Benchmarking sobre técnicas de otimização para modelos de apoio à decisão na medicina intensiva

Dissertação de mestrado integrado em Engenharia e Gestão de Sistemas de Informação

Big data e data analysis: visualização de informação

Dissertação de mestrado integrado em Engenharia e Gestão de Sistemas de Informação

Incorporation of antimicrobial peptides on functionalized cotton gauzes for medical applications

A large group of low molecular weight natural compounds that exhibit antimicrobial activity has been isolated from animals and plants during the past two decades. Among them, peptides are the most widespread resulting in a new generation of antimicrobial agents with higher specific activity. In the present study we have developed a new strategy to obtain antimicrobial wound-dressings based on the incorporation of antimicrobial peptides into polyelectrolyte multilayer films built by the alternate deposition of polycation (chitosan) and polyanion (alginic acid sodium salt) over cotton gauzes. Energy dispersive X ray microanalysis technique was used to determine if antimicrobial peptides penetrated within the films. FTIR analysis was performed to assess the chemical linkages, and antimicrobial assays were performed with two strains: Staphylococcus aureus (Gram-positive bacterium) and Klebsiella pneumonia (Gram-negative bacterium). Results showed that all antimicrobial peptides used in this work have provided a higher antimicrobial effect (in the range of 4 log–6 log reduction) for both microorganisms, in comparison with the controls, and are non-cytotoxic to normal human dermal fibroblasts at the concentrations tested.

Contributos dos ambientes digitais online para a aprendizagem em contexto de atividades de apoio extraescolar

Dissertação de mestrado em Ciências da Educação (área de especialização em Tecnologia Educativa)

Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring

OBJECTIVE: A double-blind, placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of trandolapril, an angiotensin I converting enzyme inhibitor, in the treatment of mild-to-moderate systemic arterial hypertension. METHODS: Of 262 patients enrolled in this study, 127 were treated with trandolapril 2 mg/day for 8 consecutive weeks, and the remaining 135 patients received placebo for the same period of time. Reduction in blood pressure (BP) and the occurrence of adverse events during this period were evaluated in both groups. RESULTS: Significant reductions in both systolic and diastolic pressures were observed in patients treated with trandolapril when compared with those on placebo. Antihypertensive efficacy was achieved in 57.5% of the patients on trandolapril and in 42% of these normal values of BP were obtained. The efficacy of trandolapril was similar in all centers, regardless of the area of the country. In a subset of 30 patients who underwent ABPM, responders showed a significant hypotensive effect to trandolapril throughout the 24 hour day. The adverse event profile was similar in both trandolapril and placebo groups. CONCLUSION: Our results demonstrate, for the first time in a large group of hypertensive patients from different regions in Brazil, good efficacy and tolerability of trandolapril during treatment of mild-to-moderate essential systemic hypertension.

Advances in preservation of fruits and vegetables with bioactive coatings

Bioactive compounds are a large group of compounds (antimicrobials, antioxidants, nutrients, etc.), but its use in edible fi lms and coatings for application on fruits and vegetables has been very important because nowadays the consumers demand fruits and vegetables that are fresh, healthy, high quality and easy to prepare. A number of investigations have shown that the use of additives in edible fi lms and coatings improve its functionability and provide compounds for human health. However, it is necessary to continue research that can generate specifi c or tailor-made edible fi lms and coatings for each product with the best characteristics for preservation. In this review we present and analyze the concepts, progress and perspectives in the design and application of edible fi lms and coatings for fruits and vegetables in order to defi ne the challenges and opportunities that this topic of study in the fi eld of science, technology and food engineering.

Is sociality driven by the costs of dispersal or the benefits of philopatry? A role for kin-discrimination mechanisms.

The role of ecological constraints in promoting sociality is currently much debated. Using a direct-fitness approach, we show this role to depend on the kin-discrimination mechanisms underlying social interactions. Altruism cannot evolve under spatially based discrimination, unless ecological constraints prevent complete dispersal. Increasing constraints enhances both the proportion of philopatric (and thereby altruistic) individuals and the level of altruistic investments conceded in pairwise interactions. Familiarity-based discrimination, by contrast, allows philopatry and altruism to evolve at significant levels even in the absence of ecological constraints. Increasing constraints further enhances the proportion of philopatric (and thereby altruistic) individuals but not the level of altruism conceded. Ecological constraints are thus more likely to affect social evolution in species in which restricted cognitive abilities, large group size, and/or limited period of associative learning force investments to be made on the basis of spatial cues.

The Good, the Bad and the Populist: A Model of Political Agency with Emotional Voters

This paper attempts to extend existing models of political agency to an environment in which voting may be divided between informed and instrumental, informed and ‘expressive’ (Brennan and Lomasky (1993)) and uninformed due to ‘rational irrationality’ (Caplan (2007)). It constructs a model where politicians may be good, bad or populist. Populists are more willing than good politicians to pander to voters who may choose inferior policies in a large-group electoral setting because their vote is insignificant compared with those that voters would choose were their vote decisive in determining the electoral outcome. Bad politicians would ideally like to extract tax revenue for their own ends. Initially we assume the existence of only good and populist politicians. The paper investigates the incentives for good politicians to pool with or separate from populists and focuses on three key issues – (1) how far the majority of voter’s preferences are from those held by the better informed incumbent politician (2) the extent to which the population exhibits rational irrationality and expressiveness (jointly labelled as emotional) and (3) the cost involved in persuading uninformed voters to change their views in terms of composing messages and spreading them. This paper goes on to consider how the inclusion of bad politicians may affect the behaviour of good politicians and suggests that a small amount of potential corruption may be socially useful. It is also argued that where bad politicians have an incentive to mimic the behaviour of good and populist politicians, the latter types of politician may have an incentive to separate from bad politicians by investing in costly public education signals. The paper also discusses the implications of the model for whether fiscal restraints should be soft or hard.

What you need to know about E. Coli 0157

E. coli O157 belongs to a large group of bacteria called Escherichia coli (or E. coli for short). Many E. coli are harmless and they occur naturally in the gut of animals and humans. One of these, E. coli O157, which is a harmless germ in cattle can cause a serious disease in humans.

Long-term risk of incident type 2 diabetes and measures of overall and regional obesity: the EPIC-InterAct case-cohort study

BACKGROUND Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI). METHODS AND FINDINGS The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5-22.4 kg/m(2)) with a low WC (<94/80 cm in men/women), the hazard ratio of T2D was 22.0 (95% confidence interval 14.3; 33.8) in men and 31.8 (25.2; 40.2) in women with grade 2 obesity (BMI≥35 kg/m(2)) and a high WC (>102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50-103 per 1,000 person-years in men and 28-74 per 1,000 person-years in women). CONCLUSIONS WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.

Viri, Remote execution of Python scripts

Viri is a system for automatic distribution and execution of Python code on remote machines. This is especially useful when dealing with a large group of hosts.With Viri, Sysadmins can write their own scripts, and easily distribute and execute them on any number of remote machines. Depending on the number of computers to administrate, Viri can save thousands of hours, that Sysadmins would spend transferring files, logging into remote hosts, and waiting for the scripts to finish. Viri automates the whole process.Viri can also be useful for remotely managing host settings. It should work together with an application where the information about hosts would be maintained. This information can include cron tasks, firewall rules, backup settings,... After a simple Integration of this application with your Viri infrastructure, you can change any settings in the application, and see how it gets applied on the target host automatically.

Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years.

BACKGROUND: Age and the Glasgow Coma Scale (GCS) score on admission are considered important predictors of outcome after traumatic brain injury. We investigated the predictive value of the GCS in a large group of patients whose computerised multimodal bedside monitoring data had been collected over the previous 10 years. METHODS: Data from 358 subjects with head injury, collected between 1992 and 2001, were analysed retrospectively. Patients were grouped according to year of admission. Glasgow Outcome Scores (GOS) were determined at six months. Spearman's correlation coefficients between GCS and GOS scores were calculated for each year. RESULTS: On average 34 (SD: 7) patients were monitored every year. We found a significant correlation between the GCS and GOS for the first five years (overall 1992-1996: r = 0.41; p<0.00001; n = 183) and consistent lack of correlations from 1997 onwards (overall 1997-2001: r = 0.091; p = 0.226; n = 175). In contrast, correlations between age and GOS were in both time periods significant and similar (r = -0.24 v r = -0.24; p<0.002). CONCLUSIONS: The admission GCS lost its predictive value for outcome in this group of patients from 1997 onwards. The predictive value of the GCS should be carefully reconsidered when building prognostic models incorporating multimodality monitoring after head injury.

Recanalization and Collaterals Predict Outcome in Proximal MCA Occlusion, but neither Penumbra nor Core of Stroke

Data on new predictors of outcome include penumbra core or collaterals.Objective: To test the predictive value of recanalization, collaterals, penumbra and core of ischemia for functional outcome in a large group of patients with MCA occlusion. Method: Consecutive events included prospectively in the Acute Stroke Registry and Analysis of Lausanne from April 2002 to April 2009 with an acute stroke due to proximal MCA occlusion (M1) were considered for analysis. Acute CTA were reviewed to grade the collaterals (dichotomized in poor __50% or good _50% compared to the normal side) and localization of M1 occlusion (proximal or mid-distal). Acute CTP were reviewed and reconstructed to determine penumbra, core and stroke index (penumbra/penumbra_core) of brain ischemia. Good outcome was defined by mRS 0-2 at 3 months.Results: Among 242 events (115 male, mean NIHSS 18.1, SD 5.8, mean age 66, SD 15), 42% were treated with intravenous thrombolysis, and 3% with intraarterial thrombolysis. Collateral status was rated as poor in 53% of events and proximal M1 occlusion was present in 64%. Recanalization determined at 24 hours with CTA was complete in 26% events and partial/absent in 54%.CTP was available for 212 events. Mean penumbra was 88.6 cm3 (median 84.4, SD 53.8), mean core was 54.1 cm3 (median 46.2, SD 45.7) and stroke index was 64% (median 68%, SD 25%). Good outcome was observed in 87 events (36%) and was associated in multivariate logistic regression with thrombolysis (p_0.02, OR_2.5, 95% CI 1.2-5.4), recanalization (p_0.001, OR_4.1, 95% CI 1.9-8.9), lower NIHSS (p_0.001, OR_0.84, 95% CI 0.78-0.91), male gender (p_0.01, OR_2.8, 95% CI 1.3-5.9), mRS prior to stroke (p_0.02, OR_0.5, 95% CI 0.28-0.9) and good collateral status (p_0.005, OR_3, 95% CI 1.4-6.4). Nor penumbra, nor core, nor stroke index were significant in the multivariate model, even if an association was present in the univariate model between good functional outcome and penumbra (p_0.004, OR_1.008, 95% CI 1.003-1.01), core (p_0.001, OR_0.98, 95% CI 0.976-0.99) and strokeindex (p_0.001, OR_16.7, 95% CI 4.6 59.9).Conclusion: MCA recanalization is the best predictor for good functional outcome, followed by collateral status. CTP data did not predict the functional outcome in our large group of M1 occlusion. Author Disclosures: C. Odier: None. P. Michel: Research Grant; Significant; Paion, Lundbeck. Speakers; Modest; Boehringer-Ingelheim. Consultant/Advisory Board; Modest; Boehringer- Ingelheim. Consultant/Advisory Board; Significant; Servier, Lundbeck.

Current drug discovery strategies against arenavirus infections.

Arenaviruses are a large group of emerging viruses including several causative agents of severe hemorrhagic fevers with high mortality in man. Considering the number of people affected and the currently limited therapeutic options, novel efficacious therapeutics against arenaviruses are urgently needed. Over the past decade, significant advances in knowledge about the basic virology of arenaviruses have been accompanied by the development of novel therapeutics targeting different steps of the arenaviral life cycle. High-throughput, small-molecule screens identified potent and broadly active inhibitors of arenavirus entry that were instrumental for the dissection of unique features of arenavirus fusion. Novel inhibitors of arenavirus replication have been successfully tested in animal models and hold promise for application in humans. Late in the arenavirus life cycle, the proteolytic processing of the arenavirus envelope glycoprotein precursor and cellular factors critically involved virion assembly and budding provide further promising 'druggable' targets for novel therapeutics to combat human arenavirus infection.

Cytochrome P450 1A2 activity and inducibility: impact of smoking, smoking cessation and genetic polymorphisms

Aims: Cytochrome P4501A2 (CYP1A2) is involved in the metabolism of severaldrugs (clozapine, olanzapine, theopylline, caffeine, etc) and is induced by smoking.This can result in decreased plasma levels of drugs metabolized by thisisoenzyme, causing a decrease in therapeutic response. After quitting smoking,increased plasma levels can lead to adverse effects of the concerned drugs, such asconfusion and seizures, described under clozapine treatment. The present studyaimed to examine the variation of CYP1A2 activity in a large group of smokersbefore and after smoking cessation. Moreover, we aimed to determine whethergenetic polymorphisms of CYP1A2 gene could influence the inducibility ofCYP1A2. Methods: CYP1A2 activity was determined by the paraxanthine/caffeineratio in 194 smokers and in 118 of them being abstinent during a 4-weekperiod. Participants were genotyped for CYP1A2*1F (rs762551), *1D(rs35694136) and *1C (rs2069514) polymorphisms. Results: Smokers had higherCYP1A2 activity (1.55-fold; p < 0.0001). Individual change of CYP1A2 activityafter smoking cessation ranged from 1.0-fold (no change) to 7.3-fold decreasedactivity. In five participants with low initial CYP1A2 activity, an increase wasobserved after smoking cessation. During smoking, CYP1A2*1F (p = 0.005), CYP1A2*1D (p = 0.014), the number of cigarettes/day (p = 0.012), contraceptives use(p < 0.001) and - 163A/- 2467T/- 3860G haplotype (p = 0.002) influencedCYP1A2 activity, while after quitting smoking, CYP1A2*1F (p = 0.017) and contraceptives(p = 0.05) did. No influence of CYP1A2 polymorphisms on the inducibilityof CYP1A2 was observed. Conclusion: Higher CYP1A2 activity wasmeasured in smokers, but with a large interindividual variability of its inductionby smoking. Careful clinical management with the help of therapeutic drug monitoringis therefore needed for patients receiving drugs which are metabolized byCYP1A2, who stop or start smoking. Unidentified genetic variations in theCYP1A2 gene and/or in other genes controlling CYP1A2 activity and other environmentalfactors could be responsible of the observed differences in CYP1A2enzymatic activity and inducibility.