The relevance and accuracy of an AI algorithm-based descriptor on 23 facial attributes in a diverse female US population.

BACKGROUND: The response of AI in situations that mimic real life scenarios is poorly explored in populations of high diversity. OBJECTIVE: To assess the accuracy and validate the relevance of an automated, algorithm-based analysis geared toward facial attributes devoted to the adornment routines of women. METHODS: In a cross-sectional study, two diversified groups presenting similar distributions such as age, ancestry, skin phototype, and geographical location was created from the selfie images of 1041 female in a US population. 521 images were analyzed as part of a new training dataset aimed to improve the original algorithm and 520 were aimed to validate the performance of the AI. From a total 23 facial attributes (16 continuous and 7 categorical), all images were analyzed by 24 make-up experts and by the automated descriptor tool. RESULTS: For all facial attributes, the new and the original automated tool both surpassed the grading of the experts on a diverse population of women. For the 16 continuous attributes, the gradings obtained by the new system strongly correlated with the assessment made by make-up experts (r ≥ 0.80; p < 0.0001) and supported by a low error rate. For the seven categorical attributes, the overall accuracy of the AI-facial descriptor was improved via enrichment of the training dataset. However, some weaker performance in spotting specific facial attributes were noted. CONCLUSION: In conclusion, the AI-automatic facial descriptor tool was deemed accurate for analysis of facial attributes for diverse women although some skin complexion, eye color, and hair features required some further finetuning.

The Trotter collection: A review of Mildred Trotter's hair research and an update for studies of human variation.

OBJECTIVES: Mildred Trotter was an anatomist and physical anthropologist whose studies on hair morphology, growth, somatic distribution, and trait relationships to age and ethnogeographic population were foundational to the field of microscopical hair analysis. The collection of human hair samples she assembled for her research has been an underutilized resource for studies on human hair variation. We applied updated methods and reviewed Trotter's original data to reassess the relationship hair traits have to diverse population labels. METHODS: Hair form and pigmentation patterns were measured from a subset of the hair samples accumulated by Trotter and we compared our data to Trotter's original results. Variability in hair traits were tested within individuals, within populations, and among ethnogeographic groups. RESULTS: Measured hair cross-section dimensions and melanosome density and distribution revealed substantial variability within individuals and ethnogeographic populations. Hair traits were found to not be distinctly separable by ancestry but instead showed continuous variation across human populations. Trotter's measurements were precise and the dataset she compiled remains valid, though the conclusions should be reviewed in light of our current understanding of human variation. DISCUSSION: Our findings support moving away from categorical ancestry classifications and eliminating the use of outdated racial typologies in favor of more descriptive trait analysis. Detailed analysis of trait pattern distributions are presented that may be useful for future research on human variation. We point to the need for additional research on human variation and hair trait relationships with reference to known population affinity.

A Bayesian network meta-analysis of 14 molecules inhibiting UV daylight-induced pigmentation.

INTRODUCTION: Hyperpigmentation disorders are very frequent, affect the quality of life and may become a psychological burden for afflicted patients. Many anti-pigmenting or depigmenting agents are available with various efficacy and almost no comparative data. 2-mercaptonicotinoyl glycine (2-MNG) was recently proposed as a viable candidate showing safe and effective results on hyperpigmentation control in vitro and in vivo. OBJECTIVES: A Bayesian network meta-analysis (BNMA) was conducted to map and rank the anti-pigmenting and depigmenting efficacy of 2-MNG 0.5% on UV daylight (UVDL)-induced pigmentation together with 13 other reference molecules. A comparison in the kinetics of 2-MNG 0.5% was also performed. METHODOLOGY: Fourteen studies were conducted, for each, on 15-30 women of skin phototype III in Shanghai, China and Paris, France. The products were applied on mini zone, in randomized and blinded protocol, on the back, 5 days a week during 6 weeks, at a dose of 4 mg/cm2 . During the second week, volunteers were exposed under to varying minimum erythemal dose of UVDL during 4 consecutive days-adapted to obtain a similar induction of skin pigmentation regardless of the population. Assessments were performed instrumentally using Chromameter®. Ascorbic acid 7% was used as a positive control for all experiments. A Bayesian network meta-analysis was then established to map and follow the kinetics of 2-MNG 0.5% performance with 13 reference molecules (glutathione 2%, kojic acid 1%, hydroquinone 4%, ascorbyl glucoside 2%, niacinamide 4%, etc.). RESULTS: 2-MNG 0.5% dominated the ranking at all time points with a significant high probability of strong efficacy against UVDL-induced pigmentation. Ascorbic acid 7% ranks second after 4 days of irradiations (D12 ) whereas hydroquinone 4% ranks second 1 month after irradiations (D40 ). In the kinetics, 2-MNG at 0.5% was effective as from the end of irradiations (D12 ) to the study endpoint (D40 ). This suggested an immediate and persistent efficacy across all timepoints evaluated. CONCLUSION: The BNMA revealed a rapid and lasting efficacy of 2-MNG 0.5% on the anti-pigmenting and depigmenting phases of the clinical protocol. 2-MNG 0.5% ranked first, with immediate and lasting effect compared to 13 other references. This study is the first allowing comparison between reference anti-pigmenting and depigmenting agents and will help clinicians for proposing the most effective approach for their patients.

Human scalp hair as a thermoregulatory adaptation.

Humans are unique among mammals in having a functionally naked body with a hair-covered scalp. Scalp hair is exceptionally variable across populations within Homo sapiens. Neither the function of human scalp hair nor the consequences of variation in its morphology have been studied within an evolutionary framework. A thermoregulatory role for human scalp hair has been previously suggested. Here, we present experimental evidence on the potential evolutionary function of human scalp hair and variation in its morphology. Using a thermal manikin and human hair wigs at different wind speeds in a temperature and humidity-controlled environment, with and without simulated solar radiation, we collected data on the convective, radiative, and evaporative heat fluxes to and from the scalp in relation to properties of a range of hair morphologies, as well as a naked scalp. We find evidence for a significant reduction in solar radiation influx to the scalp in the presence of hair. Maximal evaporative heat loss potential from the scalp is reduced by the presence of hair, but the amount of sweat required on the scalp to balance the incoming solar heat (i.e., zero heat gain) is reduced in the presence of hair. Particularly, we find that hair that is more tightly curled offers increased protection against heat gain from solar radiation.

The earliest most complete skeleton of Theropithecus.

The middle Pliocene site of Woranso-Mille in the Afar Region of Ethiopia has yielded numerous significant early hominin fossils representing multiple, coexisting taxa. Here we report on another significant discovery, the oldest partial skeleton of the papionin, Theropithecus. The specimen was recovered from the Aralee Issie collection area over multiple field seasons from 2004 through 2019. The specimen was unearthed in situ from the fluvial facies of the Mesgid Dora Tuff dated to 3.66-3.57 Ma. The partial skeleton, ARI-VP-1/26, is that of a subadult male lacking a skull. In the absence of unambiguously associated craniodental remains, the male status of the specimen was established from the dimensions of the long bones in comparison to those of other Theropithecus from Woranso-Mille. ARI-VP-1/26 is noteworthy because it preserves partial hand and foot skeletons, including a complete set of metacarpals from the left side. The theropith status of ARI-VP-1/26 was established based on the detailed anatomy of the postcranial skeleton, especially the proximal and distal humerus, proximal radius, and proximal femur. The morphology of the postcranium of ARI-VP-1/26 is consistent with that of recognized Theropithecus from Woranso-Mille and, specifically, with specimens recognized as Theropithecus oswaldi cf. darti from other sites. The ratio of the lengths of the first metacarpal to metacarpals 2-5 in ARI-VP-1/26 is intermediate between that seen in extant Papio and Theropithecus. In Theropithecus gelada and Theropithecus brumpti, the pairing of pollical and indical metacarpals of near equal length contributes to the species' high opposability index and is associated with a 'manual grazing' feeding habit. Cercopithecids constitute 43% of the identified vertebrates at Aralee Issie, and T. oswaldi cf. darti is the most common mammalian species. The monkeys of Aralee Issie lived in an open shrubland habitat, but the specific reasons for their high prevalence at the site are unclear.

Accuracy and clinical relevance of an automated, algorithm-based analysis of facial signs from selfie images of women in the United States of various ages, ancestries and phototypes: A cross-sectional observational study.

BACKGROUND: Real-life validation is necessary to ensure our artificial intelligence (AI) skin diagnostic tool is inclusive across a diverse and representative US population of various ages, ancestries and skin phototypes. OBJECTIVES: To explore the relevance and accuracy of an automated, algorithm-based analysis of facial signs in representative women of different ancestries, ages and phototypes, living in the same country. METHODS: In a cross-sectional study of selfie images of 1041 US women, algorithm-based analyses of seven facial signs were automatically graded by an AI-based algorithm and by 50 US dermatologists of various profiles (age, gender, ancestry, geographical location). For automated analysis and dermatologist assessment, the same referential skin atlas was used to standardize the grading scales. The average values and their variability were compared with respect to age, ancestry and phototype. RESULTS: For five signs, the grading obtained by the automated system were strongly correlated with dermatologists' assessments (r ≥ 0.75); cheek skin pores were moderately correlated (r = 0.63) and pigmentation signs, especially for the darkest skin tones, were weakly correlated (r = 0.40) to the dermatologist assessments. Age and ancestry had no effect on the correlations. In many cases, the automated system performed better than the dermatologist-assessed clinical grading due to 0.3-0.5 grading unit differences among the dermatologist panel that were not related to any individual characteristic (e.g. gender, age, ancestry, location). The use of phototypes, as discontinuous categorical variables, is likely a limiting factor in the assessments of grading, whether obtained by automated analysis or clinical assessment of the images. CONCLUSIONS: The AI-based automatic procedure is accurate and clinically relevant for analysing facial signs in a diverse and inclusive population of US women, as confirmed by a diverse panel of dermatologists, although skin tone requires further improvement.

Skin pigmentation is negatively associated with circulating vitamin D concentration and cutaneous microvascular endothelial function.

Darkly pigmented individuals are at the greatest risk of hypovitaminosis D, which may result in microvascular endothelial dysfunction via reduced nitric oxide (NO) bioavailability and/or increased oxidative stress and inflammation. We investigated the associations among skin pigmentation (M-index; skin reflectance spectrophotometry), serum vitamin D concentration [25(OH)D], circulating inflammatory cytokine (TNF-α, IL-6, and IL-10) concentrations, and the NO contribution to local heating-induced cutaneous vasodilation (%NO-mediated vasodilation) in a diversely pigmented cohort of young adults. An intradermal microdialysis fiber was placed in the forearms of 33 healthy adults (14 men/19 women; 18-27 yr; M-index, 30-81 AU) for local delivery of pharmacological agents. Lactated Ringer's solution was perfused through the fiber during local heating-induced (39°C) cutaneous vasodilation. After attaining stable elevated blood flow, 15 mM NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibiter) was infused to quantify %NO-mediated vasodilation. Red cell flux was measured (laser-Doppler flowmetry; LDF) and cutaneous vascular conductance (CVC = LDF/MAP) was normalized to maximal (%CVCmax; 28 mM sodium nitroprusside + 43°C). Serum [25(OH)D] and circulating cytokines were analyzed by ELISA and multiplex assay, respectively. M-index was negatively associated with [25(OH)D] (r = -0.57, P < 0.0001) and %NO-mediated vasodilation (r = -0.42, P = 0.02). Serum[25(OH)D] was positively related to %NO (r = 0.41, P = 0.02). Controlling for [25(OH)D] weakened the association between M-index and %NO-mediated dilation (P = 0.16, r = -0.26). There was a negative curvilinear relation between [25(OH)D] and circulating IL-6 (r = -0.56, P < 0.001), but not TNF-α or IL-10 (P ≥ 0.14). IL-6 was not associated with %NO-mediated vasodilation (P = 0.44). These data suggest that vitamin D insufficiency/deficiency may contribute to reduced microvascular endothelial function in healthy, darkly pigmented young adults.NEW & NOTEWORTHY Endothelial dysfunction, an antecedent to hypertension and overt CVD, is commonly observed in otherwise healthy Black adults, although the underlying causes remain unclear. We show that reduced vitamin D availability with increasing degrees of skin pigmentation is associated with reduced microvascular endothelial function, independent of race or ethnicity, in healthy young adults. Greater prevalence of vitamin D deficiency in more darkly pigmented individuals may predispose them to increased risk of endothelial dysfunction.

Earliest giant panda false thumb suggests conflicting demands for locomotion and feeding.

Of the many peculiarities that enable the giant panda (Ailuropoda melanoleuca), a member of the order Carnivora, to adapt to life as a dedicated bamboo feeder, its extra "thumb" is arguably the most celebrated yet enigmatic. In addition to the normal five digits in the hands of most mammals, the giant panda has a greatly enlarged wrist bone, the radial sesamoid, that acts as a sixth digit, an opposable "thumb" for manipulating bamboo. We report the earliest enlarged radial sesamoid, already a functional opposable "thumb," in the ancestral panda Ailurarctos from the late Miocene site of Shuitangba in Yunnan Province, China. However, since the late Miocene, the "thumb" has not enlarged further because it must be balanced with the constraints of weight bearing while walking in a plantigrade posture. This morphological adaptation in panda evolution thus reflects a dual function of the radial sesamoid for both bamboo manipulation and weight distribution. The latter constraint could be the main reason why the panda's false thumb never evolved into a full digit. This crude "thumb" suggests that the origin of the panda's dedicated bamboo diet goes back to as early as 6-7 Ma.

The Eumelanin Human Skin Colour Scale: a proof-of-concept study.

BACKGROUND: At present there is no standard nomenclature for describing the diversity of human constitutive skin colour. OBJECTIVES: To develop a standard nomenclature to describe human constitutive skin colour. METHODS: Monthly focus group discussions were carried out among a multidisciplinary group of specialists over a 7-month period. Topics covered were (i) limitations and unmet needs of current nomenclature(s) pertaining to human cutaneous diversity, (ii) practical considerations about the function and role of any proposed nomenclature pertaining to human cutaneous diversity, (iii) review of the cellular basis and current molecular genetic understanding of variation in human skin pigmentation and (iv) in vivo methods to evaluate human skin pigmentation. In addition, a preliminary review of the published literature was undertaken to collate data on published skin reflectance measurements, notably melanin index values for well-referenced human populations. RESULTS: We developed a five-point scale to describe the full spectrum of human constitutive skin colour, termed the Eumelanin Human Skin Colour Scale. The nomenclature of the scale uses eumelanin, the dominant chromophore of human skin, as a central descriptive word. The categories of the scale (nomenclature and melanin index values) are eumelanin low (EML), < 25; eumelanin intermediate low (EMIL), 25 to < 50; eumelanin intermediate (EMI), 50 to < 75; eumelanin intermediate high (EMIH), 75 to < 100; and eumelanin high (EH), ≥ 100. CONCLUSIONS: The Eumelanin Human Skin Colour Scale enables the complete range of human constitutive skin colour to be described in an objective, equitable and understandable manner. In future, this scale can be used as the basis for developing other scales that address the specific functional aspects of human skin, such as response to ultraviolet radiation.

Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation.

OBJECTIVE: To test the "vitamin D-folate hypothesis for the evolution of human skin pigmentation." METHODS: Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV-irradiance in a large (n = 649) Australian cross-sectional study population. Genetic analysis was used to score vitamin D- and folate-related gene polymorphisms (n = 22), along with two pigmentation gene variants (IRF4-rs12203592/HERC2-rs12913832). Red cell folate and vitamin D3 were measured by immunoassay and HPLC, respectively. RESULTS: Ultraviolet radiation (UVR) and pigmentation genes interact to modify blood vitamin levels; Light skin IRF4-TT genotype has greatest folate loss while light skin HERC2-GG genotype has greatest vitamin D3 synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose-response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D3 photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. Three dietary antioxidants (vitamins C, E, and ß-carotene) interact with UVR and pigmentation genes preventing oxidative loss of labile reduced folate vitamers, with greatest benefit in light skin IRF4-TT subjects. The putative photosensitiser, riboflavin, did not sensitize red cell folate to UVR and actually afforded protection. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D3 synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D3 . CONCLUSION: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.

High-throughput phenotyping methods for quantifying hair fiber morphology.

Quantifying the continuous variation in human scalp hair morphology is of interest to anthropologists, geneticists, dermatologists and forensic scientists, but existing methods for studying hair form are time-consuming and not widely used. Here, we present a high-throughput sample preparation protocol for the imaging of both longitudinal (curvature) and cross-sectional scalp hair morphology. Additionally, we describe and validate a new Python package designed to process longitudinal and cross-sectional hair images, segment them, and provide measurements of interest. Lastly, we apply our methods to an admixed African-European sample (n = 140), demonstrating the benefit of quantifying hair morphology over classification, and providing evidence that the relationship between cross-sectional morphology and curvature may be an artefact of population stratification rather than a causal link.

Evolution: How to evolve a thick skin.

A new study examines anatomy and genetics of skin in whales and hippos and reveals that adaptations to aquatic and semi-aquatic lifestyles evolved convergently in these lineages.

The evolution of human skin pigmentation involved the interactions of genetic, environmental, and cultural variables.

The primary biological role of human skin pigmentation is as a mediator of penetration of ultraviolet radiation (UVR) into the deep layers of skin and the cutaneous circulation. Since the origin of Homo sapiens, dark, protective constitutive pigmentation and strong tanning abilities have been favored under conditions of high UVR and represent the baseline condition for modern humans. The evolution of partly depigmented skin and variable tanning abilities has occurred multiple times in prehistory, as populations have dispersed into environments with lower and more seasonal UVR regimes, with unique complements of genes and cultural practices. The evolution of extremes of dark pigmentation and depigmentation has been rare and occurred only under conditions of extremely high or low environmental UVR, promoted by positive selection on variant pigmentation genes followed by limited gene flow. Over time, the evolution of human skin pigmentation has been influenced by the nature and course of human dispersals and modifications of cultural practices, which have modified the nature and actions of skin pigmentation genes. Throughout most of prehistory and history, the evolution of human skin pigmentation has been a contingent and non-deterministic process.

The Human Bone Collection of the Faculty of Dentistry at the University of Hong Kong: History and description of cranial and postcranial skeletal remains.

OBJECTIVES: The present work describes the status and contents of The Human Bone Collection of the Faculty of Dentistry at the University of Hong Kong. MATERIALS AND METHODS: The Collection originates from the 1980s and became officially established in 2017 for teaching and research purposes. Most of the Collection consists of unclaimed human remains of southern Chinese individuals exhumed from local cemeteries and donated to the Faculty in the last few decades. The demographic information was provided largely from burial records and forensic estimations. Since 2016, the Collection has undergone a process of reorganization into cranial and postcranial remains, followed by preservation procedures that included cleaning and classification. RESULTS: The Collection currently consists of remains belonging to about 368 individuals (243 males, 54 females, 71 unknown), with ages ranging from 0.8 to 90 years (mean 57.4 years). It comprises cranial remains belonging to 260 individuals (169 males, 39 females, 52 unknown), and postcranial remains belonging to 248 individuals (180 males, 42 females, 26 unknown). The preservation status ranges from poor to good, with the cranial remains better preserved than the postcranial elements. For a large number of individuals, ear ossicles, soil samples, and other materials are also available. DISCUSSION: The Collection is accessible to local and international institutions for teaching and research.

Microscopical discrimination of human head hairs sharing a mitochondrial haplogroup.

In forensic analyses, determining the level of consensus among examiners for hair comparison conclusions and ancestry identifications is important for assessing the scientific validity of microscopical hair examinations. Here, we present data from an interlaboratory study on the accuracy of microscopical hair comparisons among a subset of experienced hair examiners currently analyzing hair in forensic laboratories across the United States. We examined how well microscopical analysis of hair can reliably be used to differentiate hair samples, many of which were macroscopically similar. Using cut hair samples, many sharing similar macroscopic and microscopic features, collected from individuals who share the same mitochondrial haplogroup as an indication of genetic relatedness, we tested multiple aspects that could impact hair comparisons. This research tested the extent to which morphological features related to ancestry and hair length influence conclusions. Microscopical hair examinations yielded accurate assessments of inclusion/exclusion relative to the reference samples among 85% of the pairwise comparisons. We found shorter hairs had reduced levels of accuracy and hairs from populations examiners were not familiar with may have impacted their ability to resolve features. The reliability of ancestry determinations is not yet clear, but we found indications that the existing categories are only somewhat related to current ethnic and genetic variation. Our results provide support for the continued utility of microscopical comparison of hairs within forensic laboratories and to advocate for a combined analytical approach using both microscopical analysis and mtDNA data on all forensic analyses of hair.

Skin color and race.

Skin color is the primary physical criterion by which people have been classified into groups in the Western scientific tradition. From the earliest classifications of Linnaeus, skin color labels were not neutral descriptors, but connoted meanings that influenced the perceptions of described groups. In this article, the history of the use of skin color is reviewed to show how the imprint of history in connection with a single trait influenced subsequent thinking about human diversity. Skin color was the keystone trait to which other physical, behavioral, and culture characteristics were linked. To most naturalists and philosophers of the European Enlightenment, skin color was influenced by the external environment and expressed an inner state of being. It was both the effect and the cause. Early investigations of skin color and human diversity focused on understanding the central polarity between "white" Europeans and nonwhite others, with most attention devoted to explaining the origin and meaning of the blackness of Africans. Consistently negative associations with black and darkness influenced philosophers David Hume and Immanuel Kant to consider Africans as less than fully human and lacking in personal agency. Hume and Kant's views on skin color, the integrity of separate races, and the lower status of Africans provided support to diverse political, economic, and religious constituencies in Europe and the Americas interested in maintaining the transatlantic slave trade and upholding chattel slavery. The mental constructs and stereotypes of color-based races remained, more strongly in some places than others, after the abolition of the slave trade and of slavery. The concept of color-based hierarchies of people arranged from the superior light-colored people to inferior dark-colored ones hardened during the late seventeenth century and have been reinforced by diverse forces ever since. These ideas manifest themselves as racism, colorism, and in the development of implicit bias. Current knowledge of the evolution of skin color and of the historical development of color-based race concepts should inform all levels of formal and informal education. Awareness of the influence of color memes and race ideation in general on human behavior and the conduct of science is important.

Social and affective touch in primates and its role in the evolution of social cohesion.

Primates are long-lived, highly social mammals who maintain long-term social bonds and cohesive social groups through many affiliative mechanisms, foremost among them social touch. From birth through adulthood, social touch - primarily mutual grooming - creates and maintains relationships of trust and reliance, which are the basis for individual physical and emotional well-being and reproductive success. Because social touch helps to establish, maintain, and repair social alliances in primates, it contributes to the emotional stability of individuals and the cohesion of social groups. In these fundamental ways, thus, social touch supports the slow life histories of primates. The reinforcing neurochemistry of social touch insures that it is a pleasurable activity and this, in turn, makes it a behavioral commodity that can be traded between primates for desirable rewards such as protection against future aggression or opportunities to handle infants. Social touch is essential to normal primate development, and individuals deprived of social touch exhibit high levels of anxiety and lower fertility compared to those receiving regular social touch. Understanding the centrality of social touch to primate health and well-being throughout the lifespan provides the foundation for appreciating the importance of social touch in human life.

Examining "race" in physiology.

Racial disparities in cardiovascular and cerebrovascular health outcomes are well described, and recent research has shed light on the mechanistic underpinnings of those disparities. However, "race" is a social construct that is poorly defined and continually evolving and is historically based on faulty premises. The continued categorization by race in physiological research suggests that there are inherent differences between races, rather than addressing the specific underlying factors that result in health disparities between groups. The purpose of this Perspectives article is to provide a brief history of the genesis of categorization by race, why such categorization should be reconsidered in physiology research, and offer recommendations to more directly investigate the underlying factors that result in group disparities in cardiovascular and cerebrovascular health.