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

2006 AIDS Conference in Toront

Characterization of two new alleles at the goat CSN1S2 locus.

Two novel alleles at the goat CSN1S2 locus have been identified: CSN1S2(F) and CSN1S2(D). Sequence analyses revealed that the CSN1S2(F) allele is characterized by a G --> A transition at the 13th nucleotide in exon 3 changing the seventh amino acid of the mature protein from Val to Ile. The CSN1S2(D) allele, apparently associated with a decreased synthesis of alpha s2-casein, is characterized by a 106-bp deletion, involving the last 11 bp of the exon 11 and the first 95 bp of the following intron. Methods (PCR-RFLP and PCR) for identification of carriers of these alleles have been developed

On random flights with non-uniformly distributed directions

This paper deals with a new class of random flights $\underline{\bf X}_d(t),t>0,$ defined in the real space $\mathbb{R}^d, d\geq 2,$ characterized by non-uniform probability distributions on the multidimensional sphere. These random motions differ from similar models appeared in literature which take directions according to the uniform law. The family of angular probability distributions introduced in this paper depends on a parameter $\nu\geq 0$ which gives the level of drift of the motion. Furthermore, we assume that the number of changes of direction performed by the random flight is fixed. The time lengths between two consecutive changes of orientation have joint probability distribution given by a Dirichlet density function. The analysis of $\underline{\bf X}_d(t),t>0,$ is not an easy task, because it involves the calculation of integrals which are not always solvable. Therefore, we analyze the random flight $\underline{\bf X}_m^d(t),t>0,$ obtained as projection onto the lower spaces $\mathbb{R}^m,m<d,$ of the original random motion in $\mathbb{R}^d$. Then we get the probability distribution of $\underline{\bf X}_m^d(t),t>0.$ Although, in its general framework, the analysis of $\underline{\bf X}_d(t),t>0,$ is very complicated, for some values of $\nu$, we can provide some results on the process. Indeed, for $\nu=1$, we obtain the characteristic function of the random flight moving in $\mathbb{R}^d$. Furthermore, by inverting the characteristic function, we are able to give the analytic form (up to some constants) of the probability distribution of $\underline{\bf X}_d(t),t>0.$Comment: 28 pages, 3 figure

Tendinopathy: Pathophysiology, therapeutic options, and role of nutraceutics. a narrative literature review

Tendinopathies are very common in general population and a huge number of tendon-related procedures take place annually worldwide, with significant socio-economic repercussions. Numerous treatment options are commonly used for tendon disorders. Besides pharmacological and physical therapy, nutrition could represent an additional tool for preventing and treating this complex pathology that deserve a multidisciplinary approach. In recent years, nutraceutical products are growing up in popularity since these seem to favor the prevention and the healing processes of tendon injuries. This narrative literature review aims to summarize current understanding and the areas of ongoing research about the management of tendinopathies with the help of oral supplementation

Large deviations for a damped telegraph process

In this paper we consider a slight generalization of the damped telegraph process in Di Crescenzo and Martinucci (2010). We prove a large deviation principle for this process and an asymptotic result for its level crossing probabilities (as the level goes to infinity). Finally we compare our results with the analogous well-known results for the standard telegraph process

Tumor site immune markers associated with risk for subsequent basal cell carcinomas.

BackgroundBasal cell carcinoma (BCC) tumors are the most common skin cancer and are highly immunogenic.ObjectiveThe goal of this study was to assess how immune-cell related gene expression in an initial BCC tumor biopsy was related to the appearance of subsequent BCC tumors.Materials and methodsLevels of mRNA for CD3ε (a T-cell receptor marker), CD25 (the alpha chain of the interleukin (IL)-2 receptor expressed on activated T-cells and B-cells), CD68 (a marker for monocytes/macrophages), the cell surface glycoprotein intercellular adhesion molecule-1 (ICAM-1), the cytokine interferon-γ (IFN-γ) and the anti-inflammatory cytokine IL-10 were measured in BCC tumor biopsies from 138 patients using real-time PCR.ResultsThe median follow-up was 26.6 months, and 61% of subjects were free of new BCCs two years post-initial biopsy. Patients with low CD3ε CD25, CD68, and ICAM-1 mRNA levels had significantly shorter times before new tumors were detected (p = 0.03, p = 0.02, p = 0.003, and p = 0.08, respectively). Furthermore, older age diminished the association of mRNA levels with the appearance of subsequent tumors.ConclusionsOur results show that levels of CD3ε, CD25, CD68, and ICAM-1 mRNA in BCC biopsies may predict risk for new BCC tumors

The role of constitutional justice in contemporary democracies

The evolution of constitutional justice in contemporary democracies. The Italian Constitutional Court’s role in case of legislature’s inertia: the issue of euthanasia the risks and potential of constitutional courts in democratic context

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

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 &lt; 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