Increasing Support for Contraception as HIV Prevention: Stakeholder Mapping to Identify Influential Individuals and Their Perceptions

BACKGROUND: Voluntary contraceptive use by HIV-positive women currently prevents more HIV-positive births, at a lower cost, than anti-retroviral drug (ARV) regimens. Despite this evidence, most prevention of mother-to-child transmission (PMTCT) programs focus solely on providing ARV prophylaxis to pregnant women and rarely include the prevention of unintended pregnancies among HIV-positive women. METHODOLOGY/PRINCIPAL FINDINGS: To strengthen support for family planning as HIV prevention, we systematically identified key individuals in the field of international HIV/AIDS-those who could potentially influence the issue-and sought to determine their perceptions of barriers to and facilitators for implementing this PMTCT strategy. We used a criteria-based approach to determine which HIV/AIDS stakeholders have the most significant impact on HIV/AIDS research, programs, funding and policy and stratified purposive sampling to conduct interviews with a subset of these individuals. The interview findings pointed to obstacles to strengthening linkages between family planning and HIV/AIDS, including the need for: resources to integrate family planning and HIV services, infrastructure or capacity to provide integrated services at the facility level, national leadership and coordination, and targeted advocacy to key decision-makers. CONCLUSIONS/SIGNIFICANCE: The individuals we identified as having regional or international influence in the field of HIV/AIDS have the ability to leverage an increasingly conducive funding environment and a growing evidence base to address the policy, programmatic and operational challenges to integrating family planning with HIV/AIDS. Fostering greater support for implementing contraception for HIV prevention will require the dedication, collaboration and coordination of many such actors. Our findings can inform a targeted advocacy campaign

X-ray Absorption and Reflection in Active Galactic Nuclei

X-ray spectroscopy offers an opportunity to study the complex mixture of emitting and absorbing components in the circumnuclear regions of active galactic nuclei, and to learn about the accretion process that fuels AGN and the feedback of material to their host galaxies. We describe the spectral signatures that may be studied and review the X-ray spectra and spectral variability of active galaxies, concentrating on progress from recent Chandra, XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for absorption covering a wide range of column densities, ionization and dynamics, and discuss the growing evidence for partial-covering absorption from data at energies > 10 keV. Such absorption can also explain the observed X-ray spectral curvature and variability in AGN at lower energies and is likely an important factor in shaping the observed properties of this class of source. Consideration of self-consistent models for local AGN indicates that X-ray spectra likely comprise a combination of absorption and reflection effects from material originating within a few light days of the black hole as well as on larger scales. It is likely that AGN X-ray spectra may be strongly affected by the presence of disk-wind outflows that are expected in systems with high accretion rates, and we describe models that attempt to predict the effects of radiative transfer through such winds, and discuss the prospects for new data to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58 pages, 9 figures. V2 has fixed an error in footnote

Getting into hot water:sick guppies frequent warmer thermal conditions

Ectotherms depend on the environmental temperature for thermoregulation and exploit thermal regimes that optimise physiological functioning. They may also frequent warmer conditions to up-regulate their immune response against parasite infection and/or impede parasite development. This adaptive response, known as ‘behavioural fever’, has been documented in various taxa including insects, reptiles and fish, but only in response to endoparasite infections. Here, a choice chamber experiment was used to investigate the thermal preferences of a tropical freshwater fish, the Trinidadian guppy (Poecilia reticulata), when infected with a common helminth ectoparasite Gyrodactylus turnbulli, in female-only and mixed-sex shoals. The temperature tolerance of G. turnbulli was also investigated by monitoring parasite population trajectories on guppies maintained at a continuous 18, 24 or 32 °C. Regardless of shoal composition, infected fish frequented the 32 °C choice chamber more often than when uninfected, significantly increasing their mean temperature preference. Parasites maintained continuously at 32 °C decreased to extinction within 3 days, whereas mean parasite abundance increased on hosts incubated at 18 and 24 °C. We show for the first time that gyrodactylid-infected fish have a preference for warmer waters and speculate that sick fish exploit the upper thermal tolerances of their parasites to self medicate

Formation of orogenic gold deposits by progressive movement of a fault-fracture mesh through the upper crustal brittle-ductile transition zone

Orogenic gold deposits are comprised of complex quartz vein arrays that form as a result of fluid flow along transcrustal fault zones in active orogenic belts. Mineral precipitation in these deposits occurs under variable pressure conditions, but a mechanism explaining how the pressure regimes evolve through time has not previously been proposed. Here we show that extensional quartz veins at the Garrcon deposit in the Abitibi greenstone belt of Canada preserve petrographic characteristics suggesting that the three recognized paragenetic stages formed within different pressure regimes. The first stage involved the growth of interlocking quartz grains competing for space in fractures held open by hydrothermal fluids at supralithostatic pressures. Subsequent fluid flow at fluctuating pressure conditions caused recrystallization of the vein quartz and the precipitation of sulfide minerals through wall-rock sulfidation, with some of the sulfide minerals containing microscopic gold. These pressure fluctuations between supralithostatic to near-hydrostatic conditions resulted in the post-entrapment modification of the fluid inclusion inventory of the quartz. Late fluid flow occurred at near-hydrostatic conditions and resulted in the formation of fluid inclusions that have not been affected by post-entrapment modification as pressure conditions never returned to supralithostatic conditions. This late fluid flow is interpreted to have formed the texturally late, coarse native gold that occurs along quartz grain boundaries and in open spaces. The systematic evolution of the pressure regimes in orogenic gold deposits such as Garrcon can be explained by relative movement of fault-fracture meshes across the base of the upper crustal brittle-ductile transition zone. We conclude that early vein quartz in orogenic deposits is precipitated at near-lithostatic conditions whereas the paragenetically late gold is introduced at distinctly lower pressure

High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

Cosmic ray diffusion near the Bohm limit in the Cassiopeia A supernova remnant

Supernova remnants (SNRs) are believed to be the primary location of the acceleration of Galactic cosmic rays, via diffusive shock (Fermi) acceleration. Despite considerable theoretical work the precise details are still unknown, in part because of the difficulty in directly observing nucleons that are accelerated to TeV energies in, and affect the structure of, the SNR shocks. However, for the last ten years, X-ray observatories ASCA, and more recently Chandra, XMM-Newton, and Suzaku have made it possible to image the synchrotron emission at keV energies produced by cosmic-ray electrons accelerated in the SNR shocks. In this article, we describe a spatially-resolved spectroscopic analysis of Chandra observations of the Galactic SNR Cassiopeia A to map the cutoff frequencies of electrons accelerated in the forward shock. We set upper limits on the electron diffusion coefficient and find locations where particles appear to be accelerated nearly as fast as theoretically possible (the Bohm limit).Comment: 18 pages, 5 figures. Accepted for publication in Nature Physics (DOI below), final version available week of August 28, 2006 at http://www.nature.com/nphy

Tripotential Differentiation of Adherently Expandable Neural Stem (NS) Cells

BACKGROUND: A recent study has shown that pure neural stem cells can be derived from embryonic stem (ES) cells and primary brain tissue. In the presence of fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF), this population can be continuously expanded in adherent conditions. In analogy to continuously self-renewing ES cells, these cells were termed ‘NS’ cells (Conti et al., PLoS Biol 3: e283, 2005). While NS cells have been shown to readily generate neurons and astrocytes, their differentiation into oligodendrocytes has remained enigmatic, raising concerns as to whether they truly represent tripotential neural stem cells. METHODOLOGY/PRINCIPAL FINDINGS: Here we provide evidence that NS cells are indeed tripotent. Upon proliferation with FGF2, platelet-derived growth factor (PDGF) and forskolin, followed by differentiation in the presence of thyroid hormone (T3) and ascorbic acid NS cells efficiently generate oligodendrocytes (∼20%) alongside astrocytes (∼40%) and neurons (∼10%). Mature oligodendroglial differentiation was confirmed by transplantation data showing that NS cell-derived oligodendrocytes ensheath host axons in the brain of myelin-deficient rats. CONCLUSIONS/SIGNIFICANCE: In addition to delineating NS cells as a potential donor source for myelin repair, our data strongly support the view that these adherently expandable cells represent bona fide tripotential neural stem cells

Environment Orientation : a structured simulation approach for agent-based complex systems

Complex systems are collections of independent agents interacting with each other and with their environment to produce emergent behaviour. Agent-based computer simulation is one of the main ways of studying complex systems. A naive approach to such simulation can fare poorly, due to large communication overhead, and due to the scope for deadlock between the interacting agents sharing a computational platform. Agent interaction can instead be considered entirely from the point of view of the environment(s) within which the agents interact. Structuring a simulation using such Environment Orientation leads to a simulation that reduces communication overhead, that is effectively deadlock-free, and yet still behaves in the manner required. Additionally the Environment Orientation architecture eases the development of more sophisticated large-scale simulations, with multiple kinds of complex agents, situated in and interacting with multiple kinds of environments. We describe the Environment Orientation simulation architecture. We report on a number of experiments that demonstrate the effectiveness of the Environment Orientation approach: a simple flocking system, a flocking system with multiple sensory environments, and a flocking system in an external environment

ERBB4 confers metastatic capacity in Ewing sarcoma.

Metastatic spread is the single-most powerful predictor of poor outcome in Ewing sarcoma (ES). Therefore targeting pathways that drive metastasis has tremendous potential to reduce the burden of disease in ES. We previously showed that activation of the ERBB4 tyrosine kinase suppresses anoikis, or detachment-induced cell death, and induces chemoresistance in ES cell lines in vitro. We now show that ERBB4 is transcriptionally overexpressed in ES cell lines derived from chemoresistant or metastatic ES tumours. ERBB4 activates the PI3K-Akt cascade and focal adhesion kinase (FAK), and both pathways contribute to ERBB4-mediated activation of the Rac1 GTPase in vitro and in vivo. ERBB4 augments tumour invasion and metastasis in vivo, and these effects are blocked by ERBB4 knockdown. ERBB4 expression correlates significantly with reduced disease-free survival, and increased expression is observed in metastatic compared to primary patient-matched ES biopsies. Our findings identify a novel ERBB4-PI3K-Akt-FAK-Rac1 pathway associated with aggressive disease in ES. These results predict that therapeutic targeting of ERBB4, alone or in combination with cytotoxic agents, may suppress the metastatic phenotype in ES