Lattice structures are periodic porous bodies which are becoming popular since they are a good compromise between rigidity and weight and can be built by additive manufacturing techniques. Their ...optimization has recently attracted some attention, based on the homogenization method, mostly for compliance minimization. The goal of our two-part work is to extend lattice optimization to stress minimization problems two-dimensionally. The present first part is devoted to the choice of a parametrized periodicity cell that will be used for structural optimization in the second part of our work. In order to avoid stress concentration, we propose a square cell microstructure with a super-ellipsoidal hole instead of the standard rectangular hole often used for compliance minimization. This type of cell is parametrized two-dimensionally by one orientation angle, two semi-axis and a corner smoothing parameter. We first analyse their influence on the stress amplification factor by performing some numerical experiments. Second, we compute the optimal corner smoothing parameter for each possible microstructure and macroscopic stress. Then, we average (with specific weights) the optimal smoothing exponent with respect to the macroscopic stress. Finally, to validate the results, we compare our optimal super-ellipsoidal hole with the Vigdergauz microstructure which is known to be optimal for stress minimization in some special cases.
This article is part of the theme issue ‘Topics in mathematical design of complex materials’.
Definition of minimal disease activity in psoriasis Carretero, G.; Carrascosa, J.M.; Puig, L. ...
Journal of the European Academy of Dermatology and Venereology,
February 2021, 2021-Feb, 2021-02-00, 20210201, Letnik:
35, Številka:
2
Journal Article
Recenzirano
Objective
To generate an operational definition to adequately reflect the construct ‘Minimal Disease Activity (MDA)’ in psoriasis.
Methods
A systematic review of domains included in clinical trials ...of psoriasis was presented to a panel of dermatologists and patients. Further domains were elicited by panel discussions. Domains (and instruments measuring these) were items of two consecutive Delphi rounds targeting dermatologists from the Psoriasis Group of the Spanish Academy of Dermatology and Venereology and patients from the Acción Psoriasis association. The instruments selected were used to generate 388 patient vignettes. The expert group then classified these vignettes as ‘No MDA/MDA/Unclassifiable’. The items were further reduced by factorial analysis. Using the classification variable as gold standard, several operational constructions were tested in regression models and ROC curves and accuracy was evaluated with area under the curve (AUC).
Results
The following domains were included: itching, scaling, erythema and visibility by 0–10 scales, extension by BSA, impact on quality of life by DLQI, special location and presence of arthritis as yes/no. The definition with the highest AUC and best balance between sensitivity and specificity was the one including no presence of arthritis plus at least three others below the upper limit of the 95% confidence interval (AUC, 0.897; sensitivity, 95.2%, specificity, 84.1%).
Conclusion
This study provides, for the very first time, the construct of ‘Minimal Disease Activity’ in psoriasis as agreed by dermatologists and patients. MDA is defined as absence of active arthritis plus 3 out of 6: itching ≤ 1/10; scaling ≤ 2/10; redness ≤ 2/10; visibility ≤ 2/10; BSA ≤ 2; DLQI ≤ 2; and no lesions in special locations. By design, domains are representative of disease impact. This MDA definition may be used as a measure of adequate management and replace other subjective or restrictive tools.
The geography, histories, and ethnic composition of the Latin American continent pose a great challenge when attempting to identify and describe the region’s constitutive religious traditions and ...experiences. This task is further complexified by the hybridity, fluidity, and porosity of the region’s cultural groups. However, there is an aspect of Latin American religiosity that shares a significant family resemblance across the continent: the small community settings in which religiosity often emerges and consolidates as a worldview, commonly known as Ecclesial base communities. Informed by liberation theology, these communities are a uniquely generative experiment in social, political, and religious life. Scholarly accounts of liberation theology fail to identify key aspects of how Ecclesial base communities generate ways of being, knowing, and making meaning. While many of these accounts depict liberation theology as a socio-political discourse of theological origin, they do not unearth the multidirectional interaction between political practice and theological thought at the heart of these communities. In this paper, I aimed to fill this gap in the literature by reframing liberation theology as a set of social imaginaries, making use of Paul Ricoeur’s theories of memory and cultural imagination to provide the philosophical ground to understand the lived theology of Ecclesial base communities. In doing so, I maintain that liberation theology is not only a theoretical discourse that emerges from these communities, but also the inarticulate background of their ways of thinking, communicating, and living, one that provides an existential orientation through which Latin Americans can provide coherence to their collective action and recognize their own capacity to change their reality of oppression.
The purpose of this meta-analysis was to examine the efficacy of exercise to reduce depressive symptoms among cancer survivors. In addition, we examined the extent to which exercise dose and clinical ...characteristics of cancer survivors influence the relationship between exercise and reductions in depressive symptoms.
We conducted a systematic search identifying randomized controlled trials of exercise interventions among adult cancer survivors, examining depressive symptoms as an outcome. We calculated effect sizes for each study and performed weighted multiple regression moderator analysis.
We identified 40 exercise interventions including 2,929 cancer survivors. Diverse groups of cancer survivors were examined in seven exercise interventions; breast cancer survivors were examined in 26; prostate cancer, leukemia, and lymphoma were examined in two; and colorectal cancer in one. Cancer survivors who completed an exercise intervention reduced depression more than controls, d(+) = -0.13 (95% CI: -0.26, -0.01). Increases in weekly volume of aerobic exercise reduced depressive symptoms in dose-response fashion (β = -0.24, p = 0.03), a pattern evident only in higher quality trials. Exercise reduced depressive symptoms most when exercise sessions were supervised (β = -0.26, p = 0.01) and when cancer survivors were between 47-62 yr (β = 0.27, p = 0.01).
Exercise training provides a small overall reduction in depressive symptoms among cancer survivors but one that increased in dose-response fashion with weekly volume of aerobic exercise in high quality trials. Depressive symptoms were reduced to the greatest degree among breast cancer survivors, among cancer survivors aged between 47-62 yr, or when exercise sessions were supervised.
The purpose of this meta-analysis was to explore the efficacy of exercise as a nonpharmacologic intervention to reduce cancer-related fatigue (CRF) among adult cancer survivors. We also investigated ...how different components of the exercise prescription (Ex R(x)), methodologic considerations, and subject characteristics modulate CRF.
A systematic search for randomized controlled trials was conducted using words related to cancer, exercise, and fatigue.
In total, 44 studies with 48 interventions qualified, including 3,254 participants of varying cancer types, stages of diagnosis, treatments, and exercise interventions. Cancer survivors in exercise interventions reduced their CRF levels to a greater extent than usual care controls, d(+) = 0.31 (95% CI = 0.22-0.40), an effect that appeared to generalize across several types of cancer. CRF levels improved in direct proportion to the intensity of resistance exercise (β = 0.60, P = 0.01), a pattern that was stronger in higher quality studies (β = 0.23, P < 0.05). CRF levels also reduced to a greater extent when interventions were theoretically driven (β = 0.48, P < 0.001) or cancer survivors were older (β = 0.24, P = 0.04).
Exercise reduced CRF especially in programs that involved moderate-intensity, resistance exercise among older cancer survivors and that were guided by theory.
Our results indicate exercise interventions for adult cancer survivors should be multi-dimensional and individualized according to health outcome and cancer type.
Background
Infiximab has been shown to be highly effective in phase III clinical trials, but limited information is available regarding drug survival and maintenance of efficacy beyond 1 year in ...real‐life clinical setting.
Objectives
To analyse the efficacy and safety of infliximab in a large number of patients with a long follow‐up and to identify clinical factors associated with long‐term drug survival.
Methods
A retrospective review of patients with moderate‐to‐severe psoriasis treated with infliximab from March 2004 to August 2012 at a tertiary dermatology centre was carried out.
Results
In total, 63 treatment courses with infliximab were administered to 56 patients. The mean duration of treatment was 31.6 months. The only significant positive predictor of drug survival was combination treatment hazard ratio (HR) vs. monotherapy 2.90, 95% confidence interval (CI) 1.42–5.92. Significant negative predictors of drug survival were obesity (HR 0.40, 95% CI 0.19–0.87) and infusion reactions (HR 0.40, 95% CI 0.19–0.87). Infusion reactions occurred in 13 (23%) of our patients and were a reason for discontinuation of treatment in 5.
Conclusions
This retrospective review of a cohort of patients with moderate‐to‐severe psoriasis treated with infliximab in daily practice shows that the PASI75 response rates at 24 and 52 weeks of treatment are similar to those of the pivotal studies, but 37 courses of treatment (59%) had to be discontinued after a median of 12 months. The major cause for discontinuation was loss of response, in 18 cases. Combination treatment, obesity and infusion reactions were found to be predictors of drug survival.
The mechanical behavior of three crosslinked polyurea (PU) elastomers obtained by sol-gel chemistry under uniaxial monotonic and cyclic tests has been assessed. These elastic networks are composed of ...hard and soft domains, where the segmental molecular weight between crosslinking points differs among the samples and allow studying the effect of this parameter on the mechanical properties. In this paper, uniaxial tension tests were performed in order to capture the main characteristics of the stress-strain behavior of these PU elastomers, e.g., non-linear hyperelastic behavior, hysteresis, and softening. In addition, a constitutive model that properly represents their behavior was proposed showing that the non-linear stress-strain behavior at large strain values exhibits strong hysteresis and softening.
Regardless of the etiology, acute kidney injury involves aspects of mitochondrial dysfunction and ATP depletion. Fatty acid oxidation is the preferred energy source of the kidney and is inhibited ...during acute kidney injury. A pivotal role for the mitochondrial matrix protein, cyclophilin D in regulating overall cell metabolism is being unraveled. We hypothesize that mitochondrial interaction of proximal tubule cyclophilin D and the transcription factor PPARα modulate fatty acid beta-oxidation in cisplatin-induced acute kidney injury. Cisplatin injury resulted in histological and functional damage in the kidney with downregulation of fatty acid oxidation genes and increase of intrarenal lipid accumulation. However, proximal tubule-specific deletion of cyclophilin D protected the kidneys from the aforementioned effects. Mitochondrial translocation of PPARα, its binding to cyclophilin D, and sequestration led to inhibition of its nuclear translocation and transcription of PPARα-regulated fatty acid oxidation genes during cisplatin-induced acute kidney injury. Genetic or pharmacological inhibition of cyclophilin D preserved nuclear expression and transcriptional activity of PPARα and prevented the impairment of fatty acid oxidation and intracellular lipid accumulation. Docking analysis identified potential binding sites between PPARα and cyclophilin D. Thus, our results indicate that proximal tubule cyclophilin D elicits impaired mitochondrial fatty acid oxidation via mitochondrial interaction between cyclophilin D and PPARα. Hence, targeting their interaction may be a potential therapeutic strategy to prevent energy depletion, lipotoxicity and cell death in cisplatin-induced acute kidney injury.
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Investigations into the sensitivity of heart rate‐(HR) derived indices for tracking parasympathetic nervous system (PNS) changes in functionally overreached (F‐OR) endurance‐trained athletes have ...produced equivocal findings. Lack of clarity may be a result of methodological inconsistencies. Therefore, the aims of this systematic review and meta‐analysis were (a) to determine the sensitivity of resting and post‐exercise vagal‐related HR variability (HRV) and HR recovery (HRR) indices to detect PNS modulation in F‐OR and non‐overreached (non‐OR) athletes, and (b) to investigate the influence of methodological factors on the sensitivity of HR‐based indices to detect PNS hyperactivity in F‐OR athletes. We searched CENTRAL, Scopus, PubMed, Embase, and Web of Science up to May 2020 for the following terms: male and female endurance‐trained athletes, controlled and uncontrolled studies that carried out an overload training period, and PNS modulation measured in resting and post‐exercise, pre‐ and post‐overload training period. A random‐effects model of standardized mean difference (SMD) was estimated for each outcome measure based on the training‐induced fatigue status (F‐OR vs non‐OR athletes), and the influence of methodological issues to detect PNS hyperactivity in F‐OR was assessed by subgroup analyses. Pooled analysis showed that resting vagal‐related HRV indices did not detect PNS hyperactivity in F‐OR athletes (SMD+ = −0.01; 95% confidence interval CI = −0.51, 0.50), and no statistical difference (P = .600) was found with non‐OR athletes (SMD+ = 0.15; 95% CI = −0.14, 0.45). However, subgroup analysis based on HRV parameter showed a moderate statistical increase in weekly averaged HRV in F‐OR athletes (SMD+ = 0.81; 95% CI = 0.35, 1.26), while isolated HRV values did not reach statistical significance (SMD+ = −0.45; 95% CI = −0.96, 0.06). We observed a moderate and statistically significant increase in HRR indices among F‐OR athletes (SMD+ = 0.65; 95% CI = 0.44, 0.87), no changes for non‐OR athletes (SMD+ = 0.10; 95% CI = −0.15, 0.34), and statistically significant differences between F‐OR and non‐OR athletes (P < .001). Insufficient data prevented meta‐analysis for post‐exercise vagal‐related HRV indices. Our findings show that when methodological factors are considered, HR‐based indices are sensitive to increased PNS modulation in F‐OR.
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