Drivers of Vaginal Drug Delivery System Acceptability from Internet-Based Conjoint Analysis

Vaginal microbicides potentially empower women to protect themselves from HIV and other sexually transmitted infections (STIs), especially when culture, religion, or social status may prevent them from negotiating condom use. The open literature contains minimal information on factors that drive user acceptability of women’s health products or vaginal drug delivery systems. By understanding what women find to be most important with regard to sensory properties and product functionality, developers can iteratively formulate a more desirable product. Conjoint analysis is a technique widely used in market research to determine what combination of elements influence a consumer’s willingness to try or use a product. We applied conjoint analysis here to better understand what sexually-active woman want in a microbicide, toward our goal of formulating a product that is highly acceptable to women. Both sensory and non-sensory attributes were tested, including shape, color, wait time, partner awareness, messiness/leakage, duration of protection, and functionality. Heterosexually active women between 18 and 35 years of age in the United States (n = 302) completed an anonymous online conjoint survey using IdeaMap software. Attributes (product elements) were systematically presented in various combinations; women rated these combinations of a 9-point willingness-to-try scale. By coupling systematic combinations and regression modeling, we can estimate the unique appeal of each element. In this population, a multifunctional product (i.e., broad spectrum STI protection, coupled with conception) is far more desirable than a microbicide targeted solely for HIV protection; we also found partner awareness and leakage are potentially strong barriers to use.     

Growth-promoting effects of acidic and basic fibroblast growth factor on rabbit articular chondrocytes aging in culture

Rabbit articular chondrocytes have a limited growth potential in vitro. After four passages in culture, chondrocytes have accomplished more than 50% of their life span. At this stage of culture, they are considered to be senescent-like, since a dramatic decrease in proliferative capacity and enhanced cell size and protein content are observed. These aged cells are, however, still able to respond to fibroblast growth factor (FGF). The addition of either acidic or basic FGF (10 ng/ml) to culture medium permitted an enhanced proliferation. The attenuation of FGF mitogenic activity during aging was not observed for both fractions. Moreover, when treated with acidic or basic FGF, aged chondrocytes had a smaller size and a lower protein content. The acidic FGF was less potent than the basic FGF in delaying the evolution of aged chondrocytes to senescence.     

Response of resident murine peritoneal macrophages to in vivo administration of granulocyte-macrophage colony-stimulating factor

The effect of s.c. inoculation of purified recombinant derived granulocyte-macrophage (GM)-CSF on resident murine peritoneal macrophages was assessed in this study. From 18 to 24 h after s.c. administration of GM-CSF to normal mice, the resident peritoneal macrophages were harvested and the levels of membrane-bound IL-1, FcR, Mac-1 cell-surface Ag, and class II MHC expression were assessed. Peritoneal cells from GM-CSF-inoculated mice had significantly greater levels of membrane-bound IL-1 than did control mice. In addition when resident peritoneal macrophages from normal mice were purified by adherence and grown in the presence of GM-CSF, they produced greater levels of both membrane-bound and secreted IL-1. The peritoneal cells from GM-CSF-inoculated mice did not differ from controls in the expression of class II MHC-encoded Ag. This observation was confirmed by the finding that GM-CSF was unable to induce class II MHC expression on P388D1 cells, whereas a secondary mixed leukocyte culture supernatant was. Peritoneal cells from GM-CSF-inoculated mice also exhibited greater levels of expression of FcR and the Mac-1 cell-surface Ag. This resulted in an increase in their ability to phagocytose opsonized SRBC in vitro.     

GM-CSF administration augments the survival of ity-resistant A/J mice, but not ity-susceptible C57BL/6 mice, to a lethal challenge with Salmonella typhimurium

Ity resistant A/J mice were challenged with a lethal dose (2 x 10(3) organisms) of Salmonella typhimurium. Infected mice treated with 1 microgram of GM-CSF twice daily showed increased median survival time and had a higher survival fraction than untreated controls. GM-CSF was most effective when given for a brief period (1 to 2 days) after infection. Pretreatment of the mice or delayed treatment with GM-CSF had no effect on the survival of the mice. Studies on the effect of GM-CSF on the bacterial load showed that mice treated with GM-CSF had fewer S. typhimurium in the spleen and peritoneal cavity on day 4 but not on day 2 after infection. GM-CSF treatment of ity-susceptible C57BL/6 mice infected with 10 organisms had no therapeutic effect.     

The role of sexual isolation during rapid ecological divergence: Evidence for a new dimension of isolation in Rhagoletis pomonella

The pace of divergence and likelihood of speciation often depends on how and when different types of reproductive barriers evolve. Questions remain about how reproductive isolation evolves after initial divergence. We tested for the presence of sexual isolation (reduced mating between populations due to divergent mating preferences and traits) in Rhagoletis pomonella flies, a model system for incipient ecological speciation. We measured the strength of sexual isolation between two very recently diverged (~170 generations) sympatric populations, adapted to different host fruits (hawthorn and apple). We found that flies from both populations were more likely to mate within than between populations. Thus, sexual isolation may play an important role in reducing gene flow allowed by early-acting ecological barriers. We also tested how warmer temperatures predicted under climate change could alter sexual isolation and found that sexual isolation was markedly asymmetric under warmer temperatures – apple males and hawthorn females mated randomly while apple females and hawthorn males mated more within populations than between. Our findings provide a window into the early speciation process and the role of sexual isolation after initial ecological divergence, in addition to examining how environmental conditions could shape the likelihood of further divergence.     

Biological samples taken from Native American Ancestors are human remains under NAGPRA

In the United States, the Native American Graves Protection and Repatriation Act (NAGPRA) provides a specific framework for the disposition of Native American Ancestral remains within its purview. However, samples such as a bone fragment, tooth, or other biological tissue taken from the remains of these Ancestors have been treated by institutions and researchers as independent of the individual from whom they were removed and used in destructive research such as paleogenomic and other archaeometric analyses without consultation, consent, and collaboration from Native American communities; are not cared for in keeping with the current best practices for Indigenous Ancestors; and are not likely to be repatriated to their communities. Here, we demonstrate that any biological samples removed from Ancestors who are covered under NAGPRA must also be handled according to the stipulations defined for “human remains” within the legislation. As such, we are not proposing a change to existing legislation, but rather best practices, specific to the context of the United States and NAGPRA, relating to the use of and care for biological samples taken from Native American Ancestors.     

INDIVIDUALITY IN THE VOICE OF FUR SEAL FEMALES: AN ANALYSIS STUDY OF THE PUP ATTRACTION CALL IN ARCTOCEPHALUS TROPICALIS

Like most otariids species, the Subantarctic fur seal breeds on land in large, dense colonies. Pups are confronted by the long and repetitive absences of their mother throughout lactation. At each mother's return, pups have to find her among several hundreds of congeners. This recognition process mainly relies on acoustic signals. We performed an acoustic analysis on 125 calls from 20 females recorded during the 1999–2000 breeding season on Amsterdam Island (Indian Ocean). Ten variables were measured in both temporal and frequency domains. To find the acoustic parameters supporting individual signature, we assessed the differences between individuals using Kruskall-Wallis univariate analysis of variance. For each variable, we also calculated the potential of individuality coding (PIC) as the ratio between the between-individual coefficient of variation and the mean value of the within-individual coefficients of variation. We found that the frequency spectrum, the characteristics of the frequency modulation of the initial and middle part of the call and the call duration exhibit an important individual stereotypy (PIC values ranging between 1.5 and 3), whereas features relative to amplitude and the frequency modulation of the final part of the call are weakly individualized (PIC values between 1 and 1.2).     

Les ostracodes neogenes du bassin de Savigne-sur-Lathan(Faluns de Touraine) I. Biostratigraphie et paleoecologie

The Neogen formations from the basin of Savigné-su-Lathan (Indre-et-Loire) have yielded 53 species of ostracods.The connections with the best known fauna from the Aquitaine basin and the Rhône basin are discussed.     

Modulation of adenylate cyclase/cyclic AMP response by thyrotropin and prostaglandin E2 in cultured thyroid cells. 1. Negative regulation.

Isolated porcine thyroid cells, cultured in the presence of thyrotropin (greater than or equal to 0.25 mU/ml) or prostaglandin E2 (greater than or equal to 0.1 micron), showed decreased adenosine 3':5'-monophosphate (cyclic AMP) response to further thyrotropin or prostaglandin E2 stimulation, respectively. Kinetics of the refractory process to thyrotropin and prostaglandin E2 are different: (a) maximal refractoriness to prostaglandin E2 was attained after 2--6 h exposure to prostaglandin E2 while refractoriness to thyrotropin was maximal only after 12--24 h; (b) the degree of refractoriness to prostaglandin E2 was much greater than that to thyrotropin. Refractoriness to thyrotropin or prostaglandin E2 is characterized: by specificity for each thyroid stimulator; by dependence upon the dose of thyrotropin or prostaglandin E2 in culture, e.g. induction of high degree of refractoriness with 0.5 mU/ml thyrotropin (or 1 micron prostaglandin E2), which elicits only a small cyclic AMP increase; by time requirement for induction; by partial effect; by changes of maximum activation of cyclic AMP response; by reversibility. This refractoriness of the cyclic AMP response was not induced by dibutyryl adenosine 3':5'-monophosphate. It was not attributed to increased cyclic AMP-phosphodiesterase activity, but to alterations in the receptor-adenylate cyclase system. Prevention of refractoriness to thyrotropin or prostaglandin E2 by incubation of cells in the presence of actinomycin D, puromycin and cycloheximide suggests that new RNA and protein syntheses are required for the development of the refractory state.