collected in two periods with high precipitation (March 2008 and January 2009) from Inceptisols under primary tropical rainforest, secondary forest (5-20 year old), agricultural systems of indigenous people and cattle pasture. Denaturing gradient gel electrophoresis of polymerase chain reaction-amplified DNA (PCR-DGGE) using the 16S rRNA gene as a biomarker showed that archaeal community structures in crops and pasture soils are different from those in primary forest soil, which is more similar to the community structure in secondary forest soil. Sequence analysis of excised DGGE bands indicated the presence of crenarchaeal and euryarchaeal organisms. Based on clone library analysis of the gene coding the subunit of the enzyme ammonia monooxygenase (amoA) of Archaea (306 sequences), the Shannon-Wiener function and Simpson's index showed a greater ammonia-oxidizing archaeal diversity in primary forest soils (H' = 2.1486; D = 0.1366), followed by a lower diversity in soils under pasture (H' = 1.9629; D = 0.1715), crops (H' = 1.4613; D = 0.3309) and secondary forest (H' = 0.8633; D = 0.5405). All cloned inserts were similar to the Crenarchaeota amoA gene clones (identity > 95 %) previously found in soils and sediments and distributed primarily in three major phylogenetic clusters. The findings indicate that agricultural systems of indigenous people and cattle pasture affect the archaeal community structure and diversity of ammonia-oxidizing Archaea in western Amazon soils.

2011 Road Use Tax Fund (RUTF) Study A report to the Iowa Legislature, per 2011 Iowa Code Section 307.31

The transportation system is in demand 24/7 and 365 days a year irrespective of neither the weather nor the conditions. Iowa’s transportation system is an integral and essential part of society serving commerce and daily functions of all Iowans across the state. A high quality transportation system serves as the artery for economic activity and, the condition of the infrastructure is a key element for our future growth opportunities. A key component of Iowa’s transportation system is the public roadway system owned and maintained by the state, cities and counties. In order to regularly re-evaluate the conditions of Iowa’s public roadway infrastructure and assess the ability of existing revenues to meet the needs of the system, the Iowa Department of Transportation’s 2006 Road Use Tax Fund (RUTF) report to the legislature included a recommendation that a study be conducted every five years. That recommendation was included in legislation adopted in 2007 and signed into law. The law specifically requires the following (2011 Iowa Code Section 307.31): •“The department shall periodically review the current revenue levels of the road use tax fund and the sufficiency of those revenues for the projected construction and maintenance needs of city, county, and state governments in the future. The department shall submit a written report to the general assembly regarding its findings by December 31 every five years, beginning in 2011. The report may include recommendations concerning funding levels needed to support the future mobility and accessibility for users of Iowa's public road system.” •“The department shall evaluate alternative funding sources for road maintenance and construction and report to the general assembly at least every five years on the advantages and disadvantages and the viability of alternative funding mechanisms.” Consistent with this requirement, the Iowa Department of Transportation (DOT) has prepared this study. Recognizing the importance of actively engaging with the public and transportation stakeholders in any discussion of public roadway conditions and needs, Governor Terry E. Branstad announced on March 8, 2011, the creation of, and appointments to, the Governor’s Transportation 2020 Citizen Advisory Commission (CAC). The CAC was tasked with assisting the Iowa DOT as they assess the condition of Iowa’s roadway system and evaluate current and future funding available to best address system needs. In particular the CAC was directed to gather input from the public and stakeholders regarding the condition of Iowa’s public roadway system, the impact of that system, whether additional funding is needed to maintain/improve the system, and, if so, what funding mechanisms ought to be considered. With this input, the CAC prepared a report and recommendations that were presented to Governor Branstad and the Iowa DOT in November 2011 for use in the development of this study. The CAC’s report is available at www.iowadot.gov/transportation2020/pdfs/CAC%20REPORT%20FINAL%20110211.pdf. The CAC’s report was developed utilizing analysis and information from the Iowa DOT. Therefore, the report forms the basis for this study and the two documents are very similar. Iowa is fortunate to have an extensive public roadway system that provides access to all areas of the state and facilitates the efficient movement of goods and people. However, it is also a tremendous challenge for the state, cities and counties to maintain and improve this system given flattening revenue, lost buying power, changing demands on the system, severe weather, and an aging system. This challenge didn’t appear overnight and for the last decade many studies have been completed to look into the situation and the legislature has taken significant action to begin addressing the situation. In addition, the Iowa DOT and Iowa’s cities and counties have worked jointly and independently to increase efficiency and streamline operations. All of these actions have been successful and resulted in significant changes; however, it is apparent much more needs to be done. A well-maintained, high-quality transportation system reduces transportation costs and provides consistent and reliable service. These are all factors that are critical in the evaluation companies undertake when deciding where to expand or locate new developments. The CAC and Iowa DOT heard from many Iowans that additional investment in Iowa’s roadway system is vital to support existing jobs and continued job creation in the state of Iowa. Beginning June 2011, the CAC met regularly to review material and discuss potential recommendations to address Iowa’s roadway funding challenges. This effort included extensive public outreach with meetings held in seven locations across Iowa and through a Transportation 2020 website hosted by the Iowa DOT (www.iowadot.gov/transportation2020). Over 500 people attended the public meetings held through the months of August and September, with 198 providing verbal or written comment at the meetings or through the website. Comments were received from a wide array of individuals. The public comments demonstrated overwhelming support for increased funding for Iowa’s roads. Through the public input process, several guiding principles were established to guide the development of recommendations. Those guiding principles are: • Additional revenues are restricted for road and bridge improvements only, like 95 percent of the current state road revenue is currently. This includes the fuel tax and registration fees. • State and local governments continue to streamline and become more efficient, both individually and by looking for ways to do things collectively. • User fee concept is preserved, where those who use the roads pay for them, including non¬residents. • Revenue-generating methods equitable across users. • Increase revenue generating mechanisms that are viable now but begin to implement and set the stage for longer-term solutions that bring equity and stability to road funding. • Continue Iowa’s long standing tradition of state roadway financing coming from pay-as-you-go financing. Iowa must not fall into the situation that other states are currently facing where the majority of their new program dollars are utilized to pay the debt service of past bonding. Based on the analysis of Iowa’s public roadway needs and revenue and the extensive work of the Governor’s Transportation 2020 Citizen Advisory Commission, the Iowa DOT has identified specific recommendations. The recommendations follow very closely the recommendations of the CAC (CAC recommendations from their report are repeated in Appendix B). Following is a summary of the recommendations which are fully documented beginning on page 21. 1. Through a combination of efficiency savings and increased revenue, a minimum of $215 million of revenue per year should be generated to meet Iowa’s critical roadway needs. 2. The Code of Iowa should be changed to require the study of the sufficiency of the state’s road funds to meet the road system’s needs every two years instead of every five years to coincide with the biennial legislative budget appropriation schedule. 3.Modify the current registration fee for electric vehicles to be based on weight and value using the same formula that applies to most passenger vehicles. 4.Consistent with existing Code of Iowa requirements, new funding should go to the TIME-21 Fund up to the cap ($225 million) and remaining new funding should be distributed consistent with the Road Use Tax Fund distribution formula. 5.The CAC recommended the Iowa DOT at least annually convene meetings with cities and counties to review the operation, maintenance and improvement of Iowa’s public roadway system to identify ways to jointly increase efficiency. In direct response to this recommendation, Governor Branstad directed the Iowa DOT to begin this effort immediately with a target of identifying $50 million of efficiency savings that can be captured from the over $1 billion of state revenue already provided to the Iowa DOT and Iowa’s cities and counties to administer, maintain and improve Iowa’s public roadway system. This would build upon past joint and individual actions that have reduced administrative costs and resulted in increased funding for improvement of Iowa’s public roadway system. Efficiency actions should be quantified, measured and reported to the public on a regular basis. 6.By June 30, 2012, Iowa DOT should complete a study of vehicles and equipment that use Iowa’s public roadway system but pay no user fees or substantially lower user fees than other vehicles and equipment.

Physical quality of an Oxisol after different periods of management systems

Management systems may lead to a loss of soil physical quality as a result of removal of the plant cover and excessive agricultural mechanization. The hypothesis of this study was that the soil aggregate stability, bulk density, macro- and microporosity, and the S index and saturated hydraulic conductivity may be used as indicators of the soil physical quality. The aim was to study the effects of different periods and managements on the physical attributes of a medium-textured Red Oxisol under soybean and corn for two growing seasons, and determine which layers are most susceptible to variations. A completely randomized experimental design was used with split plots (five treatments and four layers), with four replications. The treatments in 2008/09 consisted of: five years of no-tillage (NTS5), seven years of no-tillage (NTS7), nine years of no-tillage (NTS9), conventional tillage (CTS) and an adjacent area of native forest (NF). The treatments were extended for another year, identified in 2009/10 as: NTS6, NTS8, NTS10, CTS and NF. The soil layers 0-0.05, 0.05-0.10, 0.10-0.20 and 0.20-0.30 m were sampled. The highest S index values were observed in the treatment CTS in the 0-0.05 m layer (0.106) and the 0.05-0.10 m layer (0.099) in 2008/09, and in the 0-0.05 m layer (0.066) in 2009/10. This fact may be associated with soil turnover, resulting in high macroporosity in this treatment. In contrast, in the NTS, limiting macroporosity values were observed in some layers (below 0.10 m³ m-3). Highest aggregate stability as well as the highest saturated hydraulic conductivity (Kθ) values were observed in NF in relation to the other treatments. In 2009/10, the Kθ in NF differed only from NTS10. This study showed that the use of the S index alone cannot be recommended as an absolute indicator of the soil physical quality, even at values greater than 0.035.

Soil water erosion under different cultivation systems and different fertilization rates and forms over 10 years

The action of rain and surface runoff together are the active agents of water erosion, and further influences are the soil type, terrain, soil cover, soil management, and conservation practices. Soil water erosion is low in the no-tillage management system, being influenced by the amount and form of lime and fertilizer application to the soil, among other factors. The aim was to evaluate the effect of the form of liming, the quantity and management of fertilizer application on the soil and water losses by erosion under natural rainfall. The study was carried out between 2003 and 2013 on a Humic Dystrupept soil, with the following treatments: T1 - cultivation with liming and corrective fertilizer incorporated into the soil in the first year, and with 100 % annual maintenance fertilization of P and K; T2 - surface liming and corrective fertilization distributed over five years, and with 75 % annual maintenance fertilization of P and K; T3 - surface liming and corrective fertilization distributed over three years, and with 50 % annual maintenance fertilization of P and K; T4 - surface liming and corrective fertilization distributed over two years, and with 25 % annual maintenance fertilization of P and K; T5 - fallow soil, without liming or fertilization. In the rotation the crops black oat (Avena strigosa ), soybean (Glycine max ), common vetch (Vicia sativa ), maize (Zea mays ), fodder radish (Raphanus sativus ), and black beans (Phaseolus vulgaris ). The split application of lime and mineral fertilizer to the soil surface in a no-tillage system over three and five years, results in better control of soil losses than when split in two years. The increase in the amount of fertilizer applied to the soil surface under no-tillage cultivation increases phytomass production and reduces soil loss by water erosion. Water losses in treatments under no-tillage cultivation were low in all crop cycles, with a similar behavior as soil losses.

International collaborative proficiency study of Human Papillomavirus type 16 serology.

We performed an international proficiency study of Human Papillomavirus (HPV) type 16 serology. A common methodology for serology based on virus-like particle (VLP) ELISA was used by 10 laboratories in 6 continents. The laboratories used the same VLP reference reagent, which was selected as the most stable, sensitive and specific VLP preparation out of VLPs donated from 5 different sources. A blinded proficiency panel consisting of 52 serum samples from women with PCR-verified HPV 16-infection, 11 control serum samples from virginal women and the WHO HPV 16 International Standard (IS) serum were distributed. The mean plus 3 standard deviations of the negative control serum samples was the most generally useful "cut-off" criterion for distinguishing positive and negative samples. Using sensitivity of at least 50% and a specificity of 100% as proficiency criteria, 6/10 laboratories were proficient. In conclusion, an international Standard Operating Procedure for HPV serology, an international reporting system in International Units (IU) and a common "cut-off" criterion have been evaluated in an international HPV serology proficiency study.

Effectiveness of Work Zone Intelligent Transportation Systems, TPF-5(081), 2013

In the last decade, Intelligent Transportation Systems (ITS) have increasingly been deployed in work zones by state departments of transportation. Also known as smart work zone systems they improve traffic operations and safety by providing real-time information to travelers, monitoring traffic conditions, and managing incidents. Although there have been numerous ITS deployments in work zones, a framework for evaluating the effectiveness of these deployments does not exist. To justify the continued development and implementation of smart work zone systems, this study developed a framework to determine ITS effectiveness for specific work zone projects. The framework recommends using one or more of five performance measures: diversion rate, delay time, queue length, crash frequency, and speed. The monetary benefits and costs of ITS deployment in a work zone can then be computed using the performance measure values. Such ITS computations include additional considerations that are typically not present in standard benefit-cost computations. The proposed framework will allow for consistency in performance measures across different ITS studies thus allowing for comparisons across studies or for meta analysis. In addition, guidance on the circumstances under which ITS deployment is recommended for a work zone is provided. The framework was illustrated using two case studies: one urban work zone on I-70 and one rural work zone on I-44, in Missouri. The goals of the two ITS deployments were different – the I-70 ITS deployment was targeted at improving mobility whereas the I-44 deployment was targeted at improving safety. For the I-70 site, only permanent ITS equipment that was already in place was used for the project and no temporary ITS equipment was deployed. The permanent DMS equipment serves multiple purposes, and it is arguable whether that cost should be attributed to the work zone project. The data collection effort for the I-70 site was very significant as portable surveillance captured the actual diversion flows to alternative routes. The benefit-cost ratio for the I-70 site was 2.1 to 1 if adjusted equipment costs were included and 6.9 to 1 without equipment costs. The safety-focused I-44 ITS deployment had an estimated benefit-cost ratio of 3.2 to 1.

Distributing State Road Use Tax Funds to Counties, HR-386, 1996

Iowa's county road system serves many critical functions in a changing environment. Many counties with very different social, economic, and demographic circumstances do not have adequate resources to provide the desired level of service on their secondary road systems. How the state's Road Use Tax Fund (RUTF) is distributed among counties is therefore of great importance. This report presents the results of a year-long study of how to distribute RUTF resources among Iowa's 99 counties. The project was undertaken at the request of county engineers who wish to replace the current method of allocation with one that is more stable, comprehensible, and predictable. This report describes the current allocation method, examines how other states distribute road funds to counties, and discusses potential allocation factors that could be included in a revised procedure. The process undertaken to narrow the range of possible formulas and determine the one to recommend is summarized. Finally, the report presents the allocation formula recommended by the project advisory committee, along with how it would operate.

Accuracy of out-of-field dose calculation of tomotherapy and cyberknife treatment planning systems: A dosimetric study.

PURPOSE: Late toxicities such as second cancer induction become more important as treatment outcome improves. Often the dose distribution calculated with a commercial treatment planning system (TPS) is used to estimate radiation carcinogenesis for the radiotherapy patient. However, for locations beyond the treatment field borders, the accuracy is not well known. The aim of this study was to perform detailed out-of-field-measurements for a typical radiotherapy treatment plan administered with a Cyberknife and a Tomotherapy machine and to compare the measurements to the predictions of the TPS. MATERIALS AND METHODS: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The measured dose distributions from 6 MV intensity-modulated treatment beams for CyberKnife and TomoTherapy machines were compared to the dose calculations from the TPS. RESULTS: The TPS are underestimating the dose far away from the target volume. Quantitatively the Cyberknife underestimates the dose at 40cm from the PTV border by a factor of 60, the Tomotherapy TPS by a factor of two. If a 50% dose uncertainty is accepted, the Cyberknife TPS can predict doses down to approximately 10 mGy/treatment Gy, the Tomotherapy-TPS down to 0.75 mGy/treatment Gy. The Cyberknife TPS can then be used up to 10cm from the PTV border the Tomotherapy up to 35cm. CONCLUSIONS: We determined that the Cyberknife and Tomotherapy TPS underestimate substantially the doses far away from the treated volume. It is recommended not to use out-of-field doses from the Cyberknife TPS for applications like modeling of second cancer induction. The Tomotherapy TPS can be used up to 35cm from the PTV border (for a 390 cm(3) large PTV).

Survival of pathogens on soybean debris under no-tillage and conventional tillage systems

A study was conducted in the subtropical area of Southern Brazil to determine the survival of pathogens in soybean residues under conventional and no-tillage cultivation systems from March to September of 1998 and 1999. The pathogens most frequently isolated were Colletotrichum truncatum, Phomopsis spp., Cercospora kikuchii, Fusarium spp., Macrophomina phaseolina, and Rhizoctonia solani. Other fungi isolated were Myrothecium roridum, Penicillium sp., Chaetomium sp., Epicoccum sp., Corynespora cassiicola and Trichoderma sp. The percent of survival of each pathogen varied according to the month and the year. Survival of C. truncatum, Phomopsis spp. and C. kikuchii were significantly reduced (p<0.05) from the first to the last evaluation either on buried debris or maintained on the soil surface. On the other hand, M. phaseolina and Fusarium spp. were either not affected or favored by burying the debris. The frequency of recovery of Fusarium spp. increased specially in debris kept under the soil. The loss of biomass, measured by debris weight along the period of this study, showed a reduction of 44.4% in the conventional system and 34.9% in the no-tillage system in 1998, when rain was better distributed. In 1999, the reduction was 48.2% and 39.0% for the conventional and no-tillage system, respectively.

How to prescribe nutritional support using computers.

As other intensive care unit (ICU) therapies, nutritional support has become more complex requiring tight supervision and monitoring. It has repeatedly been shown that despite awareness of guidelines and prescription of the recommended amounts of energy (25 kcal/kg), underfeeding remains a prominent problem worldwide. In patients with prolonged stays, overfeeding has also become an issue. This lack of fit between prescription and delivery is largely caused by the lack of visibility of the nutritional results to nurses and clinicians. Computerized systems have brought major improvements, mainly through the customization of nutrition relevant variables in a single place, making them visible. Another important point is the possibility to change the ICU time constant to days and weeks which is the delay relevant for nutritional changes to appear, instead of minutes and hours which are more relevant for critical care.

Controlled delivery of 5-chlorouracil using poly(ortho esters) in filtering surgery for glaucoma.

PURPOSE: To evaluate the antimitotic and toxic effects of 5-chlorouracil (5-CU) and 5-fluorouracil (5-FU) and study their potential to delay filtering bleb closure in the rabbit eye when released by poly(ortho esters) (POE). METHODS: Rabbit Tenon fibroblasts and human conjunctival cells were incubated with various 5-CU and 5-FU concentrations. Antiproliferative effects and toxicity were evaluated at 24 and 72 hours by monotetrazolium, neutral red, and Hoechst tests and cell counting. Mechanisms of cell death were evaluated using TUNEL assay, annexin V binding, immunohistochemistry for anti-apoptosis-inducing factor (AIF) and LEI/L-DNase II. Trabeculectomy was performed in pigmented rabbits. Two hundred microliters of POE loaded with 1% wt/wt 5-FU or 5-CU was injected into the subconjunctival space after surgery. Intraocular pressure (IOP) and bleb persistence were monitored for 150 days. RESULTS: In vitro, 5-FU showed a higher antiproliferative effect and a more toxic effect than 5-CU. 5-FU induced cell necrosis, whereas 5-CU induced mostly apoptosis. The apoptosis induced by 5-CU was driven through a non-caspase-dependent pathway involving AIF and LEI/L-DNase II. In vivo, at 34 days after surgery, the mean IOP in the POE/5-CU-treated group was 83% of the baseline level and only 40% in the POE/5-FU-treated group. At 100 days after surgery, IOP was still decreased in the POE/5-CU group when compared with the controls and still inferior to the preoperative value. The mean long-term IOP, with all time points considered, was significantly (P < 0.0001) decreased in the POE/5-CU-treated group (6.0 +/- 2.4 mm Hg) when compared with both control groups, the trabeculectomy alone group (7.6 +/- 2.9 mm Hg), and the POE alone group (7.5 +/- 2.6 mm Hg). Histologic analysis showed evidence of functioning blebs in the POE-5-CU-treated eyes along with a preserved structure of the conjunctiva epithelium. CONCLUSIONS: The slow release of 5-CU from POE has a longstanding effect on the decrease of IOP after glaucoma-filtering surgery in the rabbit eye. Thus, the slow release of POE/5-CU may be beneficial for the prevention of bleb closure in patients who undergo complicated trabeculectomy.

Automatic filtering and substantiation of drug safety signals

Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions