A genome wide association study identifies new genes potentially associated with eyelid sagging.

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10-10 ) and rs4746957 (P = 1.06 × 10-8 ), were significantly associated with eyelid sagging severity. The rs16927253-T and rs4746957-A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.

What Do People Know and Believe about Vitamin D?

People have been exposed to a lot of information regarding vitamin D, with evidence suggesting that vitamin D may be involved in numerous health conditions, subsequently creating concerns about vitamin D insufficiency. As a result, what do people really know or believe about this topic? In this cross-sectional study, we assessed vitamin D-related knowledge and beliefs in 59,273 French adults (NutriNet-Santé cohort) using a specific questionnaire. Answers to this questionnaire were weighted according to the French sociodemographic distribution and compared across individual characteristics, using χ²-tests. Physicians and media were identified as key information providers. Participants did not always accurately cite vitamin D sources (e.g., 72% only for sun exposure, fatty fish: 61%) or established health effects (e.g., bone health: 62%-78%). Conversely, they mentioned incorrect sources and health effects for which there is no consensus yet (e.g., skin cancer). These findings were modulated by age/generational and socioeconomic factors. A strong inconsistency was also observed between participants' true vitamin D status (plasma 25-hydroxyvitamin D concentration) and their opinion about it. This study, the first in Europe with such a large sample, stresses the need for simple and up-to-date supports of communication for the public and healthcare professionals regarding sources and health effects of vitamin D.

Determinants of vitamin D status in Caucasian adults: influence of sun exposure, dietary intake, sociodemographic, lifestyle, anthropometric, and genetic factors.

Very few studies have investigated the determinants of serum vitamin D levels using a set of variables that include simultaneously sun exposure, phototype, dietary intake, sociodemographics, anthropometric, lifestyle data, and genetic polymorphisms. Our objective was to investigate the associations between all these parameters and vitamin D status in a large sample of French adults. This cross-sectional survey was based on 1,828 middle-aged Caucasian adults from the SU.VI.MAX (SUpplémentation en VItamines et Minéraux AntioXydants) study. Plasma 25-hydroxyvitamin D (25OHD) concentration was lower among women (P<0.0001), older subjects (P=0.04), obese/underweight (P<0.0001), those living at higher latitudes (P<0.0001), those whose blood draw occurred in early spring (P<0.0001), less physically active (P<0.0001), with low sun exposure (P<0.0001), and with no-to-low alcohol intake (P=0.0001). Mutant GC rs4588 and rs7041 single nucleotide polymorphisms were associated with lower and higher 25OHD concentrations, respectively (P<0.0001). Dietary intake was not a major determinant of vitamin D status (P=0.7). This study provides an overall picture of determinants of vitamin D status. Several modifiable factors were identified, such as daily-life moderate sun exposure, physical activity, and normal-weight maintenance, which should be targeted by public health policies in order to improve vitamin D status in the general population, while avoiding active/intensive sun exposure, in line with recommendations for skin cancer prevention.

Hierarchical reorganization of dimensions in OLAP visualizations.

In this paper, we propose a new method for the visual reorganization of online analytical processing (OLAP) cubes that aims at improving their visualization. Our method addresses dimensions with hierarchically organized members. It uses a genetic algorithm that reorganizes k-ary trees. Genetic operators perform permutations of subtrees to optimize a visual homogeneity function. We propose several ways to reorganize an OLAP cube depending on which set of members is selected for the reorganization: all of the members, only the displayed members, or the members at a given level (level by level approach). The results that are evaluated by using optimization criteria show that our algorithm has a reliable performance even when it is limited to 1 minute runs. Our algorithm was integrated in an interactive 3D interface for OLAP. A user study was conducted to evaluate our approach with users. The results highlight the usefulness of reorganization in two OLAP tasks.

Association between dietary intake of n-3 polyunsaturated fatty acids and severity of skin photoaging in a middle-aged Caucasian population.

BACKGROUND: Intake of long-chain n-3 polyunsaturated fatty acid (PUFAs) supplementation has been reported to be associated with reduced UVB-erythemal sensitivity, but their relationship to photoaging has not been studied to date. OBJECTIVE: To investigate associations between daily n-3 PUFA intake and the severity of skin photoaging. METHODS: A cross-sectional study was conducted on 2919 subjects aged 45-60 years from the SU.VI.MAX cohort. At baseline, trained investigators graded the severity of facial skin photoaging using a validated 6-grade scale during a clinical examination. Intake of α-linolenic (ALA), eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic acids (DHA) were evaluated by dietary source using ten 24-h dietary record questionnaires during the first 2.5 years of the follow-up period. RESULTS: After adjustment for possible confounders, severe photoaging was found to be inversely associated with higher intake of ALA in men and with higher intake of EPA in women. When considering the different food sources of ALA for men, an inverse association appeared between severe photoaging and ALA from vegetable oils, as well as with ALA from fruit and vegetables, whereas no association was observed for ALA from dairy products. In women, ALA from vegetable oils also tended to be inversely linked to photoaging. CONCLUSIONS: These findings suggest a possible benefit effect of n-3 PUFAs on skin aging. Nonetheless, further epidemiological studies are necessary to confirm our results and to gain additional insights into underlying mechanisms.

A genome-wide association study in Caucasian women points out a putative role of the STXBP5L gene in facial photoaging.

A genome-wide association study (GWAS) was conducted on 502 French middle-aged Caucasian women to identify genetic factors that may affect skin aging severity. A high-throughput Illumina Human Omni1-Quad beadchip was used. After single-nucleotide polymorphism (SNP) quality controls, 795,063 SNPs remained for analysis purposes. Possible stratification was first examined using the Eigenstrat method, and then the relationships between genotypes and four skin aging indicators (global photoaging, lentigines, wrinkles, and sagging) were investigated separately by linear regressions adjusted on age, smoking habits, lifetime sun exposure, hormonal status, and the two main Eigen vectors. One signal passed the Bonferroni threshold (P=1.53 × 10(-8)) and was significantly associated with global photoaging. It was also correlated with the wrinkling score and the sagging score. According to HapMap, this SNP, rs322458, was in linkage disequilibrium (LD) with intronic SNPs of the STXBP5L gene, which is expressed in the skin. In addition, it was also in LD with another SNP that increases the expression of the FBXO40 gene in the skin. These two genes, which were not previously described in the context of aging, may constitute good candidates for the investigation of molecular mechanisms of skin photoaging.

Dietary monounsaturated fatty acids intake and risk of skin photoaging.

BACKGROUND: Intake of monounsaturated fatty acids has been reported to reduce oxidative stress, insulin resistance and related inflammatory processes and may thus protect from skin photoaging. The objective of this study was to investigate the association between the risk of photoaging, monounsaturated fatty acids intake and the sources of monounsaturated fatty acids. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional study was conducted within the framework of the SUVIMAX cohort. The survey included 1264 women and 1655 men aged between 45 and 60 years old. Dietary monounsaturated fatty acids intakes were estimated by dietary source through at least ten 24-h diet records completed during the first 2.5 years of the follow-up period. Severity of facial skin photoaging was graded by trained investigators at baseline during a clinical examination using a 6-grade scale illustrated by photographs. A lower risk of severe photoaging was associated with higher intakes of monounsaturated fatty acids from olive oil in both sexes. Strikingly, no association was found with intake of monounsaturated fatty acids from animal sources whether from dairy products, meat or processed meat. CONCLUSION/SIGNIFICANCE: These findings support the beneficial effect of dietary olive oil or healthy diet habits associated with olive oil consumption on the severity of facial photoaging.

Incidence of skin cancers during 5-year follow-up after stopping antioxidant vitamins and mineral supplementation.

CONTEXT: In the SU.VI.MAX study, antioxidant supplementation for 7.5 years was found to increase skin cancer risk in women but not in men. OBJECTIVE: To investigate the potential residual or delayed effect of antioxidant supplementation on skin cancer incidence after a 5-year post-intervention follow-up. DESIGN, SETTING AND PARTICIPANTS: Assessment of skin cancer including melanoma and non-melanoma during the post-intervention follow-up (September 2002-August 2007). The SU.VI.MAX study was a double-blind, placebo-controlled, randomised trial, in which 12,741 French adults (7713 women aged 35-60 years and 5028 men aged 45-60 years) received daily a placebo or a combination of ascorbic acid (120 mg), vitamin E (30 mg), ß-carotene (6 mg), selenium (100 µg) and zinc (20mg), from inclusion in 1994 to September 2002. MAIN OUTCOME MEASURES: Total skin cancer incidence, including melanoma, squamous cell carcinoma and basal cell carcinoma. RESULTS: During the post-intervention period, 10 melanomas appeared in women and 9 in men (26 and 18, respectively, for the total period of supplementation+post-supplementation). Six squamous cell carcinomas were found in women and 15 in men (10 and 25, respectively, for the total period). Finally, 40 basal cell carcinomas appeared in women and 36 in men (98 and 94, respectively, for the total period). Regarding potential residual or delayed effects of supplementation in women, no increased risk of melanoma was observed during the post-intervention follow-up period. No delayed effects, either on melanoma or non-melanoma skin cancers, were observed for either gender. CONCLUSIONS: The risk of skin cancers associated with antioxidant intake declines following interruption of supplementation. This supports a causative role for antioxidants in the evolution of skin cancers.

Functional MC1R-gene variants are associated with increased risk for severe photoaging of facial skin.

The objective of this study was to assess the association between melanocortin-1 receptor (MC1R) variants and the severity of facial skin photoaging. The study population comprised 530 middle-aged French women. A trained dermatologist graded the severity of facial skin photoaging from photographs using a global scale. Logistic regressions were performed to assess the influence of MC1R polymorphisms on severe photoaging with adjustment for possible confounders (demographic and phenotypic data and sun exposure intensity). Among the fifteen MC1R variants identified, the nine most common were V60L, V92M, R151C, R160W, R163Q, R142H, D294H, D84E, and I155T. One hundred and eighty-five individuals (35%) were WT homozygotes, 261 (49%) had one common variant, 78 (15%) had two common variants, and six (1%) had at least one rare variant. After adjustment for possible confounders, the presence of two common variants was already a risk factor for severe photoaging (AOR (95% confidence interval): 2.33 (1.17-4.63)). This risk reached 5.61 (1.43-21.96) when two major diminished-function variants were present. Surprisingly, the minor variant, V92M, was associated with increased risk of photoaging (2.57 (1.23-5.35)). Our results suggest that genetic variations of MC1R are important determinants for severe photoaging.

Variations of skin biophysical properties after recreational swimming.

BACKGROUND/PURPOSE: Sensations of itching and skin tightness are frequently reported after recreational swimming in pool water. Our objective was to measure the potential changes occurring at the skin surface under such conditions. METHODS: Nine women participated in this study, which consisted of two periods. During a 4-day control period, basal biophysical skin parameters were assessed every morning. On the first day, measurements were also performed in the afternoon. The second study period followed the same study design as for the control period, except that, on the first day, women swam for 1 h in a public pool, between the measurements performed in the morning and the afternoon. Skin capacitance, transepidermal water loss, skin temperature, skin pH and sebum casual level (SCL) were measured on facial and body sites. RESULTS: During the control period, biophysical skin parameters did not show significant variations. By contrast, h after swimming, biophysical values showed significant changes for all test sites: skin pH increased, whereas skin capacitance and SCL decreased. Biophysical parameters returned to baseline values the day after swimming. CONCLUSION: Our results demonstrate that recreational swimming leads to significant transient changes in skin surface properties of women with healthy skin.

MC1R gene polymorphism affects skin color and phenotypic features related to sun sensitivity in a population of French adult women.

The melanocortin-1 receptor (MC1R) gene is known to play a major role in skin and hair pigmentation and to be highly polymorphic in Caucasians. This study was performed to investigate the relationships between MC1R gene polymorphisms and skin color in a large sample of French middle-aged Caucasian women. The codons 60 to 265 and the codon 294 of the MC1R gene were sequenced in 488 women. The skin color was measured on the inner side of the forearm using a spectrophotometric instrument. Fifteen variants were identified: Arg151Cys, Arg160Trp, Arg142His, Asp294His, Ile155Thr, Asp84Glu, Val60Leu, Val92Met, Arg163Gln, Ser83Pro, Thr95Met, Pro256Ser, Val265Ile, Ala166Ala and Gln233Gln. Women carrying Arg151Cys, Asp294His, Arg160Trp and Asp84Glu variants had a significantly higher reflectance in the red region, which indicates a lower level of functional melanin. This association was the most pronounced for women carrying Asp84Glu. In contrast, no significant difference was observed for other variants. Moreover, associations between MC1R polymorphisms and the risks of experiencing sunburn and of having freckles were found independently of skin color. Our findings support the hypothesis that MC1R polymorphisms do not necessarily alter the skin color but should sensitize the skin to UV-induced DNA damage.

Psoriasis: characterization of six different clinical phenotypes.

Until recently, psoriasis was considered as a single disease entity. However, the discovery of major differences between early- or late-onset psoriasis suggests the presence of distinct disease phenotypes which may differ in their pathophysiology and in their treatment responsiveness. The objective of this study was to use exploratory data analysis methods to identify potential clinical psoriasis phenotypes without a priori hypotheses. A prospective questionnaire-based survey collected comprehensive informations on the main clinical characteristics of 1484 psoriatic patients. Six statistically different clusters of clinical symptoms were observed, corresponding at least to six different clinical psoriasis phenotypes. Moreover, discriminant functions allow patients to be assigned to one or other of these phenotypes. Our findings open the way to focus genetic, pharmaco-genetic, pathophysiological and therapeutic studies on more homogenous group of patients.

Quality assessment of ordinal scale reproducibility: log-linear models provided useful information on scale structure.

OBJECTIVE: In health research, ordinal scales are extensively used. Reproducibility of ratings using these scales is important to assess their quality. This study aimed to compare two methods analyzing reproducibility: weighted Kappa statistic and log-linear models. STUDY DESIGN AND SETTING: Contributions of each method to the reproducibility assessment of ratings using ordinal scales were compared using intra- and interobserver data chosen in three different fields: Crow's feet scale in dermatology, dysplasia scale in oncology, updated Sydney scale in gastroenterology. RESULTS: Both methods provided an agreement level. In addition, log-linear models allowed evaluation of the structure of agreement. For the Crow's feet scale, both methods gave equivalent high agreement levels. For the dysplasia scale, log-linear models highlighted scale defects and Kappa statistic showed a moderate agreement. For the updated Sydney scale, log-linear models underlined a null distinguishability between two adjacent categories, whereas Kappa statistic gave a high global agreement level. CONCLUSION: Methods that can investigate level and structure of agreement between ordinal ratings are valuable tools, since they may highlight heterogeneities within the scales structure and suggest modifications to improve their reproducibility.

Antioxidant supplementation increases the risk of skin cancers in women but not in men.

This research aimed to test whether supplementation with a combination of antioxidant vitamins and minerals could reduce the risk of skin cancers (SC). It was performed within the framework of the Supplementation in Vitamins and Mineral Antioxidants study, a randomized, double-blinded, placebo-controlled, primary prevention trial testing the efficacy of nutritional doses of antioxidants in reducing incidence of cancer and ischemic heart disease in the general population. French adults (7876 women and 5141 men) were randomized to take an oral daily capsule of antioxidants (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg selenium, and 20 mg zinc) or a matching placebo. The median time of follow-up was 7.5 y. A total of 157 cases of all types of SC were reported, from which 25 were melanomas. Because the effect of antioxidants on SC incidence varied according to gender, men and women were analyzed separately. In women, the incidence of SC was higher in the antioxidant group [adjusted hazard ratio (adjusted HR) = 1.68; P = 0.03]. Conversely, in men, incidence did not differ between the 2 treatment groups (adjusted HR = 0.69; P = 0.11). Despite the small number of events, the incidence of melanoma was also higher in the antioxidant group for women (adjusted HR = 4.31; P = 0.02). The incidence of nonmelanoma SC did not differ between the antioxidant and placebo groups (adjusted HR = 1.37; P = 0.22 for women and adjusted HR = 0.72; P = 0.19 for men). Our findings suggest that antioxidant supplementation affects the incidence of SC differentially in men and women.

A new approach of data clustering using a flock of agents.

This paper presents a new bio-inspired algorithm (FClust) that dynamically creates and visualizes groups of data. This algorithm uses the concepts of a flock of agents that move together in a complex manner with simple local rules. Each agent represents one data. The agents move together in a 2D environment with the aim of creating homogeneous groups of data. These groups are visualized in real time, and help the domain expert to understand the underlying structure of the data set, like for example a realistic number of classes, clusters of similar data, isolated data. We also present several extensions of this algorithm, which reduce its computational cost, and make use of a 3D display. This algorithm is then tested on artificial and real-world data, and a heuristic algorithm is used to evaluate the relevance of the obtained partitioning.

Influence of skin colour on the detection of cutaneous erythema and tanning phenomena using reflectance spectrophotometry.

BACKGROUND/PURPOSE: This research aims at assessing the influence of baseline skin colour on the ability of reflectance spectrophotometry to detect cutaneous erythema induced by a low concentration of methyl nicotinate (2.5 mM) (first objective), and to detect tanning induced by ultraviolet rays (UVA+UVB) at infra-erythemal doses (second objective). METHODS: Two independent studies were conducted to reach their respective objectives, on 27 women for the first study and on 12 women for the second study. Skin colour measurements were expressed in two different ways: percentages of reflected light at increasing wavelengths lambda (400 nm or =40 degrees. The assumption is that in the darkest skins, the emitted light is mainly absorbed by the melanin in the epidermis. Otherwise, after UV irradiation, the tanning was detectable only for individuals with fair to dark skin defined by ITA <50 degrees. This can be explained by the fact that UV stimulation of the fairest skin subjects, known to be melano-compromised individuals, can only produce a weak tanning that our study did not succeed in detecting.

Travellers to high UV-index countries: sun-exposure behaviour in 7822 French adults.

BACKGROUND: Travel health information includes warning on sun exposure, particularly for fair-skinned individuals travelling to tropical countries. METHOD: A self-completed questionnaire on sun exposure behaviour was sent to the 12,741 French adults enrolled in the SU.VI.MAX cohort. Among the 7822 participants, 196 (110 women and 86 men) declared at least one visit to a high UV-index country over the past year for more than 1 month, subsequently referred to as long-term travellers. The remaining 7626 participants (non-travellers) accounted for 4862 women and 2764 men. RESULTS: Women travellers declared more frequently skin exposure to the sun over the past year, practised tanning in high UV-index areas more than 2h daily, experienced intensive sun exposure than non-travellers. Moreover, they asserted that basking in the sun is very important. Comparable results were found in men. The use of sun protection products was similar in travellers and non-travellers, but women tended to use sunscreen products more often, more regularly and with a higher sun protection factor (SPF) than men. CONCLUSIONS: Specific health education campaigns and pre-travel advice aiming to reduce sun exposure and to improve protective measures against ultraviolet (UV) radiation should be addressed to travellers to countries with high UV-index.

Expatriates in high-UV index and tropical countries: sun exposure and protection behavior in 9,416 French adults.

BACKGROUND: Overexposure to sunlight during long stays in tropical countries can reveal short- and long-term harmful effects on the skin of Caucasian residents, especially for fair-skinned subjects. The aim of this study was to describe sun exposure and sun protection behaviors during lifetime among French adults who declared having experienced at least one expatriation period in tropical or high-sun index areas for a duration of more than three consecutive months. METHODS: A self-reported questionnaire on sun exposure behavior was addressed two times, in 1997 and 2001, to the 12,741 French adult volunteers enrolled in the SU.VI.MAX cohort. A total of 8,084 subjects answered to the first survey and 1,332 additional responders answered to the second. Among the 9,416 individuals, 1,594 (652 women and 942 men) corresponded to expatriates and the remaining 7,822 to nonexpatriates (4,972 women and 2,850 men). A descriptive analysis of sun exposure and sun protection behaviors during lifetime of expatriates and nonexpatriates was performed by gender. RESULTS: Among women, 39% of expatriates belonged to the 50 to 60 class of age at inclusion, versus 33% in nonexpatriates (72 and 55% in men, respectively). In women, expatriates declared more frequently having during lifetime exposed voluntarily their skin to the sun, practiced tanning between 11 a.m. and 4 p.m., less gradually exposed their skin, experienced intensive sun exposure, and exposed their skin during nautical sports and practiced naturism. In men, expatriates declared more frequently having experienced intensive sun exposure and exposed their skin during outdoor occupations and during nautical and mountain sports. CONCLUSIONS: Although expatriates are aware of travel health advices concerning the countries where they planned to stay, they are usually poorly informed about sun exposure risk factors. Such individuals who planned to expatriate in countries with a high ultraviolet index should benefit from a visit to a travel clinic including specific health care information for risk related to sun exposure, ie, skin cancers and photoaging.

Relationships between visual and tactile features and biophysical parameters in human facial skin.

BACKGROUND/PURPOSE: Skin properties, such as colour, hydration and texture, can be studied on a qualitative basis by a clinical assessment or on a quantitative basis using techniques that measure biophysical properties of the skin. The aim of this study was to explore the links between facial skin features and a range of skin biophysical parameters using multivariate methods. METHODS: A study was conducted on 256 female volunteers from Ile-de-France with apparent healthy skin, aged between 20 and 50, under controlled environmental conditions (mean+/-standard deviation: room temperature 22.9+/-0.3 degrees C; relative humidity 48.5+/-2.3%). The study included a medical questionnaire and a clinical examination of the skin performed by a dermatologist, and a biophysical evaluation of the skin properties. Seventy visual and tactile skin features were assessed on the forehead and the cheek using ordinal variables illustrated by photographic scales. Twenty-eight biophysical measurements were taken in the same areas using the following equipment: Chromameter, Evaporimeter, Corneometer, Skicon, Sebumeter, Sebutape, skin thermometer, skin pH-meter and Silflo. In order to group the variables illustrating a same unimodal phenomenon, a typology of the skin features and a typology of the biophysical parameters were carried out using a clustering method. Then, the relationships between each group of clinical features and each group of biophysical parameters were studied using a series of partial least squares (PLS) regressions. RESULTS: From eight groups of clinical features and three groups of biophysical parameters that were identified, 12 significant PLS regression models were built. Our findings suggest that differences in chromametric measurements express not only differences in skin colour but also differences in skin surface properties, such as skin vascularity status, thickness, and existence of wrinkles, and also demonstrate that the level of sebum excretion can affect other aspects of the skin surface. CONCLUSION: Some skin features assessed clinically do not appear to be linked to any biophysical parameter. This finding confirms that certain phenomena evaluated on the basis of visual or tactile skin features are not assessed on the basis of the biophysical properties of the skin measured by our bioengineering techniques. Indeed, visual skin features mainly appreciate the skin surface aspect, contrary to some biophysical surrogate markers known to provide information on underlying epidermal structures. Therefore, both clinical and biophysical assessments must be associated to supply a relevant and accurate approach for skin aspect characterisation.

Log-linear non-uniform association models for agreement between two ratings on an ordinal scale.

In agreement studies, when objects are rated independently by two raters (or twice by the same rater), an association between their ratings on two categories arises, reflecting the distinguishability of these two categories for these raters. When ratings are performed on an ordinal scale, this association between ratings on two categories increases when the distance between these categories increases on the ordinal scale. Goodman's log-linear models derived for the analysis of agreement between two raters on an ordinal scale assume that distinguishabilities between adjacent categories are either constant, or a priori fixed. Log-non-linear models that allow variations of the distinguishabilities between adjacent categories along the scale, may lead to difficulties in parameter estimation. This paper describes a new class of log-linear non-uniform association models. These models extend the log-linear uniform association model by allowing variations of distinguishability between adjacent categories (along the scale). These new models are used to analyse ordinal agreement between dermatologists when assessing the severity of different cutaneous signs of ageing on women faces.