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Vaginal microbicides are believed to have substantial potential to empower women to protect themselves from HIV, although clinical trials to date have had mixed results at best. Issues with patient adherence in these trials suggest additional emphasis should be placed on optimizing acceptability. Acceptability is driven, in part, by the sensory properties of the microbicide, so better understanding of the relationships between sensory properties and the physical and rheological properties of microbicides should facilitate the simultaneous optimization of sensory properties in parallel with the biophysical properties required for drug deployment. Recently, we have applied standard methods to assess the potential acceptability of microbicide prototypes ex vivo and to quantify the sensory properties of microbicide surrogates. Here, we link quantitative perceptual data to the rheological properties of 6 over-the counter (OTC) vaginal products used as ex vivo microbicide surrogates. Shear-thinning behavior (n) and tan δ (10 rad/s) showed no relationship with any perceptual attributes while shear storage modulus, G' (10 rad/s) was correlated with some attributes, but did not appear to be a strong predictor of sensory properties. Conversely, the storage loss modulus, G" (10 rad/s) and the consistency coefficient, K, were correlated with several sensory attributes: stickiness, rubberiness, and uniform thickness for G'' and stickiness, rubberiness, and peaking for K. Although these relationships merit confirmation in later studies, this pilot study suggests rheological principles can be used to understand the sensory properties evoked by microbicide surrogates assessed ex vivo. Additional work is needed to determine if these findings would apply for microbicides in vivo.
Citation: Mahan ED, Zaveri T, Ziegler GR, Hayes JE (2014) Relationships between Perceptual Attributes and Rheology in Over-the-Counter Vaginal Products: A Potential Tool for Microbicide Development. PLoS ONE 9(9): e105614. https://doi.org/10.1371/journal.pone.0105614
Editor: Clive M. Gray, University of Cape Town, South Africa
Received: November 1, 2013; Accepted: July 26, 2014; Published: September 4, 2014
Copyright: © 2014 Mahan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by seed funds from the Pennsylvania State University and a grant from the National Institute of Allergy and Infectious Diseases [R33AI094514] to JEH and GRZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
A microbicide is a product containing agents known to block HIV and other sexually transmitted diseases that can be inserted into the vagina prior to intercourse in the form of a gel, cream, foam, sponge, suppository, or film [1]. Currently, a number of microbicide products are in clinical trial [2], but there are no conclusive reports of effectiveness. Studies with different use protocols (coitally associated dosing versus daily use) have demonstrated varying levels of effectiveness in HIV prevention and this may be attributed to some extent to user adherence [3], [4]. Previously, work on microbicide development has proceeded in two parallel and generally independent tracks, as studies either focused on behavior or formulation but not both. In the former, focus groups and clinical trials were used to identify factors that influence user acceptability [5], [6], while the latter approach emphasized the way various physicochemical properties affect pharmacokinetics [7]. More recently, a stronger emphasis has been placed on efforts that combine these two approaches to study the interaction between physical properties and consumer acceptability [8]–[12]. However, attempts to link human perception (as defined by sensory or consumer studies) to instrumental data are complicated. Still, this approach appears to have good face validity, as many terms associated with the texture profile of a product are tied to rheological principles [13].
Recently, we adapted standardized methods from human sensory science to over-the-counter (OTC) vaginal products [14]. Although this was the first time these methods had been applied to commercially available microbicide surrogates, sensory specialists and product developers have used similar methods for decades to optimize product formulations. Specifically, quantitative descriptive profiling (descriptive analysis) has been utilized by the food and consumer products industries since the middle of the last century [15], [16]. These methods capitalize on the assumption that a group of individuals, often referred to as a panel, can be trained to describe and reliably quantify product perceptions. In order to be recruited into such descriptive panels, individuals must be able to detect small differences between products, describe these differences verbally and use scales accurately to quantify their observations. Once these criteria are met, the selected panelists go through an intensive training process, where a panel leader facilitates development of a lexicon the participants use to describe relevant attributes of the products. Concrete references with and without the property in question are provided to align panelists to the attribute concept, and reference stimuli are used to define a range of sensations along the continuum of the attribute. For example 'peaking' might be defined 'as degree to which a product stands up when tapped', and exemplified with mineral oil (none) and lanolin (a lot) [14]. After the training phase is complete, quantitative data are collected independently and blindly and then analyzed statistically. The goal is to get consistent and reliable quantitative data that describe perceptual attributes of a product [15]. Originally applied to food products, these methods have also been applied to non-food consumer goods like lotions and skin creams [17], [18]. Notably, descriptive panelists are never asked for hedonic or affective information about products [15], [16]; instead larger numbers of untrained consumers are used for affective data collection (e.g. [19], [20]).
Exploring the relationships between sensory and instrumental measures has been the focus of numerous studies (e.g. [21]–[23]). While many attempts are product specific, others have sought to create models using classical instrumental measurements [24], [25] or develop new instrumental evaluation techniques [26] that could be applied to predict sensory properties for a broad range of products. Replacing human assessors with instrumental measurements is advantageous as instrumental methods are less expensive and time consuming, and are often reproducible even when collected by instruments in different locations [27]. However, as with any instrumental method, these analytical tools may measure properties of a product that cannot be perceived by humans. Physical properties can also fall into this realm, a matter that has led Szczesniak [28], a seminal researcher in this area, to stress that only physical properties that are actually perceived by humans can fall under the definition of "texture". Textural attributes are often multifaceted and evaluated using multiple senses including sight, touch, and sound [28]. Further, though some instrumental measurements can reliably predict sensory perception, extreme care must be taken to avoid 'out of range' problems that may result when a sensory system is saturated (i.e., at terminal threshold) [15], [27]. A simple example of this is hardness; glass and diamond have different hardness values when measured instrumentally, but are equally hard to the human finger. As such, finding an instrumental measurement, or group of instrumental measurements, to replace human assessor must be handled carefully.
Relationships between sensory and instrumental measures are usually defined using correlations; however, given the large number of attributes assessed during descriptive profiling, interpreting a large correlation matrix can become unmanagable. Multivariate data reduction techniques are commonly applied to simplify and analyze large data sets; forming factors allows data to be reduced and resulting plots easily visualize the relationships within and between products and attributes [15]. Previously, we used applied descriptive profiling methods to 6 OTC vaginal products in a panel of human assessors [14]. Here, rheological properties were measured, and Principal Components Analysis (PCA) was used to characterize sensory and rheological attributes separately on over-the-counter (OTC) vaginal products. Multiple Factor Analysis (MFA) was then used to integrate sensory (e.g. human) and rheological (e.g. instrumental) measures into a composite space. The behavioral data collection process and summary of results have been reported elsewhere [14].
Three sexual lubricants (Astroglide, KY, PreSeed), two vaginal moisturizers (Replens, RepHresh), and one vaginal contraceptive (Gynol II) were used in this study. Replens and PreSeed were donated by a collaborator; all other products were purchased at a retail location in State College, PA.
Ethics Statement
Human methods and data were described previously [14]. Participants provided written informed consent and were reimbursed for their time. All procedures, including the consent process, were approved by the Pennsylvania State University Institutional Review Board (protocol #32606).
Sensory Data
Perceptual evaluation of the 6 OTC vaginal products was performed ex vivo (in between fingers and on the forearm) and these were reported previously. Briefly, 36 variables rated in triplicate using quantitative descriptive profiling were evaluated by 10 individuals [14]. As in our previous report, only one measurement from each construct (thickness, slipperiness, graininess, etc) was used for analysis; however, the exact variables used in the present analyses differ from those used previously, as they were selected using a more sophisticated algorithm (described below in the statistics section). This is not expected to affect interpretation of the sensory data as within-construct variables were highly correlated (data not shown).
Rheological Data
Instrumental data were collected in triplicate using an ARES rheometer (TA Instruments) at 25°C. Cone-and-plate geometry was used (0.04 radian cone angle, 50 mm diameter and 43 µm gap). A sample (1.5 ml) was loaded onto the plate and both oscillatory and steady-shear flow behavior were measured. Oscillatory measurements were collected using a dynamic frequency sweep conducted over the frequency range of 1–100 rad/s at 5% strain; preliminary testing determined that 5% strain produced a measureable torque within the linear viscoelastic range. Steady-shear flow behavior characterization followed. Viscosity was measured as a function of shear rate using a steady rate sweep from 1–100 s−1. Preliminary testing showed some samples to be thixotropic (viscosity decreased over time when a constant stress was applied) so all samples were subjected to a 300 s preshear at the corresponding shear rate (1–100 s−1). Temperature and shear rate for rheological analysis were selected to correspond to conditions similar to those used by the human assessors [14].
Statistical Analyses
Multivariate data reduction techniques are a common approach in sensory science to simplify large data sets by restructuring them into a usable form based on patterns within products and attributes. Principal Components Analysis (PCA) and Multiple Factor Analysis (MFA) are multivariate techniques that are often applied to sensory datasets [15]. These techniques identify highly correlated variables within a data set and combine them into a new variable (factor); the first factor accounts for the maximum amount of variance within the data and additional uncorrelated factors are created from the remaining variance. The formation of factors allows data to be reduced to easily visualize the relationships within and between products and attributes [15]. PCA and MFA differ in that PCA groups together the variance of all attributes together while MFA allows the variance to be segmented by groups of attributes, for instance between a group of sensory attributes and a group of rheological attributes [29].
The decat (DEscription of CATegories) function in the SensoMineR package for the R statistical environment was used to determine which of the variables within each sensory construct were most discriminating among the product set [30]. The final attributes selected showed more significant differences among products and thus were more capable of distinguishing products in terms of their corresponding underlying sensory constructs.
Multiple Factor Analysis was conducted on the means of both the sensory and rheological data using the MFA function in the FactoMineR package for the R environment [31]. Kaiser's criterion (eigenvalues >1) was used in determining the number of dimensions (principal components or factors) to retain [15]. When defining the significant attribute loadings for each dimension, the dimdesc function in SensoMineR was used with α = 0.1. Correlations among attributes, among rheological parameters, and between attributes and rheological parameters were calculated using StatPlus in Excel; correlations were considered significant at α = 0.05 and no adjustments were made for multiple comparisons, as the appropriate Bonferroni correction factor varies depending on the question of interest. Statistical analyses of the rheological data were performed in SAS 9.2 (Cary, NC) using a 2-way ANOVA (PROC GLM) followed by Tukey's HSD for multiple comparisons. Significance was determined at α = 0.05.
Sensory Data
A detailed presentation of the perceptual descriptive panel data from human assessors is provided elsewhere [14]. A brief summary follows. The contraceptive, Gynol, was thicker, stickier, grainier, more rubbery, had more air bubbles, was the least slippery, least smooth, and had the most uneven spread of all the samples. Gynol was the most perceptually different sample; this was confirmed by PCA (not reported). The two vaginal moisturizers, Replens and RepHresh, had very similar properties and only differed significantly from each other for the attributes stickiness and air bubbles (RepHresh is stickier while Replens has more air bubbles). Two lubricants, Pre-Seed and Astroglide, were very similar on several attributes; both products spread evenly, were very slippery (Astroglide >Pre-Seed), thin, smooth and clear and showed minimal peaking, air bubbles, stickiness, graininess, and rubberiness. The other lubricant, KY had more similarities with the moisturizers as it was thicker, stickier, more rubbery, and showed peaking and air bubbles; it also did not spread as evenly as Pre-Seed or Astroglide. However, KY was as slippery as Pre-Seed and was the only product besides Astroglide that was ropy. (Ropiness was defined as the 'ability of the product to string between the finger and remaining product'; as discussed in [14], it could also be described as 'snotty' or 'spinnbarkeit').
In keeping with standard practices in the field, descriptive panelists are asked to rate the intensity of attributes using an analytical frame of mind following a lengthy training process; accordingly, no hedonic or acceptability data is collected from these panelists, as the attributes they have been trained to attend to and evaluate may or may not be drivers of acceptability in consumers. The resulting analytical data is then used to gain insight to affective/hedonic data collected separately from a group of naïve consumers who evaluate the product qualitatively or quantitatively.
To examine the relationship between the rheological and sensory data on the sample set, MFA was performed using the sample means of both data sets (Figure 1). The first two factors were retained according to Kaiser's criteria and these factors accounted for 84.1% of the total variance in the data set. Attribute loadings are displayed in Table 1. Factor 1 was positively correlated with the sensory attributes clumpiness, thickness, stickiness, peaking, rubberiness, and uniform thickness and with the rheological attributes G" and K; it was negatively correlated with the sensory attribute slipperiness. Factor 2 was positively correlated with the rheological attribute tan δ. Plotting of the attribute vectors onto the factor plot allows visualization of how attributes interact with samples (Figure 1). PreSeed was strongly influenced by the rheological attributes tan δ and n and by the sensory attribute slipperiness. Astroglide was distinguished primarily by the sensory attributes slipperiness, amount left, and ropiness. Gynol's position was due to the sensory attributes graininess, air bubbles, clumpiness, uniform thickness, rubberiness, and stickiness as well as the rheological attributes G" and K. Replens and RepHresh were distinguished from each other primarily by their relative values of G'. KY did not have any variables that set it apart from the sample set and thus was positioned near the origin.
Products are shown as squares. Rheological measures and sensory attributes are shown as vectors.
To further explore interactions between sensory and rheological variables, correlation coefficients between attributes are listed in Table 2; correlations that were significant at α = 0.05 appear in bold. As seen in the positioning of the vectors in the MFA plot, tan δ and n were not significantly correlated with any of the sensory attributes. G' was only significantly correlated with peaking. G" and K were significantly correlated with uniform thickness, stickiness, peaking, rubberiness, and clumpiness. G" was additionally correlated with graininess and air bubbles and K was correlated with thickness and slipperiness. Interpretations from the correlation coefficients should be considered cautiously, however, given the limited product space. Gynol, being high in many attributes and the only sample with attributes such as graininess and clumpiness, had a strong influence on the data set. The sample set influences correlations, such that the observed correlation between clumpiness and graininess may not be present, depending on the samples included. Also, sensory attributes that are highly correlated, such as peaking and thickness, may be redundant variables that measure the same underlying sensory construct [15]. Correlation graphs between G" and the PC1 correlated sensory attributes are shown in Figure 2 and between K and the PC1 correlated attributes are presented in Figure 3. Although correlation coefficients for all relationships were high (≥0.79) consideration of the plotted data again shows the strong influence of Gynol; Gynol had high values in many sensory attributes as well as G" and K and the influence of this product on the proposed perceptual-rheological relationships is visualized in the correlation plots. However, some relationships appeared to show perceptual properties could be explained by rheological factors, specifically the relationships between G" and uniform thickness, rubberiness, and stickiness and between K and peaking, rubberiness, and stickiness.
Rheology Data
Most microbicidal vaginal "gels" described to date are not in fact gels in the strict rheological sense; rather, they are thick viscoelastic liquids or semi-solid creams. Viscoelastic materials are those intermediate between viscous liquids and elastic solids, and their properties are often measured using oscillatory rheological techniques. In these methods, the rheological response is deconvoluted into the relative elastic or solid component (characterized by the storage modulus, G') and the viscous or liquid component (characterized by the loss modulus, G"). The ratio of the two is quantified as the tangent of the phase shift (phase angle), called tan δ, and directly related to the ratio of the energy lost to the energy stored per oscillation. Values for Tan δ can vary from 0 to infinity, and the closer Tan δ is to 0, the more solid the material's character.
The results of the oscillatory frequency sweep can be seen in Figure 4; data at 10 rad/s was formally tested via ANOVA (Table 3). Tan δ (again, the ratio of energy lost (G") to the energy stored (G')) differed significantly among the samples (F (5,17) = 220.3, p<0.001).
Within each plot, G' and G'' are plotted on the left y-axis and tan delta is plotted on the right y-axis. To provide better resolution, the range differs for the left y-axis for the bottom two figures.
PreSeed had the greatest tan δ value (tan δ>1), indicating a viscous liquid [32], [33]. Astroglide, Gynol, and KY did not differ significantly from one another and their tan δ values (tan δ<1) fell in the range of a viscoelastic solid while Replens and RepHresh, which did not differ significantly from one another, had the lowest tan δ values, implying they had the most solid-like character.
In terms of relative magnitude of G' and G", PreSeed and Astroglide were easily distinguished; G' (F (5,17) = 944.4, p<0.001) and G" (F (5,17) = 634.7, p<0.001) differed significantly across the samples. At 10 rad/s, the G' and G" of PreSeed and Astroglide are significantly lower than the other samples. Coinciding with tan δ values, RepHresh, followed by Replens, had the highest G' values, while Gynol, followed by KY, had the highest G" values.
Flow behavior data was analyzed using the Ostwald-de Waele power law equation: η = Kγn–1 with η as shear viscosity, K as consistency coefficient, γ as shear rate, and n as the power law index; all R2 values were greater than 0.99, indicating the data fit this model very well. The data are presented in Table 4. All samples showed pseudoplastic behavior (n<1); however, the degree of pseudoplasticity differed significantly across samples (F (5,17) = 1822.2, p<0.001). PreSeed was least shear thinning with a power law index close to 1 (n = 0.846); all other samples had power law coefficients between 0.36–0.197, with Replens and RepHresh being the most shear thinning.
The consistency coefficient (K) also differed significantly among samples (F (5,17) = 209.9, p<0.001). The consistency coefficient of Gynol was the greatest, followed by RepHresh, then Replens and KY. Astroglide and PreSeed had the lowest consistency coefficients and did not differ significantly from each other.
The results discussed here, which were confirmed by Principal Components Analysis (PCA) (not reported), indicate that PreSeed was the most rheologically different sample as it displayed predominantly viscous liquid behavior and was the least shear thinning.
Textural attributes are a common focus of participants involved in microbicide acceptability studies. Terms such as "slippery", "thick", and "sticky" are often used by focus group participants to describe potential and surrogate microbicide products [34]–[36]; these attributes can be positive or negative, depending on the individual. Therefore, being able to predict the level of these attributes in a candidate microbicide during preclinical formulation may help predict its future success in the field. The use of quantitative descriptive profiling in this study, which provides objective quantitative measurements of perceptual attributes such as slipperiness and thickness, can provide a crucial link between focus groups and instrumental measures. Through this type of quantitative data, we can gain additional insight on the relationships between human perception and physical properties of microbicides and microbicide surrogates.
Correlations indicate whether an instrumental variable potentially predicts a sensory/perceptual attribute. This study found significant correlations between the perception of graininess, uniform thickness, stickiness, peaking, rubberiness, clumpiness, and air bubbles and the rheological attributes G" and K; peaking was also correlated with G' and K was correlated with thickness and slipperiness. However, Szczesniak [37] cautions that such correlations are highly subject to the range and number of samples evaluated. Given the small product set evaluated in this pilot study, correlations reported here should be treated cautiously. Many significant correlations did not appear to show a relationship between the sensory attribute and rheological measure (i.e. correlation between slipperiness and K); additionally, some of the other rheological-sensory relationships may have been strongly influenced by Gynol, which had high values of many sensory attributes and rheological attributes.
Szczesniak also points out that the strength of correlations is subject to how well instrumental measurements imitate sensory evaluation conditions [37]. In this study, instrumental measurements were taken at standard room temperature, 25°C, since sensory evaluation samples were dispensed at room temperature; it is possible that contact with skin could have increased the temperature of these samples, changing their rheological properties. Oscillatory measurements were reported at 10 rad/s, which is roughly similar to the rate at which panelists manipulated samples (2 rotations/s); how well these frequencies align and influence oscillatory measurements should be considered. Often, instrumental measures are collected using novel instruments or techniques that mimic sensory evaluation [15], [38]. The measurements we selected here were based on measurements being used by other microbicide researchers to characterize the physical nature of potential microbicides [39]–[41].
In future studies, limitations of this initial proof of concept study should be addressed. Increasing the size and diversity of samples within the product space should eliminate any undue leverage of individual products on perceptual-rheological correlations. To better understand how rheological variables influence sensory perception of microbicides, the samples could be rationally designed to cover the complete rheological design space, which would reduce confounding variables introduced by using OTC products. Relating sensory properties to rationally designed samples would better demonstrate putatively causal relationships; these data could then used to build more complex regression models to predict sensory properties through the rheological variables.
Further, the rheological data we collected was by no means exhaustive; our parameters were chosen based on microbicide studies already being conducted and to gain an understanding of the physical structure of the products. However, when relating sensory attributes to instrumental data one must consider the multifaceted nature of human perception. Increasing the range and variety of rheological variables studied (including the measurements of G', G", and tan δ at different frequencies) will give a better perspective on physical structure of samples and any relationship with textural properties. Expanding the physical analyses beyond rheology may also provide more insight; approaches such as tribology, which measures a sample's interaction with various surfaces (skin, glass, mucosa, etc), as well as yield stress which measures plastic deformation of the sample may be able to predict various attributes and enhance understanding of the perceptual properties. A recent study by our group shows how elastic properties of semisoft suppositories influences women's perceived ease of insertion and willingness to try [42].
Addressing the issues with the sample set, rheological variables, and profiling procedure may help clarify relationships between the human and instrumental data. Some difficulty is introduced through the complex nature of the perceptual attributes, which could be redundant (meaning separately measured attributes are actually measuring the same underlying sensory construct) or too complex to be summarized by a single instrumental measurement. The improvements suggested above, including rationally designing samples and increasing rheological measurements, would enable a better demonstration of any relationships between the data; these data sets could further be used to build regression models that predict sensory perception through the rheological variables. However, useable information can still be gained, especially if this analysis is considered as a proof of concept study. Common rheological measures, shear-thinning behavior (n) and tan δ at 10 rad/s, showed no relationship with any textural attributes measured by the human participants; G' at 10 rad/s was correlated with some attributes but did not appear to be a strong predictor of these attributes. G" at 10 rad/s and K were correlated with several sensory attributes; still, these correlations merit confirmation in later studies. The relationships between G" and stickiness, rubberiness, and uniform thickness and between K and stickiness, rubberiness, and peaking are more promising and suggest that these viscosity related measurements predict the perceptual attributes.
G" at a given frequency is a measure of dynamic viscosity [43] while K is related to the viscosity. As both these parameters measure viscosity in some form, it could explain their relationship with stickiness, uniform thickness, and peaking; for instance, a material with a high resistance to flow (viscosity) would require a great amount of force to separate the fingers after the sample had been compressed (stickiness). Beyond the obviously Gynol-influenced correlations with clumpiness, graininess, and air bubbles, the remaining perceptual-rheological correlations seem to point to an overall separation of the samples into two groups: a 'low structure' group (Astroglide and PreSeed), and a 'high structure' group (Replens, RepHresh, KY, and Gynol). Samples with positive PC1 values ('high structure') on the PCA and MFA plots were high in attributes G', G", K, uniform thickness, stickiness, peaking, thickness, and rubberiness while those to the left ('low structure') were low in those attributes. This may be due to a greater concentration of rheologically relevant materials in the 'high structure' group that allowed formation of structures within the sample that influence texture.
Recently, microbicide research has been shifting to try to explain user acceptability through biophysical properties [11]. Though this type of research is still in infancy, the studies that have been conducted already show how insight from descriptive profiling approaches can contribute and help inform study designs. A study by Verguet and colleagues, assessed women's preferences for various OTC vaginal products including KY [8]. In their study, the samples were pre-qualified by the researchers as more or less 'slippery' and 'thick' based on the viscosity of the samples; participants were asked how they would potentially use these products based on the attributes specified by the researchers [8]. The goal of the Verguet study was only to assess women's potential preferences and behaviors and were not actually tested in vivo, so data was not completely dependent on user perceptions of the slipperiness or thickness of the samples. Likewise, van der Berg and colleagues [44] characterized Pre-seed, KY, and Replens rheologically as part of an in mano acceptability study, stating that viscosity "corresponds to the colloquial notion of thickness". They also provide instrumental data that Preseed had a lower viscosity than KY or Replens. Similarly, we previously generated quantitative perceptual data showing PreSeed is perceived as less thick than KY or Replens on the forearm [14]. Here, we extend those data, showing that perceptual attributes like thickness correspond to rheological measures like G'' (the loss modulus) and K (the consistency coefficient) (see Figure 2). We also find that PreSeed and Replens differ greatly in their sheer thinning behavior; it is unknown how properties like sheer thinning influence user acceptability either in mano, or peri-coitally, but this would seem to be a fruitful area for future research. Given present results, we would recommend that future microbicide research should systematically consider how well physical measurements relate to the specific perceptual attributes they want to explore.
Quantitative descriptive profiling, through its use of humans as calibrated sensors, can help close the gap between instrumental data and consumer acceptability (e.g. [19], [20]). By determining the ranges in which humans can perceive and differentiate rheological properties among samples, the process of relating sensory and instrumental data can help eliminate erroneous assumptions made when instrumental data are directly linked to acceptability data. Although present data are subject to the range of samples and instrumental methods selected, it demonstrates how descriptive profiling and rheological data of vaginal products can be integrated. Certainly, we do not mean to imply that sensations in the hand are a direct surrogate for sensations in the vagina, but rejection (and thus non-use) may arise from sensory properties well before a product is ever taken into the body. For example, an individual may reject natto (fermented soybeans) solely on the basis of their slimy texture without ever putting them in her mouth. Accordingly, the approach described here may provide new insights on perceptual-rheological relationships, as well as helping to rapidly eliminate unacceptable prototypes early in preclinical testing. Here, both sensory and instrumental measures appeared to discriminate between samples that had a high degree of internal structure from samples with a low degree of internal structure; however, separation of samples within each group are caused by variations in both sensory and rheological properties for individual samples. This analysis should inform those working in rational design of microbicides, and highlight the need to examine any instrumental measurements before attempting to relate them to human perception or acceptability.
The authors thank our study participants for their time and participation. A preliminary draft of this manuscript was completed in partial fulfillment of the requirements for a Masters of Science at the Pennsylvania State University by EDM.
Author Contributions
Conceived and designed the experiments: EDM JEH GRZ. Performed the experiments: EDM. Analyzed the data: EDM. Contributed reagents/materials/analysis tools: JEH GRZ. Wrote the paper: EDM TZ GRZ JEH.
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Bourne MC (2002) Correlation Between Physical Measurements and Sensory Assessments of Texture and Viscosity. Food Texture and Viscosity. 2nd ed. London: Academic Press. 293–323.
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Mezger TG (2006) The Rheology Handbook: For users of rotational and oscillatory rheometers. Hannover, Germany: Vincentz Network. 293 p.
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- 34. Morrow K, Rosen R, Richter L, Emans A, Forbes A, et al. (2003) The acceptability of an investigational vaginal microbicide, PRO 2000 Gel, among women in a phase I clinical trial. J Womens Health (Larchmt) 12: 655–666.
- 35. Zubowicz EA, Oakes JK, Short MB, Perfect MM, Succop PS, et al. (2006) Adolescents' descriptions of the physical characteristics of microbicide surrogates and experiences of use. J Womens Health (Larchmt) 15: 952–961.
- 36. Bentley ME, Fullem AM, Tolley EE, Kelly CW, Jogelkar N, et al. (2004) Acceptability of a microbicide among women and their partners in a 4-country phase I trial. Am J Public Health 94: 1159–1164.
- 37. Szczesniak AS (1987) Correlating sensory with instrmental texture measurements - an overview of recent developments. J Texture Stud 18: 1–15.
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text: Uncategorized Mercedes GP wants Jenson Button but not at any price Published 9 years ago on 2009/11/17 By thisisf1 Jenson Button's Formula One future remains uncertain after Mercedes-Benz secured a controlling interest in his Brawn GP team. The German manufacturer will buy 75.1 percent of Brawn GP in partnership with an Abu Dhabi investment company, with the team to be rebranded as Mercedes Grand Prix and based in Brackley. Team principal Ross Brawn will remain in his role but the future of Button is less certain. The 2009 Champion remains in contract talks with his current team over a new deal and while chief executive Nick Fry – who will also remain in his role – said he and Brawn would prefer Button to remain, he admitted financial constraints may prevent that. "We have had discussions with Jenson about what we think are a sensible salary," Fry said. "This (takeover by Mercedes) is not going to change anything in that respect. "The decision at the end of the day on drivers will be made by Ross principally with my help. "We're going to continue to run the team and it will be our decision on who is going to drive the car." Brawn and Button forged a close relationship during a remarkable 2009 season when Button claimed the drivers' title while the team won the Constructors' Championship at the first time of asking. Despite their success it has been widely reported that the new manufacturer has already signed a deal to make German driver Nico Rosberg their new number one, with Button tipped to join McLaren as he seeks a salary increase. Fry for one is keen for that scenario to be avoided and added: "I hope Jenson is still with us next season. "We've been together for a good few years now and we have succeeded in winning the World Championship together and we want Jenson to be with us. "But we have to recognise that Formula One is not divorced from the rest of the world. "We have worked within a budget (and) if we spend in one area then we cannot spend in another area. "The reason we survived as a team was that we operated in a sensible way and operated within our means and as the chief executive that is my job and we're going to continue to do the same." Fry also served to play down speculation that Mercedes will look to employ an all-German team next season, with Nick Heidfeld and Timo Glock also linked to the team alongside Rosberg. "I can confidently say that (speculation) is totally incorrect – Mercedes is an international company," he added. "Clearly a German driver would be nice for them but we don't need two German drivers, that's not the intent." Mercedes motorsport vice-president Norbert Haug, however, intimated that a change in personnel was on the cards, saying: "Hopefully we can announce this in the next couple of weeks. "We will do a good job in that point of view and maybe we can cause some surprises." Mercedes-Benz's deal with Brawn ushers in a slow break from their current ties with McLaren, who will buy back the German manufacturers' 40% shareholding by 2011. Mercedes will, however, continue to supply engines to McLaren until 2015. McLaren will continue to be branded as Vodafone McLaren Mercedes. http://www.formula1onlive.com/feeds/posts/default?alt=rss Related Topics: You may like Comments Latest Results 2018 F114 mins ago Practice 1 Results: German Grand Prix 1Share2018 German Grand Prix Practice 1 Results (FP1): First free practice results and Timings (FP1) for the eleventh round of... Latest F1 News 2018 F12 hours ago Bottas signed, Mercedes completed its driver line-up for 2019 50SharesValtteri Bottas has signed a new one-year contract extension with Mercedes, his team Mercedes have officially announced. 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After Sebastian got... 2018 F11 day ago McLaren, Williams, admit need for change 70SharesAn anonymous engineer says struggling once-great F1 teams Williams and McLaren need to make sweeping changes. Both British teams have... 2018 F12 days ago Hamilton is stronger than Vettel – Briatore 257SharesFlavio Briatore thinks Mercedes is still the favourite for the 2018 world championship. Ferrari's Sebastian Vettel has taken an 8... 2018 F12 days ago Sirotkin reveals his biggest problem with Williams' 2018 car 2SharesSergey Sirotkin has given more details about his biggest problem with Williams' 2018 car. While the car is obviously uncompetitive,... 2018 F12 days ago F1 eyes 20-year deal for Miami Grand Prix 1ShareYet another meeting could finally mean the green light for a grand prix in Miami. We have reported that Liberty... Most Popular 2018 F16 months ago 2018 Formula 1 Driver Salaries: Who is Highest Paid F1 Driver? 2018 F15 months ago 2018 F1 Live Timing: Day 1 – Barcelona Testing 2018 F14 months ago 2018 F1 Live Timing: Day 7 – Barcelona F1 Testing 2018 F15 months ago Williams F1 Launches Its 2018 Season with First Look at The FW41 2018 F15 months ago 2018 F1 Live Timing: Day 2 – Barcelona Testing 2018 F15 months ago 2018 F1 Live Timing: Day 4 – Barcelona F1 Testing 2018 F15 months ago 2018 Force India VF-18 'similar' to 2017 F1 car 2018 F14 months ago Haas F1 VF-18 100% a Ferrari, don't build, they buy one – Renault

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Talita Nogueira Wants Quick Win Over Bellator Champion Julia Budd | Latest News RSS feed
Talita Nogueira Wants Quick Win Over Bellator Champion Julia Budd - Latest News
Talita Nogueira wants quick win over Bellator champion Julia Budd
Talita Nogueira only needed one win inside the Bellator cage to earn a shot at the featherweight championship, and bringing the belt back home to Brazil would be unprecedented for women's jiu-jitsu. B...
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Bellator 202 'Budd vs Nogueira' streaming play-by-play updates
BELLATOR 202 "Budd vs. Nogueira" QUICK RESULTS: Julia Budd vs. Talita ... over as Herzog saves Nogueira at 4:07! Final result: "The Jewel" Julia Budd retains via TKO at 4:07 of the third round. Eduard...
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Colby Covington: I 'hold all the cards' vs. Tyron Woodley
Newly-crowned UFC interim welterweight champion Colby Covington is the one calling the shots over official champ Tyron Woodley. After beating Rafael dos Anjos to win the ... highlights from Bellator 2...
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UFC 138 post-fight notebook: Brits Pickett, Etim, Mills, Maguire and Young reflect
I just want to beat people who are in front of me. I got beaten tonight, so I want to get in there as soon as possible and try and knock someone's head off." UFC president Dana White was quick to his ...
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Bellator champ Julia Budd wants to be best at 145, knows Cris Cyborg shadow looms
For one night at least, Julia ... picked up a win over Gina Carano, Budd made the transition to full-time MMA fighter and hasn't looked back. With a win on Friday, Budd will have the most consecutive ...
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Bellator 202 'Budd vs Nogueira' recap with results, .gifs and interviews
The Featherweight title was up for grabs as defending champion Julia Budd (11-2) squared off against undefeated BJJ world champion Talita Nogueira ... off and took over the fight standing, doing damag...
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Running Time: 90 min.
In theatres: July 27, 2018 (limited)
Current rating:
Rate Movie | Not yet Reviewed
Cast: James Marsden, Woody Harrelson, Jessica Biel, Milla Jovovich, Tommy Lee Jones, Rob Reiner
Two Washington reporters, Jonathan Landay (Woody Harrelson) and Warren Strobel (James Marsden), along with their boss, John Walcott (Rob Reiner), and war correspondent, Joe Galloway (Tommy Lee Jones), expose the truth about what led to the 2003 Iraq war.
In the aftermath of the terrorist attacks of September 11, 2001, President George W. Bush builds a case to invade Iraq to remove Saddam Hussein from power, rather than go after the real culprit, Osama bin Laden, who's believed to be in hiding in Afghanistan or Pakistan. When no one questions the President's decision, Landay and Strobel decide to dig deeper. Chasing down leads, they get intel from anonymous government sources in an effort to discover the President's reasoning for going to war with Iraq.
Based on a true story.
Rob Reiner
Studio: Pacific Northwest Pictures
Producer(s): Rob Reiner, Matthew George, Elizabeth A. Bell, Michelle Reiner
Screenplay: Joey Hartstone


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Than adults.ncreases Adult Fertility, regardless of educationA new study published in the Journal of Personality shows that personality in adolescence predicts reproductive success later in life. The results of the study showed that male and female youths were with socially dominant personalities rather have children than adults. Continue reading
The major challenges in designing an effective peptide-based vaccine to treat cancer is to improve the immunogenicity of the selected peptides and overcoming tumor-induced immunosuppression. To stand any chance of producing prolonged cellular immune responses tumor cells tumor cells, a vaccine must first activate the immune system against the targeted antigens without activating or amplifying antigen-specific regulatory mechanisms. The formulation was used in DepoVax DPX-0907 was able to achieve this in the preclinical mouse model.
About Breast and Ovarian Cancersbreast cancer the second leading cause of cancer-related deaths among American women and ovarian cancer is the eighth most common cancer in women and the fifth leading cause of female cancer death, according to the National Cancer Institute. Continue reading
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Please provide the link to the published versions of your ARTICLE IN ONLINE REPORTCONTACT: Raffaele Bugiardini University of Bologna Via Internal Medicine and Cardiology Massaranti 9 – 40139 Bologna, Italy padiglione 11Everything published by PLoS Medicine is Open access: freely available for anyone to read, download, distribute or otherwise use, as long as the authorship is correctly attributed.Please noted PLoS Medicine in your report , and use the links above,this morningArrest Four Men But WFP food aid ship still HijackedThe UN World Food Programme said today that Puntland authorities arrested this morning, four men who say they were part of a group that hijacked a WFP ship off the northeastern coast from Somalia. The men were arrested when they buy the supplies went ashore in the town of Bargal. But some four hijackers remain in control of the MV Rozen. The arrest welcome news, but the safe release of the crew and the vessel remains our main concern We hope this ordeal will soon be over, 'said WFP Somalia Country Director Peter Goossens. Continue reading
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Jeff Sessions expressed concern about the bill of $ 50 billion over five years. Identification of at least four of the six clinical features was associated with poor swallowing results at admission and discharge from hospital.. One-third of GOP Continues To Bill To Global HIV / AIDS Bill Despite Bush's support readmit Block – Several Senate Republicans again on Friday blocked efforts to a bill to the Senate, the funding would be for the President Emergency Plan for AIDS Relief allow bringing although President Bush says that support for the measures, CQ Today. Senate Majority Leader Harry Reid been been placed crosswise to add the billing address. The agreement includes a requirement that more than half of PEPFAR funds for treatment and care are used, according to CQ Today. Continue reading
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You can view the entire Kaiser Daily Global Health Policy Report search the archives and sign up for email delivery of global health. On Wednesday, the U.S. Pulls his team from the field hospital beside[ the HIV / AIDS clinic] Gheskio. The final temp of a handful of field hospitals, which were from U.S. Health officials set Gheskio officials originally the U.S. Team stay remain until mid-March, said[ Jean William Pape, founder of Gheskio], and were surprised to find to take to take in this week.
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tv KTVU News at 730pm FOX October 30, 2013 7:30pm-8:01pm PDT
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watch yacht starter. they chant the name of lackey, a guy who came here in 2010 given a big deal. pitching this october better than i ever has with the boston red sox. ground ball fair. passed fist down the right-field line. descalso watches victorino make a great play to hold descalso to a two out single. >> tim: that's what john farrell to reiterate what you said earlier, that's why he told us before the game that victorino gives him so much flexibility in right field. he's by far the best right fielder he has. and he shows it.
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tazawa getting loose just in case. you know john lackey doesn't want to give up the baseball. >> tim: never does. >> joe: ahead on the count to carpenter, 1-2. that's past third and a diving bogaerts. descalso goes to thirdment they're going to hold him there on a double by carpenter. matt carpenter is three out of
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four here in game six. >> tim: good two strike hitting by carpenter. getting it past bogaerts. we don't have a real good shot from this angle. but it looked like the ball really got hung up in the corner there. if it weren't a 6-0 ball game, i think descalso tried to score. but when you're trailing by six in the seventh inning, no chance. got to hold him up. >> now they have a chance to cut the lead in half. second and their. beltran takes strike one. a little more urgency with tazawa and the bull pen. beltran 4 for 4 this postseason with runners in scoring position. two out.
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strike two. one of the quirks is when a ball is in the left field corner, the third base coach almost thooz go to the sign to see it. from the box you can't see down there. holding him up is certainly proper. here's the 0-2. base hit left field. one run scores. carpenter will be held at third. the cardinals are on the board. it's a 6-1 game. beltran knocks home descalso. >> tim: through the deserted third base position. the shift was on. so the shift give edge and take
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hollid holliday. that gets away. send beltran down to second. and it's a 3-1 count on the cardinal left fielder. >> tim: now a single cuts it in half. >> joe: should be the second wild pitch of the night for john lackey. it is. holliday sitting on a pitch on 3-1. fouled straight back. it's a full koupt. holliday had a pitch to hit then. he missed it. found it back.
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>> joe: another one out of play. >> tim: so far, six straight fastballs from lackey to matt holliday. >> joe: holliday four home runs this postseason. came in to tonight a career in ten games .381 hitter in this park. the last hurdle for lackey. and he has walked holliday to load the bases. david ross is going to go out. farrell is going to come out and that's it for lackey.
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[ whirring ] ♪ ♪ one, two, one, two, three ♪ come on, come on ♪ come on, come on ♪ come on, come on [ male announcer ] this is an invitation... xbox, on. [ male announcer ] ...to a new generation... where your games and entertainment are no longer separated... xbox, go to "star trek into darkness." [ male announcer ] ...but together in one. the all-in-one, xbox one. ♪ everybody, come on >> joe: tazaw will enter in a
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five-run game here in the seventh. allen craig coming up. hit .545 during the regular season with runners in the scoring position. third highest average since 1974. allen craig in his career with the bases loaded has hit .424 including the postseason. lackey's night is over. and he gives way to tazawa with a bases loaded in a five-run game. allen craig, two for three tonight. lights up with men on. ball one.
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>> joe: here's the 1-0. ground ball. stopped by napoli. flips for the out. and the cardinals now have left nine. they get only one and trail by five. ladies and gentlemen, this has been a world series to remember in more ways than one. thanks to the support you've shown for our troops all season long. bank of america recently donated $1 million to welcome back veterans and wounded warrior projects to help our service members and veterans succeed here at home. and as a result, the overwhelming gratitude you've
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shown for their service, bank of america will continue to donate $1 for each message of support using #troopthanks through the conclusion of this world series. and now we join pa announcer for the introduction of "god bless america." >> to lead us in the singing of "god bless america" and representing all of the active duty reserve guard and civilian professionals faithfully serving in the united states air force across the globe, please welcome master sergeant jennifer dashnog, technical sergeant richard vazquez, technical sergeant nico ellis son and rachael webber. the united states air force heritage of america quartet. ♪ god bless america
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he's got four of the six rbis for boston. he missed two games with a bad back. breaking ball stays inside. the count 1-1. >> tim: when shane was a senior in high school, he kicked a 48-yard field goal. university of hawaii offered him a scholarship to be the defensive back. after tonight, i think shane made the right decision. >> joe: he's involved in his third world series. he already has a ring. first year with the red sox. brandon workman started the season in aa is getting loose. count has gone to 2-1 for carlos martinez. flyball into left. holiday comes to get it. one out.
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let's look what the red sox have been able to do throughout this postseason. they took care of matt moore and david price at the tampa bay rays in the division series in games one and two. they got ver lander in game three. scherzer in game six. and now here in this world series, they defeated the top starter for the cardinals, adam wainwright two times in games one and five. here's a flyball into right. two out. in this world series, adam wainwright is 0-2 juan e.r.a. of 4.50. he's gone head-to-head with jon lester twice. and lester, tim, is 2-0 in this world series. one earned run. 15 and a third innings pitched. he's 4-1 with an e.r.a. of just over 1.5. >> tim: and being masterful with
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that cutter. stephen drew takes the strike. this is a red sox team that up is here in game six, 6-1. lead this world series prior to this inning as a group hitting only .214. but they have had big hits. different guys who it's mattered the most. he has one of them. break a 1-1 tie in the two-run seventh. here's the flyball into left. a base hit. and stephen drew is 2 for 4 tonight. >> tim: red sox fans in the area were chanting for jose iglesias to play instead of stephen drew.
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iglesias was traded to the detroit tigers. and then stephen drew had to battle xander bogaerts who is a natural shortstop. and, yet, john farrell persisted with the best defensive shortstop he had and drew has rewarded him with two hits tonight, one home run. >> joe: and really good defense throughout the entire postseason. >> tim: yeah. >> joe: one on, two out. ross takes ball one. in the eighth inning, st. louis will have molina, adams and freese. workman getting ready for that. tazawa came on to get allen craig on a groundout with bases loaded.
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>> joe: 1-0. hard hit but right at jon jay. and the inning is over. the new galaxy note 10.1 allows you to run two programs simultaneously so you can multi task like never before. cmon man, we going to make this trade or what? it lets you check stats while you talk trades... harris for kruz? hi mom! write down the details while you chat... four cups of breadcrumbs. drag and drop pictures so you can share faster. and follow the recipe while seeing how it's done. right, so... oh celery. now featuring over $600 in added value. including samsung hub and google play.
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>> joe: coming up after the world series, no one covers the off-season like the mlb network with three prime time shows and the only morning show dedicated to baseball. it's on mlb network beginning monday, november 4th. third pitcher of the night. lackey was tremendous. tazawa got the only man he faced with bases loaded in the seventh. and here's brandan workman. a big piece of the bull pen for john farrell this october.
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ball one. >> tim: cardinals with six outs and get five runs at least. >> joe: here's the 1-2. 2-2. bull pen for the red sox is quiet. breslow has been up. cardinals proved in the seventh inning in a this game is not over. they stranded nine. 2-2 pitch to molina. into right field. victorino got a good jump. one out. he almost got too good of a jump. >> you're right. almost overran it. the home plate umpire is making
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a friend here at fenway. >> how are you? >> good. >> how long you been coming here? >> 70 years. >> great to see you. >> how sflu. >> pretty good. later on. and there he is. 1953 he's been coming here. we saw the splendid splinter many times. first pitch, a ball to matt adams. cardinals still do not have an rbi from the six through nine spot. they've had their chances here tonight. but that group hasn't had an rbi in this series. there's pedroia. two out.
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Lockheed C130 Hercules
by Peter C. Smith
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A very, very comprehensive book on the C-130 Hercules. Seems to be a list of every C-130 aircraft - in any variant - that ever took of from terra firma. I would regard it as a work of reference. And as such, it is an impressive work. A must for all Hercules buffs
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