Advancements in the Investigation of Vertical Profiles of Thunderstorm Outflows

The dynamic complexity and unpredictability of the occurrence of thunderstorms make it difficult to collect reliable and systematic measurements of this atmospheric phenomenon, which are definitely needed to evaluate its action on structures. The area of the Northern Tyrrhenian Sea is a \u201chot-spot\u201d for the genesis of severe potentially damaging wind phenomena, such as downbursts, whose occurrence in this geographical region is not well documented. In the context of the two European projects \u201cWind and Ports\u201d and \u201cWind, Ports and Sea\u201d, a large and complex wind monitoring network has been installed in this area. Since the years 2014-2015, this network is equipped with three LiDAR profilers which provide vertical scanning of the atmosphere up to 250 m above the ground level. All the wind profiles have been systematically analysed in order to detect the ones that can be referred to thunderstorm events. The aim of this study is to extend a first set of analyses up to mid-2018 to provide a preliminary investigation of the main parameters describing the non-synoptic events and a first classification of thunderstorm events into different subsets

Loop analysis of blood pressure/volume homeostasis

We performed a mathematical analysis of the dynamic control loops regulating the vasomotor tone of vascular smooth muscle, blood volume, and mean arterial pressure, which involve the arginine vasopressin (AVP) system, the atrial natriuretic peptide system (ANP), and the renin-angiotensin-aldosterone system (RAAS). Our loop analysis of the AVP-ANP-RAAS system revealed the concurrent presence of two different regulatory mechanisms, which perform the same qualitative function: one affects blood pressure by regulating vasoconstriction, the other by regulating blood volume. Both the systems are candidate oscillators consisting of the negative-feedback loop of a monotone system: they admit a single equilibrium that can either be stable or give rise to oscillatory instability. Also a subsystem, which includes ANP and AVP stimulation of vascular smooth muscle cells, turns out to be a candidate oscillator composed of a monotone system with multiple negative feedback loops, and we show that its oscillatory potential is higher when the delays along all feedback loops are comparable. Our results give insight into the physiological mechanisms ruling long-term homeostasis of blood hydraulic parameters, which operate based on dynamical loops of interactions

Geosites and geological landscape map of Liguria (Italy)

Since the beginning of the Third Millennium, an ever-increasing interest of geoheritage has been observed, either in scientific terms or in practical point of view, with the resulting socio-economic consequences. Geoheritage represents the basic element of the landscape and it often has strong links with other elements of the territory like historical geography, land-use setting, landscape protection, nature conservation, etc. Oneimportant link is tied to the environmental protection task, because most part of the Italian protected areas are mainly established above Earth Sciences features. Consequently, a lot of geosite sare included into these important natural sites. The issue of geoheritage and geosites has become object of national and regional laws: in Italy the cultural heritage and landscape code was issued in 2004 while in Liguria the Regional Law n. 39/2009 establishes the rules for the valorisation of the geodiversity, geosites and karst areas. Here we present an overview of geosites and geological landscape of Liguria (North West Italy); in addition to the recent regional database and georeferencing activities of the Ligurian geosites, through a reworking of a simplified geological map addressed also for non-geologists, a geotematic map has been defined. In particular, this product emphasizes the relationship between geology and landscape, showing how different rock masses produce several landforms of outstanding natural beauty in the ligurian territory. The map shows the basic concepts of geoscience by looking closely at the landscape we see in front of us every day. From the coast to the Alps and Apennines watershed, we identified several geological landscape units characterized by specific rock masses, soils and particular geological and geomorphological features, such as: 1) Palaeolandslides landscape; 2) Ligurian alluvial floodplains; 3)Ligurian coastal plains; 4) the Flysch rock masses; 5) Ophiolitic crags; 6) Conglomerate peaks; 7) Karstic massif; 8) Quartzite and Cherts rock masses; 9) Sandstone spurs; 10) Shales and schists domain; 11) Windows on the Paleozoic; 12) Plio- Quaternary landscape. More than 500 geosites classified in a recent specific regional database were then overlapped on the geological landscape units: they have been distinguished according to interest, for different geothematic categories, according to the proposal of enhancement. The Ligurian geosites and geological landscape overview map could represents a friendly tool to identify the most relevant regional geological heritage

A multistationary loop model of ALS unveils critical molecular interactions involving mitochondria and glucose metabolism

Amyotrophic lateral sclerosis (ALS) is a poor-prognosis disease with puzzling pathogenesis and inconclusive treatments. We develop a mathematical model of ALS based on a system of interactive feedback loops, focusing on the mutant SOD1G93A mouse. Misfolded mutant SOD1 aggregates in motor neuron (MN) mitochondria and triggers a first loop characterized by oxidative phosphorylation impairment, AMP kinase over-activation, 6-phosphofructo-2-kinase (PFK3) rise, glucose metabolism shift from pentose phosphate pathway (PPP) to glycolysis, cell redox unbalance, and further worsening of mitochondrial dysfunction. Oxidative stress then triggers a second loop, involving the excitotoxic glutamatergic cascade, with cytosolic Ca2+ overload, increase of PFK3 expression, and further metabolic shift from PPP to glycolysis. Finally, cytosolic Ca2+ rise is also detrimental to mitochondria and oxidative phosphorylation, thus closing a third loop. These three loops are overlapped and positive (including an even number of inhibitory steps), hence they form a candidate multistationary (bistable) system. To describe the system dynamics, we model the interactions among the functional agents with differential equations. The system turns out to admit two stable equilibria: the healthy state, with high oxidative phosphorylation and preferential PPP, and the pathological state, with AMP kinase activation, PFK3 over expression, oxidative stress, excitotoxicity and MN degeneration. We demonstrate that the loop system is monotone: all functional agents consistently act toward the healthy or pathological condition, depending on low or high mutant SOD1 input. We also highlight that molecular interactions involving PFK3 are crucial, as their deletion disrupts the system\u2019s bistability leading to a single healthy equilibrium point. Hence, our mathematical model unveils that promising ALS management strategies should be targeted to mechanisms that keep low PFK3 expression and activity within MNs

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

Fractal geometry of spin-glass models

Stability and diversity are two key properties that living entities share with spin glasses, where they are manifested through the breaking of the phase space into many valleys or local minima connected by saddle points. The topology of the phase space can be conveniently condensed into a tree structure, akin to the biological phylogenetic trees, whose tips are the local minima and internal nodes are the lowest-energy saddles connecting those minima. For the infinite-range Ising spin glass with p-spin interactions, we show that the average size-frequency distribution of saddles obeys a power law $\sim w^{-D}$, where w=w(s) is the number of minima that can be connected through saddle s, and D is the fractal dimension of the phase space

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)