How acceptable are antiretrovirals for the prevention of sexually transmitted HIV? A review of research on the acceptability of oral pre-exposure prophylaxis and treatment as prevention

Recent research has demonstrated how antiretrovirals (ARVs) could be effective in the prevention of sexually transmitted HIV. We review research on the acceptability of oral pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) for HIV prevention amongst potential users. We consider with whom, where and in what context this research has been conducted, how acceptability has been approached, and what research gaps remain. Findings from 33 studies show a lack of TasP research, PrEP studies which have focused largely on men who have sex with men (MSM) in a US context, and varied measures of acceptability. In order to identify when, where and for whom PrEP and TasP would be most appropriate and effective, research is needed in five areas: acceptability of TasP to people living with HIV; motivation for PrEP use and adherence; current perceptions and management of risk; the impact of broader social and structural factors; and consistent definition and operationalisation of acceptability which moves beyond adherence

Anatomy and Taxonomic Status of the Chasmosaurine Ceratopsid Nedoceratops hatcheri from the Upper Cretaceous Lance Formation of Wyoming, U.S.A

Background: The validity of Nedoceratops hatcheri, a chasmosaurine ceratopsid dinosaur known from a single skull recovered in the Lance Formation of eastern Wyoming, U.S.A., has been debated for over a century. Some have argued that the taxon is an aberrant Triceratops, and most recently it was proposed that N. hatcheri represents an intermediate ontogenetic stage between ‘‘young adult’ ’ and ‘‘old adult’ ’ forms of a single taxon previously split into Triceratops and Torosaurus. Methodology/Principal Findings: The holotype skull of Nedoceratops hatcheri was reexamined in order to map reconstructed areas and compare the specimen with other ceratopsids. Although squamosal fenestrae are almost certainly not of taxonomic significance, some other features are unique to N. hatcheri. These include a nasal lacking a recognizable horn, nearly vertical postorbital horncores, and relatively small parietal fenestrae. Thus, N. hatcheri is tentatively considered valid, and closely related to Triceratops spp. The holotype of N. hatcheri probably represents an ‘‘old adult,’ ’ based upon bone surface texture and the shape of the horns and epiossifications on the frill. In this study, Torosaurus is maintained as a genus distinct from Triceratops and Nedoceratops. Synonymy of the three genera as ontogenetic stages of a single taxon would require cranial changes otherwise unknown in ceratopsids, including additions of ossifications to the frill and repeated alternation of bone surface texture between juvenile and adult morphotypes

Increasing the Effectiveness of Vaginal Microbicides: A Biophysical Framework to Rethink Behavioral Acceptability

Microbicide candidates delivered via gel vehicles are intended to coat the vaginal epithelium after application. The coating process depends on intrinsic biophysical properties of the gel texture, which restricts the potential choices for an effective product: the gel first must be physically synthesizable, then acceptable to the user, and finally applied in a manner promoting timely adequate coating, so that the user adherence is optimized. We present a conceptual framework anchoring microbicide behavioral acceptability within the fulfillment of the product biophysical requirements.We conducted a semi-qualitative/quantitative study targeting women aged 18-55 in Northern California to assess user preferences for microbicide gel attributes. Attributes included: (i) the wait time between application and intercourse, (ii) the gel texture and (iii) the trade-off between wait time and gel texture. Wait times were assessed using a mathematical model determining coating rates depending upon the gel's physical attributes.71 women participated. Results suggest that women would independently prefer a gel spreading rapidly, in 2 to 15 minutes (P<0.0001), as well as one that is thick or slippery (P<0.02). Clearly, thick gels do not spread rapidly; hence the motivation to study the trade-off. When asked the same question 'constrained' by the biophysical reality, women indicated no significant preference for a particular gel thickness (and therefore waiting time) (P>0.10) for use with a steady partner, a preference for a watery gel spreading rapidly rather than one having intermediate properties for use with a casual partner (P = 0.024).Biophysical constraints alter women's preferences regarding acceptable microbicide attributes. Product developers should offer a range of formulations in order to address all preferences. We designed a conceptual framework to rethink behavioral acceptability in terms of biophysical requirements that can help improve adherence in microbicide use ultimately enhancing microbicide effectiveness

New Information on the Cranial Anatomy of Acrocanthosaurus atokensis and Its Implications for the Phylogeny of Allosauroidea (Dinosauria: Theropoda)

Allosauroidea has a contentious taxonomic and systematic history. Within this group of theropod dinosaurs, considerable debate has surrounded the phylogenetic position of the large-bodied allosauroid Acrocanthosaurus atokensis from the Lower Cretaceous Antlers Formation of North America. Several prior analyses recover Acrocanthosaurus atokensis as sister taxon to the smaller-bodied Allosaurus fragilis known from North America and Europe, and others nest Acrocanthosaurus atokensis within Carcharodontosauridae, a large-bodied group of allosauroids that attained a cosmopolitan distribution during the Early Cretaceous.Re-evaluation of a well-preserved skull of Acrocanthosaurus atokensis (NCSM 14345) provides new information regarding the palatal complex and inner surfaces of the skull and mandible. Previously inaccessible internal views and articular surfaces of nearly every element of the skull are described. Twenty-four new morphological characters are identified as variable in Allosauroidea, combined with 153 previously published characters, and evaluated for eighteen terminal taxa. Systematic analysis of this dataset recovers a single most parsimonious topology placing Acrocanthosaurus atokensis as a member of Allosauroidea, in agreement with several recent analyses that nest the taxon well within Carcharodontosauridae.A revised diagnosis of Acrocanthosaurus atokensis finds that the species is distinguished by four primary characters, including: presence of a knob on the lateral surangular shelf; enlarged posterior surangular foramen; supraoccipital protruding as a double-boss posterior to the nuchal crest; and pneumatic recess within the medial surface of the quadrate. Furthermore, the recovered phylogeny more closely agrees with the stratigraphic record than hypotheses that place Acrocanthosaurus atokensis as more closely related to Allosaurus fragilis. Fitch optimization of body size is also more consistent with the placement of Acrocanthosaurus atokensis within a clade of larger carcharodontosaurid taxa than with smaller-bodied taxa near the base of Allosauroidea. This placement of Acrocanthosaurus atokensis supports previous hypotheses of a global carcharodontosaurid radiation during the Early Cretaceous

Prion (PrPSc)-specific epitope defined by a monoclonal antibody

Prions are infectious particles causing transmissible spongiform encephalopathies (TSEs). They consist, at least in part, of an isoform (PrPSc) of the ubiquitous cellular prion protein (PrPC). Conformational differences between PrPC and PrPSc are evident from increased beta-sheet content and protease resistance in PrPSc. Here we describe a monoclonal antibody, 15B3, that can discriminate between the normal and disease-specific forms of PrP. Such an antibody has been long sought as it should be invaluable for characterizing the infectious particle as well as for diagnosis of TSEs such as bovine spongiform encephalopathy (BSE) or Creutzfeldt-Jakob disease (CJD) in humans. 15B3 specifically precipitates bovine, murine or human PrPSc, but not PrPC, suggesting that it recognizes an epitope common to prions from different species. Using immobilized synthetic peptides, we mapped three polypeptide segments in PrP as the 15B3 epitope. In the NMR structure of recombinant mouse PrP, segments 2 and 3 of the 15B3 epitope are near neighbours in space, and segment 1 is located in a different part of the molecule. We discuss models for the PrPSc-specific epitope that ensure close spatial proximity of all three 15B3 segments, either by intermolecular contacts in oligomeric forms of the prion protein or by intramolecular rearrangement