Co-constructing a new framework for evaluating social innovation in marginalized rural areas

The EU funded H2020 project \u2018Social Innovation in Marginalised Rural Areas\u2019 (SIMRA; www.simra-h2020.eu) has the overall objective of advancing the state-of-the-art in social innovation. This paper outlines the process for co- developing an evaluation framework with stakeholders, drawn from across Europe and the Mediterranean area, in the fields of agriculture, forestry and rural development. Preliminary results show the importance of integrating process and outcome-oriented evaluations, and implementing participatory approaches in evaluation practice. They also raise critical issues related to the comparability of primary data in diverse regional contexts and highlight the need for mixed methods approaches in evaluation

Critical and Near-Critical Branching Processes

Scale-free dynamics in physical and biological systems can arise from a variety of causes. Here, we explore a branching process which leads to such dynamics. We find conditions for the appearance of power laws and study quantitatively what happens to these power laws when such conditions are violated. From a branching process model, we predict the behavior of two systems which seem to exhibit near scale-free behavior--rank-frequency distributions of number of subtaxa in biology, and abundance distributions of genotypes in an artificial life system. In the light of these, we discuss distributions of avalanche sizes in the Bak-Tang-Wiesenfeld sandpile model.Comment: 9 pages LaTex with 10 PS figures. v.1 of this paper contains results from non-critical sandpile simulations that were excised from the published versio

Polyphenol characterization and skin-preserving properties of hydroalcoholic flower extract from Himantoglossum robertianum (Orchidaceae)

Himantoglossum robertianum (Loisel.) P. Delforge is a Mediterranean orchid whose propagation in vitro has been achieved, making it eligible as a source of bioactive substances. Flowers were analyzed by light and SEM microscopy and used to obtain a polyphenol-rich, hydroalcoholic flower extract (HFE). HFE was characterized for total phenols, flavonoids and proanthocyanidins, and for polyphenol profile by RP-LC-DAD. Antioxidant assays, in vitro collagenase and elastase inhibition, and MTT and cell motility assays on HaCaT keratinocytes were done. Microscopy showed epidermal cells containing anthocyanins in the flower labellum. Flavonoids (flavones and flavan-3-ols) represented the most abundant compounds (42.91%), followed by scopoletin (33.79%), and phenolic acids (23.3%). Antioxidant assays showed strong activities, rating ORAC > FRAP > TEAC > \u3b2-carotene bleaching > DPPH > iron-chelation. Biological assays showed elastase and collagenase inhibition (up to 42% and 78%, respectively), improvement of HaCaT cell viability after treatment with 500 \u3bcM H2O2 (from 30% to 84% of control), and stimulation of cell migration rate up to 210% of control. In summary, HFE counteracted different free radicals, while protective properties were shown by cell-free and cell-based bioassays, suggesting the possible use of H. robertianum flowers for skin-preserving, repair, and anti-aging applications

Mal de Debarquement Syndrome: A Matter of Loops?

Introduction: Mal de Debarquement Syndrome (MdDS) is a poorly understood neurological disorder affecting mostly perimenopausal women. MdDS has been hypothesized to be a maladaptation of the vestibulo-ocular reflex, a neuroplasticity disorder, and a consequence of neurochemical imbalances and hormonal changes. Our hypothesis considers elements from these theories, but presents a novel approach based on the analysis of functional loops, according to Systems and Control Theory. Hypothesis: MdDS is characterized by a persistent sensation of self-motion, usually occurring after sea travels. We assume the existence of a neuronal mechanism acting as an oscillator, i.e., an adaptive internal model, that may be able to cancel a sinusoidal disturbance of posture experienced aboard, due to wave motion. Thereafter, we identify this mechanism as a multi-loop neural network that spans between vestibular nuclei and the flocculonodular lobe of the cerebellum. We demonstrate that this loop system has a tendency to oscillate, which increases with increasing strength of neuronal connections. Therefore, we hypothesize that synaptic plasticity, specifically long-term potentiation, may play a role in making these oscillations poorly damped. Finally, we assume that the neuromodulator Calcitonin Gene-Related Peptide, which is modulated in perimenopausal women, exacerbates this process thus rendering the transition irreversible and consequently leading to MdDS. Conclusion and Validation: The concept of an oscillator that becomes noxiously permanent can be used as a model for MdDS, given a high correlation between patients with MdDS and sea travels involving undulating passive motion, and an alleviation of symptoms when patients are re-exposed to similar passive motion. The mechanism could be further investigated utilizing posturography tests to evaluate if subjective perception of motion matches with objective postural instability. Neurochemical imbalances that would render individuals more susceptible to developing MdDS could be investigated through hormonal profile screening. Alterations in the connections between vestibular nuclei and cerebellum, notably GABAergic fibers, could be explored by neuroimaging techniques as well as transcranial magnetic stimulation. If our hypothesis were tested and verified, optimal targets for MdDS treatment could be found within both the neural networks and biochemical factors that are deemed to play a fundamental role in loop functioning and synaptic plasticity

Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey

Fibromyalgia (FM) is an unsolved central pain processing disturbance. We aim to provide a unifying model for FM pathogenesis based on a loop network involving thalamocortical regions, i.e., the ventroposterior lateral thalamus (VPL), the somatosensory cortex (SC), and the thalamic reticular nucleus (TRN). The dynamics of the loop have been described by three differential equations having neuron mean firing rates as variables and containing Hill functions to model mutual interactions among the loop elements. A computational analysis conducted with MATLAB has shown a transition from monostability to bistability of the loop behavior for a weakening of GABAergic transmission between TRN and VPL. This involves the appearance of a high-firing-rate steady state, which becomes dominant and is assumed to represent pathogenic pain processing giving rise to chronic pain. Our model is consistent with a bulk of literature evidence, such as neuroimaging and pharmacological data collected on FM patients, and with correlations between FM and immunoendocrine conditions, such as stress, perimenopause, chronic inflammation, obesity, and chronic dizziness. The model suggests that critical targets for FM treatment are to be found among immunoendocrine pathways leading to GABA/glutamate imbalance having an impact on the thalamocortical system

Comparison of short- and long-term effectiveness of ixekizumab and secukinumab in real-world practice

Background: Although secukinumab and ixekizumab both act by inhibiting IL-17A, some scientific evidence suggests that there are differences in efficacy between the two agents. Objective: The aim of this study was to compare the short- and long-term effectiveness of ixekizumab and secukinumab in clinical practice. Methods: A retrospective study was conducted on a cohort of 245 psoriatic patients receiving secukinumab or ixekizumab during the period from September 2016 to December 2019. The proportion of patients achieving PASI75, PASI90, and PASI100 at weeks 12 and 24 was calculated. We recorded the 12- and 24-month drug survival as a measure to assess long-term effectiveness. Results: A higher proportion of patients in the secukinumab group achieved PASI75, 90, and 100 at 12 weeks. The Kaplan-Meier survival curve for any reason of discontinuation showed no differences between the two groups. Instead, the multivariate analysis for ineffectiveness, adjusted for potential confounders, showed a lower drug survival rate in the secukinumab group, with an adjusted HR of 2.57 (95% CI 1.05–6.28, p 0.038). Conclusion: This real-life study demonstrated that ixekizumab and secukinumab are both highly effective in short- and long-term treatment of psoriasis, even though few differences exist concerning speed of action and long-term effectiveness

Profile of a Cohort of 78 Italian Patients with Mucous Membrane Pemphigoid: Correlation Between Reactivity Profile and Clinical Involvement

Direct diagnosis of mucous membrane pemphigoid (MMP) is not easy. Circulating autoantibodies targeting bullous pemphigoid antigens of 180 kDa and 230 kDa (BP180 and BP230), \u3b16\u3b24 integrin, laminin 332 and type VII collagen (Col VII) are not always present. The aims of this study were to characterize the humoral immune response of a cohort of Italian patients with MMP, its association with clinical involvement and severity, and to design an algorithm for efficient serological diagnosis. Seventy-eight MMP sera were studied retrospectively by indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Indirect immunofluorescence on salt-split skin resulted in the most sensitive approach for diagnosis of MMP. BP180 was the major autoantigen in MMP patients with oral and cutaneous involvement. Significant associations were found between BP180 reactivity and oral and cutaneous localization of the lesions (p\u2009=\u20090.006), and between Col VII positivity and Setterfield severity score (p\u2009=\u20090.020)

An urban ecohydrological model to quantify the effect of vegetation on urban climate and hydrology (UT&C v1.0)

Increasing urbanization is likely to intensify the urban heat island effect, decrease outdoor thermal comfort and enhance runoff generation in cities. Urban green spaces are often proposed as a mitigation strategy to counteract these adverse effects and many recent developments of urban climate models focus on the inclusion of green and blue infrastructure to inform urban planning. However, many models still lack the ability to account for different plant types and oversimplify the interactions between the built environment, vegetation, and hydrology. In this study, we present an urban ecohydrological model, Urban Tethys-Chloris (UT&C), that combines principles of ecosystem modelling with an urban canopy scheme accounting for the biophysical and ecophysiological characteristics of roof vegetation, ground vegetation and urban trees. UT&C is a fully coupled energy and water balance model that calculates 2 m air temperature, 2 m humidity, and surface temperatures based on the infinite urban canyon approach. It further calculates all urban hydrological fluxes, including transpiration as a function of plant photosynthesis. Hence, UT&C accounts for the effects of different plant types on the urban climate and hydrology, as well as the effects of the urban environment on plant well-being and performance. UT&C performs well when compared against energy flux measurements of eddy covariance towers located in three cities in different climates (Singapore, Melbourne, Phoenix). A sensitivity analysis, performed as a proof of concept for the city of Singapore, shows a mean decrease in 2 m air temperature of 1.1 °C for fully grass covered ground, 0.2 °C for high values of leaf area index (LAI), and 0.3 °C for high values of Vc,max (an expression of photosynthetic activity). These reductions in temperature were combined with a simultaneous increase in relative humidity by 6.5 %, 2.1 %, and 1.6 %, for fully grass covered ground, high values of LAI, and high values of Vc,max, respectively. Furthermore, the increase of pervious vegetated ground is able to significantly reduce surface runoff. These results show that urban greening can lead to a decrease in urban air temperature and surface runoff, but this effect is limited in cities characterized by a hot, humid climate.ISSN:1991-962XISSN:1991-961

Real-life effectiveness and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: A 104-week multicenter retrospective study – IL PSO (ITALIAN LANDSCAPE PSORIASIS)

BackgroundGuselkumab is a humanized monoclonal antibody that binds selectively to the p19 subunit of interleukin-23, which has shown efficacy in patients with previous incomplete response to ustekinumab in the NAVIGATE clinical trial. ObjectivesWe conducted a 104-week multicenter retrospective study to assess the effectiveness and safety of guselkumab in patients affected by plaque psoriasis with an inadequate response to ustekinumab in a real-life setting. MethodsOur retrospective study included 233 adults affected by moderate-to-severe plaque psoriasis, enrolled in 14 different Italian centres, and treated with guselkumab after failing therapy with ustekinumab. Patient characteristics and PASI (Psoriasis Area and Severity Index) score at each visit (baseline, weeks 16, 52 and 104) were recorded. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI, compared with baseline, were registered. ResultsAt week 52, PASI 75 was reached by 89.88% of patients, PASI 90 by 71.43%, PASI 100 by 58.83% and absolute PASI <= 2 by 90.48%. At week 104, similar effectiveness results were observed. Compared to the NAVIGATE trial, we observed higher rates of PASI 75/90/100. Patients with the involvement of difficult-to-treat areas were significantly less likely to achieve PASI90 and PASI100 at week 16. Obese patients had significantly lower rates of PASI75 and PASI <= 2 at week 52. At week 104, comparable responses were observed among all patients' subgroups, regardless of BMI status, involvement of difficult-to-treat areas, presence of cardiometabolic comorbidities and concomitant psoriatic arthritis. No significant safety findings were reported throughout the study. ConclusionOur data suggest that the efficacy of guselkumab in patients with inadequate response to ustekinumab for plaque psoriasis in 'real-life' clinical practice is comparable with NAVIGATE study with higher percentages of patients achieving PASI90 and PASI100 at weeks 16, 52 and 104

Why honey is effective as a medicine. 1. Its use in modern medicine

Honey has been used as a medicine for thousands of years and its curative properties are well documented. However, modern medicine turned its back on honey and it is only now, with the advent of multi-resistant bacteria, that the antibiotic properties of honey are being rediscovered