A comparative assessment of two different debris flow propagation approaches – blind simulations on a real debris flow event

Abstract. A detailed comparison between the performances of two different approaches to debris flow modelling was carried out. In particular, the results of a mono-phase Bingham model (FLO-2D) and that of a two-phase model (TRENT-2D) obtained from a blind test were compared. As a benchmark test the catastrophic event of 1 October 2009 which struck Sicily causing several fatalities and damage was chosen. The predicted temporal evolution of several parameters of the debris flow (such as flow depth and propagation velocity) was analysed in order to investigate the advantages and disadvantages of the two models in reproducing the global dynamics of the event. An analysis between the models' results with survey data have been carried out, not only for the determination of statistical indicators of prediction accuracy, but also for the application of the Receiver Operator Characteristic (ROC) approach. Provided that the proper rheological parameters and boundary conditions are assigned, both models seem capable of reproducing the inundation areas in a reasonably accurate way. However, the main differences in the application rely on the choice of such rheological parameters. Indeed, within the more user-friendly FLO-2D model the tuning of the parameters must be done empirically, with no evidence of the physics of the phenomena. On the other hand, for the TRENT-2D the parameters are physically based and can be estimated from the properties of the solid material, thus reproducing more reliable results. A second important difference between the two models is that in the first method the debris flow is treated as a homogeneous flow, in which the total mass is kept constant from its initiation in the upper part of the basin to the deposition in a debris fan. In contrast, the second approach is suited to reproduce the erosion and deposition processes and the displaced mass can be directly related to the rainfall event. Application of both models in a highly urbanized area reveals the limitation of numerical simulation which is inadequate in describing some disturbances of the flows that occurred during the alluvial event (e.g. the cars, the volume of debris within buildings etc.) which have a crucial influence on the evaluation of the maximum and final flow depths

Runoff-generated debris flows: Observation of initiation conditions and erosion–deposition dynamics along the channel at Cancia (eastern Italian Alps)

In the Dolomitic region, abundant coarse hillslope sediment is commonly found at the toe of rocky cliffs. Ephemeral channels originate where lower permeability bedrock surfaces concentrate surface runoff. Debris flows initiate along such channels following intense rainfall and determine the progressive erosion and deepening of the channels. Sediment recharge mechanisms include rock fall, dry ravel processes and channel-bank failures. Here we document debris flow activity that took place in an active debris flow basin during the year 2015. The Cancia basin is located on the southwestern slope of Mount Antelao (3264 m a.s.l.) in the dolomitic region of the eastern Italian Alps. The 2.5 km2 basin is incised in dolomitic limestone rocks. The data consist of repeated topographic surveys, distributed rainfall measurements, time-lapse (2 s) videos of two events and pore pressure measurements in the channel bed. During July and August 2015, two debris flow events occurred, following similarly intense rainstorms. We compared rainfall data to existing rainfall triggering thresholds and simulated the hydrological response of the headwater catchment with a distributed model in order to estimate the total and peak water discharge. Our data clearly illustrate how debris entrainment along the channel is the main contributor to the overall mobilized volume and that erosion is dominant when the channel slope exceeds 16°. Further downstream, sediment accumulation and depletion occurred alternately for the two successive events, indicating that sediment availability along the channel also influences the flow behaviour along the prevailing-transport reach. The comparison between monitoring data, topographical analysis and hydrological simulation allows the estimation of the average solid concentration of the two events and suggests that debris availability has a significant influence on the debris flow volume. © 2020 John Wiley & Sons, Ltd

Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area

open24noTafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18 % was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but progression slowed significantly thereafter. Autonomic function remained stable in 33 %, worsened in 56 % and improved in 10 %. Fifteen percent of patients showed cardiac disease progression and 30 % new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43 %) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.openCortese, A.; Vita, G.; Luigetti, M.; Russo, M.; Bisogni, G.; Sabatelli, M.; Manganelli, F.; Santoro, L.; Cavallaro, T.; Fabrizi, G.M.; Schenone, A.; Grandis, M.; Gemelli, C.; Mauro, A.; Pradotto, L.G.; Gentile, L.; Stancanelli, C.; Lozza, A.; Perlini, S.; Piscosquito, G.; Calabrese, D.; Mazzeo, A.; Obici, L.; Pareyson, DCortese, Andrea; Vita, G.; Luigetti, M.; Russo, M.; Bisogni, G.; Sabatelli, M.; Manganelli, F.; Santoro, L.; Cavallaro, T.; Fabrizi, G. M.; Schenone, A.; Grandis, M.; Gemelli, C.; Mauro, A.; Pradotto, L. G.; Gentile, L.; Stancanelli, C.; Lozza, A.; Perlini, Stefano; Piscosquito, G.; Calabrese, D.; Mazzeo, A.; Obici, L.; Pareyson, D

Wave overtopping at near-vertical seawalls: Influence of foreshore evolution during storms

This work presents the results of an investigation on how wave overtopping at a near-vertical seawall at the back of a sandy foreshore is influenced by sequences of erosive storms. The experiments were carried out in the Large Wave Flume (GWK) at Leibniz University, Hannover (Germany). The tested layout consisted of a near-vertical 10/1 seawall and a sandy foreshore with an initial 1/15 slope. Three sequences of idealised erosive storms were simulated. Within each storm both the incident wave conditions and still water level were varied in time to represent high and low tide conditions. Each sequence started from a 1/15 configuration and the beach was not restored in between storms. The measurements included waves, beach profile, wave overtopping volumes. The profile of the beach was measured after each sea state tested. Wave overtopping at each stage of the tested storms was significantly influenced by bed changes. This was linked to the measured evolution of the beach. Measurements showed that a barred profile developed quickly at the start of each sequence, and scour developed at the toe of the structure during high water level conditions, while accretion or partial backfilling developed during low water level conditions. Due to these processes, the position of a sea state in the tested sequence is shown to be an important factor in determining the wave overtopping volume. Remarkably, when a weaker idealised storm followed a more energetic one, nearly the same level of overtopping was recorded. This is explained by the foreshore erosion, leading to increased water depths and wave heights at the toe of the structure. This finding allows to quantify and to explain the variability of wave overtopping in storms following one another at intervals shorter than the recovery time of the foreshore

Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Antibodies to neurofascin, contactin-1, and contactin-associated protein 1 in CIDP: Clinical relevance of IgG isotype.

Objective: To assess the prevalence and isotypes of anti-nodal/paranodal antibodies to nodal/paranodal proteins in a large chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cohort, compare clinical features in seronegative vs seropositive patients, and gather evidence of their isotype-specific pathogenic role. Methods: Antibodies to neurofascin-155 (Nfasc155), neurofascin-140/186 (Nfasc140/186), contactin-1 (CNTN1), and contactin-associated protein 1 (Caspr1) were detected with ELISA and/or cell-based assay. Antibody pathogenicity was tested by immunohistochemistry on skin biopsy, intraneural injection, and cell aggregation assay. Results: Of 342 patients with CIDP, 19 (5.5%) had antibodies against Nfasc155 (n = 9), Nfasc140/186 and Nfasc155 (n = 1), CNTN1 (n = 3), and Caspr1 (n = 6). Antibodies were absent from healthy and disease controls, including neuropathies of different causes, and were mostly detected in patients with European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite CIDP (n = 18). Predominant antibody isotypes were immunoglobulin G (IgG)4 (n = 13), IgG3 (n = 2), IgG1 (n = 2), or undetectable (n = 2). IgG4 antibody-associated phenotypes included onset before 30 years, severe neuropathy, subacute onset, tremor, sensory ataxia, and poor response to intravenous immunoglobulin (IVIG). Immunosuppressive treatments, including rituximab, cyclophosphamide, and methotrexate, proved effective if started early in IVIG-resistant IgG4-seropositive cases. Five patients with an IgG1, IgG3, or undetectable isotype showed clinical features indistinguishable from seronegative patients, including good response to IVIG. IgG4 autoantibodies were associated with morphological changes at paranodes in patients' skin biopsies. We also provided preliminary evidence from a single patient about the pathogenicity of anti-Caspr1 IgG4, showing their ability to penetrate paranodal regions and disrupt the integrity of the Nfasc155/CNTN1/Caspr1 complex. Conclusions: Our findings confirm previous data on the tight clinico-serological correlation between antibodies to nodal/paranodal proteins and CIDP. Despite the low prevalence, testing for their presence and isotype could ultimately be part of the diagnostic workup in suspected inflammatory demyelinating neuropathy to improve diagnostic accuracy and guide treatment. Classification of evidence: This study provides Class III evidence that antibodies to nodal/paranodal proteins identify patients with CIDP (sensitivity 6%, specificity 100%)

Antibodies to neurofascin, contactin-1, and contactin-associated protein 1 in CIDP: Clinical relevance of IgG isotype

OBJECTIVE To assess the prevalence and isotypes of anti-nodal/paranodal antibodies to nodal/paranodal proteins in a large chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cohort, compare clinical features in seronegative vs seropositive patients, and gather evidence of their isotype-specific pathogenic role. METHODS Antibodies to neurofascin-155 (Nfasc155), neurofascin-140/186 (Nfasc140/186), contactin-1 (CNTN1), and contactin-associated protein 1 (Caspr1) were detected with ELISA and/or cell-based assay. Antibody pathogenicity was tested by immunohistochemistry on skin biopsy, intraneural injection, and cell aggregation assay. RESULTS Of 342 patients with CIDP, 19 (5.5%) had antibodies against Nfasc155 (n = 9), Nfasc140/186 and Nfasc155 (n = 1), CNTN1 (n = 3), and Caspr1 (n = 6). Antibodies were absent from healthy and disease controls, including neuropathies of different causes, and were mostly detected in patients with European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite CIDP (n = 18). Predominant antibody isotypes were immunoglobulin G (IgG)4 (n = 13), IgG3 (n = 2), IgG1 (n = 2), or undetectable (n = 2). IgG4 antibody-associated phenotypes included onset before 30 years, severe neuropathy, subacute onset, tremor, sensory ataxia, and poor response to intravenous immunoglobulin (IVIG). Immunosuppressive treatments, including rituximab, cyclophosphamide, and methotrexate, proved effective if started early in IVIG-resistant IgG4-seropositive cases. Five patients with an IgG1, IgG3, or undetectable isotype showed clinical features indistinguishable from seronegative patients, including good response to IVIG. IgG4 autoantibodies were associated with morphological changes at paranodes in patients' skin biopsies. We also provided preliminary evidence from a single patient about the pathogenicity of anti-Caspr1 IgG4, showing their ability to penetrate paranodal regions and disrupt the integrity of the Nfasc155/CNTN1/Caspr1 complex. CONCLUSIONS Our findings confirm previous data on the tight clinico-serological correlation between antibodies to nodal/paranodal proteins and CIDP. Despite the low prevalence, testing for their presence and isotype could ultimately be part of the diagnostic workup in suspected inflammatory demyelinating neuropathy to improve diagnostic accuracy and guide treatment. CLASSIFICATION OF EVIDENCE This study provides Class III evidence that antibodies to nodal/paranodal proteins identify patients with CIDP (sensitivity 6%, specificity 100%)