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Byline: Jarmila. ?elakovská, K. Ettler, K. Ettlerová, J. Van??ková Background: Patients suffering from atopic dermatitis often describe food hypersensitivity. Rising prevalence of food hypersensitivity and severe allergic reactions to foods [...]

Byline: J. Celakovská, K. Ettlerová, K. Ettler, J. Vanecková, J. Bukac Sir, I would like to inform you about our results concerning the evaluation of food hypersensitivity in patients suffering [...]

This article gives an overview of the basic concepts of the textiles composition and introduces the main clothing materials. Optimal properties can be achieved by final adjustments of the product. The authors provide a list of important requirements for the clothing of dermatologic patients and give some suggestion for addressing these requirements. [ABSTRACT FROM AUTHOR]

Byline: Jarmila. Celakovská, K. Ettlerová, K. Ettler, J. Bukac, M. Belobrádek Aim: To evaluate the effect of a diagnostic hypoallergenic diet on the severity of atopic dermatitis in patients over [...]

Background Work-related skin diseases ( WSD) are caused or worsened by a professional activity. Occupational skin diseases ( OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. Objective To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment and rehabilitation in different European countries. Methods A questionnaire-based survey of the current situation regarding OSD patient management pathways was carried out with experts on occupational dermatology and/or occupational medicine from 28 European countries contributing to the European Cooperation in Science and Technology ( COST) Action TD 1206 (StanDerm) (). Results Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks (synonyms: insurance against work accidents and occupational injuries; statutory social accident insurance)]. Legal standards for the assessment of occupationally triggered diseases with a genetic background differ between different countries, however, in most European member states recognition as OSD is possible. In one-third of the countries UV light-induced tumours can be recognized as OSD under specific conditions. Conclusion OSD definitions vary between European countries and are not directly comparable, which hampers comparisons between statistics collected in different countries. Awareness of this fact and further efforts for standardization are necessary. [ABSTRACT FROM AUTHOR]

Copyright of Czecho-Slovak Dermatology / Cesko-Slovenska Dermatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Psoriasis is a systemic inflammatory disease. Genetic and environmental factors play a role in its pathogenesis. Recent studies refer to association between psoriasis with metabolic syndrome and cardiovascular disease. In our study we examined changes in serum levels of selected indicators of inflammation such as C-reactive protein (CRP), lipoprotein associated phospholipase A2 (LpPLA2), adiponectin, leptin, lipocalin 2, resistin and retinol binding protein 4 (RBP4). Serum indicators were measured and compared in 32 patients with moderate to severe psoriasis (median PASI 17,1) and in 24 healthy controls (donors of blood). Significantly higher levels of CRP, LpPLA2, lipocalin 2 and leptin were found in patients with psoriasis compared to the control group. Negative correlation were observed between body mass index BMI and adiponectin, positive correlations were found between BMI and leptin and between BMI and lipocalin 2 in patients with psoriasis. Indicators like CRP, LpPLA2, lipocalin 2 and leptin could be used to asses the systemic involvement in psoriasis and to recognition and treatment of psoriatic comorbidities early. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is associated with food allergies. The aim of this study is to evaluate soy allergy in patients suffering from atopic dermatitis. Altogether 228 persons were included; specific IgE, skin prick tests, atopy patch tests, challenge tests with soy and history of soy allergy were evaluated. Soy allergy was confirmed in eight patients (3.5%, in four patients with worsening of atopic dermatitis, in four patients with oral allergy syndrome), sensitisation to soy was found in another 47 patients (20%) with no clinical manifestation after soy ingestion. Dependence was confirmed statistically between soy allergy and pollen allergy and soy sensitivity and pollen allergy. About 20% of patients suffering from atopic dermatitis are sensitised to soy. Clinical symptoms of soy allergy occur only in 3.5% of patients suffering from atopic dermatitis. [ABSTRACT FROM AUTHOR]

Few large studies concerning the importance of food allergy in adolescents and adult patients with atopic dermatitis exist. The evaluation of food allergy to egg white and yolk, peanuts, soy, cow milk and wheat in patients suffering from atopic dermatitis. Two hundred forty patients (70 men, 170 women) were examined. Complete dermatological and allergological examination was performed in all patients, including specific IgE, skin prick test and atopy patch test. The challenge test was performed according to the results of examinations with suspected foods. The food allergy to peanuts was confirmed in 20% of patients, to egg in 6%, to soy in 3.3%, to wheat in 2.5% and to milk in 0.8% – altogether in 65 patients (27.5%). The positive results in examinations without clinical symptoms of food allergy were recorded in another 78 patients (32.5%). The diagnostic work-up should comprise not only the laboratory methods, but also the diagnostic hypoallergenic diet and the challenge test. [ABSTRACT FROM AUTHOR]

Biological therapy of psoriasis is modern, expensive and highly effective therapeutical modality for this chronic disease. Currently. there are 4 biologies registered for the treatment of severe psoriasis in the Czech Republic: etanercept, adalimumab, infliximab and ustekinumab. Retrospective analysis performed in the Faculty Hospital Hradec Kralove in the period 2006-2011 did not show statistically significant difference of efficacy among biologies used after the first three months of therapy. The main reason for therapy discontinuation was loss of efficacy (57,3 %). No complications and side effects were recorded in 54,8 % of patients. [ABSTRACT FROM AUTHOR]

Copyright of Czecho-Slovak Dermatology / Cesko-Slovenska Dermatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czecho-Slovak Dermatology / Cesko-Slovenska Dermatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czecho-Slovak Dermatology / Cesko-Slovenska Dermatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czecho-Slovak Dermatology / Cesko-Slovenska Dermatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim. The evaluation of the occurrence of peanut allergy in adolescent and adult patients suffering from atopic dermatitis. Methods. Altogether 175 persons suffering from atopic dermatitis were included in the study. A diagnostic work-up for food allergy to peanuts was performed (specific IgE, skin prick tests, atopy patch tests, history), and the patients were also examined for pollen allergy containing Bet v 1 and Bet v 2 allergens. Results. Allergic reactions to peanuts were recorded in 23% of patients, and another 16% of patients were sensitised to peanuts. A dependency between the occurrence of pollen allergy with Bet v 1 and Bet v 2 allergens and the results of the examination for peanut allergy is confirmed in our study. Conclusion. One-fifth of patients with atopic dermatitis suffer from peanut allergy; the most common symptom is oral allergy syndrome. [ABSTRACT FROM PUBLISHER]

Copyright of Czecho-Slovak Dermatology / Cesko-Slovenska Dermatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Psoriasis is one of the most frequent inflammatory skin diseases in which abnormal individual immune reactivity plays an important role. The aim of the present study was to describe selected immunological changes, concerning pro-inflammatory cytokines (TNF-alpha, IL-8) and adhesion molecules (sE-selectin, sP-selectin, sICAM-1), in 56 patients cured by Goeckerman's therapy (GT). GT includes dermal application of crude coal tar (containing polycyclic aromatic hydrocarbons) and exposure to UV radiation. When compared with the control group (healthy blood donors), the patients before GT had significantly increased serum levels of sE-selectin (p<0.001), sP-selectin (p<0.001), sICAM-1 (p<0.001) and IL-8 (p<0.001). Significantly decreased serum levels of sE-selectin (p<0.05) and significantly increased serum levels of IL-8 (p<0.05) were found after GT therapy. Serum levels of sICAM significantly correlated with the disease activity and with serum levels of sE-selectin. The level of PASI score (Psoriasis Area and Severity Index) significantly decreased after GT (p<0.001) and confirms the high efficiency GT. These findings confirmed that pro-inflammatory chemokine (IL-8) and adhesion molecules (sE-selectin, sP-selectin, sICAM-1) play an important role in the development and regulation of inflammation in psoriasis. Determination of sE-selectin and sICAM seems to be a promising marker of psoriasis's activity. Chemokine pathway (IL-8) and TNF-alpha activity seem to be modulated by Goeckerman's therapy (polycyclic aromatic hydrocarbons). [ABSTRACT FROM AUTHOR]

Hand foot and mouth disease is an viral exanthematic disease typical for children, often ocurring in adults as well. Authors report three cases observed in the same period in the region of Hradec Králové. They describe clinical picture, laboratory diagnostic methods, differential diagnosis, complications and possible epidemiologie relations of the disease. [ABSTRACT FROM AUTHOR]

The authors describe two cases of intensively itching lichenoid dermatitis developed after an injury caused by a sea coral while diving in the Red Sea. The rash reacted to topical steroid and antihistamine treatment. In the first case a partial improvement occurred within two weeks, in the other patient dermatological lesions persisted for more than a month. The article gives an overview of skin lesions caused by the sea corals and their therapy. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 77-year-old woman suffering from clitoral enlargement with a 6 months history. Histologic evaluation determined nodular malignant melanoma of the clitoris exceeding the excision. The woman underwent bilateral superficial inguinal lymphadenectomy performed through small separate inguinal incisions. The researchers reach the conclusion that sentinel lymph node biopsy is feasible for clitoral melanoma.

4412 patients with hand dermatitis were patch tested with a standard series in an occupational dermatology clinic during the past 10 years. 15 hospital employees related their symptoms to the use of rubber surgical gloves. Each of these was also patch tested with glove material. 9 of this group were subsequently retested with separate rubber chemicals supplied by Vulkan AG, Hr&acutedek n. Nisou, currently the monopoly producer of surgical gloves in the Czech Republic. Because of reports of contact urticaria and anaphylactoid reactions.

Introduction: Atopic dermatitis (AD), a predominantly type 2 inflammatory skin disease, affects approximately 2-5% of adults, with a high burden of disease. In moderate-to-severe AD, lesions can be extensive and pruritus intense with patients experiencing skin pain, sleep and mental health disturbances, and diminished quality of life (QoL)., Methods: The objective of this study was to evaluate the efficacy of dupilumab for the treatment of AD from the patients' perspective using patient-reported outcome data from four clinical trials (CHRONOS, SOLO 1&2, and CAFÉ) in patients (N = 1553) receiving either the approved 300 mg q2w dupilumab with/without topical corticosteroids (TCS) dose or control (placebo or placebo + TCS). Patient Global Assessment of Disease Status (PGADS) was used to measure patients' well-being and Patient Global Assessment of Treatment Effect (PGATE) was used to measure treatment efficacy. Patients were asked "Considering all the ways in which your eczema affects you, indicate how well you are doing" to assess their perception of well-being and "How would you rate the way your eczema responded to the study medication?" to assess their perception of treatment effect. Possible responses for both metrics included poor, fair, good, very good, and excellent., Results: In all four studies, a significantly higher proportion of dupilumab-treated patients reported "Good"/"Very Good"/"Excellent" disease status from week 2 through study end versus control (CHRONOS, 52 weeks: 69.8% vs. 25.1%; SOLO 1&2, 16 weeks: 59.5% vs. 24.6%; CAFÉ, 16 weeks: 84.1% vs. 45.4%; all P < 0.0001), and significantly more dupilumab-treated patients reported "Good"/"Very Good"/"Excellent" treatment efficacy versus control (CHRONOS: 72.6% vs. 24.8%; SOLO 1&2: 65.0% vs. 21.1%; CAFÉ, 16 weeks: 85.0% vs. 36.1%; all P < 0.0001)., Conclusion: Adult patients with AD perceived that dupilumab with/without concomitant TCS was highly efficacious and improved overall disease status and well-being as early as week 2 and throughout treatment periods up to 1 year. Video Abstract (MP4 90521 kb)., (© 2021. The Author(s).)

Background: Although epidemiologic data are scarce, there is no doubt that the increase in pollen allergies is going to be followed by an increase in the so-called pollen-related food allergies. The aim of this study was the evaluation of the food hypersensitivity reactions in atopic dermatitis patients and the relation to the sensitization to grass and trees., Methods: The complete dermatological and allergological examinations were performed in all included patients; the occurrence of food hypersensitivity reactions was recorded and the sensitization to inhalant allergens (grass and trees) was examined (skin prick test, and specific IgE). The statistical evaluation of the relation between the sensitization to these inhalant allergens and the occurrence of food hypersensitivity reactions was performed., Results: A total of 321 patients were included, with an average age of 26.7 years (±9.2 years) and with an average SCORAD of 33.2 (±13.3) points. The significant relation was recorded between the patients suffering from sensitization to grass and the reactions to peanuts, celery and walnuts; another significant relation was demonstrated between the patients suffering from sensitization to trees and reactions to apple, peanuts, and walnuts. In patients suffering from sensitization to grass and trees, the occurrence of food hypersensitivity reactions to tomatoes, kiwi, spices, oranges, capsicum, tangerines, and carrot was higher also, but the relation was not significant., Conclusion: The significant relation was found between the reactions to peanuts and walnuts and sensitization to grass and trees, another significant relation was found between the sensitization to grass and celery and between the sensitization to trees and apple., Competing Interests: There are no conflicts of interest.

Background: Eosinophils play an important pathogenic role in atopic dermatitis (AD), but its exact function remains to be determined., Aims and Objectives: The aim of this study was to correlate the eosinophil count with the manifestations such as asthma bronchiale, rhinitis, level of total IgE, sensitization to mites, animal dander, bird feather, dust, mixture of grass, mixture of trees, mixture of fungi, duration of lesions (persistent or occasional during last year), family history about atopy, and onset of AD (under or above 5 year of age)., Materials and Methods: Two hundred and seventy-two patients suffering from AD at the age of 14 year or older were examined - 100 men and 172 women with the average age of 26.7±9.5 years and with the average SCORAD index of 32.9±14.1. Complete dermatological and allergological examinations were performed in all patients with the evaluation of monitored manifestations. Mann-Whitney test for difference in medians was used for statistical evaluation., Results: The count of eosinophils in peripheral blood was significantly higher in patients with total IgE ≥200 IU/ml, with sensitization to dust, with persistent eczematous lesions and in patients with the onset of AD under 5 year of age. The count of eosinophils above 5% was recorded as well in patients suffering from asthma bronchiale, rhinitis, sensitization to mites, and in patients with positive family history about atopy, but the difference was not significant. On the other hand, the count of eosinophils was under 5% in patients with sensitization to animal dander, bird feather, mixture of grass and trees., Conclusion: Our results demonstrated the difference in the count of eosinophils in peripheral blood according to different manifestations in patients suffering from AD., Competing Interests: There are no conflicts of interest.

The aim of this study is the evaluation of the relation between the sensitisation to outdoor and indoor fungi and allergy to peanuts and walnuts in atopic dermatitis patients aged 14 years and older. The complete dermatological and allergological examinations were performed in all included patients; the occurrence of food allergy to peanuts and walnuts was recorded (specific IgE, skin prick test, history of allergic reaction) and the sensitisation to mixture of outdoor fungi and indoor fungi was also examined (skin prick test, specific IgE). The statistical evaluation of the relation between the sensitisation to outdoor and indoor fungi and the occurrence of food allergy to peanuts and walnuts was performed; 329 patients were included in the study, 110 men and 219 women, the average age 26.8 years. The sensitisation to outdoor fungi was recorded in 91 patients (28%), the sensitisation to indoor fungi was recorded in 61 patients (18.5%), the occurrence of food allergy to peanuts was confirmed in 90 (27%) patients and to walnuts in 121 (36.7%) patients. We confirmed, that patients suffering from sensitisation to outdoor fungi suffer significantly more from food allergy to peanuts and walnuts. The significant relation between the sensitisation to indoor fungi and food allergy to peanuts and walnuts was not confirmed., (© 2018 Blackwell Verlag GmbH.)

Background: Fungi as a source of allergen are still largely neglected in basic research as well as in clinical practice. This study aimed to highlight the impact of fungal allergens in a group of patients suffering from atopic dermatitis (AD)., Aims and Objectives: The evaluation of the sensitization to fungi in AD patients aged 14 year and older and the evaluation of the relation of fungal sensitization to the occurrence of other atopic diseases and parameters., Materials and Methods: All patients satisfying inclusion criteria attending our hospital between 2008 and 2017 were included in the study. The complete dermatological and allergological examinations were performed in all included patients including examination of specific immunoglobulin E, skin prick test to mixture of fungi and inhalant allergens, evaluation of asthma bronchiale, rhinitis, onset of AD, family history about atopy, duration of eczematous lesions, severity of AD. Pairs of these categories were entered in the contingency tables and the Chi-square test for relationship of these variables was performed with the level of significance set below 5%., Results: Three hundred and thirty-one patients were included in the study; the average age was 26.8 years. The sensitization to fungi was recorded in 100 patients (30%). In these patients, the occurrence of asthma bronchiale, rhinitis, family history about atopy, sensitization to grass and trees was significantly higher than in patients without sensitization to fungi. We did not find any significant relation between the sensitization to fungi and the severity of AD, no relation was also found between the sensitization to fungi and sensitization to mites, animal dander, bird feather, and dust., Conclusion: The occurrence of asthma bronchiale, rhinitis, family history about atopy, sensitization to grass and trees was significantly higher in AD patients with sensitization to fungi. No relation was found between the severity of AD and the sensitization to fungi., Competing Interests: There are no conflicts of interest.

Background: In adult patients suffering from atopic dermatitis (AD), studies investigating the co-prevalence of AD and food allergy are still scarce, and exact data are not available., Aims and Objectives: To evaluate the occurrence of food allergy to peanuts in significant relation to food hypersensitivity, inhalant allergy and to asthma bronchial and rhinitis., Materials and Methods: Altogether 332 patients of AD 14 year or older were included in the study. The complete dermatological and allergological examinations were performed in all included patients (including examination of specific immunoglobulin E, skin prick test to different food and inhalant allergens, anamnestic data about food reactions, evaluation of allergic rhinitis, and allergic asthma bronchiale). We evaluated whether there was some relation between the food allergy to peanuts and followed parameters. Pairs of these categories were entered in the contingency tables, and the Chi-square test for the relationship of these variables was performed with the level of significance set to 5%., Results: Altogether 332 persons suffering from AD were included in the study of which 120 were male and 212 were female; the average age was 27.2 year. The significant relation between the allergy to peanuts and the occurrence of food hypersensitivity (FH) reactions to tomatoes, kiwi, apples, oranges, carrot and to the sensitization to grass, trees, mites, and the occurrence of rhinitis was found., Conclusion: The significant relation between the allergy to peanuts and the occurrence of FH reactions and the sensitization to inhalant allergens and rhinitis was found. The future studies may show if the decrease in food allergy to peanuts can lead to the decrease of the occurrence of other FH reactions and sensitization to inhalant allergens and rhinitis in AD patients., Competing Interests: There are no conflicts of interest. What is new? The occurrence of peanut allergy was significantly correlated with other food allergies in adult atopic dermatitis patients.

Background: Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis., Methods: In this 1-year, randomised, double-blinded, placebo-controlled, phase 3 study (LIBERTY AD CHRONOS), adults with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids were enrolled at 161 hospitals, clinics, and academic institutions in 14 countries in Europe, Asia-Pacific, and North America. Patients were randomly assigned (3:1:3) to subcutaneous dupilumab 300 mg once weekly (qw), dupilumab 300 mg every 2 weeks (q2w), or placebo via a central interactive voice/web response system, stratified by severity and global region. All three groups were given concomitant topical corticosteroids with or without topical calcineurin inhibitors where inadvisable for topical corticosteroids. Topical corticosteroids could be tapered, stopped, or restarted on the basis of disease activity. Coprimary endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-point or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week 16. Week 16 efficacy and week 52 safety analyses included all randomised patients; week 52 efficacy included patients who completed treatment by US regulatory submission cutoff. This study is registered with ClinicalTrials.gov, NCT02260986., Findings: Between Oct 3, 2014, and July 31, 2015, 740 patients were enrolled: 319 were randomly assigned to dupilumab qw plus topical corticosteroids, 106 to dupilumab q2w plus topical corticosteroids, and 315 to placebo plus topical corticosteroids. 623 (270, 89, and 264, respectively) were evaluable for week 52 efficacy. At week 16, more patients who received dupilumab plus topical corticosteroids achieved the coprimary endpoints of IGA 0/1 (39% [125 patients] who received dupilumab plus topical corticosteroids qw and 39% [41 patients] who received dupilumab q2w plus topical corticosteroids vs 12% [39 patients] who received placebo plus topical corticosteroids; p<0·0001) and EASI-75 (64% [204] and 69% [73] vs 23% [73]; p<0·0001). Week 52 results were similar. Adverse events were reported in 261 (83%) patients who received dupilumab qw plus topical corticosteroids, 97 (88%) patients who received dupilumab q2w, and 266 (84%) patients who received placebo, and serious adverse events in nine (3%), four (4%), and 16 (5%) patients, respectively. No significant dupilumab-induced laboratory abnormalities were noted. Injection-site reactions and conjunctivitis were more common in patients treated with dupilumab plus topical corticosteroids-treated patients than in patients treated with placebo plus topical corticosteroids., Interpretation: Dupilumab added to standard topical corticosteroid treatment for 1 year improved atopic dermatitis signs and symptoms, with acceptable safety., Funding: Sanofi and Regeneron Pharmaceuticals Inc., (Copyright © 2017 Elsevier Ltd. All rights reserved.)