Water resource management through systemic approach: The case of Lake Bracciano

Today natural water resources are becoming scarce, both due to global climate change but also due to irresponsible behaviour of human beings. Lakes are among the most delicate aquatic systems due to their limited size. The objective of this paper is to propose a System Dynamics model, employed in a real case study regarding the city of Rome and one of its water reserves, the Bracciano Lake, for the evaluation of different strategies and policies to reduce environmental impacts, considering different climatic and context scenarios. The results indicate that, as the system is currently exposed to a high risk of ecological disaster, the situation might worsen, and the disaster effectively happen. Simulation models may help agencies and administrations to explore policies and find solutions to address this fundamental problem, that may become even worst over the next years, given the potential severe consequences deriving from the current global warming trends

Green Fluorescent Protein in the sea urchin: new experimental approaches to transcriptional regulatory analysis in embryos and larvae

The use of Green Fluorescent Protein (GFP) as a reporter for expression transgenes opens the way to several new experimental strategies for the study of gene regulation in sea urchin development. A GFP coding sequence was associated with three different previously studied cis-regulatory systems, viz those of the SM50 gene, expressed in skeletogenic mesenchyme, the CyIIa gene, expressed in archenteron, skeletogenic and secondary mesenchyme, and the Endo16 gene, expressed in vegetal plate, archenteron and midgut. We demonstrate that the sensitivity with which expression can be detected is equal to or greater than that of whole-mount in situ hybridization applied to detection of CAT mRNA synthesized under the control of the same cis-regulatory systems. However, in addition to the important feature that it can be visualized nondestructively in living embryos, GFP has other advantages. First, it freely diffuses even within fine cytoplasmic cables, and thus reveals connections between cells, which in sea urchin embryos is particularly useful for observations on regulatory systems that operate in the syncytial skeletogenic mesenchyme. Second, GFP expression can be dramatically visualized in postembryonic larval tissues. This brings postembryonic larval developmental processes for the first time within the easy range of gene transfer analyses. Third, GFP permits identification and segregation of embryos in which the clonal incorporation of injected DNA has occurred in any particular desired region of the embryo. Thus, we show explicitly that, as expected, GFP transgenes are incorporated in the same nuclei together with other transgenes with which they are co-injected

Improving management effectiveness and overall performance of software development projects through a system dynamics approach

While existing research has mainly focused on project management’s static view, our work investigates the impacts of projects’ structure and behavioural dynamics on their performance, with a specific focus on the influence of some peculiar development processes. A dynamic simulation model of a single phase project was built using the system dynamics methodology. The model integrates several previously developed and tested project structures and adds a separate structure for the negotiation process. Simulations describe the behaviours generated by the interaction of customized development processes in single-phase projects. Project performances are measured in terms of time, quality and cost. Our research aims to show that development processes, as well as shared resource levelling techniques, significantly impact the dynamic behaviour of projects through the feedback, delays and nonlinear relationships which are usually omitted in traditional project management practice, as well as in methods, tools and models, but are very important descriptors of project complexity. Expanding the models used to manage projects to include dynamic features requires a change of focus by researchers and practitioners. The system dynamics methodology provides some of the tools for developing and implementing such an expansion in project models

Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients

Objectives To compare the frequency of previously in vitro-selected integrase mutations (T124A, T124A/S153F, S153Y, T124A/S153Y and L101I/T124A/S153Y) conferring resistance to S/GSK1349572 between HIV-1 subtype B integrase inhibitor (INI)-naive and raltegravir-treated patients. Methods Integrase sequences from 650 INI-naive patients and 84 raltegravir-treated patients were analysed. Results The T124A mutation alone and the combination T124A/L101I were more frequent in raltegravir-failing patients than in INI-naive patients (39.3% versus 24.5%, respectively, P = 0.005 for T124A and 20.2% versus 10.0%, respectively, P = 0.008 for T124A/L101I). The S153Y/F mutations were not detected in any integrase sequence (except for S153F alone, only detected in one INI-naive patient). Conclusions T124A and T124A/L101I, more frequent in raltegravir-treated patients, could have some effect on raltegravir response and their presence could play a role in the selection of other mutations conferring S/GSK1349572 resistance. The impact of raltegravir-mediated changes such as these on the virological response to S/GSK1349572 should be studied further

Estudio e investigaciones realizadas en el LEMIT sobre materiales empleados en edificios históricos

Cuando se abordan problemas de restauración, reparación y conservación de edificios y construcciones de valor histórico se debe realizar, antes de iniciar las tareas de puesta en valor, un estudio integral de las causales que han provocado los deterioros. Esta situación es de primordial importancia, ya que si no se eliminan las causales, rápidamente reaparecen los signos externos de las alteraciones. Sin embargo, muchas de las alteraciones y/o deterioros de las construcciones de valor patrimonial y/o de los materiales que las constituyen se deben, con exclusividad, al pasaje del tiempo (vida en servicio de la construcción). Los materiales empleados en la construcción experimentan procesos de deterioro por reacciones físico, químicas o físico-químicas entre el material y los agentes agresivos o el originado por el crecimiento de microorganismos, en particular algas en sectores húmedos y sombríos y/o líquenes o plantas mayores como por ejemplo helechos. En este trabajo se presentan investigaciones y estudios de distintos materiales constituyentes de construcciones de valor patrimonial, en particular, se analizan ladrillos cerámicos comunes, mezclas de asiento, morteros internos y externos, tejas y materiales de revestimiento (cerámicos, pinturas y papel). Estos estudios fueron realizados para la caracterización de los materiales y/o para disponer de información técnica para su restauración o reemplazo. En todos los casos, se informan las técnicas de caracterización mecánica, física y química empleadas para su evaluación. En algunos casos, se realizan estudios de difracción de rayos X, microscopia electrónica de barrido (SEM), cortes petrográficos, análisis en lupa microscópica y microscopio petrográfico. Además, se han aplicado técnicas para determinar color y rugosidad

A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.

Background: We previously found that a very low geno2pheno false positive rate (FPR ≤2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. Methods: The analysis was performed on 305 HIV-1 B subtype infected drug-naı¨ve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤2; 2–5; 5–10; 10–20; 20–60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥150 cells/mm3) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses. Results: Overall, at therapy start, 27% of patients had FPR ≤10 (6%, FPR ≤2; 7%, FPR 2–5; 14%, FPR 5–10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2–5; 77.5%, FPR 5–10; 71.7%, FPR 10–20; 81.8%, FPR 20–60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20–0.71], p = 0.003) and to achieve virological success (0.50 [0.26–0.94], p = 0.031) than those with pre-HAART FPR >60%. Conclusions: Beyond the genotypically-inferred tropism determination, FPR ≤2% predicts both a poor immunological reconstitution and a lower virological response in drug-naı¨ve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability

The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing

The false-positive rate (FPR) is a percentage-score provided by Geno2Pheno-algorithm indicating the likelihood that a V3-sequence is falsely predicted as CXCR4-using. We evaluated the correlation between FPR obtained by V3 population-sequencing and the burden of CXCR4-using variants detected by V3 ultra-deep sequencing (UDPS) and Enhanced-Sensitivity Trofile assay (ESTA)

Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease

Objectives: To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options. Methods: HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm. Results: Overall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33-211) and 312 (155-517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%-10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count &lt;200 cells/mm3, who were perinatally infected and with a long treatment history significantly increased as FPR levels decreased. Regarding resistance, 933 (67.5%) individuals accumulated at least one class resistance, with 52.7%, 48.2%, 23.5% and 13.2% of individuals showing resistance to NRTIs, NNRTIs, PIs and INIs; while 23.2%, 27.2%, 14.3% and 2.8% harboured resistance to 1, 2, 3 and 4 classes, respectively. Individuals with FPR ≤5% showed a significantly higher level of resistance to PIs, NRTIs and INIs compared with others. The proportion of individuals harbouring strains susceptible to ≤2 active drugs was only about 2%; nonetheless, this proportion doubled (4.6%) in patients infected with FPR ≤5%. Conclusions: Our findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease