Rates and Factors Associated with Major Modifications to First-Line Combination Antiretroviral Therapy: Results from the Asia-Pacific Region

Background: In the Asia-Pacific region many countries have adopted the WHO's public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART) in resource-rich and resource-limited countries in the region. Methods: We selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD). We dichotomised each country's per capita income into high/upper-middle (T-H) and lower-middle/low (T-L). Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV) or a substitution of two or more ARV agents from within the same ARV class. Results: A total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI) of treatment modification was 0.48 (0.44-0.52), 0.33 (0.30-0.36) and 0.21 (0.18-0.23) for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL), quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL), monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring. Conclusions: Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher-income countries, an increased rate of RNA-VL monitoring was associated with increased modifications to first-line ART. © 2013 Wright et al

A novel primary cilium‐mediated mechanism through which osteocytes regulate metastatic behavior of both breast and prostate cancer cells

Bone metastases are a common cause of suffering in breast and prostate cancer patients, however, the interaction between bone cells and cancer cells is poorly understood. Using a series of co-culture, conditioned media, human cancer spheroid, and organ-on-a-chip experiments, this study reveals that osteocytes suppress cancer cell proliferation and increase migration via tumor necrosis factor alpha (TNF-α) secretion. This action is regulated by osteocyte primary cilia and associated intraflagellar transport protein 88 (IFT88). Furthermore, it shows that cancer cells block this mechanism by secreting transforming growth factor beta (TGF-β), which disrupts osteocyte cilia and IFT88 gene expression. This bi-directional crosstalk signaling between osteocytes and cancer cells is common to both breast and prostate cancer. This study also proposes that osteocyte inhibition of cancer cell proliferation decreases as cancer cells increase, producing more TGF-β. Hence, a positive feedback loop develops accelerating metastatic tumor growth. These findings demonstrate the importance of cancer cell-osteocyte signaling in regulating breast and prostate bone metastases and support the development of therapies targeting this pathway

Relative spins and excitation energies of superdeformed bands in 190Hg: Further evidence for octupole vibration

An experiment using the Eurogam Phase II gamma-ray spectrometer confirms the existence of an excited superdeformed (SD) band in 190Hg and its very unusual decay into the lowest SD band over 3-4 transitions. The energies and dipole character of the transitions linking the two SD bands have been firmly established. Comparisons with RPA calculations indicate that the excited SD band can be interpreted as an octupole-vibrational structure.Comment: 12 pages, latex, 4 figures available via WWW at http://www.phy.anl.gov/bgo/bc/hg190_nucl_ex.htm

Modelling spectral and timing properties of accreting black holes: the hybrid hot flow paradigm

The general picture that emerged by the end of 1990s from a large set of optical and X-ray, spectral and timing data was that the X-rays are produced in the innermost hot part of the accretion flow, while the optical/infrared (OIR) emission is mainly produced by the irradiated outer thin accretion disc. Recent multiwavelength observations of Galactic black hole transients show that the situation is not so simple. Fast variability in the OIR band, OIR excesses above the thermal emission and a complicated interplay between the X-ray and the OIR light curves imply that the OIR emitting region is much more compact. One of the popular hypotheses is that the jet contributes to the OIR emission and even is responsible for the bulk of the X-rays. However, this scenario is largely ad hoc and is in contradiction with many previously established facts. Alternatively, the hot accretion flow, known to be consistent with the X-ray spectral and timing data, is also a viable candidate to produce the OIR radiation. The hot-flow scenario naturally explains the power-law like OIR spectra, fast OIR variability and its complex relation to the X-rays if the hot flow contains non-thermal electrons (even in energetically negligible quantities), which are required by the presence of the MeV tail in Cyg X-1. The presence of non-thermal electrons also lowers the equilibrium electron temperature in the hot flow model to <100 keV, making it more consistent with observations. Here we argue that any viable model should simultaneously explain a large set of spectral and timing data and show that the hybrid (thermal/non-thermal) hot flow model satisfies most of the constraints.Comment: 26 pages, 13 figures. To be published in the Space Science Reviews and as hard cover in the Space Sciences Series of ISSI - The Physics of Accretion on to Black Holes (Springer Publisher

Relative quadrupole moments of exotic shapes at ultrahigh spin in 154Er: Calibrating the TSD/SD puzzle

Transition quadrupole moments, Qt, of two ultrahigh-spin, collective structures in 154Er have been measured for the first time using the Doppler Shift Attenuation Method (DSAM). Data were acquired at the ATLAS accelerator facility of Argonne National Laboratory, using the Gammasphere detector array. A thick, gold-backed 110Pd foil was bombarded by a beam of 48Ti ions at 215 MeV. The Qt for each band was determined from the Doppler shift of gamma rays emitted by the resulting recoil nuclei. The extracted transition quadrupole moments are significantly different in magnitude, suggesting the two structures in 154Er represent distinct exotic nuclear shapes, namely axial superdeformed (SD) with Q t 20 eb, and triaxial strongly deformed (TSD) with Qt ≈ 11 eb. Indeed, the results calibrate the quadrupole moments of TSD bands recently measured in light erbium nuclei, 157,158Er

Quadrupole moments of coexisting collective shapes at high spin in 154Er

Four high-spin collective bands have been populated in 68154Er86 via the 110Pd(48Ti,4nγ)154Er reaction. Average transition quadrupole moments Qt have been measured for three of the bands by using the Doppler-shift attenuation method. The strongest band has a value of Q t=11.0±1.0eb, similar to values found recently for four triaxial strongly deformed (TSD) bands in 157,158Er. The second band has a value of Qt=19.5±3.2eb, consistent with a predicted axially symmetric superdeformed (SD) shape, similar in deformation to the 152Dy isotone, and is used as a calibration point. The third, new band has a value of Qt=9.9±2.2eb. The results confirm the unexpectedly large Qt moments for the favored TSD bands in light erbium isotopes

High-spin yrast structure of 159Ho

An investigation of the yrast structure of the odd-Z 159Ho nucleus to high spin has been performed. The 159Ho nucleus was populated by the reaction 116Cd(48Ca,p4nγ) at a beam energy of 215 MeV, and resulting γ decays were detected by the Gammasphere spectrometer. The h11/2 yrast band has been significantly extended up to Iπ=75/2- (tentatively 79/2-). A lower frequency limit for the second (h11/ 2)2 proton alignment was extracted consistent with the systematics of this alignment frequency, indicating an increased deformation with neutron number in the Ho isotopes. The energy-level splitting between the signature partners in the h11/2 structures of the Ho isotopes and the neighboring N=92 isotones is discussed

Structure changes in Er160 from low to ultrahigh spin

A spectroscopic investigation of the γ decays from excited states in Er160 has been performed in order to study the changing structural properties exhibited from low spin up toward ultrahigh spin (I~60). The nucleus Er160 was populated by the reaction Cd116(Ca48,4nγ) at a beam energy of 215 MeV, and resulting γ decays were studied using the Gammasphere spectrometer. New rotational structures and extensions to existing bands were observed, revealing a diverse range of quasiparticle configurations, which are discussed in terms of the cranked shell model. At spins around 50 there is evidence for oblate states close to the yrast line. Three rotational bands that have the characteristics of strongly deformed triaxial structures are observed, marking a return to collectivity at even higher spin. The high-spin data are interpreted within the framework of cranked Nilsson-Strutinsky calculations

Core-excited smoothly terminating band in 114Xe

High-spin states have been studied in neutron-deficient 54114Xe, populated through the 58Ni(58Ni,2p) fusion-evaporation reaction at 230 MeV. The Gammasphere γ-ray spectrometer has been used in conjunction with the Microball charged-particle detector in order to select evaporation residues of interest. The yrast band has been greatly extended to a tentative spin of 52hℏ and shows features consistent with smooth band termination. This band represents the first evidence for a core-excited (six-particle, two-hole) proton configuration above Z = 53

Quadrupole moments of collective structures up to spin ̃65h in 157Er and 158Er: A challenge for understanding triaxiality in nuclei

The transition quadrupole moments, Qt, of four weakly populated collective bands up to spin ̃65h in 157,158Er have been measured to be ̃11 eb demonstrating that these sequences are associated with large deformations. However, the data are inconsistent with calculated values from cranked Nilsson-Strutinsky calculations that predict the lowest energy triaxial shape to be associated with rotation about the short principal axis. The data appear to favor either a stable triaxial shape rotating about the intermediate axis or, alternatively, a triaxial shape with larger deformation rotating about the short axis. These new results challenge the present understanding of triaxiality in nuclei