Eating Behaviors 18 (2015) 125–130

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Eating Behaviors

Is level of intuitive eating associated with plate size effects? Drew A. Anderson a, Katherine Schaumberg a,b, Lisa M. Anderson a,⁎, Erin E. Reilly a a b

University at Albany-State University of New York, Department of Psychology, 1400 Washington Avenue, Social Sciences 399, Albany, NY 12222, United States Drexel University, Department of Psychology, 3141 Chestnut Street, Stratton Hall 119, Philadelphia, PA 19104, United States

a r t i c l e

i n f o

Article history: Received 6 December 2014 Received in revised form 20 March 2015 Accepted 13 May 2015 Available online 19 May 2015 Keywords: Intuitive eating Portion size Satiety/hunger cues

a b s t r a c t Objective: Intuitive eating is an eating approach that emphasizes increased focus on internal hunger and fullness cues to regulate eating behavior; thus, successful intuitive eating should curb the influence of environmental factors such as plate and portion size on consumption. The current study examined whether self-reported levels of intuitive eating moderated the influence of portion size on college students' food consumption during an afternoon meal of pasta and tomato sauce. Method: Participants (N = 137, 63.5% female) were randomly assigned to either a large plate (12-inch) or small plate (8-inch) external cue condition. All participants fasted for four daytime hours, completed the Intuitive Eating Scale, and then were asked to rate a meal of pasta and tomato sauce on different dimensions of taste. Participants were told that they could eat as much pasta as they would like. Results: Higher levels of intuitive eating were associated with greater food consumption. At the mean level of intuitive eating, participants ate more pasta in the large plate condition. Furthermore, the influence of plate size on food consumption increased as levels of intuitive eating increased. Discussion: Individuals who report high levels of intuitive eating may be more likely to eat an objectively larger amount of food in a permissive food environment, and may have implications for eating approaches that promote eating in response to internal hunger and fullness cues. © 2015 Elsevier Ltd. All rights reserved.

1. Introduction Many studies suggest that environmental variables, such as portion and plate size, can influence the amount that individuals consume, such that larger sizes consistently correlate with greater food intake (Diliberti, Bordi, Conklin, Roe, & Rolls, 2004; Fisher & Kral, 2008; Rolls, Morris, & Roe, 2002; Van Ittersum & Wansink, 2012; Wansink, van Ittersum, & Painter, 2006). Schachter (1968) originally suggested that the eating behavior of obese individuals was more strongly influenced by environmental cues than those of non-obese individuals. However, more recent studies have found that environmental cues can affect food intake among individuals of all weight classes (e.g., Wansink, Painter, & North, 2005). Research shows that larger portion sizes are accompanied by increased caloric intake, and changes in portion sizes appear to affect the consumption of a wide range of individuals (Fisher & Kral, 2008; Rolls, Roe, Kral, Meengs, & Wall, 2004; Wansink et al., 2005; Wansink, Payne, & Shimizu, 2011). Importantly, portion size effects are not limited to single meals, but affect eating behavior over longer time frames.

⁎ Corresponding author. E-mail addresses: [email protected] (D.A. Anderson), [email protected] (K. Schaumberg), [email protected] (L.M. Anderson), [email protected] (E.E. Reilly).

http://dx.doi.org/10.1016/j.eatbeh.2015.05.005 1471-0153/© 2015 Elsevier Ltd. All rights reserved.

For example, Rolls, Roe, and Meengs (2006) provided normal-weight and overweight women with meals for two consecutive days, during which time they were instructed to follow meal plans provided by the research team. These two-day meal plans were followed once per week, for four weeks. Meals varied in portion size from a standard level (i.e., a single meal designed by the researchers to maintain a 2000 kCal/ day diet) to a reduced portion size (75% of the standard meal size), provided and served by the research team. On reduced portion size days, women ate fewer calories than they do on standard portion days, though they did not differ in ratings of hunger and fullness. Plate or container size represents another external variable that may have some influence on eating patterns. Although some research have shown no effect of plate size on consumption (Shah, Schroeder, Winn, & Adams-Huett, 2011; Yip, Wiessing, Budgett, & Poppitt, 2013), other works indicate that plate size can impact the amount that individuals consume (e.g., Wansink et al., 2011) and their self-served portion sizes (e.g., Sharp & Sobal, 2012; Wansink & Kim, 2005; Wansink et al., 2006). For instance, movie patrons who were randomly assigned to either stale or fresh popcorn conditions consistently ate more when given a larger popcorn container (Wansink & Kim, 2005). This effect persisted in the stale (unpalatable) popcorn condition, as individuals who were given large containers of stale popcorn continued to eat more than those given medium containers, indicating that container size influences consumption despite discrepant internal cues (i.e., negative taste reactions that might reduce motivation to eat).

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Overall, external variables such as portion size and container size seem to exert effects on eating behaviors across different samples, regardless of weight status. (e.g., Rolls et al., 2006; Wansink et al., 2011) Therefore, strategies to decrease the effects of environmental/external control (i.e., controlling portion size) may be important for both weight loss and healthy weight management (Ello-Martin, Ledikwe, & Rolls, 2005; Ledikwe, Ello-Martin, & Rolls, 2005). Traditional methods of dieting, including cutting down on portion size or restricting high calorie food groups, represent one popular method of controlling the impact of external cues on eating; however, approaches to weight management that are based on dietary restraint may result in higher risk for disordered eating behaviors, such as binge eating (Polivy & Herman, 1985; Stice, 2001). Internally-focused eating approaches, such as mindful or intuitive eating (IE), offer an alternative to decrease the impact of external cues on eating behaviors while simultaneously circumventing the risk for eating pathology. Varying from more traditional models of dietary restraint, these approaches promote changing eating behavior using internal cues (i.e., increasing awareness and response to hunger or satiety), rather than relying on external, environmentally-based strategies (i.e., limiting calories or portion sizes). In particular, IE is central to non-dieting approaches that promote using internal sensations to determine hunger and fullness (Mathieu, 2009; Tribole & Resch, 2012), and appears to be a negative correlate of disordered eating (Tylka & Wilcox, 2006). In particular, advocates of IE caution that engaging in restriction of certain foods or limiting portion size can lead individuals to feel deprived, which can then place individuals at risk for experiences of counterregulatory eating in which they violate dietary rules and binge eat (Herman & Polivy, 1990; Polivy & Herman, 1985; Tribole & Resch, 2012). Cross-sectional studies have shown that higher levels of IE are associated with lower levels of chronic dieting and binge eating, as well as lower BMI (Denny, Loth, Eisenberg, & Neumark-Sztainer, 2013; Hawks, Madanat, Hawks, & Harris, 2005; Madden, Leong, Gray, & Horwath, 2012; Smith & Hawks, 2006; Webb & Hardin, 2012). Additionally, there is a growing body of research suggesting that interventions designed to increase IE are associated with beneficial outcomes on both psychological and physiological variables, although the magnitude of the effects are generally modest (Anglin, 2012; Bacon et al., 2002; Bacon, Stern, Van Loan, & Keim, 2005; Gagnon-Girouard et al., 2010; Hawks et al., 2005; Leblanc et al., 2012; Provencher et al., 2009; Van Dyke & Drinkwater, 2014). However, limited research has examined whether elevated levels of IE are consistently related to positive and negative health outcomes across various populations. For example, elevated awareness to internal cues may differentially relate to eating behaviors among healthy weight individuals, as compared to overweight or obese individuals. Better clarification of whether the apparent benefits of IE are consistent across different populations and weight classes is warranted. While existing work suggests that IE is associated with positive outcomes, there are still questions about the consistency of and mechanisms underlying the observed positive effects. For example, a recent review of interventions designed to increase intuitive and mindful eating behaviors found mixed effects on dietary intake and eating patterns (Van Dyke & Drinkwater, 2014). To date, no studies have directly evaluated the objective success of IE in utilizing internal cues, as opposed to external cues, to regulate food intake. If IE works as hypothesized, environmental cues (i.e., plate and portion size) should have less influence on food consumption among individuals who report high levels of IE, as compared to those who report low levels of IE. However, the influence of external variables (i.e., plate or portion size effects) has been shown to be robust to changes in mindfulness, a related construct, leading researchers to suggest that external cue effects may act independently from internal cues (Marchiori & Papies, 2013). Therefore, the current study sought to clarify whether individuals who reported elevated IE, a construct that has been consistently linked with successful weight

management and lower BMI, would be less influenced by external cue effects. In particular, this study examined the effect of external cues (i.e., plate size and portion size) on eating behavior across different levels of reported IE. Given the consistent findings on the impact of portion size on consumption and the mixed results for the impact of IE, we hypothesized that, regardless of self-reported IE levels, the impact of portion-size manipulation would exert a more robust effect across participants, such that individuals receiving larger plates (and, thus, larger serving sizes) would eat more than individuals receiving smaller plates. 2. Material and method 2.1. Participants and procedure A total of 137 college students participated in the study, and participants received course credit for study completion. The university's Institutional Review Board approved this study. The sample was primarily female (63.5%), had a mean age of 19.3 ± 1.3 years, and reported a mean BMI in the non-obese range (23.0 ± 3.8 kg/m2). The majority of participants self-identified as Caucasian (65.7%), while other participants identified as Black (12.4%), Asian (12.4%), Multiracial (4.4%), and Other (4.6%). Participants were screened for relevant food allergies and ability to fast for four daytime hours. They were instructed not to eat for 4 h prior to their appointment to control for baseline hunger. All appointments were held on a weekday afternoon. Upon arrival to the laboratory, participants provided informed consent and were asked to complete several survey measures. Prior to completing the survey measures, participants were asked to provide verbal confirmation that they had completed a 4-hour fast. During this time, research assistants cooked a meal of pasta and tomato sauce for participants. Participants were randomly assigned to either a small (8-inch) plate condition, which included two servings of pasta with one serving of tomato sauce (n = 72), or a large (12-inch) plate condition, which included four servings of pasta with two servings of tomato sauce (n = 65). Across both conditions, a single serving of pasta was equal to 2 oz (measured when dry; totaling 212 cal); a single serving of tomato sauce was equal to 4 oz (1/2 cup; 70 cal). Participants were instructed to complete a taste-test of the pasta, in which they rated the pasta on several taste qualities. Similar to other experimental eating paradigms (e.g., Polivy, Heatherton, & Herman, 1988; Polivy, Herman, & McFarlane, 1994; Stice, Fisher, & Lowe, 2004), participants were told that they could eat as much pasta as they would like, and that any leftovers would be thrown out. Plates were weighed before and after consumption to measure the amount of pasta eaten. 2.2. Measures 2.2.1. Intuitive Eating Scale (IES; Tylka, 2006) The IES is a 21-item self-report measure that evaluates the degree to which individuals utilize an intuitive approach to eating. The IES includes 3 subscales: unconditional permission to eat, eating for physical rather than emotional reasons, and reliance on internal hunger/satiety cues, which load onto a higher order factor of intuitive eating. Each item is rated on a 5-point scale that ranges from 1 (strongly disagree) to 5 (strongly agree). IES scores are shown to be internally consistent and stable over a 3-week period (r = .90; Tylka, 2006). Scores on the IES positively relate to body acceptance, body appreciation, and overall well-being, and negatively relate to eating disorder symptomology, body dissatisfaction, pressure for thinness, and body mass (Avalos & Tylka, 2006; Tylka, 2006). To our knowledge, the psychometric properties of the IES have not yet been documented in men. 2.2.2. Hunger ratings To ensure that participants did not differ in current hunger levels according to plate size or level of intuitive eating, participants were asked

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“On a scale of 1–100, with 1 being not hungry at all and 100 being as hungry as you have ever been, how hungry are you right now?” prior to the taste test. 2.2.3. Pasta consumption Pasta consumption was evaluated by weighing the pasta before and after participants had eaten on a digital food scale. Research assistants weighed the food out of sight from participants. Pasta consumption was measured in ounces. 2.2.4. Demographic information Participants completed a brief demographic questionnaire, including questions assessing racial and ethnic background, gender, and selfreported height (inches) and weight (pounds), in order to calculate BMI. 3. Analytic plan Prior to conducting the main analyses, data was screened to ensure normality and homogeneity of variance for variables of interest within the sample. For all analyses, missing data was treated as missing completely at random. First, the overall effect of plate size on pasta consumption was examined by evaluating differences in the amount of pasta eaten in each plate size condition. Second, models were estimated to examine intuitive eating as a potential moderator of the relationship between plate size and pasta consumption. The PROCESS SPSS macro (Hayes, 2013) was used to conduct moderation analyses. All variables were mean-centered prior to analyses and corrected for heteroscedasticity as recommended (Hayes, 2013; Hayes & Cai, 2007), and BMI was included as a covariate in moderation analyses. The PROCESS macro computes two conditional main effects (b1 and b2) and one interaction effect (b3). The conditional effects (b1 and b2) reflect the change in the dependent variable (pasta consumption) for every one-unit increase in the independent variable (plate size) or moderator (intuitive eating), only when the other predictor equals its own average score (e.g., the impact of plate size on pasta consumption at the average level of intuitive eating). Notably, this value may significantly increase or decrease depending on the level of the moderating variable in instances where the interaction effect is statistically significant (Hayes, 2013). 4. Results

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Table 1 The moderating effect of intuitive eating on the relationship between plate size condition and pasta consumption.

b1 b2 b3

Intuitive eating → pasta consumption Plate size → pasta consumption Intuitive eating × plate size → pasta consumption

b

se

t

p

3.76 1.89 3.38

.76 .84 .09

4.89 2.27 2.55

b0.001 .027 .033

Note. b-values for b1 and b2 reflect unstandardized conditional coefficients when the value of the alternate predictor variable is equal to the mean (e.g., b1 equals 3.76 at the average level of intuitive eating). SE = standard error.

4.2. Primary analyses The results revealed a significant conditional effect of intuitive eating on pasta consumption indicating that, across both plate size conditions, a one unit increase in mean intuitive eating score corresponded to a 3.76 oz increase in pasta consumption (see Table 1 for the full model). The results also revealed a conditional effect of plate size on pasta consumption at the mean value for intuitive eating, indicating that, for individuals with average levels of intuitive eating, larger plate size condition was associated with increased pasta consumption, and smaller plate size condition was associated with decreased pasta consumption. Finally, the interaction between plate size condition and level of intuitive eating was examined as a predictor of outcome. Calculation of the interaction revealed that intuitive eating significantly moderated the relationship between plate size condition and pasta consumption. Specifically, at lower levels of intuitive eating, there was no significant relationship between plate size condition and pasta consumption; however, as self-reported intuitive eating increased, the relationship between plate size condition and pasta consumption was significant. An analysis of simple slopes was conducted to examine the effect of plate size on pasta consumption at varying levels of intuitive eating. The slope of the relationship between plate size and intuitive eating was computed for scores corresponding to the 10th, 25th, 50th, 75th, and 90th percentiles of intuitive eating. Visual representation (Fig. 1) of this analysis revealed that plate size was not related to consumption at lower levels of intuitive eating; however, as self-reported intuitive eating increased, the relationship between plate size and pasta consumption became stronger. In particular, individuals with high levels of intuitive eating assigned to the large plate size condition ate the most pasta. Within the small plate condition, intuitive eating and pasta consumption were unrelated, r = .19, p = .12. Within the large plate condition, levels of intuitive eating and pasta consumption were

4.1. Preliminary descriptive analyses 12

10

Pasta Consumption (oz)

Similar to other studies, intuitive eating was significantly negatively correlated with self-reported BMI in our sample, r = −.21, p b .05. Intuitive eating scores were unrelated to reports of current hunger, r = .05, p = .52, and participants in the large and small plate conditions did not differ on ratings of current hunger, t (129) = 1.16, p = .11. Average hunger rating at the time of the study was 2.85 (SD = 1.68) on a scale of 0 (not at all) to 6 (very much), indicating that participants were moderately hungry at the time of the study. Participants' mean report of liking pasta was 4.06 (SD = 1.68) on this same scale, and reports of liking pasta did not differ in the large and small plate conditions. The smalland large-plate groups were similar in terms of gender, IES scores, self-report BMI, and age. Several participants (n = 22) only ate minimal amounts of pasta, despite the fact that the experiment occurred during a mealtime following a brief fast. As such, we also evaluated the difference between small and large plate consumption for those who ate a 1/2 serving of cooked pasta and sauce (1.06 oz) or more. In this instance, those in the large plate condition, n = 54, Mamount served = 8.41 ± 5.41 oz, did eat significantly more pasta than those in the small plate condition, n = 57, Mamount served = 6.43 ± 4.19 oz, t (99) = 2.04, p b .05. All participants were included in subsequent moderation analyses, regardless of amount of pasta eaten.

8

6 Small Plate Large Plate

4

2

0 10

25

50

75

90

Intuitive Eating (Percentile) Fig. 1. Pasta consumption as a function of plate size and intuitive eating.

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significantly related, r = .53, p b .001. A supplemental analysis utilizing the Johnson–Neyman technique (Hayes, 2013; Johnson & Fay, 1950) revealed that intuitive eating was not associated with pasta consumption until a participant's intuitive eating score exceeded a raw score of 3.26, corresponding to, approximately, the 47th percentile. This indicates that, for participants scoring above this value, plate size had a significant impact on pasta consumption. Moderation analyses were re-evaluated excluding participants who ate minimal amounts of pasta. In this case, the main effects of intuitive eating, b = 3.03, se = .86, t (108) = 3.49, p = .007, and plate size, b = 2.06, se = .90, t (108) = 2.29, p = .02. The interaction between plate size and intuitive eating was only at trend level in this smaller sample, b = 3.04, t (108) = 1.70, p = .09. 5. Discussion Contrary to our original hypothesis that higher levels of intuitive eating would be unrelated to external cue effects, this study found that selfreported intuitive eating related to a higher, not lower, sensitivity to the external influence of portion size. Individuals who reported high levels of intuitive eating ate more as plate size increased. The theory behind the Intuitive Eating weight management approach (Tribole & Resch, 2012) would predict that intuitive eaters would be more sensitive to internal cues for food intake, such as feelings of hunger and satiety, rather than external cues such as portion and plate size. Thus, the current results were unexpected, as large plate and portion size appeared to consistently relate to increased consumption. Although unexpected, our results are not implausible, as the significantly larger amount consumed by individuals reporting high IES scores may reflect their ability to eat appropriately following a 4-hour fast (i.e., allowing themselves unconditional permission to eat when hungry). Because we did not specifically assess whether individuals were actively attempting to restrict caloric intake during the taste test meal, we were unable to determine whether participants who reported high IES scores were more likely to engage in problematic eating behaviors or patterns (i.e., loss of control eating, eating past the point of fullness or in the absence of hunger) during the in-lab taste test meal. In the case that participants did not experience the taste test meal consumption as an overeating or subjective binge eating episode, the tendency for participants who reported higher IES scores to eat more permissively following a 4-hour fast may reflect adaptive consumption, in response to hunger. Another possibility is that awareness of internal hunger and satiety cues may not be the exact mechanisms that drive the inverse relation between intuitive eating and food consumption. Interestingly, no longitudinal studies that have found benefits for training individuals in an intuitive-eating-consistent approach have measured intuitive eating using the IES (e.g., Anglin, 2012; Bacon et al., 2002, 2005; GagnonGirouard et al., 2010; Leblanc et al., 2012; Provencher et al., 2009). It is possible, then, for intuitive eating to impact consumption patterns by way of a mechanism not assessed by the IES or the current study (e.g., something other than increasing awareness of internal hunger and satiety cues). Eating approaches that emphasize increasing awareness of physiological hunger and satiety cues, such as mindful eating (Kristeller, Baer, & Quillian-Wolever, 2006) and intuitive eating (Tribole & Resch, 2012) may share common mechanisms that relate to healthy eating behaviors (Bush, Rossy, Mintz, & Schopp, 2014; Herbert, Blechert, Hautzinger, Matthias, & Herbert, 2013) and body mass index (BMI) (Smith & Hawks, 2006) that are not necessarily driven by awareness of internal hunger and satiety cues. Some common mechanisms that may underlie both mindfulness-based and intuitive eating approaches include increased emotion regulation, awareness, and acceptance (Katterman, Kleinman, Hood, Nackers, & Corsica, 2014). Therefore, it seems possible that developing these constructs might interact with internal hunger/satiety cues, or independently influence eating behaviors.

One other possibility for the unexpected findings may be that the IES is not a valid measure of intuitive eating, and thus does not identify true intuitive eaters (i.e., those who would self-identify as purposefully following an intuitive eating approach). The IES, however, has been used in several previous studies, including those that have found similar correlations to those found in this study between intuitive eating and BMI (Denny et al., 2013; Hawks et al., 2005; Smith & Hawks, 2006; Webb & Hardin, 2012).

5.1. Limitations and future directions Interpreting the results of the current study requires acknowledgement of several limitations. First, several of the variables of interest, including intuitive eating, were collected using self-report measurements. It is possible that while an individual may believe that they are aware of and eat in accordance with satiety or hunger cues, this may not be the case in practice. Therefore, using behavioral paradigms or physiological measurements of satiety that gauge the facets of intuitive eating (e.g., awareness of hunger and satiety cues) in conjunction with selfreport measurement may provide a more realistic measurement of intuitive eating. Second, as participants in the current study were undergraduates with relatively low levels of eating pathology, results may not be generalized to other samples. Replication of the current results in other relevant samples (e.g., those with clinical levels of eating pathology or individuals of varying weight classes) is warranted. In addition, it may be useful to evaluate individual difference factors that may impact the relation between intuitive eating and eating-related outcomes. For example, in some individuals, elevated levels of the unconditional permission to eat when hungry may lead to episodes of overeating and subsequent weight gain; in others, this response may simply motivate moderate, healthy consumption. Thus, future work should seek to evaluate whether individual difference factors (i.e., emotional or disinhibited eating) differentially impact the relation between intuitive eating and weight or eating-related outcomes. Third, various individual differences could be assessed in future studies. In particular, although the current study was novel in its use of a mixed-gender sample, there were not enough males in our sample to test for differences in the observed effects across gender. Therefore, future research must address the lack of investigation into intuitive eating in male samples and examine whether the relation between intuitive eating, consumption, and environmental effects varies by gender. Additionally, individual differences, including emotional eating and eating-related histories, were not assessed in our study. It seems possible that the informing all participants that leftover food would be discarded, might have altered subsequent eating behaviors for individuals who might have specific learning histories that established that throwing food away was wasteful, or who grew up (or currently reside) in a household that struggled with food insecurities. Moreover, the main effect of intuitive eating noted in our results may be ex plained by numerous factors, including, but not limited to, differential responses to a permissive eating environment, social desirability effects (i.e., eating more or less due to the presence of a research assistant during the test meal), and the potential for individuals to have engaged in compensatory behavior such as increased restriction following test meal intake. Although these factors were not assessed in the current study, future research should investigate whether these influence the relation between intuitive eating and subsequent eating behaviors. Finally, as our study manipulated both plate size and portion size and did not employ a 2 ×2 methodological design, it is impossible to determine whether the effects observed demonstrate a link between intuitive eating and plate size, intuitive eating and portion size, or both. Future research should employ methods that allow the unique contributions of both portion and plate size to be tested.

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5.2. Conclusions Despite the generally positive effects associated with intuitive eating and related interventions (Anglin, 2012; Bacon et al., 2002, 2005; Gagnon-Girouard et al., 2010; Leblanc et al., 2012; Provencher et al., 2009; Van Dyke & Drinkwater, 2014), the results from this investigation suggest that hungry individuals who report high levels of intuitive eating, as measured by the IES, are more likely to eat an objectively larger amount when presented with larger plate and portion sizes, compared to individuals who report lower levels of intuitive eating. These findings are particularly interesting, as the intuitive eating approach (Tribole & Resch, 2012) purports to include an increased focus on internal hunger and fullness cues, which presumably functions to minimize external eating cue effects. However, it is also possible that particular facets of intuitive eating (i.e., unconditional permission to eat when hungry) influenced participants' eating behaviors in the laboratory — an environment in which they were given permission to eat as much pasta as they wanted. Longitudinal studies that replicate the current findings across a longer period of time are necessary to enhance confidence in the finding that intuitive eaters are, in fact, more sensitive to portion and plate size variations. Furthermore, examining changes in intuitive eating using both the IES and actual eating behavior over time, as well as testing differences between naïve and formally trained intuitive eaters, will be necessary to better understand the mechanisms involved in these approaches. While intuitive eating holds promise as an alternative to traditional dieting approaches, much research remains to determine its efficacy, effectiveness, and mechanism of action. Role of funding sources No funding sources were obtained or used to conduct any portion of this study. Contributors All the authors materially participated in the research and/or the manuscript preparation. Dr. Drew Anderson and Dr. Katherine Schaumberg designed the study, wrote the protocol, and were involved in writing the manuscript. Dr. Schaumberg conducted analyses for the current study. Lisa Anderson and Erin Reilly were involved in drafting and editing the manuscript. All the authors have contributed to and have approved the final manuscript. Conflict of Interest No authors have any conflicts of interest to report.

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