Capsule Networks with Routing Annealing

International audienc

New conditions for finite-time stability of impulsive dynamical systems via piecewise quadratic functions

In this paper, the use of time-varying piecewise quadratic functions is investigated to characterize the finite-time stability of state-dependent impulsive dynamical linear systems. Finite-time stability defines the behavior of a dynamic system over a bounded time interval. More precisely, a system is said to be finite-time stable if, given a set of initial conditions, its state vector does not exit a predefined domain for a certain finite interval of time. This paper presents new sufficient conditions for finite-time stability based on time-varying piecewise quadratic functions. These conditions can be reformulated as a set of Linear Matrix Inequalities that can be efficiently solved through convex optimization solvers. Dif ferent numerical analysis are included in order to prove that the presented conditions are able to improve the results presented so far in the literature

Improving in vitro ciguatoxin and brevetoxin detection: selecting neuroblastoma (Neuro-2a) cells with lower sensitivity to ouabain and veratridine (OV-LS).

Abstract Marine biotoxins accumulating in seafood products pose a risk to human health. These toxins are often potent in minute amounts and contained within complex matrices; requiring sensitive, reliable, and robust methods for their detection. The mouse neuroblastoma (Neuro-2a) cytotoxicity assay (N2a-assay) is a sensitive, high-throughput, in vitro method effective for detecting sodium channel-specific marine biotoxins. The N2a-assay can be conducted to distinguish between specific effects on voltage-gated sodium (NaV) channels, caused by toxins that activate (e.g., ciguatoxins (CTXs), brevetoxins (PbTxs)) or block (e.g., tetrodotoxins, saxitoxins) the target NaV. The sensitivity and specificity of the assay to compounds activating the NaV are achieved through the addition of the pharmaceuticals ouabain (O) and veratridine (V). However, these compounds can be toxic to Neuro-2a cells and their application at insufficient or excessive concentrations can reduce the effectiveness of this assay for marine toxin detection. Therefore, during growth incubation, Neuro-2a cells were exposed to O and V, and surviving cells exhibiting a lower sensitivity to O and V (OV-LS) were propagated. OV-LS Neuro-2a cells were selected for 60–80% survival when exposed to 0.22/0.022 mM O/V during the cytotoxicity assay. At these conditions, OV-LS N2a cells demonstrated a 3.5-fold higher survival rate 71% ± 7.9 SD (n = 232), and lower sensitivity to O/V, compared to the original Neuro-2a cells 20% ± 9.0 SD (n = 16). Additionally, OV-LS N2a cells were 1.3–2.6-fold more sensitive for detecting CTX3C 1.35 pg/ml, CTX1B 2.06 pg/ml, and PbTx-3 3.04 ng/ml compared to Neuro-2a cells using 0.1/0.01 mM O/V. Detection of CTX3C in a complex fish matrix using OV-LS cells was 0.0048 pg CTX3C/mg fish tissue equivalent. This work shows the potential for a significant improvement in sensitivity for CTX3C, CTX1B, and PbTx-3 using the OV-LS N2a-assay

Ciguatera mini review: 21st century environmental challenges and the interdisciplinary research efforts rising to meet them

Globally, the livelihoods of over a billion people are affected by changes to marine eco-systems, both structurally and systematically. Resources and ecosystem services, provided by the marine environment, contribute nutrition, income, and health benefits for communities. One threat to these securities is ciguatera poisoning; worldwide, the most commonly reported non‐bacterial seafood‐related illness. Ciguatera is caused by the consumption of (primarily) finfish contaminated with ciguatoxins, potent neurotoxins produced by benthic single‐cell microalgae. When consumed, ciguatoxins are biotransformed and can bioaccumulate throughout the food‐web via complex path-ways. Ciguatera‐derived food insecurity is particularly extreme for small island‐nations, where fear of intoxication can lead to fishing restrictions by region, species, or size. Exacerbating these com-plexities are anthropogenic or natural changes occurring in global marine habitats, e.g., climate change, greenhouse‐gas induced physical oceanic changes, overfishing, invasive species, and even the international seafood trade. Here we provide an overview of the challenges and opportunities of the 21st century regarding the many facets of ciguatera, including the complex nature of this illness, the biological/environmental factors affecting the causative organisms, their toxins, vectors, detection methods, human‐health oriented responses, and ultimately an outlook towards the future. Ciguatera research efforts face many social and environmental challenges this century. However, several future‐oriented goals are within reach, including digital solutions for seafood supply chains, identifying novel compounds and methods with the potential for advanced diagnostics, treatments, and prediction capabilities. The advances described herein provide confidence that the tools are now available to answer many of the remaining questions surrounding ciguatera and therefore protection measures can become more accurate and routine

Treating Thalassemia Patients with Luspatercept: An Expert Opinion Based on Current Evidence

Luspatercept has recently been approved for the treatment of beta-thalassemia and its use in clinical practice has been increasing. As it is the first erythroid maturation drug available for this diagnosis, the expertise about its use is still limited. To address this point, and to promote awareness and guide the clinical use of luspatercept in beta-thalassemia, this paper was developed as a consensus by experts from the Italian Society of Thalassemia and Hemoglobinopathies (SITE). After a brief presentation of the core features of luspatercept, a comprehensive set of questions is addressed, covering relevant aspects for the practical management of this new therapeutic option

Does autonomic neuropathy play a role in erythropoietin regulation in non-proteinuric Type 2 diabetic patients?

Aims Erythropoietin (EPO)-deficient anaemia has been described in Type 1 diabetic patients with both severe autonomic neuropathy (AN) and proteinuria. This study was aimed at distinguishing between the effects of AN and nephropathy on haemoglobin and EPO levels in Type 2 diabetic patients at an early stage of diabetic nephropathy. Methods In 64 Type 2 diabetic patients (age 52 +/- 10 years, duration 10 +/- 9 years) without overt nephropathy and other causes of anaemia or EPO deficit, we assessed cardiovascular tests of AN, 24-h blood pressure (BP) monitoring, urinary albumin excretion rate (UAE), a full blood count, and serum EPO. Results Although the Type 2 diabetic patients with AN did not show differences in haemoglobin and EPO when compared with patients without AN, the presence of haemoglobin < 13 g/dl was associated with the presence of AN (chi(2)= 3.9, P < 0.05) and of postural hypotension (chi(2)= 7.8, P < 0.05). In a multiple regression analysis including as independent variables gender, body mass index, duration of diabetes, smoking, creatinine, 24-h UAE, 24-h diastolic BP, ferritin, erythrocyte sedimentation rate, and autonomic score, we found that the only variables independently related to haematocrit were autonomic score, ferritin and erythrocyte sedimentation rate. Finally, the physiological inverse relationship between EPO and haemoglobin present in a control group of 42 non-diabetic non-anaemic subjects was completely lost in Type 2 diabetic patients. The slopes of the regression lines between EPO and haemoglobin of the control subjects and the Type 2 diabetic patients were significantly different (t = 14.4, P < 0.0001). Conclusion This study documents an early abnormality of EPO regulation in Type 2 diabetes before clinical nephropathy and points to a contributory role of AN in EPO dysregulation

Two-year long safety and efficacy of deferasirox film-coated tablets in patients with thalassemia or lower/intermediate risk MDS: phase 3 results from a subset of patients previously treated with deferasirox in the ECLIPSE study

Background: Despite the proven benefits of iron chelation therapy (ICT) in the management of chronic iron overload and related complications, compliance to long-term ICT is challenging. Results from the ECLIPSE study, an open-label, randomized, multicenter, 2-arm, phase 2 study evaluated the safety of deferasirox dispersible tablet and film-coated tablet (FCT) formulations in patients with transfusion-dependent thalassemia (TDT) or very low, low, or intermediate risk myelodysplastic syndrome (MDS) treated over 24 weeks. Methods: The aim of the current study (a 2-year, open-label, multicenter, single-arm, phase 3 study) is to evaluate the long-term safety and efficacy of deferasirox FCT in a subset of patients with TDT or lower/intermediate-risk MDS treated for 2 years after the completion of 24 weeks of treatment with deferasirox in the ECLIPSE phase 2 study. Results: Of 53 patients enrolled, 34 (64.2%) completed treatment and study. Adverse events (AEs) reported in most patients (similar to 70%) were of mild to moderate severity. Headache and diarrhea were the most frequently (&gt; 25%) reported AEs. None of the serious AEs (including 1 death) were considered treatment related. No new safety signal was identified, and long-term safety of deferasirox FCT was consistent with the known safety profile of deferasirox. No major concerns associated with gastrointestinal tolerability, renal safety, or hematological abnormalities (thrombocytopenia/neutropenia) were reported during the 2 years. Patients receiving deferasirox FCT had a treatment compliance (by pill count) of similar to 90% and persistence (continuous use for &gt;= 30 days) of &gt; 95%. Reduction in serum ferritin level was almost consistent starting from week 2 across all post-baseline time points (relative reduction: month 6, 19%; month 12, 29%). Conclusions: The results from this 2-year interventional study suggest that the recommended dosing of deferasirox FCT, with better tolerability, palatability, and compliance, offers a favorable option of ICT for long-term management of iron overload and associated complications in TDT

Ovatoxin-a, a palytoxin analogue isolated from Ostreopsis cf. ovata Fukuyo: cytotoxic activity and ELISA detection

This study provides the first evaluation of the cytotoxic effects of the recently identified palytoxin (PLTX) analog, ovatoxin-a (OVTX-a), the major toxin produced by Ostreopsis cf. ovata in the Mediterranean Sea. Its increasing detection during Ostreopsis blooms and in seafood highlights the need to characterize its toxic effects and to set up appropriate detection methods. OVTX-a is about 100 fold less potent than PLTX in reducing HaCaT cells viability (EC50 = 1.1 7 10 129 M vs 1.8 7 10 1211 M, MTT test) in agreement with a reduced binding affinity (Kd = 1.2 7 10 129 vs 2.7 7 10 1211 M, saturation experiments on intact cells). Similarly, OVTX-a hemolytic effect is lower than that of the reference PLTX compound. Ost-D shows the lowest cytotoxicity toward HaCaT keratinocytes, suggesting the lack of a hydroxyl group at C44 as a critical feature for PLTXs cytotoxic effects. A sandwich ELISA developed for PLTX detects also OVTX-a in a sensitive (LOD = 4.2 and LOQ = 5.6 ng/mL) and accurate manner (Bias = 0.3%), also in O. cf. ovata extracts and contaminated mussels. Although in vitro OVTXa appears less toxic than PLTX, its cytotoxicity at nanomolar concentrations after short exposure time rises some concern for human health. The sandwich ELISA can be a viable screening method for OVTXs detection in monitoring program