Assessing effects of behavioral intervention on treatment outcomes among patients initiating HIV care: Rationale and design of iENGAGE intervention trial.

During the initial year of HIV diagnosis, while patients are often overwhelmed adjusting to this life changing diagnosis, they must develop self-care behaviors for attending regular medical care visits and antiretroviral therapy (ART) adherence to achieve and sustain viral suppression (VS). Maintaining "HIV adherence" and integrating it into one's daily life is required to sustain VS over time. The HIV care continuum or "treatment cascade," an epidemiological snapshot of the national epidemic in the United States (US), indicates that a minority of persons living with HIV (PLWH) have achieved VS. Little evidence exists regarding the effects of interventions focusing on PLWH newly initiating outpatient HIV care. An intervention that focuses on both retention in care and ART adherence skills delivered during the pivotal first year of HIV care is lacking. To address this, we developed a theory-based intervention evaluated in the Integrating Engagement and Adherence Goals upon Entry (iENGAGE) study, a National Institute of Allergy and Infectious Diseases (NIAID) funded randomized behavioral intervention trial. Here we present the study objectives, design and rationale, as well as the intervention components, targeting rapid and sustained VS through retention in HIV care and ART adherence during participants' first year of HIV care. The primary outcome of the study is 48-week VS (<200 c/mL). The secondary outcomes are retention in care, including HIV visit adherence and visit constancy, as well as ART adherence.

Exploration of Victoria crater by the Mars rover Opportunity.

The Mars rover Opportunity has explored Victoria crater, an approximately 750-meter eroded impact crater formed in sulfate-rich sedimentary rocks. Impact-related stratigraphy is preserved in the crater walls, and meteoritic debris is present near the crater rim. The size of hematite-rich concretions decreases up-section, documenting variation in the intensity of groundwater processes. Layering in the crater walls preserves evidence of ancient wind-blown dunes. Compositional variations with depth mimic those approximately 6 kilometers to the north and demonstrate that water-induced alteration at Meridiani Planum was regional in scope.

Hydrated silicate minerals on Mars observed by the Mars Reconnaissance Orbiter CRISM instrument.

Phyllosilicates, a class of hydrous mineral first definitively identified on Mars by the OMEGA (Observatoire pour la Mineralogie, L'Eau, les Glaces et l'Activitié) instrument, preserve a record of the interaction of water with rocks on Mars. Global mapping showed that phyllosilicates are widespread but are apparently restricted to ancient terrains and a relatively narrow range of mineralogy (Fe/Mg and Al smectite clays). This was interpreted to indicate that phyllosilicate formation occurred during the Noachian (the earliest geological era of Mars), and that the conditions necessary for phyllosilicate formation (moderate to high pH and high water activity) were specific to surface environments during the earliest era of Mars's history. Here we report results from the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) of phyllosilicate-rich regions. We expand the diversity of phyllosilicate mineralogy with the identification of kaolinite, chlorite and illite or muscovite, and a new class of hydrated silicate (hydrated silica). We observe diverse Fe/Mg-OH phyllosilicates and find that smectites such as nontronite and saponite are the most common, but chlorites are also present in some locations. Stratigraphic relationships in the Nili Fossae region show olivine-rich materials overlying phyllosilicate-bearing units, indicating the cessation of aqueous alteration before emplacement of the olivine-bearing unit. Hundreds of detections of Fe/Mg phyllosilicate in rims, ejecta and central peaks of craters in the southern highland Noachian cratered terrain indicate excavation of altered crust from depth. We also find phyllosilicate in sedimentary deposits clearly laid by water. These results point to a rich diversity of Noachian environments conducive to habitability.

Mineralogy at Meridiani Planum from the Mini-TES Experiment on the Opportunity Rover.

The Miniature Thermal Emission Spectrometer (Mini-TES) on Opportunity investigated the mineral abundances and compositions of outcrops, rocks, and soils at Meridiani Planum. Coarse crystalline hematite and olivine-rich basaltic sands were observed as predicted from orbital TES spectroscopy. Outcrops of aqueous origin are composed of 15 to 35% by volume magnesium and calcium sulfates [a high-silica component modeled as a combination of glass, feldspar, and sheet silicates (approximately 20 to 30%)], and hematite; only minor jarosite is identified in Mini-TES spectra. Mini-TES spectra show only a hematite signature in the millimeter-sized spherules. Basaltic materials have more plagioclase than pyroxene, contain olivine, and are similar in inferred mineral composition to basalt mapped from orbit. Bounce rock is dominated by clinopyroxene and is close in inferred mineral composition to the basaltic martian meteorites. Bright wind streak material matches global dust. Waterlain rocks covered by unaltered basaltic sands suggest a change from an aqueous environment to one dominated by physical weathering.

Initial results from the Mini-TES experiment in Gusev Crater from the Spirit Rover.

The Miniature Thermal Emission Spectrometer (Mini-TES) on Spirit has studied the mineralogy and thermophysical properties at Gusev crater. Undisturbed soil spectra show evidence for minor carbonates and bound water. Rocks are olivinerich basalts with varying degrees of dust and other coatings. Dark-toned soils observed on disturbed surfaces may be derived from rocks and have derived mineralogy (+/-5 to 10%) of 45% pyroxene (20% Ca-rich pyroxene and 25% pigeonite), 40% sodic to intermediate plagioclase, and 15% olivine (forsterite 45% +/-5 to 10). Two spectrally distinct coatings are observed on rocks, a possible indicator of the interaction of water, rock, and airfall dust. Diurnal temperature data indicate particle sizes from 40 to 80 microm in hollows to approximately 0.5 to 3 mm in soils.

Basaltic rocks analyzed by the Spirit Rover in Gusev Crater.

The Spirit landing site in Gusev Crater on Mars contains dark, fine-grained, vesicular rocks interpreted as lavas. Pancam and Mini-Thermal Emission Spectrometer (Mini-TES) spectra suggest that all of these rocks are similar but have variable coatings and dust mantles. Magnified images of brushed and abraded rock surfaces show alteration rinds and veins. Rock interiors contain

CpG DNA functions as an effective adjuvant for the induction of immune responses in aged mice.

The present studies demonstrate that the immunization of aged mice with Diphtheria toxoid in formulations containing unmethylated immunostimulatory CpG motifs, promotes the successful development of immune responses that are qualitatively and quantitatively comparable to those induced in young animals vaccinated in a similar manner. Aged mice given vaccines containing CpG oligodeoxynucleotides (ODNs) expressed primary and secondary systemic humoral immune responses having isotype profiles consistent with an enhancement in Th-1 type immunity. The ability to generate common mucosal immunity was also restored in aged animals given CpG ODN-containing vaccines. Dendritic cells (DCs) were determined to represent one of the cellular targets of CpG ODN activities in aged mice since restoration of immune function was observed when DCs from aged donors were pulsed with antigen and CpG ODNs, prior to injection into syngeneic young adult or aged recipients. Interestingly, antigen-pulsed DCs from young donors were fully capable of stimulating immune responses following their injection into syngeneic young adult or aged hosts, without a need for exposure to CpG ODNs. Although the mechanism(s) by which CpG DNA exerts its beneficial adjuvant effects on the aged immune system remains unclear, our findings suggest that the incorporation of CpG ODNs into vaccine formulations provided to the aged could prove useful in the development of more effective vaccines for the elderly.

Two genetic hits (more or less) to cancer.

Most cancers have many chromosomal abnormalities, both in number and in structure, whereas some show only a single aberration. In the era before molecular biology, cancer researchers, studying both human and animal cancers, proposed that a small number of events was needed for carcinogenesis. Evidence from the recent molecular era also indicates that cancers can arise from small numbers of events that affect common cell birth and death processes.

Chasing the cancer demon.

Boveri's idea that somatic mutations are at the root of cancer found its first specific support with the investigation of leukemia and Burkitt's lymphoma, and the discovery of the mechanism of oncogene activation by balanced translocation. The study of retinoblastoma later led to the cloning of the first antioncogene, or tumor suppressor gene, and to understanding the mechanisms by which the wild-type genes lose activity. Only a small subset of cancer involves simple mechanisms. A category of hereditary disorders called the phakomatoses provide a perspective on the chain of oncogenic events in such cancers because of two-hit precursor lesions that have a low probability of malignant transformation. The common carcinomas are much more complex and are typically genetically unstable, owing either to mutational instability or chromosomal instability.

Mechanism and relevance of ploidy in neuroblastoma.

Neuroblastoma has a broad spectrum of clinical behavior, ranging from spontaneous regression to dissemination and fatality. The heterogeneity that has long puzzled many investigators has been shown by more recent studies to be closely correlated with various clinical and genetic factors. Tumor cell ploidy is one of the factors; diploid and near-triploid neuroblastomas show poor and excellent clinical outcomes, respectively. We offer a hypothesis that explains how the ploidy state of the tumor plays a fundamental role in this heterogeneity, and why various prognostic factors are correlated with each other. This hypothesis may be applicable to tumors other than neuroblastoma.

Inverse radiation dose-rate effects on somatic and germ-line mutations and DNA damage rates.

The mutagenic effect of low linear energy transfer ionizing radiation is reduced for a given dose as the dose rate (DR) is reduced to a low level, a phenomenon known as the direct DR effect. Our reanalysis of published data shows that for both somatic and germ-line mutations there is an opposite, inverse DR effect, with reduction from low to very low DR, the overall dependence of induced mutations being parabolically related to DR, with a minimum in the range of 0.1 to 1.0 cGy/min (rule 1). This general pattern can be attributed to an optimal induction of error-free DNA repair in a DR region of minimal mutability (MMDR region). The diminished activation of repair at very low DRs may reflect a low ratio of induced ("signal") to spontaneous background DNA damage ("noise"). Because two common DNA lesions, 8-oxoguanine and thymine glycol, were already known to activate repair in irradiated mammalian cells, we estimated how their rates of production are altered upon radiation exposure in the MMDR region. For these and other abundant lesions (abasic sites and single-strand breaks), the DNA damage rate increment in the MMDR region is in the range of 10% to 100% (rule 2). These estimates suggest a genetically programmed optimatization of response to radiation in the MMDR region.