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

2006 AIDS Conference in Toront

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

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

Genistein supplementation and cardiac function in postmenopausal women with metabolic syndrome: Results from a pilot strain-echo study

Genistein, a soy-derived isoflavone,may improve cardiovascular risk profile in postmenopausal women with metabolic syndrome (MetS), but few literature data on its cardiac effects in humans are available. The aim of this sub-study of a randomized double-blind case-control study was to analyze the effect on cardiac function of one-year genistein dietary supplementation in 22 post-menopausal patients with MetS. Participants received 54 mg/day of genistein (n = 11) or placebo (n = 11) in combination with a Mediterranean-style diet and regular exercise. Left ventricular (LV) systolic function was assessed as the primary endpoint, according to conventional and strain-echocardiography measurements. Also, left atrial (LA) morphofunctional indices were investigated at baseline and at the final visit. Results were expressed as median with interquartile range (IQ). A significant improvement of LV ejection fraction (20.3 (IQ 12.5) vs. -1.67 (IQ 24.8); p = 0.040)), and LA area fractional change (11.1 (IQ 22.6) vs. 2.8 (9.5); p = 0.034)) were observed in genistein patients compared to the controls, following 12 months of treatment. In addition, body surface area indexed LA systolic volume and peak LA longitudinal strain significantly changed from basal to the end of the study in genistein-treated patients. One-year supplementation with 54 mg/day of pure genistein improved both LV ejection fraction and LA remodeling and function in postmenopausal women with MetS

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

Search for an annual modulation of dark-matter signals with a germanium spectrometer at the Sierra Grande Laboratory

Data collected during three years with a germanium spectrometer at the Sierra Grande underground laboratory have been analyzed for distinctive features of annual modulation of the signal induced by WIMP dark matter candidates. The main motivation for this analysis was the recent suggestion by the DAMA/NaI Collaboration that a yearly modulation signal could not be rejected at the 90% confidence level when analyzing data obtained with a high-mass low-background scintillator detector. We performed two different analyses of the data: First, the statistical distribution of modulation-significance variables (expected from an experiment running under the conditions of Sierra Grande) was compared with the same variables obtained from the data. Second, the data were analyzed in energy bins as an independent check of the first result and to allow for the possibility of a crossover in the expected signal. In both cases no statistically significant deviation from the null result was found, which could support the hypothesis that the data contain a modulated component. A plot is also presented to enable the comparison of these results to those of the DAMA collaboration.Comment: New version accepted by Astroparticle Physics. Changes suggested by the referee about the theoretical prediction of rates are included. Conclusions remain unaffected. 14 pages, LaTeX, 7 figures. Uses epsfig macr

Brain morphology and immunohistochemical localization of the gonadotropin-releasing hormone in the bluefin tuna, <i>Thunnus thynnus</i>

The present study was focused on the morphology of the diencephalic nuclei (likely involved in reproductive functions) as well as on the distribution of GnRH (gonadotropin-releasing hormone) in the rhinencephalon, telencephalon and the diencephalon of the brain of bluefin tuna (Thunnus thynnus) by means of immunohistochemistry. Bluefin tuna has an encephalization quotient (QE) similar to that of other large pelagic fish. Its brain exhibits well-developed optic tecta and corpus cerebelli. The diencephalic neuron cell bodies involved in reproductive functions are grouped in two main nuclei: the nucleus preopticus-periventricularis and the nucleus lateralis tuberis. The nucleus preopticus-periventricularis consists of the nucleus periventricularis and the nucleus preopticus consisting of a few sparse multipolar neurons in the rostral part and numerous cells closely packed and arranged in several layers in its aboral part. The nucleus lateralis tuberis is located in the ventral-lateral area of the diencephalon and is made up of a number of large multipolar neurones. Four different polyclonal primary antibodies against salmon (s)GnRH, chicken (c)GnRH-II (cGnRH-II 675, cGnRH-II 6) and sea bream (sb)GnRH were employed in the immunohistochemical experiments. No immunoreactive structures were found with anti sbGnRH serum. sGnRH and cGnRH-II antisera revealed immunoreactivity in the perikarya of the olfactory bulbs, preopticus-periventricular nucleus, oculomotor nucleus and midbrain tegmentum. The nucleus lateralis tuberis showed immunostaining only with anti-sGnRH serum. Nerve fibres immunoreactive to cGnRH and sGnRH sera were found in the olfactory bulbs, olfactory nerve and neurohypophysis. The significance of the distribution of the GnRHimmunoreactive neuronal structures is discussed

A search for pre-substellar cores and proto-brown dwarf candidates in Taurus: multiwavelength analysis in the B213-L1495 clouds

In an attempt to study whether the formation of brown dwarfs (BDs) takes place as a scaled-down version of low-mass stars, we conducted IRAM30m/MAMBO-II observations at 1.2 mm in a sample of 12 proto-BD candidates selected from Spitzer/IRAC data in the B213-L1495 clouds in Taurus. Subsequent observations with the CSO at 350 micron, VLA at 3.6 and 6 cm, and IRAM30m/EMIR in the 12CO(1-0), 13CO(1-0), and N2H+(1-0) transitions were carried out toward the two most promising Spitzer/IRAC source(s), J042118 and J041757. J042118 is associated with a compact (<10 arcsec or <1400 AU) and faint source at 350 micron, while J041757 is associated with a partially resolved (~16 arcsec or ~2000 AU) and stronger source emitting at centimetre wavelengths with a flat spectral index. The corresponding masses of the dust condensations are ~1 and ~5 Mjup for J042118 and J041757, respectively. In addition, about 40 arcsec to the northeast of J041757 we detect a strong and extended submillimetre source, J041757-NE, which is not associated with NIR/FIR emission down to our detection limits, but is clearly detected in 13CO and N2H+ at ~7 km/s, and for which we estimated a total mass of ~100 Mjup, close to the mass required to be gravitationally bound. In summary, our observational strategy has allowed us to find in B213-L1495 two proto-BD candidates and one pre-substellar core candidate, whose properties seem to be consistent with a scaled-down version of low-mass stars.Comment: MNRAS, 424, 2778; corrected typos, mass estimate refined in Section 3.2.1 and Section 5.3; conclusions unchange

Maximising transparency in a doctoral thesis: The complexities of writing about the use of QSR*NVIVO within a grounded theory study

This paper discusses the challenges of how to provide a transparent account of the use of the software programme QSR*NVIVO (QSR 2000) within a Grounded Theory framework (Glaser and Strauss 1967; Strauss and Corbin 1998). Psychology students are increasingly pursuing qualitative research projects such to the extent that the UK Economic and Social Research Council (ESRC) advise that students should have skill in the use of computer assisted qualitative data analysis software (CAQDAS) (Economic and Social Research Council 2001). Unlike quantitative studies, rigid formulae do not exist for writing-up qualitative projects for doctoral theses. Most authors, however, agree that transparency is essential when communicating the findings of qualitative research. Sparkes (2001) recommends that evaluative criteria for qualitative research should be commensurable with the aims, objectives, and epistemological assumptions of the research project. Likewise, the use of CAQDAS should vary according to the research methodology followed, and thus researchers should include a discussion of how CAQDAS was used. This paper describes how the evolving process of coding data, writing memos, categorising, and theorising were integrated into the written thesis. The structure of the written document is described including considerations about restructuring and the difficulties of writing about an iterative process within a linear document