The relation between constitutional skin color and photosensitivity estimated from UV-induced erythema and pigmentation dose-response curves

In 54 healthy volunteers we assessed predictors of sensitivity to ultraviolet (UV) light, including Fitzpatrick's sun reactive skin types and constitutional skin color, and compared these with one another and with responses of the skin to UV irradiation, as determined experimentally by a minimal erythema dose (MED), a minimal melanogenic dose (MMD), and dose-response curves for UV-induced erythema and pigmentation. For these studies, a xenon arc solar simulator was used as the source of UV irradiation, and a chromameter interfaced with a computer for objective measurement of UV-induced erythema and pigmentation was employed. The skin type did not correspond well to the constitutional skin color, as measured by a chromameter prior to UV irradiation. Within each skin type, there were large ranges of MED and MMD values and great variability in the shapes of the dose-response curves. Constitutional skin color was also not a good predictor of the measured MED and MMD values but did appear to correlate with the steepness of the dose-response curves for erythema and for pigmentation. From these studies, we propose that objectively measured constitutional skin color is a better predictor of UV responses of the skin than skin type and that steepness of dose-response curves for erythema is a better measure of the response of the skin to UV irradiation than is a MED measurement.     

Cutaneous reaction to ultraviolet irradiation in human-immunodeficiency-virus-infected patients. A case-control study.

BACKGROUND: HIV-infected patients, like renal transplant recipients, are at increased risk of developing skin cancer in photoexposed areas. Previous studies demonstrated that prolonged ultraviolet (UV)-induced erythema and a decreased and delayed tanning could be correlated with an increased risk of skin cancers. OBJECTIVE: As HIV-infected patients are at an increased risk of developing skin cancers, we aimed to assess the cutaneous response to UV irradiation in these patients. METHODS: Twelve HIV-infected patients and 12 healthy volunteers were included in a prospective case-control study. No patient or volunteer had a history of skin cancer or photodermatosis. The minimal erythemal dose (MED) was determined using a solar simulator UV source, and, then, each subject underwent an exposure of 6 MED. The erythemal and pigmentation responses were studied using a visual scale and a tristimulus colorimeter over a 4-week period. RESULTS: We failed to demonstrate any significant differences between HIV-infected patients and controls for erythema and delayed pigmentation. No difference was found for MED between the two groups although most HIV-infected patients received potentially photosensitive drugs. CONCLUSIONS: Our results suggest that, as a group, the HIV-infected patients without a history of photosensitivity or skin cancer did not demonstrate a greater susceptibility to intense UV irradiation in terms of erythema and pigmentation induced by intense UV exposition.     

人工紫外线诱导正常皮肤色素斑的初步研究

目的:建立人工紫外线诱导正常皮肤色素斑的模型。方法:采用日光模拟器人工光源,以连续紫外线(波段290～400nm)照射健康受试者上臂内侧皮肤,观察不同照射剂量及照射后不同测量时间局部皮肤黑素测量值的变化。结果:照射后1周,2.0倍最小红斑量(MED)照射剂量组产生黑素的强度高于1.5MED组(P<0.05),与2.5MED组的差异无统计学意义(P>0.05);2.0MED组红斑消退及表面光滑度较2.5MED组轻(P<0.05),与1.5MED组差异无统计学意义(P>0.05)。紫外线照射后1周,各剂量组黑素测量值(L值)均达到高峰,其后随时间延长迅速下降(P<0.05),在第4、5周下降趋势变缓(P>0.05);而红斑测量值(a值)在紫外线照射1周时达到高峰后呈持续递减趋势(P<0.05)。结论:2.0MED照射剂量是紫外线在正常皮肤诱导色素斑的最佳剂量,照射后1～4周是观察色素变化的最佳时机。     

非甾体类抗炎药和糖皮质激素对紫外线诱导红斑的影响

【摘要】 目的 探讨非甾体和糖皮质激素对紫外线红斑的抑制效应。 方法 日光模拟器和紫外线光疗仪对30例受试者的后背部进行1 ~ 3个最小红斑量（MED）照射。照射前0.5 h和照射后即刻抹药两种方式,照射后的4 h、24 h、48 h用色度仪进行红斑程度评价。组内比较用t检验,组间比较用方差分析。 结果 日光模拟器照射前0.5 h给药,2.5%和5％的氟芬那酸丁酯可以抑制1 ～ 3 MED的UV照射后红斑 （P ＞ 0.05）;双氯芬酸只对1MED紫外线红斑有抑制作用（4 h和48 h）,P ＞ 0.05;卤米松会增加红斑反应的强度（P ＜ 0.05）。日光模拟器照射后即刻抹药外用非甾体和糖皮质激素对紫外线红斑的作用与空白对照相比,差异无统计学意义。紫外线光疗仪照射后即刻抹药,2.5%氟芬那酸丁酯、5%氟芬那酸丁酯和卤米松在4 h时,对于1 MED的紫外线照射的红斑反应有抑制作用（P ＜ 0.05）;双氯芬酸对于1 ～ 3 MED的紫外线照射引起的红斑反应在4、24、48 h时均有明显的抑制作用（P ＜ 0.05）。 结论 照射前外用氟芬那酸丁酯可以抑制1 ～ 3 MED紫外线红斑反应。照射后立即给药,抑制红斑反应的作用强度由强到弱依次为双氯芬酸、氟芬那酸丁酯和卤米松。 【关键词】 氟芬那酸; 糖皮质激素类; 紫外线; 红斑     

Physical measurement and evaluation of skin color changes under normal condition and post‐ultraviolet radiation: a comparison study of Chromameter CM 2500d and Maxmeter MX18

Objective: To compare the data correlation between two kinds of instruments, Chromameter CM2500d and Maxmeter MX18, in the measurement of skin color changes under normal condition and post‐ultraviolet (UV) radiation. Method: The data points of Chromameter CM2500d are based on L^*a^* values, while Maxmeter MX18 are based on M and E values, in order to compare the data correlation between these two kinds of instruments in skin color measurement on both non‐exposed and exposed sites. In addition, an evaluation of the correlation of post‐UV irradiation between these two instruments was conducted. Four different kinds of parameters post‐UV radiation were measured including minimal erythema dose (MED), immediate pigmentation dose (IPD), minimal persistent pigmentation dose (MPPD) and repeated UV radiation. The following UV radiation dosages were applied as Day 1=1.0 MED, Day 2=0.5 MED and Day 3=0.5 MED for repeated UV radiation, of which the erythema and pigmentation changes were recorded. Result: Chromameter CM2500d and Maxmeter MX18 showed good data correlation when measuring both non‐exposed and exposed sites on normal skin. L^* values were affected more easily by UV‐induced erythema than M values on skin color changes after 1 MED and repeated UV exposures. IPD, MPPD and the pigmentation data showed good correlations with the measurement of the intensive erythema formation induced by repeated UV exposures. a^* value was shown to be equally effective as E value with skin erythema measurements in response to various MEDs. However, increased erythema induced by repeated UV radiations was able to reduce the correlations between a^* and E values. On the other hand, a^* and E were shown to be equally effective in recording the erythema change courses after strong erythema responses post‐UV radiations. Conclusion: This comparative study showed that the data correlations between the two kinds of instruments were different depending on measurement conditions. Both Chromameter CM2500d and Maxmeter MX18 instrumental measurement results should be carefully evaluated by experimental conditions.     

Skin temperature and phototest evaluation

The degree of erythema following UV irradiation is known to depend upon skin temperature at the time of UV exposure. We investigated whether changes in skin temperature at the time of erythema assessment influenced the level of erythema. Twenty-two healthy people (mean age 26 years) were irradiated with solar simulated radiation on previously UV un-exposed buttock skin. The erythematous reactions were evaluated 20–24 h after irradiation by visual scoring and by measurements of skin reflectance and laser Doppler flowmetry. The readings were done at the baseline level at 21°C room temperature where skin temperature was 30.0±1.7°C and subsequently after skin warming to 37.2±2.5°C and after cooling to 22.8±2.6°C. After skin warming, a clinically evaluated erythema grade [0, (+), +, + +, +++] was scored higher for at least one reaction in 10 of 22 individuals (45%). In the same proportion of subjects, changes to lower erythema grades were detected upon cooling. Skin warming caused an increase in laser Doppler blood flux, but skin cooling did not have a significant effect on cutaneous perfusion. Skin redness measured by skin reflectance was relatively stable during the cooling phase, but a significant increase in skin redness was noted for 0 reaction upon skin warming. For + + and + + + reactions a small but significant decrease in reflectance was noted. Our results indicate that alterations in skin temperature, especially a temperature increase, modulates the degree of UV-induced erythema moderately. The temperature-dependent changes as an assessment of the (+) reaction are of practical significance, since this reaction is used for the assessment of cutaneous photosensitivity.     

Age dependence of ultraviolet light-induced erythema following narrow-band UVB exposure

BACKGROUND/PURPOSE: A report in the literature suggests longer duration and greater intensity of late phase UVB erythema in older people. The aim of this study was to identify differences in minimum erythema dose (MED) and intensity of UV-induced erythema after narrow band UVB exposure between older and younger individuals in the late phase of UVB erythema. METHODS: Using the UVA/TL 01 UV skin tester (Waldmann Medizintechnik, Villingen-Schwenningen, Germany), MED was determined for narrow-band UVB exposure in 20 young subjects aging from 20-40, and 20 elderly subjects over 70 years of age. The intensity of UV-induced erythema was measured by chromametry (a*-value and L-value) and laser Doppler 48 h after irradiation. Minimum erythema dose (MED) was additionally assessed visually. RESULTS: Elderly subjects showed no statistical different MED compared to younger subjects. However, the erythema intensity 48 h after narrow-band UVB exposure was significantly greater in the elderly. CONCLUSIONS: Narrow-band UVB therapy may, in case of over dosage, produce more intense erythema in the late phase of UVB erythema in old people than in younger individuals.     

Spectral reflectance of human skin in vivo

A newly developed skin reflectance spectrophotometer was evaluated for measurements of both melanin pigmentation and erythema. Physiological changes in blood flow and blood content in normal humans were induced by compression with an arm cuff during recording of skin reflectance spectra. Reflectance spectra of UV-induced erythema were also recorded and compared with laser-Doppler flow measurements. Spectral reflectance measurements were found to be highly sensitive in determining minimal erythema, which was not clinically detectable. The measurements of erythema using reflectance spectroscopy and UV irradiation were very highly correlated (r = 0.996). It was possible to calculate the in vivo absorbance of oxygenized haemoglobin. The melanin pigmentation following UV irradiation was quantified by reflectance spectroscopy and correlates highly with the dose of UV irradiation (r = 0.995). Furthermore, regional variations in skin melanin and haemoglobin were analysed for fair Caucasian skin.     

Prediction of minimal erythema dose with a reflectance melanin meter

The relationship between skin pigmentation and sensitivity to ultraviolet (UV) radiation-induced erythema was investigated in 60 healthy subjects of sun-reactive skin types I-V. Using a portable reflectance spectrometer, skin pigmentation was measured as the melanin index (MI) in all subjects. A solar-simulated array of filtered UVA and UVB-emitting fluorescent lamps was then used to determine the UVB minimal erythema dose (MED) of each subject. MI readings and MED testing were both performed on the subjects mid to upper backs. Using this technique, we found a close correlation between MI and MED. Comparison of the mean MI or MED of subjects with different skin types revealed progressive differences in MI and MED between all five skin types. Erythema doseresponse curves, which provide further information about UV sensitivity, were also calculated for 43 subjects. A significant negative correlation was found between the gradients of these curves and both MI and MED. indicating that paler subjects respond more strongly to increments of UV above the MED than subjects with greater pigmentation. Our results indicate that although traditional, subjective means of predicting UV sensitivity to erythema are not without some value. MED correlates particularly strongly with objective measures of skin pigmentation. We therefore conclude that the reflectance spectrometer can rapidly and accurately predict UVB sensitivity, and should prove clinically useful for planning and optimizing UVB phototherapy.     

Delayed ultraviolet erythema not suppressed by oral prednisolone: a randomized crossover study

Background: The anti-inflammatory potency of topical dermatological corticosteroids in suppressing ultraviolet (UV) erythema is routinely measured. No such model exists to assess the potency of systemically administered steroids.
Objective: To determine whether or not suppression of delayed UV erythema by a systemic corticosteroid could provide a useful model for assessing the anti-inflammatory potency of systemic corticosteroids.
Methods: We conducted a randomized, placebo-controlled, patient and assessor blinded, crossover study of oral prednisolone effects on the delayed UV-induced erythemal response in normal subjects. Six healthy volunteers were phototested with a xenon arc monochromator and then dosed with 30 mg of oral prednisolone or matching placebo daily for 4 days. Repeat phototesting was performed on the 4th day of dosing. The minimal erythema dose (MED) was assessed immediately after test UV doses were administered and 24 h later. After a 2-week washout period, the dosing and testing were repeated in a crossover fashion.
Results: A suppression index (SI) [1/(baseline MED value divided by on prednisolone/placebo value)] allowed comparison of the degree of suppression on and off prednisolone. Oral prednisolone did not significantly suppress the threshold UV erythema response (MED). We may have missed small effects in this study and possibly a larger dose or a longer duration of corticosteroid would have had an effect. Possibly, assessment of corticosteroid potency in suppressing established UV erythema rather than on the development of threshold erythema would have yielded different results.
Conclusion: The threshold UV erythema suppression model assessed in this study could not distinguish between oral prednisolone and placebo. This UV-erythema suppression test system is not promising as a model to test the anti-inflammatory potency of systemic steroids.     

Melanin differentially protects from the initiation and progression of threshold UV-induced erythema depending on UV waveband

BACKGROUND/PURPOSE: This study aimed to determine the relationship between various measures of constitutive skin pigmentation and erythema caused by solar-simulated UV (ssUV), 290 and 310 nm UV. METHODS: Skin pigmentation was assessed clinically by skin typing as well as objectively by measurement of the melanin index (MI) by reflectance spectroscopy. Subjects having Fitzpatrick skin types I-IV were exposed to graded doses of ssUV and either narrowband 310 nm (n=70) or 290 nm (n=69) UV, and assessed 24 h after exposure. Minimal erythema dose (MED) was assessed visually as the lowest dose that caused minimally perceptible erythema. Susceptibility to further development of erythema with higher exposure doses was measured by the gradient of erythema dose-response curves. This was determined by linear regression using reflectance spectrometry data beyond the MED. RESULTS: Although there was considerable variation within each skin type, MI and ssUV MED increased with increasing Fitzpatrick skin type. MI correlated with ssUV MED and 310 nm UV MED, but not 290 nm UV MED. There was also a significant negative correlation between MI and erythema dose-response gradients caused by ssUV, 310 and 290 nm UV. CONCLUSION: Melanin situated near the basal epidermis may not protect from the initial development of threshold erythema caused by 290 nm UV because it penetrates poorly past the stratum corneum and is not well absorbed by melanin in vivo compared with 310 nm UV. Higher erythemal 290 nm UV doses may reach basal epidermal melanin, which may then afford protection against further 290 nm UV erythema.     

UV light sensitivity of the skin--possibilities and limits of clinical diagnosis

Our study on 58 test persons showed that the sensitivity of human skin to UV light is independent of the color of skin, hair, eyes or the pigmentation of the mamillae. Therefore, the sensitivity to UV light must be ascertained by subtle phototesting. By means of the new UV phototesting set SBA-LT-400, Saalmann Co., 4900 Herford/West Germany, we determined the minimal erythema doses (MED) of UV-B and UV-A as basic, reproducible parameters regarding Central European people. 7 and 24 hours after radiation, MED showed mean values of 0.032 and 0.037 Joule/cm2, resp., for UV-B, whereas 24.1 and 25.6 Joule/cm2 were measured for UV-A. The pigmentation responses to UV radiation of human skin described in the literature can be reproduced in Mediterranean skin types only.     

The minimal melanogenesis dose/minimal erythema dose ratio declines with increasing skin pigmentation using solar simulator and narrowband ultraviolet B exposure

Purpose: To investigate the relation between pre‐exposure skin pigmentation and the minimal melanogenesis dose (MMD)/minimal erythema dose (MED) ratio after a single narrowband ultraviolet B (nUVB) and solar simulator (Solar) exposure. Background: In fair‐skinned individuals, it is well known that the UV dose to give pigmentation (MMD) after a single exposure to UVB is larger than the UV dose to elicit erythema (MED) (MED<MMD), but it remains to be established if this is true also in dark‐skinned individuals. Methods: Eighty‐four volunteers with a wide variation in skin pigmentation (Fitzpatrick skin types I–V) were included. Results: After a single Solar or nUVB exposure we found that the ratio MMD/MED depends on skin pigmentation. In light‐pigmented individuals, up to 1.9 MED is required to induce pigmentation (MMD). The MMD/MED ratio is about 1.5 in medium‐pigmented and dark‐pigmented individuals. In very brown‐pigmented individuals the MMD/MED ratio is 1 (MED=MMD). This connection was most pronounced for facultative skin at wintertime. The ratio was almost stable for constitutive pigmentation with MMD/MED=1.3. The ratios were almost independent of skin type. Conclusion: The ratio MMD/MED is highly dependent on skin pigmentation after a single exposure to Solar or nUVB and is independent of skin type.     

Feasibility and accuracy of a newly developed hand-held device with a flat-type fluorescent lamp for measuring the minimal erythema dose for narrow-band UVB therapy

Background: Narrow-band ultraviolet B (NB-UVB) for the treatment of refractory skin diseases, such as psoriasis and atopic dermatitis, requires an adequate irradiation protocol based on the minimal erythema dose (MED) to establish an optimal dosage schedule. Although MED can be measured using a systemic-type irradiation unit, there are difficulties associated with this device. There is no standardized device available to determine the MED for NB-UVB. Here, we compared a conventional device with a newly developed device for measuring MED.
Method: MED was measured in 16 psoriasis patients using both a conventional measuring device and the newly developed device, which comprised a hand-held NB-UVB (311–313 nm) flat-type fluorescent lamp with neutral density filters having different transmittances ranging from 10% to 90%. This device was designed to be stably maintained on the skin surface and to provide a highly accurate measurement with only one UV irradiation exposure while also preventing UV radiation from leaking to nonirradiated areas.
Results: The MED values obtained from each patient were the same using both devices.
Conclusion: One-time irradiation using the new hand-held device with the NB-UVB flat-type fluorescent lamp is feasible and accurate for determining the MED to use in calculating the UV irradiation treatment dose.     

Long-term evaluation of erythema and pigmentation induced by ultraviolet radiations of different wavelengths

BACKGROUNDS/AIMS: Although multiple studies have been reported about the biological effects of ultraviolet (UV) radiations, the comparative and long-term reactions of human skin by several different UV-wavebands were not reported. The aim of this study was to investigate a time course of erythema and pigmentation induced by UVA 1, broad-band UVA (BBUVA), narrow-band UVB (NBUVB) and broad-band UVB (BBUVB). METHODS: Ten volunteers participated in this study for 6 months. Four skin areas, from the back of each subject, were irradiated with two minimal erythema dose (MED) of four different UV wavelengths corresponding to UVA 1, BBUVA, NBUVB and BBUVB. Skin color changes were evaluated by visual scoring and values were converted into the L*a*b color system. RESULTS: For both UVA 1 and BBUVA, erythema and pigmentation were most pronounced immediately and 1 h after exposure. Thereafter, erythema rapidly diminished but pigmentation persisted throughout the study. For both NBUVB and BBUVB, test areas reacted with erythema of maximum intensity at 1 and 2 days, respectively. A maximum tanning was reached at 3-6 days for NBUVB and 4-7 days for BBUVB, and the return toward the original color point was at 1 and 3 months, respectively. No significant difference was found in visual and colorimetric evaluation for the time course of skin color changes. CONCLUSION: Two MED of UVA produced far prolonged erythema and pigmentation than UVB. For UVA, UVA 1 and BBUVA showed similar intensity and time course of skin reaction. For UVB, erythema and pigmentation produced by NBUVB were milder in intensity and shorter in time course than those by BBUVB. These results would provide standard data on time courses and intensity of skin color changes by different UV wavelengths.     

Effects of p-coumaric acid on erythema and pigmentation of human skin exposed to ultraviolet radiation

Background. It has been recently recognized that p‐coumaric acid (PCA) is a strong inhibitor of cellular melanogenesis. Aim. To evaluate the erythema‐suppressive and skin‐lightening effects of PCA after topical application to human skin. Methods. The control and PCA cream products were applied twice daily to the skin of the forearm of 21 subjects before and after ultraviolet (UV) irradiation to determine whether they could prevent erythema formation and pigmentation. The cream products were also applied to different areas only after the induction of erythema or pigmentation to determine whether they could have a depigmenting effect. Results. A 7‐day application of control and PCA cream products before UV irradiation decreased UV‐induced erythema formation by 31% and 77%, respectively, compared with untreated skin. When the PCA cream was applied after UV irradiation, its effects on skin colour or pigmentation were less remarkable. However, the melanin index was significantly decreased at the sites treated with PCA cream for 70 days compared with control sites, and the Individual Typology Angle (ITA°) value was increased significantly. Of the 21 subjects, 2 had mild adverse skin reactions to both the PCA and control creams. Conclusion. These results suggest that PCA cream can reduce UV‐induced erythema formation and subsequent pigmentation in human skin.     

UV-induced skin changes due to regular use of commercial sunbeds

BACKGROUND/AIM: Increased pigmentation and thickening of the epidermis are the most important photoprotective skin reactions induced by ultraviolet (UV) radiation. The present study was designed to find out what changes are induced by regular use of commercial sunbeds twice weekly over a period of 6 weeks. METHODS: The parameters analysed were skin pigmentation measured by chromametry, minimal erythema dose (MED) as a parameter of light sensitivity, epidermal thickening as determined by histology, induction of keratinocyte apoptosis as determined by TUNEL staining and antioxidant metabolism as measured by changes of cis- and trans-urocanic acid (UCA) content of the skin. RESULTS: As expected, chromametry confirmed the clinically obvious increased skin pigmentation. However, no increase in MED was observed. In addition, neither epidermal thickening nor sunburn cells were seen. Significant detectable changes in proportion of the UCA isomer content of the UV-exposed skin were seen. The total UCA and cis-UCA content increased significantly between nearly all points of measurement. The amount of trans-UCA first decreased, then increased significantly between the different time points. CONCLUSION: Our data indicate that sunbed-induced tanning is non-protective, which has to be addressed for persons looking for this effect before planning a stay in a sunny climate. However, sunbed-induced tanning may influence immunological reactions.     

Suberythemal ultraviolet B radiation alters the expression of cell cycle-related proteins in the epidermis of human subjects without leading to photoprotection

Background  Deregulation of the cell cycle proteins is one of the critical factors leading to cutaneous carcinogenesis.
Objectives  To monitor the expression of cell cycle proteins in the epidermis of subjects after repeated exposure to ultraviolet (UV) B radiation, and to test for the development of photoprotection by subsequent irradiation with a single erythemal UVB dose.
Methods  A total of 26 healthy volunteers were divided into four groups: group 1 ( n  =   9) were given whole-body UVB irradiation for 10 consecutive days with 0·7 minimal erythema dose (MED), group 2 ( n  =   9) were irradiated as in group 1 followed 24 h later by a single UVB dose of 3 MED on buttock skin, group 3 ( n  =   4) were irradiated with a UVB dose of 3 MED on buttock skin, and group 4 ( n  =   4) were not irradiated. Skin biopsies were collected 24 h after the final irradiation and stained for cyclins A, B1, D1, and p16, p18, p21, p27, p53, pRB, Bax and Bcl-2.
Results  The expression of cyclin D1, p18 and p21 was significantly higher in groups 1 and 2 compared with the nonirradiated group 4 controls and, in group 2, the expression of pRB, p53 and Bax was also increased. In group 3, only p53 and Bax proteins were significantly elevated compared with group 4. The expression of cyclin D1, p16, p18, p27, pRB and Bcl-2 was higher in group 2 compared with group 3.
Conclusions  Suberythemal UVB radiation was sufficient to cause changes in the expression of several epidermal cell cycle proteins. When tested by irradiation with a single erythemal UVB dose following the repeated exposures, no photoprotection against the UV-induced alteration in cell cycle protein expression was apparent.     

Effects of temperature on ultraviolet-induced erythema of human skin

Summary Convective cooling of human skin to 20°C or less for 1 h immediately after ultraviolet-B irradiation (UV-B, 290–320 nm) results in a significant increase in erythemal threshold when erythema was observed at 4–6 h postirradiation. Cooling the skin immediately before UV-B irradiation showed no consistent influence on the erythema response. In neither case was an effect of cooling on erythemal threshold apparent when erythema was evaluated at 24 h postirradiation. These effects may be due to alterations in the diffusion kinetics of chemical mediators of inflammation, modification of vascular responsiveness, or reflect changes in temperature-dependent cellular repair or expression of UV-induced damage.This work was supported by the Wellman Laboratories