171 research outputs found

    A Dynamics and Stability Framework for Avian Jumping Take-off

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    Jumping take-off in birds is an explosive behaviour with the goal of providing a rapid transition from ground to airborne locomotion. An effective jump is predicated on the need to maintain dynamic stability through the acceleration phase. The present study concerns understanding how birds retain control of body attitude and trajectory during take-off. Cursory observation suggests that stability is achieved with relatively little cost. However, analysis of the problem shows that the stability margins during jumping are actually very small and that stability considerations play a significant role in selection of appropriate jumping kinematics. We use theoretical models to understand stability in prehensile take-off (from a perch) and also in non-prehensile take-off (from the ground). The primary instability is tipping, defined as rotation of the centre of gravity about the ground contact point. Tipping occurs when the centre of pressure falls outside the functional foot. A contribution of the paper is the development of graphical tipping stability margins for both centre of gravity location and acceleration angle. We show that the nose-up angular acceleration extends stability bounds forward and is hence helpful in achieving shallow take-offs. The stability margins are used to interrogate simulated take-offs of real birds using published experimental kinematic data from a guinea fowl (ground take-off) and a diamond dove (perch take-off). For the guinea fowl the initial part of the jump is stable, however simulations exhibit a stuttering instability not observed experimentally that is probably due to absence of compliance in the idealised joints. The diamond dove model confirms that the foot provides an active torque reaction during take-off, extending the range of stable jump angles by around 45{\deg}.Comment: 21 pages, 11 figures; supplementary material: https://figshare.com/s/86b12868d64828db0d5d; DOI: 10.6084/m9.figshare.721056

    A Case of Allergic Contact Dermatitis Due to DuoDERM Extrathin®

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    Over the past years, hydrocolloid dressings have been introduced routinely in the treatment of various types of wounds. They provide a moist environment promoting autolytic debridement, and stimulate angiogenesis. However, long-term application often leads to inflammation of the skin in the immediate area of the ulcer, causing irritant dermatitis in many cases, but sometimes also leads to contact sensitization. A 32 year-old woman burnt herself by an iron, and presented to our clinic and was treated with Duoderm extrathin®. Nine days later, she again presented with an erythematous oozing patch with edema, and allergic contact dermatitis was suspected. A patch test (TRUE test) was performed and a positive reaction to colophonium was obtained. Duoderm extrathin® contains hydrogenated rosin (colophonium) as the tackifying agent, so we could diagnose this case as allergic contact dermatitis due to the hydrogenated rosin in Duoderm extrathin®. We report another case of allergic contact dermatitis due to Duoderm extrathin® in a 32 year-old woman

    British Association of dermatologists guidelines for biologic therapy for psoriasis 2020 – a rapid update

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    The overall aim of the guideline is to provide up‐to‐date, evidence‐based recommendations on the use of biologic therapies targeting TNF (adalimumab, etanercept, certolizumab pegol, infliximab), IL12/23p40 (ustekinumab), IL17A (ixekizumab, secukinumab), IL17RA (brodalumab) and IL23p19 (guselkumab, risankizumab, tildrakizumab) in adults, children and young people for the treatment of psoriasis; consideration is given to the specific needs of people with psoriasis and psoriatic arthritis

    Exercise Intensity and Duration Effects on In Vivo Immunity

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    PURPOSE: To examine the effects of intensity and duration of exercise stress on induction of in vivo immunity in humans using experimental contact hypersensitivity (CHS) with the novel antigen diphenylcyclopropenone (DPCP). METHODS: Sixty-four healthy males completed either 30 min running at 60% V O2peak (30MI), 30 min running at 80% V O2peak (30HI), 120 min running at 60% V O2peak (120MI), or seated rest (CON). Twenty min later, the subjects received a sensitizing dose of DPCP; and 4 wk later, the strength of immune reactivity was quantified by measuring the cutaneous responses to a low dose-series challenge with DPCP on the upper inner arm. Circulating epinephrine, norepinephrine and cortisol were measured before, after, and 1 h after exercise or CON. Next, to understand better whether the decrease in CHS response on 120MI was due to local inflammatory or T-cell-mediated processes, in a crossover design, 11 healthy males performed 120MI and CON, and cutaneous responses to a dose series of the irritant, croton oil (CO), were assessed on the upper inner arm. RESULTS: Immune induction by DPCP was impaired by 120MI (skinfold thickness -67% vs CON; P < 0.05). However, immune induction was unaffected by 30MI and 30HI despite elevated circulating catecholamines (30HI vs pre: P < 0.01) and greater circulating cortisol post 30HI (vs CON; P < 0.01). There was no effect of 120MI on skin irritant responses to CO. CONCLUSIONS: Prolonged moderate-intensity exercise, but not short-lasting high- or short-lasting moderate-intensity exercise, decreases the induction of in vivo immunity. No effect of prolonged moderate-intensity exercise on the skin's response to irritant challenge points toward a suppression of cell-mediated immunity in the observed decrease in CHS. Diphenylcyclopropenone provides an attractive tool to assess the effect of exercise on in vivo immunity

    A Framework for Multi-Omic Prediction of Treatment Response to Biologic Therapy for Psoriasis.

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    Biologic therapies have shown high efficacy in psoriasis, but individual response varies and is poorly understood. To inform biomarker discovery in the Psoriasis Stratification to Optimise Relevant Therapy (i.e., PSORT) study, we evaluated a comprehensive array of omics platforms across three time points and multiple tissues in a pilot investigation of 10 patients with severe psoriasis, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used RNA sequencing to analyze mRNA and small RNA transcriptome in blood, lesional and nonlesional skin, and the SOMAscan platform to investigate the serum proteome. Using an integrative systems biology approach, we identified signals of treatment response in genes and pathways associated with TNF signaling, psoriasis pathology, and the major histocompatibility complex region. We found association between clinical response and TNF-regulated genes in blood and skin. Using a combination of differential expression testing, upstream regulator analysis, clustering techniques, and predictive modeling, we show that baseline samples are indicative of patient response to biologic therapies, including signals in blood, which have traditionally been considered unreliable for inference in dermatology. In conclusion, our pilot study provides both an analytical framework and empirical basis to estimate power for larger studies, specifically the ongoing PSORT study, which we show as powered for biomarker discovery and patient stratification

    Risk of Serious Infections in Patients with Psoriasis on Biologic Therapies: A Systematic Review and Meta-Analysis

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    A comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. No significant heterogeneity was detected in data from 32 RCTs (n = 13,359 participants) and one cohort study (n = 4,993 participants). In adults, low- to very-low-quality RCT data showed no significant difference between any biologic therapy and placebo at weeks 12–16 (overall pooled Peto odds ratio = 0.71, 95% confidence interval = 0.36–1.41) and weeks 20–30 (odds ratio = 2.27, 95% confidence interval = 0.45–11.49). No significant differences were found in any of the other comparisons in underpowered RCT data. Prospective cohort study data of low quality suggests that only adalimumab (adjusted hazard ratio [adjHR] = 2.52, 95% confidence interval = 1.47–4.32) was associated with a significantly higher risk of serious infection compared with retinoid and/or phototherapy in adults. No association between biologic therapies and serious infections in patients with psoriasis who were eligible for RCTs was detected. Further observational studies are needed to inform the uncertainty around this risk in the real world

    Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis.

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    Importance: Although palmoplantar pustulosis (PPP) can significantly impact quality of life, the factors underlying disease severity have not been studied. Objective: To examine the factors associated with PPP severity. Design, Setting, and Participants: An observational, cross-sectional study of 2 cohorts was conducted. A UK data set including 203 patients was obtained through the Anakinra in Pustular Psoriasis, Response in a Controlled Trial (2016-2019) and its sister research study Pustular Psoriasis, Elucidating Underlying Mechanisms (2016-2020). A Northern European cohort including 193 patients was independently ascertained by the European Rare and Severe Psoriasis Expert Network (2014-2017). Patients had been recruited in secondary or tertiary dermatology referral centers. All patients were of European descent. The PPP diagnosis was established by dermatologists, based on clinical examination and/or published consensus criteria. The present study was conducted from October 1, 2014, to March 15, 2020. Main Outcomes and Measures: Demographic characteristics, comorbidities, smoking status, Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI), measuring severity from 0 (no sign of disease) to 72 (very severe disease), or Physician Global Assessment (PGA), measuring severity as 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). Results: Among the 203 UK patients (43 men [21%], 160 women [79%]; median age at onset, 48 [interquartile range (IQR), 38-59] years), the PPPASI was inversely correlated with age of onset (r = -0.18, P = .01). Similarly, in the 159 Northern European patients who were eligible for inclusion in this analysis (25 men [16%], 134 women [84%]; median age at onset, 45 [IQR, 34-53.3] years), the median age at onset was lower in individuals with a moderate to severe PGA score (41 years [IQR, 30.5-52 years]) compared with those with a clear to mild PGA score (46.5 years [IQR, 35-55 years]) (P = .04). In the UK sample, the median PPPASI score was higher in women (9.6 [IQR, 3.0-16.2]) vs men (4.0 [IQR, 1.0-11.7]) (P = .01). Likewise, moderate to severe PPP was more prevalent among Northern European women (57 of 134 [43%]) compared with men (5 of 25 [20%]) (P = .03). In the UK cohort, the median PPPASI score was increased in current smokers (10.7 [IQR, 4.2-17.5]) compared with former smokers (7 [IQR, 2.0-14.4]) and nonsmokers (2.2 [IQR, 1-6]) (P = .003). Comparable differences were observed in the Northern European data set, as the prevalence of moderate to severe PPP was higher in former and current smokers (51 of 130 [39%]) compared with nonsmokers (6 of 24 [25%]) (P = .14). Conclusions and Relevance: The findings of this study suggest that PPP severity is associated with early-onset disease, female sex, and smoking status. Thus, smoking cessation intervention might be beneficial
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