Influence of facial skin ageing characteristics on the perceived age in a Russian female population

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1 International Journal of Cosmetic Science, 2015, 37 (Suppl. 1), 3 8 doi: /ics Influence of facial skin ageing characteristics on the perceived age in a Russian female population E. Merinville*, G. Z. Grennan*, J. M. Gillbro, J. Mathieu and A. Mavon *Oriflame R&D, Bray Business Park, Kilruddery, Bray, Co Wicklow, Ireland, Oriflame Skin Research Institute, Oriflame Cosmetics AB, M aster Samuelsgatan 56, Stockholm 11121, and Oriflame Consumer Insight, Oriflame Cosmetics AB, M aster Samuelsgatan 56, Stockholm 11121, Sweden Received 7 May 2015, Accepted 17 June 2015 Keywords: hyperpigmentation, perceived age, Russian, sagging, skin ageing, wrinkles Synopsis OBJECTIVE: The desire for a youthful look remains a powerful motivator in the purchase of cosmetics by women globally. To develop an anti-ageing solution that targets the need of end consumers, it is critical to understand which signs of ageing really matter to them and which influence their age perception. To date, such research has not been performed in a Russian population. The aim of this work was to identify the signs of ageing that contribute the most to an older or younger look for Russian women aged 40 years old and above. METHODS: The age of 203 Russian female volunteers was estimated from their standard photographs by a total of 629 female na ıve assessors aged years old. Perceived age data were related to 23 facial skin features previously measured using linear correlation coefficients. Differences in average severity of the correlating skin ageing features were evaluated between women perceived older and women perceived younger than their chronological age. Volunteers responses to a ranking question on their key ageing skin concerns previously collected were analysed to provide an additional view on facial ageing from the consumer perspective. RESULTS: Nine facial skin ageing features were found to correlate the most with perceived age out of the 23 measured. Such results showed the importance of wrinkles in the upper part of the face (crow s feet, glabellar, under eye and forehead wrinkles), but also wrinkles in the lower half of the face associated with facial sagging (upper lip, nasolabial fold). Sagging was confirmed of key importance to female volunteers aged years old who were mostly concerned by the sagging of their jawline, ahead of under eye and crow s feet wrinkle. The severity of hyperpigmented spots, red and brown, was also found to contribute to perceived age although to a weaker extent. CONCLUSION: By providing a clear view on the signs of ageing really matter to Russian women who are aged 40 years old and above, this research offers key information for the development of relevant anti-ageing solutions specifically targeting their needs and their desire to achieve younger-looking skin. Resume OBJECTIF: Le desir d apparaitre jeune constitue une motivation forte dans l achat de produits cosmetiques par les femmes du Correspondence: Eve Merinville, Oriflame R&D, Bray Business Park, Kilruddery, Bray, Co Wicklow, Ireland. Tel.: fax: eve.merinville@oriflame.com monde entier. Afin de developper une solution anti-^age qui cible les besoins des consommateurs, il est cle de comprendre quels signes visibles de l ^age sont d une importance primordiale et influencent la perception de l ^age. A ce jour, une population Russe n a pas ete l objet d une telle recherche. Le but de cette etude est d identifier les signes cliniques de l ^age qui contribuent majoritairement a une apparence plus ^agee ou plus jeune pour les femmes de plus de 40 ans. METHODES: L ^age de 203 sujets feminins Russes a ete determine a partir de leur photographie standard par un total de 629 evaluatrices na ıves ^agees entre 20 et 65 ans. L ^age estime a ete evalue en relation a 23 signes visibles de la peau mesures au prealable en utilisant les coefficients de correlation lineaires. Les signes de l ^age, confirmes en correlation avec l ^age estime, ont ete evalues de facßon a mettre en evidence leur difference de valeur de severite moyenne entre les femmes percßues plus ^agees et les femmes percßues plus jeunes que leur ^age chronologique. Les volontaires ont prealablement repondu a une question visant a classer leurs signes de l ^age par ordre d importance. Ces resultats ont ete analyses afin de procurer la perspective du consommateur sur le vieillissement du visage. RESULTATS: Parmi les 23 signes de l ^age mesures, neuf ont ete identifies avec une correlation plus importante avec l ^age percßu. De tels resultats demontrent l importance des rides de la partie superieure du visage (pates d oies, glabellaire, sous les yeux et du front), mais aussi des rides de la moitie inferieure du visage associees a l affaissement facial (dessus de la levre superieure, pli nasolabial). Cet affaissement du visage a ete confirme d importance clef pour les volontaires ^ages de 41 a 65 ans qui etaient principalement concernees par la ptose du contour de leur visage au-dela des rides sous les yeux et des rides du coin de l œil. La severite des taches pigmentaires, rouges et brunes, a ete aussi identifiee en tant que contributeur a l estimation de l ^age, bien que plus faiblement. CONCLUSION: En procurant une vue claire sur les signes de l ^age qui sont d importance primordiale pour les femmes Russes ^agees de plus de 40 ans, cette etude offre une information critique pour le developpement de solutions anti-^age pertinentes qui ciblent specifiquement leurs besoins et notamment leur desir de conserver une apparence jeune. Introduction Maintaining a youthful appearance is important to many people today, being intricately linked with beauty and health in modern society [1 3]. This desire is reflected in the large demand for 2015 Society of Cosmetic Scientists and the Societe Francßaise de Cosmetologie 3

2 anti-ageing cosmetic products and surgical solutions. As a result of progressive intrinsic and extrinsic ageing, facial skin undergoes a visible transformation of its condition in both topographic and colour cues such as wrinkles, sagging and uneven skin tone [4, 5]. To develop an anti-ageing solution which targets the need of end consumers, it is critical to understand which signs of ageing really matter to them. Apparent age, or perceived age, has been shown to be a relevant measurement of global appearance and is influenced on the face by both shape and visible skin condition [6 8]. Furthermore, facial skin-related features was shown not to impact on global appearance equally in studies where the influence of such facial ageing features on perceived age was investigated [9 13]. Wrinkling and sagging have been found to correlate strongly with perceived age [9, 12, 13], as have pigmentary spots and reduced skin uniformity [9 11]. Under eye dark circles and bags have also been shown to correlate with perceived age, further establishing the eye area as a primary focus [11]. Despite being all based on digital imaging, those studies have been performed using distinct methodologies to estimate perceived age, in term of stimuli; such as full face, cheek crop or adapted images, type of parameters studied, panel numbers and measurement techniques for features severity assessment. Such differences do not provide clarity into which feature is ultimately responsible for the older look in Caucasian women. Furthermore, although involving Caucasian women, those studies solely concentrated on Western European women such as French, Danish and British to the best of our knowledge. Facial ageing features provide important social and individual aspects and their consequences may differ among cultures [14]. To date, such research has not been performed in a Russian population. In a previous large base study performed in a Russian female panel aged years old, the authors have identified the facial skin attributes correlating with chronological age in a first step [15]. This was, to the best of our knowledge at the time of publication, the first research on age-related facial changes in such population. Twenty-three facial ageing features were measured using severity grading and image analysis based on high-resolution photographs and combined. Analysis of the correlation coefficients had demonstrated that 19 of those features correlated with age. Although all wrinkles deepened with increasing age, the strongest correlations were found with crow s feet, under eye, glabellar, upper lip and nasolabial fold wrinkles. In the skin colour category, pigmentary spots (number of brown spots and their severity) and vascular disorders based on localized redness (severity) were the most relevant age-related changes. Key events in facial ageing were highlighted drawing the attention of the authors towards women aged 40 years old and above. Having identified the facial attributes linked to chronological age in Russian women, we aim to assess the relationship between objective measures of skin physiology, as previously captured [15], and perceived facial age from the panel photographs to deliver a first clear understanding of the critical ageing signs influencing a younger or older look in the studied population as well as their relevance from a consumer perspective. Materials and methods Photographs capture and facial attributes assessment Photographs of 203 healthy Russian female volunteers aged from years old were collected in a large base study conducted in Moscow, Russia, as previously reported [15]. Facial front and 37 profile view photographs were captured using a standard imaging device based on a high-resolution digital camera (VISIA â Complexion Analysis, Canfield Scientific Inc., Fairfield, NJ) under general standard white and cross-polarized lighting conditions. A total of 23 facial skin features were subsequently measured from photographs via 1) photographic expert grading based on published scales [16] and performed by three expert graders using cropped and randomized white light photographs or two) image analysis on cross-polarized and standard white photographs using an image analysis software (IMAGE-PRO Plus 7; Media Cybernetics Inc., Rockville, MD) customized by a colour-measuring macro and the builtin VISIA â CA 2.0 software with automatic colour and texture-feature detection ability, respectively. Self-declared skin ageing concerns Volunteers were required to answer a questionnaire regarding their lifestyle, skin care habits and skin ageing concerns. For the latter, they were requested to rank 12 skin ageing signs, laid out in Table I in order of importance. The authors had a specific interest in the skin ageing concern ranking question for women aged greater than 40 years of age. Perceived age assessment: The full face photographs (front view) captured under general white light were viewed by a total of 629 female participants of Russian nationality, aged from 20 to 65 years old, who were asked to estimate the age of the face referred to as perceived age. These female participants were na ıve assessors, which meant they had no specific skin ageing knowledge. This multicentric assessment was performed in Moscow, St Petersburg, Voronezh and Rostov-on-Don using a computer-based questionnaire (MediaLab v2008.1; Empirisoft Corporation, New York, NY) enabling the randomized display of photograph selections. To avoid assessor fatigue and age bias known in age perception [17], the study was designed so that each assessor evaluated a subset of 29 photographs with each individual photograph being assessed 96 times on average by the same age distribution profile. Statistical analysis All statistical analyses were performed with GraphPad Prism (version 5, GraphPad Software Inc., La Jolla, CA). Table I List of skin ageing concerns included in the ranking question for the panellists Wrinkles and fine lines at the outside corner of the eye Dull skin Uneven skin tone & Dark spots Wrinkles and fine lines around the mouth Skin texture and pores Wrinkles and fine lines under the eyes Bags and dark circles under the eyes Forehead wrinkles and frown lines Lip contour and fullness Jawline sagging Sagging eyelids Redness and broken capillaries Society of Cosmetic Scientists and the Societe Francßaise de Cosmetologie

3 Correlation with perceived age Twenty-three facial features were measured from the photographs captured (Table II). Linear correlation coefficients were calculated to determine the relationship with perceived age. Only parameters correlating with perceived age are shown. Age-specific relevance of skin ageing features in relation to perceived age Mann Whitney U-test was performed to study the age specificity of the facial skin attributes found to correlate the most with perceived age. Results Self-declared skin ageing concerns Russian female volunteers answered the questionnaire related to their lifestyle and skincare routine (data not shown). Figure 1 shows the skin ageing concerns that were ranked as of primary concern to women over the age of 40 years old. They were divided into two groups: years old and years old. Jawline sagging was found to be the number one skin ageing concern for Russian women aged above 40 years old as shown by the response obtained for the age groups and years old (21% and 22%, respectively, Fig. 1). This was especially a clear response for women aged years old, as Jawline sagging was represented nearly twice as much as the concern ranked second (12%). Further to this, women aged years old were also strongly concerned by the overall eye area, represented by the choice of under eye bags and dark circles (17%), wrinkles and fine lines at the corner of the eye (15%) and under eye wrinkles and lines (13%). Table II List of facial attributes measured from photographs and their category Feature Crow s foot wrinkle depth Number of Crow s feet wrinkles Nasolabial fold wrinkle depth Upper lip wrinkle depth Wrinkle at the corner of the mouth Depth Glabellar wrinkle depth Under eye wrinkle depth Forehead wrinkle depth Skin roughness Pores severity Number of pores Number of localised red areas Severity of localised red areas Number of brown spots Severity of brown spots Skin Clarity (L*) Under-eye dark circle severity Skin sallowness (b*) Skin colour intensity (C) Skin colour (ITA^) Cheek redness (a*) Facial redness (a*) Facial colour unevenness Category Wrinkle/texture Skin colour Figure 1 Percentage representation of skin ageing concerns ranked first in the study questionnaire according to Russian female volunteers split into two age groups: years old (n = 54) and years old (n = 85). Similarly, women in the age group showed a strong concern for crows foot wrinkles (e.g. wrinkles and fine lines outside the corner of the eye ) and under eye wrinkles and lines (12%). However, in this older age bracket, they were more concerned about wrinkles and lines around the mouth (11%) and eyelid sagging (10%) than under eye bags and dark circles (8%). Uneven skin tone and dark spots received a low response for both age groups (8%). These self-declared results show that Russian female volunteers were concerned primarily by their sagging skin (i.e. Jawline) followed by the eye area, specifically wrinkles and eye bags and dark circles. Facial skin ageing parameters influencing age perception in Russian women Mean perceived facial age was determined for the 203 female volunteers aged years old and was found to significantly correlate with chronological age (r = 0.9, P < 0.01) indicating that the older Russian women in the study were indeed perceived as looking older. According to the correlation analysis, we found that nine key facial skin ageing features significantly and strongly correlated with perceived age (r > 0.5 and P < ) reflecting that their increase in severity is associated with an increased perceived age. These features included crow s foot, glabellar, under eye upper lip, nasolabial fold and forehead wrinkle depth within the wrinkle/texture category (Table III) and severity of brown spots; severity of localized redness and the number of brown spots within the skin colour category (Table IV). According to the strength of the correlations, wrinkles (depth) were therefore overall found to be of larger importance over skin colour-related parameters for age perception of Russian women aged years old. Furthermore, results obtained showed wrinkles in the upper face area and specifically 2015 Society of Cosmetic Scientists and the Societe Francßaise de Cosmetologie 5

4 Table III List of facial wrinkles and texture-related features measured and their correlation with perceived age. Grey scale highlights significant correlations (P < ) with Pearson coefficient r > 0.5 Table V Number of female volunteers in each of the chronological age groups that have been perceived older, younger or the same as their chronological age Feature Perceived age Pearson coefficient (P value) All Crow s foot wrinkle depth (<0.0001) Number of crow s feet wrinkles (<0.0001) Nasolabial fold wrinkle depth (<0.0001) Upper lip wrinkle depth (<0.0001) Wrinkle at the corner of the mouth depth (<0.0001) Glabellar wrinkle depth (<0.0001) Under eye wrinkle depth (<0.0001) Forehead wrinkle depth (<0.0001) Skin roughness (<0.0001) Pore severity (0.0094) All subjects Perceived older Perceived younger Perceived real age A B Table IV List of facial features related to skin colour and pigmentation measured and their significant correlation with perceived age. Grey scale highlights significant correlations (P < ) with Pearson coefficient r > 0.5 Feature Perceived age Pearson coefficient (P value) C D Facial colour unevenness (0.0021) Facial redness (0.0018) Cheek redness (0.0005) Severity of localised red areas (<0.0001) Number of localised red areas (<0.0001) Skin Colour (ITA^) (0.0018) Skin clarity (0.0008) Number of brown spots (<0.0001) Severity of brown spots (<0.0001) Figure 2 Wrinkling severity of perceived age groups: younger looking (circle) versus older looking (triangle). Average values ( SEM) are plotted by chronological age group for (A) crow s foot wrinkle depth, (B) nasolabial fold wrinkle depth, (C) glabellar wrinkle depth, (D) under eye wrinkle depth. Statistical analysis using Mann Whitney U-test, *P < 0.05, **P < 0.01, ***P < the eye area (crow s foot, glabellar and under eye wrinkle depth) were the most important features found to correlate with perceived age in our panel. Weaker correlations were found for the number of crow s feet wrinkles, skin roughness and corner of the mouth wrinkle depth with perceived age (r > 0.4, P < , Table III). There was no relationship between under eye dark circles severity, skin sallowness, skin colour intensity, the number of pores and perceived age (data not shown). Age-specific relevance of skin ageing features in relation to perceived age To further explore the age-related impact of the facial skin ageing features found to correlate the most with perceived age, the study panel was divided into 3 subgroups according to their real age (30 39, and years old). The panel was then further categorized by perceived age into those perceived younger than their chronological age (<1 year), those perceived older (>1 year) and those perceived as their real age as shown in the Table V below. Women perceived older than their real age exhibited deeper wrinkle grades overall when compared with those perceived younger in each of the groups, as shown in Fig. 2, for crow s foot, nasolabial fold, glabellar and under eye wrinkles. The difference in average depth grades for the crow s foot wrinkle and the glabellar wrinkle remained relatively constant between the two groups and was found to be statistically significant, with the exception of the crow s foot wrinkle for the youngest age group (30 39 years old). In the light of the strongest statistical differences observed between the perceived age groups for women aged and years old (***P < , Fig. 2), this result suggests that crow s feet and glabellar wrinkles are key skin ageing features influencing age perception in Russian women aged The difference between average depth grades for the nasolabial fold and the under eye wrinkle was not as large in value as for previous wrinkles and was not consistent across the age groups (Fig. 2). There was little difference for the younger age group years old in nasolabial fold wrinkle average grade between the older-looking and the younger-looking groups, suggesting Society of Cosmetic Scientists and the Societe Francßaise de Cosmetologie

5 that the increased age perception at this age is influenced by other facial skin features. However, the difference in average depth grade increased for the age group years (>1 grade) becoming statistically significant and remaining so for the older age group years old. The age-specific relationship between nasolabial fold wrinkle depth and perceived age showed the relevance of this ageing feature for women aged 40 + as contributing to an increased perceived age. Both and age groups showed a significant difference in under eye wrinkle average depth grades between older-looking and younger-looking women, but the difference dramatically reduced for the older group (50 65 years old). Such a pattern between perceived age and under eye wrinkle depth highlighted the importance of under eye wrinkle severity in the age perception of women aged years old. When it comes to hyperpigmentation, women perceived older looking than their real age also exhibited higher average scores in comparison with women perceived younger than their real age in term of severity and number of brown spots (Fig. 3) and severity of vascular lesions (data not shown). The difference in average severity scores of brown spots was significant for both and years old age groups, while the difference in the number of brown spots was only significant for the years old group. In the light of their relationship with perceived age, hyperpigmented lesions were therefore found to contribute to an older look specifically for Russian women aged Discussion This is the first study to relate the severity of visual skin ageing features and perceived age in a Russian population. The authors had previously measured 23 facial skin features from high-resolution photographs of a large panel of Russian female volunteers aged years old and reported significant age-related changes in facial skin for 19 features [15]. Here, the further estimation of age from those photographs by 629 na ıve Russian women enabled the investigation of the relationships between perceived age and skin facial features. Linear correlation calculations with perceived age highlighted nine critical skin facial ageing attributes of the 23 measured. Those were crow s foot; glabellar, under eye, upper lip, nasolabial fold and forehead wrinkles depth and hyperpigmented spots (brown and red) and their number (brown spots only). Although this selection included a combination of topographic and colour cues, topographic cues showed overall a stronger relationship than the colour-related ones with perceived age. A Figure 3 Hyperpigmentation (brown spots) severity and number in perceived age groups: younger looking (circle) versus older looking (triangle). Average values ( SEM) are plotted by chronological age group for (A) severity of brown spots, (B) number of brown spots. Statistical analysis using Mann Whitney U-test, **P < B Wrinkles found to correlate with perceived age are located in various areas of the face. Based on their location and type, wrinkles can provide further information. Crow s feet, glabellar and under eye wrinkles, all located in the upper part of the face, showed the strongest correlations with perceived age. The eye area has been shown previously to be important in influencing age estimation [11]. However, there has been no report of the influence of the glabellar wrinkle the vertical wrinkle located between the eyebrows. The comparison of those wrinkles severity between women perceived older and women perceived younger than their real age showed a slight distinction in their age-specific impact on perceived age. Older-looking women aged years exhibited on average significantly deeper glabellar, under eye and crow s feet wrinkles than younger-looking women of the same chronological age. Crow s feet and glabellar wrinkles remained relevant for older-looking women aged years while under eye wrinkles had no impact on increased perceived age. This finding links well with the results from the skin ageing self-perception element of this study where the volunteers rated crow s foot, under eye and forehead/ frown wrinkles as being important in the similar age bracket (41 50 years). However, only 5% of women aged years expressed concern over their forehead/frown wrinkles yet showed a substantial concern for both crow s feet and under eye wrinkle (12% and 12%, concern ranked equal 2). Interestingly, this reflects a more polarized response from the older age group focusing specifically on the eye area as their second biggest concern whereas the majority of ageing signs would be visible at this age and therefore harder to segregate. Wrinkles and folds in the lower part of the face such as nasolabial fold, upper lip wrinkles and wrinkles at the corner of the mouth have been shown to be significantly influenced by the effect of gravity in the upright position [18]. The formation of the nasolabial fold specifically has been associated with facial sagging, as a result of skin elasticity loss and accumulation of adipose tissue [19]. Here, nasolabial fold and upper lip wrinkles were found to strongly correlate with perceived age showing the relevance of sagging features in the influence over perceived age in Russian women. Furthermore, the comparison of grades in nasolabial fold severity between women perceived older and women perceived younger than their real age provided further understanding of the age-specific relevance of sagging-related features in contributing to an increased perceived age. Although perceived aged groups had similar average grades in the age range years old, the difference increased between the groups from 40 years old to become significant. Women aged above 40 years old who were perceived older exhibited a significantly deeper nasolabial fold wrinkle on average, thereby suggesting that sagging is an additional key contributor to an older look for women aged 40+. Results from the self-perceived ranking of skin ageing concerns by the volunteers did not directly concur with such findings, due to the low to medium response for wrinkles and fines lines around the mouth for and years old women, respectively. The lack of specificity of the question terminology wrinkles and fine lines around the mouth may be an explanation to the low response. Yet the representation of jawline sagging was specifically relevant here as it was found to be the most represented, Number 1 skin ageing concern according to women aged and years old with more than 20% women concerned about it. It confirmed the critical importance of sagging as the primary skin ageing for the Russian female consumers. Jawline sagging was not included in the objective facial measurement on Russian female volunteers due to the 2015 Society of Cosmetic Scientists and the Societe Francßaise de Cosmetologie 7

6 study design limitations; therefore, its contribution to perceived age was not established. However, the combination of the nasolabial fold and upper lip wrinkle contribution to perceived age together with the consumer feedback on jawline sagging (for women aged 40 + ) and wrinkles around the mouth (11%, years old) provides a clear picture on the sagging contribution to perceived age and its relevance for the end consumers, in addition to wrinkles in the upper part of the face. The severity of hyperpigmented spots, brown and red, due to melanin and haemoglobin, respectively, as well as the number of brown spots was found to correlate with perceived age. Although the strength of the correlations was overall weaker that with wrinkles and sagging-related features, this finding confirms the importance of skin tone homogeneity in age estimation as reported by Matts and Nkengne in Caucasian women [10, 11]. Women aged years old perceived older than their real age exhibited significantly more severe brown spots than women perceived younger. Such a finding establishes the relevant contribution of dark spots severity to an older look for Russian women aged 40 years old and older. Yet, interestingly, this was not in accordance with the skin ageing concern ranking result by the consumers from which uneven skin tone and dark spots had a low response in both age groups (6%). This may represent an opportunity for educating the consumers on the impact of uneven skin tone of global appearance which they may not be aware according to the exercise of self-assessment. Finally, amongst the various skin ageing facial features studied, under eye dark circles were not found to correlate with perceived age. Yet under eye dark circles [and bags] were the second biggest ageing skin concern for women aged years old according to the ranking question. This discrepancy in the findings may be due to the nature of under eye dark circles as their formation is caused by many aetiologic factors including, but not limited to ageing [20, 21]. As much as under eye dark circles may appear important to the consumers at a certain point in time, they do not seem to be utilized as critical information in the assessment of youthful appearance by others. Conclusion It was concluded that, wrinkles, sagging and hyperpigmentation are key features with regards to their impact on ageing appearance on Russian women. Sagging-related features were of particular relevance from both an unconscious (age perception) and conscious (self-declaration) view on ageing. Such insights provide an opportunity to develop an anti-ageing solution which would support the ambition of younger-looking skin by improving the key signs of ageing that really matter to Russian women: that is, wrinkles and sagging features. Acknowledgements We thank Oriflame Russia and Millward Brown Poland for their assistance in the test coordination and data collection in Russia. This work was funded entirely by Oriflame Cosmetics. There are no conflicts of interest. All authors were employees of Oriflame Cosmetics at the time of writing. References 1. Fink, B. and Neave, N. The biology of facial beauty. Int. J. Cosmet. Sci. 27, (2005). 2. Rhodes, G. The evolutionary psychology of facial beauty. Annu. Rev. Psychol. 57, (2006). 3. Kwart, D.G., Foulsham, T. and Kingstone, A. Age and beauty are in the eye of the beholder. Perception 41, (2012). 4. Glogau, R.G. Physiologic and structural changes associated with aging skin. Dermatol. Clin. 15, (1997). 5. Jackson, R. Elderly and sun-affected skin: distinguishing between changes caused by aging and changes caused by habitual exposure to sun. Can. Fam. Physician 47, (2001). 6. Berry, D.S. and McArthur, L.Z. 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