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Background In the SARS-CoV-2/COVID-19 pandemic, we need to understand the impact of immunomodulatory medications on COVID-19 symptom severity in patients with inflammatory diseases, including the type 2/Th2 polarized skin disease, atopic dermatitis (AD). Objective Because it is believed that type 1/Th1 immunity controls viral infections and that there is a Th1/Th2 counter-regulation, we hypothesized that Th2 targeting with the IL-4Rα-antagonist, dupilumab, in patients with moderate-to-severe AD would rebalance the Th1/Th2 axis, potentially leading to attenuated COVID-19 symptoms. Methods A total of 1237 patients with moderate-to-severe AD in the Icahn School of Medicine at Mount Sinai Department of Dermatology were enrolled in a registry. Patients were screened for COVID-19-related symptoms and assigned a severity score (asymptomatic [0]-fatal [5]). Scores were compared among 3 treatment groups: dupilumab (n = 632), other systemic treatments (n = 107), and limited/no treatment (n = 498). Demographic and comorbid covariates were adjusted by multivariate generalized logistic regression models. Results The dupilumab-treated group showed reduced incidence and severity of COVID-19 symptoms versus other treatment groups. Dupilumab-treated patients were less likely to experience moderate-to-severe symptoms versus patients on other systemics (P = .01) and on limited/no treatment (P = .04), and less likely to experience any symptoms versus patients on other systemics (P = .01). This effect was seen in our entire cohort and in the subgroup of patients with verified COVID-19 or high-risk exposure. Conclusions Patients on dupilumab experienced less severe COVID-19 manifestations and lesser symptoms compared with patients on other systemics and on limited/no treatment. These results suggest that Th2 modulation with dupilumab may have a protective effect on anti-viral immune response in patients with AD.

Research has begun to illustrate a favorable efficacy and side-effect profile for many systemic agents used in pediatric dermatological conditions (i.e. atopic dermatitis, psoriasis, scleroderma, alopecia areata, chronic spontaneous urticaria, autoimmune blistering disorders, and hidradenitis suppurativa) despite not having extensive randomized clinical trials. The purpose of this article is to summarize the available data on the treatment regiments, safety, and efficacy of systemic immunosuppressants, including the newer biologics, focusing on the most up-to-date systematic reviews or randomized clinical trials. The review demonstrates that many of the present studies lack data on long-term efficacy and consist of small patient populations. Further research into the long-term safety of these systemic medications is of vital importance especially due to the chronic nature of most pediatric dermatological conditions that require the use of systemic agents. Keywords: systemics, immunosuppressant medications, biologics, pediatric dermatology conditions

Patients with moderate‐to‐severe atopic dermatitis (AD) or psoriasis often require systemic immunomodulatory therapy. The uncertainty of the potential of these therapies to increase the risk of more serious illness due to Coronavirus disease 2019 (COVID‐19) may have caused anxiety and led to treatment discontinuation. Therefore, we conducted an anonymous questionnaire on concerns of COVID‐19 in patients with AD or psoriasis treated with systemic immunomodulatory therapy.

Purpose: To compare the short-term cost and effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam against nonbiologic systemics in psoriasis patients for whom oral systemic or topical therapy is considered appropriate in seven European countries. Methods: Matching-adjusted indirect comparisons of four-week PASI-75 responses of Cal/BD foam were performed versus 12-week responses of methotrexate, acitretin, fumaric acid esters (FAE) and 16-week responses of apremilast. Analyses took a payer perspective and included drug, physician visit and monitoring costs. Results: In all countries, Cal/BD foam generated the lowest cost per responder (CPR). Against methotrexate, apremilast and acitretin, Cal/BD foam generated response for less than euro190 in Italy, euro195 in Portugal, euro216 in Greece, 218 pound in the United Kingdom, euro250 in Belgium, euro319 in Spain, and euro359 in the Netherlands. Relative to treatment with FAE, Cal/BD foam resulted in response for less than euro298, euro430, euro382 and 262 pound in Belgium, the Netherlands, Spain and the United Kingdom, respectively. For Cal/BD foam, apremilast and FAE, total costs were driven by drug costs; for methotrexate and acitretin, by monitoring. Conclusions: Driven by its lower costs and high response rates, Cal/BD foam is likely to be a cost-effective option over the short-term in the investigated psoriasis population.

Psoriasis vulgaris is a chronic, immune-mediated systemic disease that affectŝ7.5 million people in the US. It can be treated with many therapies, often in combination, which include topicals, phototherapy, oral systemics, and biologics. Biologic agents target specific components of the immune system involved in the pathogenesis of psoriasis including TNF-alpha, IL-12, IL-17, and IL-23. The biologic ixekizumab, approved for the treatment of moderate-severe plaque psoriasis in the US, targets IL-17. This review describes the role of IL-17 in psoriasis, the mechanism by which ixekizumab targets this cytokine, and the clinical utility of ixekizumab.

BackgroundLittle data exist on real-world treatment patterns in psoriasis, especially from European settings. ObjectiveTo estimate, for topicals, systemics and biologics, the time to non-persistency, switching, augmentation and insufficient treatment result (only for biologics), as well as to estimate the time to restart, in patients treated with each treatment class in Sweden based on registry data. MethodsThis database analysis utilized data from patients with psoriasis from several Swedish administrative registers. Patients were identified through combinations of diagnoses from two regional registers and filled prescriptions for relevant treatments from the Swedish Prescribed Drug Register. Kaplan-Meier time-to-event (survival') functions were estimated with relevant treatment events as failure and the proportions of patients having experienced an event at specific time-points were derived from the failure rates. ResultsFor topicals, systemics and biologics the number of indexed treatment episodes were 25396, 2963, and 628 respectively. One year after treatment initiation, the proportion of patients who were classed as non-persistent with topicals, systemics and biologics were estimated at 88.3%, 47.9% and 43.2% respectively. Among patients who remained persistent, within 1year of treatment start the proportions of treatment episodes in which patients were augmented were estimated at 56.0% for topicals, 45.3% for systemics and 58.9% for biologics. In addition, within 1year of non-persistence, 49.0% of topicals, 60.8% of systemics and 80.2% of biologics treatment episodes were re-initiated, with 35.4-52.5% re-initiated on the non-persistent treatment depending on treatment class. In addition, among patients on biologics, 29.2% of treatment episodes had an insufficient treatment result within 1year of treatment start. ConclusionPersistency to psoriasis treatments may be sub-optimal and patients who remain persistent relatively frequently receive augmentation therapy or switch to another therapy. Therefore, current treatment options in psoriasis may be insufficient. (Less)

Architecture is a complex idea in its own right. In architectural culture, systemic references are not new. Design theories, in Europe as well as in USA, have often referred to many concepts more or less strictly linked to Systemics and to scientific domains such as Information theories and Cybernetics. Quite often, such references have been a mere metaphorical suggestion or, as in the field of “rational” design and process engineering, they mostly have heavy functional overtones. Such is the idea of “performance”, whose original definition was meant as an industrial design tool pursuing optimization, linking together the users’ needs and the requirements an artifact must possess to satisfy those needs. But, as we know, “bottom up” emergence processes have nothing to do with “top down” design strategies for optimization. Nevertheless, the idea of performance conveys the meaning of a strong influence intercurring between two entities, one of them on the “giving” and the other one on the “taking” sides, both of them interacting through feedback. For this reason, I believe the idea of performance should not be discarded lightheartedly. Rather, a “softer” notion of performance, linked to the realm of social perception and attachment to places, should be brought to thorough definition. It might be useful to find a more productive, non-metaphorical use of systemic references to understand and (then) to design—or to redevelop—human settlements.

The silvicultural principles of a forest management plan for Canton Neuchâtel reveals itself as steeped in a systemic approach that allows us to consider the forest as a truly living system. In this context, it seems judicious to the author to conceive of the body forest personnel as a group of responsible people who share certain common ethics and who, in their work, promote the emergence of collective services recognised as beneficial to the state and which would be supported by public funding for the good of the entire community.

Avaliou-se a eficácia de lactonas macrocíclicas (ivermectina e moxidectina) sobre a eventual ocorrência de efeitos colaterais e acompanharam-se, após a alta parasitológica, por 12 meses, os cães tratados, visando detectar a recidiva do quadro dermatopático. Dos 63 animais, 59% eram fêmeas, 76% apresentavam precisa definição racial e 67% tinham pelame curto. A ivermectina (0,6mg/kg/dia) foi administrada por via oral a 31 cães, e a moxidectina (0,5mg/kg/cada 72 horas), pela mesma via, a 32 animais. Os tempos médios para a obtenção da primeira negativação do exame parasitológico do raspado cutâneo e para a consecução da alta foram, respectivamente, de 90 e 130 dias para a ivermectina e de 108 e 147 dias para a moxidectina. A ivermectina acarretou menos (16,1%) efeitos colaterais em relação à moxidectina (37,5%) (P=0,03). As recidivas foram, respectivamente, 10,3% e 13% para ivermectina e moxidectina. Não houve diferença entre os dois protocolos de terapia quanto aos percentuais de recidiva (P=0,67) e eficácia (P=0,61). Ambas as lactonas macrocíclicas mostraram-se eficazes: ivermectina 89,7% e moxidectina 87%. The efficacy of ivermectin and moxidectin for treatment of generalized canine demodicosis, was evaluated to detect the eventual occurrence of side effects caused by the use of these drugs, and to follow the treated dogs for 12 months after obtaining parasitologic cure. Of 63 dogs, 59% were females, 76% were defined as purebred and 67% had short hair. Ivermectin (0.6mg/kg/daily) was orally administered to 31 dogs and moxidectin (0.5mg/kg/every 72 hours) to 32 dogs. The average number of days to obtain the first negative skin scraping results and the parasitologic cure were, respectively, 90 and 130 days for ivermectin, and 108 and 147 days for moxidectin. Ivermectin caused fewer side effects (16.1%) than moxidectin (37.5%) (P0.67) and efficacy (P>0.61). Both drugs were effective and safe to treat generalized canine demodicosis: ivermectin 89.7% and moxidectin 87.0%.

The usefulness of the software program, Systemics 1.0 (O'Halloran and Judd 2002) for research and teaching Systemic Functional Linguistics (SFL) is examined in this paper. Systemics 1.0 is software which contains a pre-programmed SFL grammar at the rank of word, word group, clause, clause complex and discourse stratum. The software is designed to overcome the physical constraints of text analysis through features such as pull-down menus containing the grammatical systems, and search and print facilities. As the 'standard' grammar in Systemics 1.0 can be modified, discourse analyses undertaken with the software can incorporate other theoretical per spectives. Following a discussion of the functionality of the software, the ways in which the design features and interfaces in Systemics 1.0 shape the users' perceptions of systemic functional theory and practice are considered. This includes a discussion of the limitations of the program, together with recommendations for possible future developments in SFL software.

Upholds the equivalence between the sociological notion of reflexivity and the idea of self‐reference, which epistemologically and structurally distinguish those complex systems where humans participate as elements. Once there is a conceptual bridge between sociology and cybernetics, the reflexivity processes are analysed, and the expression feed‐before is proposed for the corresponding circuits, as they operate after the input, but before the output characteristic of the other complex systems is produced. After distinguishing between micro‐ and macro‐reflexivity, studies mutual connections and submits graphic designs of both types of circuit. Also briefly analyses the tempo of social reflexivity, while deducing the consequences regarding the predictability of social dynamics.

Efficacy of biologic therapies for psoriasis has been demonstrated in randomized trials, but effectiveness in real-world settings has yet to be fully determined.To compare clinical improvement and treatment satisfaction with biologic versus other therapies in patients with plaque psoriasis.European dermatologists recruited psoriasis patients into an observational study. Dermatologists reported disease severity before and after starting current therapy; dermatologists and patients reported treatment satisfaction.These analyses included 2151 patients: topicals, n = 453; phototherapy, n = 666; conventional systemics, n = 683; biologics, n = 349. The percentage with severe disease declined from 70% before to 15% after biologics, a significantly greater decline than other therapies: topicals, 22-10%; phototherapy, 20-11%; conventional systemics, 49-15% (all p ≤ 0.03). Significantly more patients (59%) receiving biologics were satisfied with treatment versus topicals (45%), phototherapy (34%), or conventional systemics (50%) (all p0.001). Significantly more dermatologists were satisfied with biologics (60%) versus topicals (35%), phototherapy (26%), or conventional systemics (42%) (all p0.001).In this study, more patients receiving biologic therapies improved from severe to moderate or mild psoriasis than patients on other treatments. More patients with plaque psoriasis and their dermatologists were satisfied with biologics than any other treatment.

This article reviews the dental literature concerning the potential impact of the removable prosthesis (RP) on the health status of patients with certain systemic diseases. Literature was surveyed using Medline/PubMed database resources, as well as a manual search, up to 2015 to identify appropriate articles that addressed the aim of this review. The research used keywords about associations between RP and six pathologies: Human immunodeficiency virus infection, diabetes mellitus, pulmonary diseases, gastric-Helicobacter pylori, cancer, and cardiovascular diseases. Analysis of literature showed that in patients with dentures having one or more of the six general conditions listed, Candida albicans organism is more frequently found in the oral flora compared to healthy denture wearer. Although causality has not been established and pending further research on this topic, the hygienic practices necessary to minimize the risk of numerous pathologies should be strengthened in the case of these patients, all the more in the presence of physical or psychological disability. The relationship between the general diseases and increasing of oral candidiasis denture patients is not explained. Therefore, attention to oral hygiene and professional care for removing C. albicans may be beneficial in these medically compromised patients.

Background Tofacitinib (CP-690,550) is a novel Janus kinase inhibitor in development as an oral formulation for the treatment of several inflammatory diseases including psoriasis. Objectives This phase 2a study aimed to assess the efficacy, systemic safety, local tolerability and systemic pharmacokinetics of topical tofacitinib in mild-to-moderate plaque psoriasis. Methods Two tofacitinib ointment formulations were evaluated in this multicentre, double-blind, vehicle-controlled trial (NCT01246583). Seventy-one patients were randomized 2 : 1 : 2 : 1 to 2% tofacitinib ointment 1, vehicle 1, 2% tofacitinib ointment 2 and vehicle 2, each administered twice daily for 4 weeks to a single fixed 300 cm2 treatment area containing a target plaque with or without one or more nontarget plaques and normal skin. Results The primary endpoint of percentage change from baseline in the Target Plaque Severity Score at week 4 demonstrated statistically significant improvement for ointment 1 [least squares mean (LSM) –54·4%] vs. vehicle 1 (LSM –41·5%), but not ointment 2 (LSM –24·2%) vs. vehicle 2 (LSM –17·2%). Secondary endpoints (target plaque area and Itch Severity Item) improved similarly for tofacitinib ointment vs. corresponding vehicle. Adverse event (AE) occurrence was similar across treatment groups. All AEs were mild or moderate and none were serious or led to subject discontinuation. One application-site AE (erythema) was reported. Tofacitinib mean systemic exposure was minimal and was greater for ointment 1 than for ointment 2. Conclusions Tofacitinib ointment 1 was well tolerated and efficacious compared with vehicle for the treatment of plaque psoriasis. Further study of topical tofacitinib for psoriasis treatment is warranted.

BEYOND OPERATIONAL RESEARCH AND HARD SYSTEMS THINKING: Operations Research as a Profession The Future of Operational Research is Past From Optimizing to Learning THE BREAK WITH SOFT SYSTEMS THINKING: Marxism and Systems Research Critical Heuristics of Social Systems Design Social Systems Theory and Practice Towards a System of Systems Methodologies Methodological Foundations of Systems Methodologies Testament to Conversations on Critical Systems Thinking Between Two Systems Practitioners CONTEMPORARY CRITICAL SYSTEMS THEORY AND PRACTICE: Critical Systems Thinking in the 1980s Between Systems Thinking and Systems Practice Systems Thinking, Systems Practice and Practical Philosophy Power-Ideology Matrix in Social Systems Control Modernism, Postmodernism and Contemporary Systems Thinking Redefining the Management and Systems Sciences Total Systems Intervention.

It is hard to imagine a more multidisciplinary topic than the subject of this symposium. Investigating the fossil remains of biomolecules requires expertise from several major branches of science: physical, chemical, biological and geological. The specializations of the scientists contributing to this volume almost reads as an A Z of science, ranging from archaeologists to zoologists, with biochemists, chemists, geneticists, geologists, immunologists, molecular biologists, palaeontologists and other, more difficult to classify, experts in between.

The way in which fungal populations respond to fungicides used for their control, and hence the risk of disease control failures due to resistance, depends primarily on the type of genetic variability available. Existing evidence indicates that the type of variability differs with the chemical rather than with the organism. With most systemic fungicides and antifungal antibiotics, high resistance can be obtained by mutation of a major gene. The population response is then qualitative and a high or moderate resistance risk is involved, depending on the effect of the major gene on fitness. Mathematical models are available, on the basis of which the establishment of resistance and the loss of effectiveness of a fungicide of this group can be predicted. With a few systemics and some protectants, a practically significant decrease of sensitivity requires the interaction of several genes, each of a rather minor effect: the response is quantitative and the resistance risk is low th moderate. In this situation, the combination of degree of resistance and fitness loss varies greatly and this has not permitted the construction of suitable mathematical models so far. Finally, there is no evidence that pathogenic fungi possess genes for resistance to most protectant fungicides, which involve a low resistance risk, if any. Selection of forms less sensitive to fungicides of this group does not seem to have taken place, in spite of many years of repeated use.

The cattle grub is a pest that has been with us for many years, but is one that has often been neglected. With the coming to our industry of the cattle feeding era, we saw much more interest in the cattle grub problem. Prior to the 50's, no materials were available except a product that would kill the cattle grub when it was in the back. Rotenone was used but only killed those larvae that had already cut an air hole in the back. In the mid 50's, systemics were discovered which did effectively control cattle grubs. Since that time, many products have come forth that will effectively control cattle grubs., American Association of Bovine Practitioners Proceedings of the Annual Conference, 1987

This chapter describes physical methods of destroying pathogens carried by planting material and the ways in which fungicides are applied to plants and plant material. The next chapter outlines the development and testing of fungicides, the more important groups of fungicides including antibiotics and systemics, the use of oils in disease control, chemotherapy, the ways in which fungicides inhibit fungi, and the development of fungicide resistant strains of fungi.

Ronnel (formerly designated Dow ET-57, O, O -dimethyl O -(2,4,5-trichlorophenyl) phosphorothioate, Trolene,® or Korlan®) was administered orally to steers at three locations at two dosage levels in the feed; 15 mg./kg./day for 7 days, and 25 mg./kg./day for 6 days. Bayer 21/199 also called Co-Ral® ( O -(3-chloro-4-methylumbelliferone) O, O -diethyl phosphorothioate) was applied to steers at two locations as either a 0.5% suspension or emulsion at 250 pounds pressure. There was no difference grub ( Hypoderma sp.) control, weight gain, feed efficiency or carcass grades between treatments at each location. Grub control at the three locations ranged from 76.3 to 98.6%.