Is ALT control really necessary for routine ART monitoring in resource poor settings?

2006 AIDS Conference in Toront

Rotational Mobility Analysis of the 3-RFR Class of Spherical Parallel Robots

none4noSpherical parallel manipulators (SPMs) are used to orient a tool in the space with three degrees of freedom exploiting the strengths of a multi-limb architecture. On the other hand, the performance of parallel kinematics machines (PKMs) is often affected by the occurrence of different kinds of singular configurations. The paper aims at characterizing a class of SPMs for which all singularities come to coincide and a single expression is able to describe all the singular configurations of the machines. The study is focused on a class of SPMs with 3-RFR topology (Revolute-Planar-Revolute pairs for each of the three limbs) addressing the mobility and singularity analysis by means of polynomial decomposition and screw theory. The neatness of the equations that are worked out, expressed in a robust formulation based on rotation invariants, allows a straightforward planning of singularity free tasks and simplifies the synthesis of dexterous machines.openCorinaldi, David; Carbonari, Luca; Palpacelli, Matteo-Claudio; Callegari, MassimoCorinaldi, David; Carbonari, Luca; Palpacelli, Matteo-Claudio; Callegari, Massim

Parallel Genetic Algorithms for calibrating Cellular Automata models: Application to lava flows

Cellular Automata are highly nonlinear dynamical systems which are suitable for simulating natural phenomena whose behaviour may be specified in terms of local interactions. The Cellular Automata model SCIARA, developed for the simulation of lava flows, demonstrated to be able to reproduce the behaviour of Etnean events. However, in order to apply the model for the prediction of future scenarios, a thorough calibrating phase is required. This work presents the application of Genetic Algorithms, general-purpose search algorithms inspired to natural selection and genetics, for the parameters optimisation of the modelSCIARA. Difficulties due to the elevated computational time suggested the adoption a Master-Slave Parallel Genetic Algorithm for the calibration of the model with respect to the 2001 Mt. Etna eruption. Results demonstrated the usefulness of the approach, both in terms of computing time and quality of performed simulations

Assortativity Decreases the Robustness of Interdependent Networks

It was recently recognized that interdependencies among different networks can play a crucial role in triggering cascading failures and hence system-wide disasters. A recent model shows how pairs of interdependent networks can exhibit an abrupt percolation transition as failures accumulate. We report on the effects of topology on failure propagation for a model system consisting of two interdependent networks. We find that the internal node correlations in each of the two interdependent networks significantly changes the critical density of failures that triggers the total disruption of the two-network system. Specifically, we find that the assortativity (i.e. the likelihood of nodes with similar degree to be connected) within a single network decreases the robustness of the entire system. The results of this study on the influence of assortativity may provide insights into ways of improving the robustness of network architecture, and thus enhances the level of protection of critical infrastructures

Integration of serum metabolomics into clinical assessment to improve outcome prediction of metastatic soft tissue sarcoma patients treated with trabectedin

Soft tissue sarcomas (STS) are a group of rare and heterogeneous cancers with few diagnostic or prognostic biomarkers. This metabolomics study aimed to identify new serum prognostic biomarkers to improve the prediction of overall survival in patients with metastatic STS. The study enrolled 24 patients treated with the same trabectedin regimen. The baseline serum metabolomics profile, targeted to 68 metabolites encompassing amino acids and bile acids pathways, was quantified by liquid chromatography-tandem mass spectrometry. Correlations between individual metabolomics profiles and overall survival were examined and a risk model to predict survival was built by Cox multivariate regression. The median overall survival of the studied patients was 13.0 months (95% CI, 5.6–23.5). Among all the metabolites investigated, only citrulline and histidine correlated significantly with overall survival. The best Cox risk prediction model obtained integrating metabolomics and clinical data, included citrulline, hemoglobin and patients’ performance status score. It allowed to distinguish patients into a high-risk group with a low median overall survival of 2.1 months and a low-to moderate-risk group with a median overall survival of 19.1 months (p < 0.0001). The results of this metabolomics translation study indicate that citrulline, an amino acid belonging to the arginine metabolism, represents an important metabolic signature that may contribute to explain the high inter-patients overall survival variability of STS patients. The risk prediction model based on baseline serum citrulline, hemoglobin and performance status may represent a new prognostic tool for the early classification of patients with metastatic STS, according to their overall survival expectancy

BCR-ABL1 doubling-times and halving-times may predict CML response to tyrosine kinase inhibitors

In Chronic Myeloid Leukemia (CML), successful treatment requires accurate molecular monitoring to evaluate disease response and provide timely interventions for patients failing to achieve the desired outcomes. We wanted to determine whether measuring BCR-ABL1 mRNA doubling-times (DTs) could distinguish inconsequential rises in the oncogene’s expression from resistance to tyrosine kinase inhibitors (TKIs). Thus, we retrospectively examined BCR-ABL1 evolution in 305 chronic-phase CML patients receiving imatinib mesylate (IM) as a first line treatment. Patients were subdivided in two groups: those with a confirmed rise in BCR-ABL1 transcripts without MR3.0 loss and those failing IM. We found that the DTs of the former patients were significantly longer than those of patients developing IM resistance (57.80 vs. 41.45 days, p = 0.0114). Interestingly, the DT values of individuals failing second-generation (2G) TKIs after developing IM resistance were considerably shorter than those observed at the time of IM failure (27.20 vs. 41.45 days; p = 0.0035). We next wanted to establish if decreases in BCR-ABL1 transcripts would identify subjects likely to obtain deep molecular responses. We therefore analyzed the BCR-ABL1 halving-times (HTs) of a different cohort comprising 174 individuals receiving IM in first line and observed that, regardless of the time point selected for our analyses (6, 12, or 18 months), HTs were significantly shorter in subjects achieving superior molecular responses (p = 0.002 at 6 months; p < 0.001 at 12 months; p = 0.0099 at 18 months). Moreover, 50 patients receiving 2G TKIs as first line therapy and obtaining an MR3.0 (after 6 months; p = 0.003) or an MR4.0 (after 12 months; p = 0.019) displayed significantly shorter HTs than individuals lacking these molecular responses. Our findings suggest that BCR-ABL1 DTs and HTs are reliable tools to, respectively, identify subjects in MR3.0 that are failing their assigned TKI or to recognize patients likely to achieve deep molecular responses that should be considered for treatment discontinuation

New insights into potocki-shaffer syndrome: Report of two novel cases and literature review

Potocki-Shaffer syndrome (PSS) is a rare non-recurrent contiguous gene deletion syndrome involving chromosome 11p11.2. Current literature implies a minimal region with haploinsufficiency of three genes, ALX4 (parietal foramina), EXT2 (multiple exostoses), and PHF21A (craniofacial anomalies, and intellectual disability). The rest of the PSS phenotype is still not associated with a specific gene. We report a systematic review of the literature and included two novel cases. Because deletions are highly variable in size, we defined three groups of patients considering the PSS-genes involved. We found 23 full PSS cases (ALX4, EXT2, and PHF21A), 14 cases with EXT2-ALX4, and three with PHF21A only. Among the latter, we describe a novel male child showing developmental delay, café-au-lait spots, liner postnatal overgrowth and West-like epileptic encephalopathy. We suggest PSS cases may have epileptic spasms early in life, and PHF21A is likely to be the causative gene. Given their subtle presentation these may be overlooked and if left untreated could lead to a severe type or deterioration in the developmental plateau. If our hypothesis is correct, a timely therapy may ameliorate PSS phenotype and improve patients’ outcomes. Our analysis also shows PHF21A is a candidate for the overgrowth phenotype