The natural history of hypertrophic cardiomyopathy

In the early years of the disease recognition, hypertrophic cardiomyopathy (HCM) was viewed as an ominous disease with unfavourable prognosis and with an annual mortality between 4% and 6%. At that time, 73% of the patients reported in the literature came from only two referral centres. With the introduction of echocardiography, our understanding of HCM has improved and non-selected patient populations were assembled in several centres. A more benign prognostic profile was documented with an annual mortality rate of 1.5% or less. In the 2000s, important therapeutic interventions further improved the prognosis of patients with HCM: implantable-cardioverter defibrillator for prevention of sudden death, heart transplantation for treatment of severe refractory heart failure, and an extensive treatment with myectomy for relief of left ventricular outflow tract gradient. The natural history of HCM has changed substantially with contemporary treatment achieving an annual mortality rate less than 1% with extended longevity and a greatly improved quality of life

Higher harmonic inverse free-electron laser interaction

We expand the theory of the inverse free electron laser (IFEL) interaction to include the possibility of energy exchange that takes place when relativistic particles traversing an undulator interact with an electromagnetic wave of a frequency that is a harmonic of the fundamental wiggler resonant frequency. We derive the coupling coefficients as a function of the IFEL parameters for all harmonics, both odd and even. The theory is supported by simulation results obtained with a three-dimensional Lorentz equation solver code. Comparisons are made between the results of theory and simulations, and the recent UCLA IFEL experimental results where higher harmonic IFEL interaction was observed

Progress on the hybrid gun project at UCLA

UCLA/INFN-LNF/Univ. Rome has been developing the hybrid gun which has an RF gun and a short linac for velocity bunching in one structure. After the cavity was manufactured at INFN-LNF in 2012, tests of the gun was carried out at UCLA. The field in the standing wave part was 20 % smaller than the simulation but the phase advance was fine. The cavity was commissioned successfully up to 13 MW. The beam test was performed at 11.5 MW and demonstrated the bunch compression

Curcumin loaded polymeric vs. Lipid nanoparticles: Antioxidant effect on normal and hypoxic olfactory ensheathing cells

Background: Curcumin (Cur) shows anti-inflammatory and antioxidant effects on central nervous system diseases. The aim of this study was to develop Cur-loaded polymeric and lipid nanoparticles for intranasal delivery to enhance its stability and increase antioxidant effect on olfactory ensheathing cells (OECs). Methods: The nanosuspensions were subjected to physico-chemical and technological evaluation through photon correlation spectroscopy (PCS), differential scanning calorimetry (DSC) and UV-spectrophotometry. The cytotoxicity studies of nanosuspensions were carried out on OECs. A viability test was performed after 24 h of exposure of OECs to unloaded and curcumin-loaded nanosuspensions. The potential protective effect of Cur was assessed on hypoxic OECs cells. Uptake studies were performed on the same cell cultures. Thermal analysis was performed to evaluate potential interaction of Cur with a 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) biomembrane model. Results: PCS analysis indicated that lipid and polymeric nanosuspensions showed a mean size of 127.10 and 338.20 nm, respectively, high homogeneity and negative zeta potential. Incorporation of Cur into both nanocarriers increased drug stability up to 135 days in cryoprotected freeze-dried nanosuspensions. Cell viability was improved when hypoxic OECs were treated with Cur-loaded polymeric and lipid nanosuspensions compared with the control. Conclusions: Both nanocarriers could improve the stability of Cur as demonstrated by technological studies. Biological studies revealed that both nanocarriers could be used to deliver Cur by intranasal administration for brain targeting

Power consumption evaluation of circuit-switched versus packet-switched optical backbone networks

While telecommunication networks have historically been dominated by a circuit-switched paradigm, the last decades have seen a clear trend towards packet-switched networks. In this paper we evaluate how both paradigms perform in optical backbone networks from a power consumption point of view, and whether the general agreement of circuit switching being more power-efficient holds. We consider artificially generated topologies of various sizes, mesh degrees and not yet previously explored in this context transport linerates. We cross-validate our findings with a number of realistic topologies. Our results show that, as a generalization, packet switching can become preferable when the traffic demands are lower than half the transport linerate. We find that an increase in the network node count does not consistently increase the energy savings of circuit switching over packet switching, but is heavily influenced by the mesh degree and (to a minor extent) by the average link length

ASAP hardware failure-cause identification in microwave networks using Venn-Abers predictors

We investigate classifying hardware failures in microwave networks via Machine Learning (ML). Although ML-based approaches excel in this task, they usually provide only hard failure predictions without guarantees on their reliability, i.e., on the probability of correct classification. Generally, accumulating data for longer time horizons increases the model’s predictive accuracy. Therefore, in real-world applications, a trade-off arises between two contrasting objectives: i) ensuring high reliability for each classified observation, and ii) collecting the minimal amount of data to provide a reliable prediction. To address this problem, we formulate hardware failure-cause identification as an As-Soon-As-Possible (ASAP) selective classification problem where data streams are sequentially provided to an ML classifier, which outputs a prediction as soon as the probability of correct classification exceeds a user-specified threshold. To this end, we leverage Inductive and Cross Venn-Abers Predictors to transform heuristic probability estimates from any ML model into rigorous predictive probabilities. Numerical results on a real-world dataset show that our ASAP framework reduces the time-to-predict by 8x compared to the state-of-the-art, while ensuring a selective classification accuracy greater than 95%. The dataset utilized in this study is publicly available, aiming to facilitate future investigations in failure management for microwave networks

Development, optimization and characterization of Eudraguard®-based microparticles for colon delivery

Development of pH-dependent systems for colon delivery of natural active ingredients is an attractive area of research in the field of nutraceutical products. This study was focused on Eudraguard® resins, that are methacrylate copolymers approved as “food grade” by European Commission and useful for the production of food supplements. In particular, Eudraguard® Biotic (EUG-B), characterized by a pH-dependent solubility and Eudraguard® Control (EUG-C), whose chemical properties support a prolonged release of the encapsulated compounds, were tested. To obtain EUG microparticles, different preparation techniques were tested, in order to optimize the preparation method and observe the effect upon drug encapsulation and specific colonic release. Unloaded microparticles were initially produced to evaluate the influence of polymer characteristics on the formulation process; subsequently microparticles loaded with quercetin (QUE) as a low solubility model drug were prepared. The characterization of microparticles in the solid-state (FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry) indicated that QUE was uniformly dispersed in a non-crystalline state in the polymeric network, without strong signs of chemical interactions. Finally, to assess the ability of EUG-C and EUG-B to control the drug release in the gastric environment, and to allow an increased release at a colonic level, suitable in vitro release tests were carried out by simulating the pH variations along the gastro-intestinal tract. Among the evaluated preparation methods, those in which an aqueous phase was not present, and in particular the emulsion-solvent evaporation method produced the best microparticle systems. The in vitro tests showed a limited drug release at a gastric level and a good specific colon release

Clinical translation of genetic testing in TTR Amyloidosis. genotype-phenotype correlations, management of asymptomatic carriers and familial screening

Transthyretin (TTR)-related amyloidosis (ATTR) is a heterogeneous disease with different organ involvement depending on the type of TTR infiltration [mutated (vTTR) or wild-type (wtTTR)]. Genetic testing in ATTR is required to define diagnosis and identify asymptomatic at-risk family members. Since new therapies are maximally effective in the early stages of the disease, there is a growing agreement about the need for close monitoring of genotype-positive, phenotype-negative individuals to assure a prompt treatment when minor disease signs are detected. This review summarizes the complexity of genotype-phenotype correlation and revises the current indications with respect to familiar screening and management of asymptomatic carriers