Profound Sexual Dysfunction Among Patients with Hidradenitis Suppurativa: A Cross-sectional Study.

INTRODUCTION: Sexual health, a critical aspect of overall well-being, is often compromised in individuals with chronic disorders. Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that mainly affects intertriginous areas, potentially impacting sexual health as a result of its specific symptoms and psychosocial burden. METHODS: This cross-sectional study utilized data from the EpiCAi project, focusing on 199 patients with HS. Participants completed digital questionnaires assessing sexual health via sex-specific instruments: the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men, alongside different psychosocial scales. The disease severity was assessed using the Hurley stage and the Lesion Identification Scheme for Acne Inversa (LISAI). RESULTS: The majority of the participants reported impaired sexual health, with significant clinical sexual dysfunctions noted in 71.8% of women (FSFI score < 26) and erectile dysfunction in 63.8% of men. Sexual dysfunction was associated with several factors, including age, and marital status. Psychosocial factors, notably depression and quality of life, showed strong correlations with sexual health outcomes. Notably, women over 40 and those treated with biologics reported more severe dysfunction, while among men, employment status significantly influenced sexual health. CONCLUSIONS: HS profoundly affects the sexual health of both male and female patients, with significant impacts on their quality of life and psychological well-being. The findings underscore the necessity for healthcare providers to address sexual health proactively in the management of HS, considering both physical symptoms and psychosocial impacts. This holistic approach is essential for improving patient outcomes and overall quality of life. TRIAL REGISTRATION: German Register for Clinical Trials, identifier DRKS00025315.

Real-world effectiveness and safety of the LAight-therapy in patients with hidradenitis suppurativa.

BACKGROUND AND OBJECTIVES: Hidradenitis suppurativa (HS)/Acne inversa (Ai) is a chronic debilitating disease with limited therapy options. The device-based LAight therapy was approved in Europe in 2017. The aim of this study was to evaluate the effect of real-world care with at least one treatment with LAight therapy on disease activity and burden in 3,437 patients. PATIENTS AND METHODS: Patients were included in the analysis if they had a diagnosis of HS and received at least one treatment. The endpoints Hidradenitis Suppurativa Severity Score System (IHS4), pain on the numeric rating scale (pain-NRS) and Dermatology Life Quality Index (DLQI) were analyzed using a linear mixed model for repeated measures (MMRM) over 26 weeks of care with LAight therapy. Furthermore, responder rates were calculated for all endpoints, and the therapy's safety profile and patient satisfaction were thoroughly examined. RESULTS: A significant decrease in IHS4, pain-NRS, and DLQI was achieved during 26 weeks of care with LAight. The BMI at baseline had a significant negative effect on therapy response for pain-NRS and DLQI. CONCLUSIONS: This study confirms that LAight therapy leads to satisfactory disease control in all stages of severity and is a valuable addition to the therapeutic repertoire of HS.

S2k guideline for the treatment of hidradenitis suppurativa / acne inversa - Short version.

The S2k guideline on hidradenitis suppurativa/acne inversa (HS/AI) aims to provide an accepted decision aid for the selection/implementation of appropriate/sufficient therapy. HS/AI is a chronic recurrent, inflammatory, potentially mutilating skin disease of the terminal hair follicle-glandular apparatus, with painful, inflammatory lesions in the apocrine gland-rich regions of the body. Its point prevalence in Germany is 0.3%, it is diagnosed with a delay of 10.0 ± 9.6 years. Abnormal differentiation of the keratinocytes of the hair follicle-gland apparatus and accompanying inflammation form the central pathogenetic basis. Primary HS/AI lesions are inflammatory nodules, abscesses and draining tunnels. Recurrences in the last 6 months with at least 2 lesions at the predilection sites point to HS/AI with a 97% accuracy. HS/AI patients suffer from a significant reduction in quality of life. For correct treatment decisions, classification and activity assessment should be done with a validated tool, such as the International Hidradenitis Suppurativa Severity Scoring System (IHS4). HS/AI is classified into two forms according to the degree of detectable inflammation: active, inflammatory (mild, moderate, and severe according to IHS4) and predominantly inactive, non-inflammatory (Hurley grade I, II and III) HS/AI. Oral tetracyclines or 5-day intravenous therapy with clindamycin are equal to the effectiveness of clindamycin/rifampicin. Subcutaneously administered adalimumab, secukinumab and bimekizumab are approved for the therapy of HS/AI. Various surgical procedures are available for the predominantly non-inflammatory disease form. Drug/surgical combinations are considered a holistic therapy method.

Insights, Advantages, and Barriers of Teledermatology vs. Face-to-Face Dermatology for the Diagnosis and Follow-Up of Non-Melanoma Skin Cancer: A Systematic Review.

BACKGROUND: Teledermatology is employed in the diagnosis and follow-up of skin cancer and its use was intensified during and after the COVID-19 pandemic. At the same time, demographic changes result in an overall increase in non-melanoma skin cancer and skin precancerous lesions. The aim of this study was to elucidate the role of teledermatology in comparison to conventional face-to-face dermatology for such lesions and determine the advantages and limitations of this workflow for patients and physicians. METHODS: Research was performed using relevant keywords in MEDLINE and CENTRAL. Relevant articles were chosen following a predetermined standardized extraction form. RESULTS: Diagnostic accuracy and interrater/intrarater agreement can be considered comparable-although lower-than in-person consultation. Improvement of particular features such as image quality, medical history availability, and teledermoscopy can further increase accuracy. Further aspects of limitations and advantages (mean time-to-assessment, time-to-treatment, cost-effectiveness) are discussed. CONCLUSIONS: Teledermatology has comparable diagnostic accuracy with face-to-face dermatology and can be utilized both for the effective triage of non-melanocytic epithelial tumors and precancerous lesions, as well as the follow-up. Easy access to dermatologic consultation with shorter mean times to diagnostic biopsy and/or treatment coupled with cost-effectiveness could compensate for the lower sensitivity of teledermatology and offer easier access to medical care to the affected populations.

Hidradenitis Suppurativa Is Associated with Severe Sexual Impairment.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of the pilosebaceous unit, often affecting and deforming intimate regions. HS is associated with severe pain, pruritus, and constant, purulent, malodorous discharge expected to impair sexual health of patients. METHODS: We performed a cross-sectional, multicentric study involving 199 German patients from the health services research project "Epidemiology and Care in Acne inversa (EpiCAi)." The sexual health, HS severity, and quality of life of the studied group were evaluated using a specially designed questionnaire. RESULTS: Regardless of gender, HS has an enormous impact on patients' sexual health. The patients scored, on average, 28.8 ± 5.3 points on the Relation and Sexuality Scale (RSS). Multiple linear regression revealed that females and patients with Hurley III stage had higher sexual dysfunction (p = 0.012). Sexual dysfunction is associated with pain (ß = 0.25), the number of active lesions, the affected areas (ß = 0.14), and psychosocial aspects, including low quality of life (ß = 0.404), stigmatization (ß = 0.411), depression (ß = 0.413), and anxiety (ß = 0.300). Patients already see a substantial decrease in sexual frequency in the early stages of HS, while functional impairment and fear increase with the severity of the disease. CONCLUSION: Sexual health and management of its dysfunctions should be part of a holistic approach to HS patients.

A center-based, ambulatory care concept for hidradenitis suppurativa improves patient outcomes and is also cost-effectiveness.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting approximately 1% of the population. The patient journey through the German health care system leads to high disease burden and substantial treatment costs. The EsmAiL study showed that an innovative, interprofessional, multimodal care-concept reduces disease activity and burden of HS compared to standard care. This paper examines the costs of treating HS in Germany and compares them with those of the innovative care concept implemented in EsmAiL. METHODS: EsmAiL was a two-arm, multicenter, prospective randomized controlled trial including 553 adults with HS. The study was registered in the German Clinical Trials Registry (DRKS00022135). The control group (CG) remained in standard care, whereas the intervention group (IG) was referred to specialized so-called 'acne-inversa-centres (AiZ)' where patients were treated with a structured, interdisciplinary approach. The present paper analyses the treatment costs for a subpopulation based on health insurance cost data from the two largest German health insurers. Quality-Adjusted Life Years (QALY) was assessed based on Dermatology Life Quality Index (DLQI). RESULTS: Total annual treatment costs per patient were €3,966.07 in standard care (n = 89) and €3,974.37 in the innovative care (n = 93). The costs per additional QALY amounted to €12,698.72 in the IG. Given the conventional and established threshold of €22,600 to €33,900 per QALY, the innovative treatment in AiZ proved to be cost-effective. CONCLUSION: Treatment costs of HS are substantial and increase with disease severity. The new form of care is cost-effective and is expected to decrease costs in the long run.

A structured, multimodal form of care reduces costs in the treatment of Hidradenitis suppurativa compared to standard care.

S2k guideline diagnosis, prevention, and therapy of hand eczema.

The consensus-based guideline "Diagnosis, prevention, and treatment of hand eczema (HE)" provides concrete instructions and recommendations for diagnosis, prevention, and therapy of HE based on an evidence- and consensus-based approach. The guideline was created based on the German guideline "Management von Handekzemen" from 2009 and the current guideline of the European Society of Contact Dermatitis (ESCD) "Guidelines for diagnosis, prevention, and treatment of hand eczema" from 2022. The general goal of the guideline is to provide dermatologists and allergologists in practice and clinics with an accepted, evidence-based decision-making tool for selecting and conducting suitable and sufficient therapy for patients with hand eczema. The guideline is based on two Cochrane reviews of therapeutic and preventive interventions for HE. The remaining chapters were mainly developed and consented based on non-systematic literature research by the expert group. The expert group consisted of members of allergological and occupational dermatological professional associations and working groups, a patient representative, and methodologists. The proposals for recommendations and key statements were consented by using a nominal group process during a consensus conference on September 15, 2022. The structured consensus-building process was professionally moderated. This guideline is valid until February 22, 2028.

Preservation of epidermal melanocyte integrity in an ex vivo co-culture skin model with sebocytes.

A direct contact co-culture of skin explants to SZ95 sebocytes (3D-SeboSkin) has been shown to preserve the integrity of epidermal keratinocytes and dermis. In this study, the properties of epidermal melanocytes were evaluated in the same 3D SeboSkin ex vivo model. Skin explants (n = 6) were maintained in the 3D-SeboSkin model, in direct contact to fibroblasts and alone in serum-free medium (SFM). Histopathological, immunohistochemical, apoptosis and oil red staining evaluations were performed at Days 0 and 6 of incubation. Results revealed preservation and prominent proliferation of basal keratinocytes of the skin explants in addition to preservation of dermal collagen and vasculature at Day 6 in the 3D-SeboSkin culture model and to a lesser extent in co-culture with fibroblasts but not in SFM alone. Melan-A+/Ki67- epidermal melanocytes remained attached to the dermis even at sites of epidermal detachment in the three skin explant models tested. However, the number of epidermal melanocytes was significantly conserved in 3D-SeboSkin cultures in comparison with skin explants in SFM (p < 0.05), whereas no difference was found in comparison with the co-culture with fibroblasts. Few DAPI/TUNEL+ apoptotic melanocytes could mostly be observed in SFM-incubated skin explants. Furthermore, only SZ95 sebocytes in contact to skin explants in 3D-SeboSkin exhibited increased lipogenesis with accumulation of abundant lipid droplets. These results denote that the 3D-SeboSkin model yielded significant preservation of epidermal melanocytes and hence it is optimal for ex vivo studies of abnormalities of skin pigmentation, melanocyte neoplasms and effects of different hormones, cytokines, carcinogens and various therapeutics in a pattern that recapitulates the in vivo environment.

A centre-based ambulatory care concept for hidradenitis suppurativa improves disease activity, disease burden and patient satisfaction: results from the randomized controlled EsmAiL trial.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory disease of the inverse skin regions that occurs in young women, in particular, and affects approximately 1% of the population. Outpatient care is often inadequate and usually cannot prevent progression. OBJECTIVES: To evaluate in the EsmAiL ('Evaluation eines strukturierten und leitlinienbasierten multmodalen Versorgungskonzepts für Menschen mit Akne inversa') trial whether an innovative care concept can decrease disease activity and burden, and improve patient satisfaction. METHODS: EsmAiL was conducted as a two-arm, multicentre, prospective, randomized controlled trial that included 553 adults with HS. Inclusion criteria were a minimum of three inflammatory lesions and at least a moderate impact of the disease on quality of life. The control group (CG) remained under standard care, while patients in the intervention group (IG) were treated according to a trial-specific, multimodal concept. The primary endpoint was the absolute change in International Hidradenitis Suppurativa Severity Score System (IHS4). RESULTS: In total, 274 patients were randomized to the IG and 279 to the CG. Altogether, 377 attended the final assessment after 12 months of intervention. Participants in the IG (n = 203) achieved a mean improvement in IHS4 of 9.3 points, while the average decrease in IHS4 in patients in the CG (n = 174) was 5.7 points (P = 0.003). Patients treated under the new care concept also reported a statistically significantly higher decrease in pain, Dermatology Life Quality Index and Hospital Anxiety and Depression Scale scores compared with those in the CG (P < 0.001). Patient satisfaction was also statistically significantly higher in the IG compared with the CG (P < 0.001). CONCLUSIONS: The establishment of standardized treatment algorithms in so-called 'acne inversa centres' in the ambulatory setting has a substantial, positive impact on the course of HS and significantly improves patient satisfaction.

Can hidradenitis suppurativa patients classify their lesions by means of a digital lesion identification scheme?

BACKGROUND AND OBJECTIVES: Hidradenitis suppurativa (HS) differs widely with respect to its clinical presentation. Literature imposes different phenotypes potentially implying different treatment modalities. The aim of this study is to develop a validated scheme that enables HS patients to identify their own lesion types. PATIENTS AND METHODS: The developed schemes for physicians and patients were implemented in a specific software. Upon patient consent, the physician used the software to document the lesions identified. Patients subsequently logged into the patient-version of the software from the convenience of their home and selected the lesions they identified on themselves. Afterwards the correlation between professionals and patients was tested. RESULTS: For seven lesion types, correlation coefficients were statistically significant. A large/strong correlation between patients and physicians was found for the draining fistulas (0.59) and double-ended comedones (0.50). For five other lesion types, correlation was medium/moderate, namely the inflammatory nodule (0.37), abscess (0.30), accordion like-/ bridged scar (0.45), epidermal cyst (0.33) and pilonidal sinus (0.39). CONCLUSIONS: HS-patients demonstrate high willingness to share their experiences and data. Therefore, a self-assessment scheme, as the developed LISAI, can be a valuable tool to enrich patient surveys with the identification of lesion types, for instance as a basis for phenotyping.

Atrophic papulosis (Köhlmeier-Degos disease) in children and adolescents-A cross-sectional study and literature review.

BACKGROUND: Atrophic papulosis (Köhlmeier-Degos disease, Degos disease) is a rare thrombo-obliterative microangiopathy of unknown pathogenesis. It usually affects people between the ages of 20 and 50. However, it can occur at any age. The condition is considered uncommon in children. OBJECTIVE: Clinical characterization of paediatric patients with atrophic papulosis. METHODS: Single-centre prospective cohort study with data derived from the international Degos Disease Registry collected between 2000 and 2021. RESULTS: Among 96 registered patients with atrophic papulosis fulfilling the criteria, 19 were aged 0 to completed 17 years at the time of onset. The median age at the time of onset was 5 years, ranging from 0 to 1 years for girls to 8 years for boys. In contrast to adult patients (male-to-female ratio 1:2.2), there was a male predominance in paediatric patients with a male-to-female ratio of 1.7:1. Systemic involvement, in particular gastrointestinal, central nervous system and cardiac, was more frequent in children than in adult patients. There were no statistically significant differences between family history, multisystem involvement, mortality and median survival time in the two groups. CONCLUSIONS: Atrophic papulosis has some distinct features in the paediatric population. It presents an important and still under-recognized problem. Therefore, it is mandatory to pay attention to the typical skin lesions in combination with neurological or gastrointestinal symptoms in order to make a prompt and accurate diagnosis.

Factors associated with treatment satisfaction in patients with hidradenitis suppurativa: results from the Global VOICE project.

BACKGROUND: Nearly half of patients with hidradenitis suppurativa (HS) report dissatisfaction with their treatment. However, factors related to treatment satisfaction have not been explored. OBJECTIVES: To measure associations between treatment satisfaction and clinical and treatment-related characteristics among patients with HS. METHODS: Treatment satisfaction was evaluated utilizing data from a cross-sectional global survey of patients with HS recruited from 27 institutions, mainly HS referral centres, in 14 different countries from October 2017 to July 2018. The primary outcome was patients' self-reported overall satisfaction with their current treatments for HS, rated on a five-point scale from 'very dissatisfied' to 'very satisfied'. RESULTS: The final analysis cohort comprised 1418 patients with HS, most of whom were European (55%, 780 of 1418) or North American (38%, 542 of 1418), and female (85%, 1210 of 1418). Overall, 45% (640 of 1418) of participants were either dissatisfied or very dissatisfied with their current medical treatment. In adjusted analysis, patients primarily treated by a dermatologist for HS had 1·99 [95% confidence interval (CI) 1·62-2·44, P < 0·001] times the odds of being satisfied with current treatment than participants not primarily treated by a dermatologist. Treatment with biologics was associated with higher satisfaction [odds ratio (OR) 2·36, 95% CI 1·74-3·19, P < 0·001] relative to treatment with nonbiologic systemic medications. Factors associated with lower treatment satisfaction included smoking (OR 0·78, 95% CI 0·62-0·99; active vs. never), depression (OR 0·69, 95% CI 0·54-0·87), increasing number of comorbidities (OR 0·88 per comorbidity, 95% CI 0·81-0·96) and increasing flare frequency. CONCLUSIONS: There are several factors that appear to positively influence satisfaction with treatment among patients with HS, including treatment by a dermatologist and treatment with a biologic medication. Factors that appear to lower treatment satisfaction include active smoking, depression, accumulation of comorbid conditions and increasing flare frequency. Awareness of these factors may support partnered decision making with the goal of improving treatment outcomes. What is already known about this topic? Nearly half of patients with hidradenitis suppurativa report dissatisfaction with their treatments. What does this study add? Satisfaction with treatment is increased by receiving care from a dermatologist and treatment with biologics. Satisfaction with treatment is decreased by tobacco smoking, accumulation of comorbid conditions including depression, and higher flare frequency. What are the clinical implications of this work? Awareness of the identified factors associated with poor treatment satisfaction may support partnered decision making and improve treatment outcomes.

LAight® Therapy Is an Effective Treatment Option to Maintain Long-Term Remission of Hurley I and II Hidradenitis Suppurativa: Results from Period B of RELIEVE, a Multicenter Randomized, Controlled Trial.

BACKGROUND: Hidradenitis suppurativa is a chronic, inflammatory, burdensome skin disease where current first-line treatments are limited to topical and/or systemic antibiotics which cannot be applied for long-term disease management. Period B of the RELIEVE study analyzes whether LAight® therapy can sustain or even increase remission after a first topical antibiotic treatment cycle. METHODS: The RELIEVE study was performed as a two-period multicenter randomized controlled trial with blinded assessment. For period A from week 0 to week 16, the 88 participating Hurley I and II patients were randomized to either a group receiving topical clindamycin 1% solution combined with 8 additional bi-weekly treatments with LAight® therapy (group TC + L) or a group which was treated with topical clindamycin 1% solution only (group TC). After 16 weeks, patients entered open-label period B and both groups were treated exclusively with LAight® therapy for an additional 16 weeks (8 sessions, group TC + L/L and group TC/L). RESULTS: In total, 88 patients were enrolled in RELIEVE. Seventy-eight patients entered period B; 39 belonged to group TC + L/L and 39 to group TC/L. The IHS4-response at the start of period B was 62% (group TC + L/L) and 33% (group TC + L). During the 16 weeks of additional monotherapy with LAight, in both groups >90% of patients who responded to therapy in period A maintained their IHS4-response at week 32. IHS4 response rates continued to rise up to 79% of the TC + L/L group and up to 71% of the TC/L group during period B at week 32. Achievement of HiSCR and certain patient reported outcomes confirmed primary endpoint results. CONCLUSION: LAight® therapy is an effective approved therapy option for Hurley I and II HS that can be used continuously to maintain treatment success. During 16 weeks of follow-up in period B, over 90% of patients with response after period A maintained their treatment outcome, while more than 60% of prior nonresponders gained response. The fact that LAight® therapy can be applied continuously, is very effective and is well tolerated makes it a valuable treatment tool in the design of HS long-term treatment modalities.

LAight® Therapy Significantly Enhances Treatment Efficacy of 16 Weeks of Topical Clindamycin Solution in Hurley I and II Hidradenitis Suppurativa: Results from Period A of RELIEVE, a Multicenter Randomized, Controlled Trial.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, burdensome skin disease where medical first-line treatment is still limited to long-term, topical and/or systemic antibiotics. The RELIEVE study aimed at evaluating the efficacy of LAight® therapy - a combination of intense pulsed light and radiofrequency - as an adjunct treatment to first-line therapies in Hurley stage I and II HS. METHODS: The RELIEVE study was performed as a two-period multicenter randomized controlled trial with blinded assessment. For period A from week 0 to week 16, the 88 participating subjects were randomized into either an intervention group (IG) or a control group (CG). The IG received topical clindamycin 1% solution combined with 8 additional bi-weekly treatments with LAight® therapy. The CG was treated with topical clindamycin 1% solution only. After 16 weeks, patients entered open-label period B and both groups were treated exclusively with LAight® therapy for an additional 16 weeks (8 sessions). The primary efficacy endpoint was the change in International Hidradenitis Suppurativa Score System (∆IHS4) at week 16 to baseline. Secondary endpoints were DLQI, HiSCR, Pain-NRS, and HADS. RESULTS: In total, from the 88 patients enrolled in RELIEVE, 81 patients were included in the endpoint analysis after period A. After 16 weeks of treatment, the ∆IHS4 of the group treated with the combination of LAight® therapy and topical clindamycin 1% solution was -7.2 ± 6.7 (-60.0%), which was significantly higher in magnitude than the ∆IHS4 in the group treated with clindamycin 1% solution alone (-1.8 ± 5.6, -17.8%, p < 0.001). Secondary endpoints, including other clinical scores as well as patient-reported outcomes, confirmed that the efficacy of the combined treatment was superior to monotherapy. CONCLUSION: The results of the primary endpoint analysis of period A of the RELIEVE study show that the combined therapy with LAight® and topical clindamycin 1% solution, resulted in a significantly higher decrease in disease severity and an improvement of quality of life in comparison to topical clindamycin 1% solution monotherapy. Treatment was well tolerated, and side effects were all mild and transitory. These data speak for the implementation of the combined treatment as a first-line therapy in Hurley stage I and II HS. LAight® therapy as long-term monotherapy (results from period B), will be analyzed in a consecutive paper.

Experimental Intestinal Stenosis Alters Crohn's Disease-Like Intestinal Inflammation in Ileitis-Prone Mice.

BACKGROUND: Clinical observations indicate that mechanical factors contribute to the expression or recurrence of Crohn's disease. We investigated whether the creation of an intestinal stenosis could alter the severity of the expected Crohn-like ileitis, in a Crohn's disease animal model, the TNFΔare/+ mouse. METHODS: Thirty-six, 6-weeks-old TNFΔare/+ mice, were divided into 3 intervention groups: triple suture, single suture and sham. In the terminal ileum, in the first group, a triple suture stenosis was created, whereas, in the second, a loose suture was placed. Same triple-suture stenosis was performed on twelve wild type mice. All animals were sacrificed at 6 weeks post-operatively and the ileum parts were evaluated histopathologically. A summative total ileitis score was applied in each sample using a bespoke semiquantitative histological scoring system for the Crohn-like changes. RESULTS: The triple suture stenosis induced significant muscular hypertrophy proximal to interventional site which was more prominent in TNFΔare/+ than wild type mice. In triple suture group, the total ileitis score was significantly increased proximal to the intervention as compared to the single suture (P: 0.004) and the sham groups (P: 0.013). The total ileitis score distally, was unaffected, regardless of the experimental intervention. Intestinal stenosis did not induce intestinal inflammation in wild type mice. CONCLUSION: The creation of a stenosis in the terminal ileum of TNFΔare/+ mice alters Crohn-like inflammation. We assume that mechanical forces, such as intraluminal pressure, may contribute as important co-factors to the pathophysiology of Crohn's disease in genetically predisposed subjects.