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Integrated sensing and communication (ISAC) is a promising paradigm to provide both sensing and communication (S&C) services in vehicular networks. However, the power of echo signals reflected from vehicles may be too weak to be used for future precise positioning, due to the practically small radar cross section of vehicles with random reflection/scattering coefficient. To tackle this issue, we propose a novel mutual assistance scheme for intelligent surface-mounted vehicles, where S&C are innovatively designed to assist each other for achieving an efficient win-win integration, i.e., sensing-assisted phase shift design and communication-assisted high-precision sensing. Specifically, we first derive closed-form expressions of the expected echo power and achievable rate under uncertain angle information. Then, the communication rate is maximized while satisfying sensing requirements, which is proved to be a monotonic optimization problem on time allocation. Furthermore, we unveil the feasible condition of the problem and propose a polyblock-based optimal algorithm. Simulation results validate that the performance trade-off bound of S&C is significantly enlarged by exploiting mutual assistance.

Purpose: To report 24 month safety and efficacy of the Tack Endovascular System for treatment of post-percutaneous transluminal angioplasty (PTA) infrapopliteal dissections in patients with critical limb-threatening ischemia (CLTI).Materials and Methods: The Tack-Optimized Balloon Angioplasty (TOBA) II below-the-knee (BTK) study was a prospective, multicenter, single-arm evaluation of the Tack Endovascular system for post-PTA infrapopliteal dissection repair. Patients with Rutherford Clinical Category (RC) 3 to 5 and a post-PTA dissection(s) of the BTK arteries were enrolled. The 30 day primary safety endpoint was a composite of major adverse limb events (MALE) and all-cause perioperative death (POD). The primary effectiveness endpoint was a composite of MALE at 6 months and 30 day POD. Outcomes were assessed as observational endpoints at 24 months.Results: Tack-Optimized Balloon Angioplasty II BTK enrolled 233 patients; all patients had a post-PTA dissection(s) and received ≥1 Tack implant (range, 1–16). Mean age was 74.4±10.0 years and 67.4% were men. Most patients had CLTI (RC 3: 16.3%; RC 4/5: 83.7%). Mean target lesion length was 80±49 mm. Moderate to severe calcium was present in 89 (35.8%) lesions and total occlusions were present in 118 (47.6%) lesions. Kaplan-Meier freedom from MALE at 24 months + POD at 30 days was 92.2% and 24 month freedom from clinically-driven target lesions revascularization was 73.6%. Kaplan-Meier target limb salvage was 95.7% and amputation-free survival was 75.4%. Improvements in functional status and quality of life were observed through 24 months.Conclusion: The TOBA II BTK study demonstrated sustained safety and efficacy through 24 months in patients treated for post-PTA dissection(s) of BTK lesions.Clinical Trial Registration: ClinicalTrials.gov identifier NCT02942966.

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Neonatal epilepsy, cerebellar dysgenesis and facial dysmorphisms may be associated with de novo PACS2missense pathogenic variants (EIEE 66) (OMIM #618067). Here, we report a toddler boy with neonatal‐onset seizures, developmental delay with hypotonia, facial dysmorphisms and prominence of the cisterna magna, mild inferior vermian and cerebellar hypoplasia. A nextgeneration epilepsy gene panel revealed a known pathogenic PACS2missense variant, p.Glu209Lys, that was inherited from his mildly affected mother. We describe the first PACS2pathogenic variant to be inherited, expanding the clinical spectrum, associated with a mild phenotype in the mother and a more severe phenotype in her son, in keeping with previously reported descriptions.

ObjectiveTo describe the clinical and paraclinical findings, treatment options and long-term outcomes in autoimmune encephalitis (AE), with a close look to epilepsy.MethodsIn this retrospective observational cohort study, we enrolled patients with new-onset seizures in the context of AE. We compared clinical and paraclinical findings in patients with and without evidence of antibodies.ResultsOverall, 263 patients (138 females; median age 55 years, range 4–86) were followed up for a median time of 30 months (range 12–120). Antineuronal antibodies were detected in 63.50%.Antibody-positive patients had multiple seizure types (p=0.01) and prevalent involvement of temporal regions (p=0.02). A higher prevalence of episodes of SE was found in the antibody-negative group (p<0.001).Immunotherapy was prescribed in 88.60%, and effective in 61.80%. Independent predictors of favourable outcome of the AE were early immunotherapy (p<0.001) and the detection of antineuronal surface antibodies (p=0.01).Autoimmune-associated epilepsy was the long-term sequela in 43.73%, associated with cognitive and psychiatric disturbances in 81.73%. Independent predictors of developing epilepsy were difficult to treat seizures at onset (p=0.04), a high number of antiseizure medications (p<0.001), persisting interictal epileptiform discharges at follow-up (p<0.001) and poor response to immunotherapy during the acute phase (p<0.001).ConclusionsThe recognition of seizures secondary to AE represents a rare chance for aetiology-driven seizures management. Early recognition and treatment at the pathogenic level may reduce the risk of long-term irreversible sequelae. However, the severity of seizures at onset is the major risk factor for the development of chronic epilepsy.This study provides class IV evidence for management recommendations.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1–3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P< 5.0 × 10−8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P< 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

The feasibility to use gellan nanohydrogels (Ge-NHs) as delivery system for the cutaneous administration of piroxicam (PRX) was investigated using gellan conjugated with cholesterol or riboflavin. The in vitroskin penetration studies through human epidermis were performed using a saturated aqueous drug solution, a 50% w/v Transcutol aqueous solution, and a commercially available PRX plaster as controls. Confocal microscopy, ATR-FTIR spectroscopy, circular dichroism, and a dynamometer assisted extrusion assay were performed to clarify the permeation mechanism of Ge-NHs. The skin permeation studies evidenced that Ge-NHs enhance the PRX retention in the epidermis and, at the same time, slow down the permeation process with respect to the controls. NHs can penetrate the stratum corneum, and then gradually disassemble thus diffusing in the viable epidermis reaching the spinosumlayer. In conclusion, NHs represent a novel strategy to target poorly permeable compounds in the epidermis, thus improving the management of cutaneous pathologies.

Smart devices and Internet-based applications (apps) are largely used in allergic rhinitis and may help to address some unmet needs. However, these new tools need to first of all be tested for privacy rules, acceptability, usability, and cost-effectiveness. Second, they should be evaluated in the frame of the digital transformation of health, their impact on health care delivery, and health outcomes. This review (1) summarizes some existing mobile health apps for allergic rhinitis and reviews those in which testing has been published, (2) discusses apps that include risk factors of allergic rhinitis, (3) examines the impact of mobile health apps in phenotype discovery, (4) provides real-world evidence for care pathways, and finally (5) discusses mobile health tools enabling the digital transformation of health and care, empowering citizens, and building a healthier society.

Plasmonic supercrystals and periodically structured arrays comprise a class of materials with unique optical properties that result from the interplay of plasmon resonances, as well as near- and far-field coupling. Controlled synthesis of such hierarchical structures remains a fundamental challenge, as it demands strict control over the assembly morphology, array size, lateral spacing, and macroscale homogeneity. Current fabrication approaches involve complicated multistep procedures lacking scalability and reproducibility, which has hindered the practical application of plasmonic supercrystal arrays. Herein, these challenges are addressed by adding an organic solvent to achieve kinetic control over the template-assisted colloidal assembly of nanoparticles from aqueous dispersion. This method yields highly regular periodic arrays, with feature sizes ranging from less than 200 nm up to tens of microns. A combined experimental/computational approach reveals that the underlying mechanism is a combination of the removal of interfacial surfactant micelles from the particle interface and altered capillary flows. Assessing the efficacy of such square arrays for surface-enhanced Raman scattering spectroscopy, we find that a decrease of the lattice periodicity from 750 nm down to 400 nm boosts the signal by more than an order of magnitude, thereby enabling sensitive detection of analytes, such as the bacterial quorum sensing molecule pyocyanin, even in complex biological media.

ABSTRACTIntroduction: Epilepsy is a chronic and debilitating neurological disease, with a peak of incidence in the first years of life. Today, the vast armamentarium of antiepileptic drugs (AEDs) available make even more challenging to select the most appropriate AED and establish the most effective dosing regimen. In fact, AEDs pharmacokinetics is under the influence of important age-related factors which cannot be ignored.Areas covered: Physiological changes occurring during development age (different body composition, immature metabolic patterns, reduced renal activity) can significantly modify the pharmacokinetic profile of AEDs (adsorption, volume of distribution, half-life, clearance), leading to an altered treatment response. We reviewed the main pharmacokinetic characteristics of AEDs used in children, focusing on age-related factors which are of relevance when treating this patient population.Expert opinion: To deal with this pharmacokinetic variability, physicians have at their disposal two tools: 1) therapeutic drug concentration monitoring, which may help to set the optimal therapeutic regimen for each patient and to monitor eventual fluctuation, and 2) the use of extended-release drug formulations, when available. In the next future, the development of ‘ad-hoc’ electronic dashboard systems will represent relevant decision-support tools making the AED therapy even more individualized and precise, especially in children.

We present an overview of important results obtained during the first 20 years of the Multicenter Allergy Study (MAS), one of the first and longest-running population-based birth cohorts focusing on asthma and allergy.

Metal colloids are of great interest in the field of nanophotonics, mainly due to their morphology-dependent optical properties, but also because they are high-quality building blocks for complex plasmonic architectures. Close-packed colloidal supercrystals not only serve for investigating the rich plasmonic resonances arising in strongly coupled arrangements but also enable tailoring the optical response, on both the nano- and the macroscale. Bridging these vastly different length scales at reasonable fabrication costs has remained fundamentally challenging, but is essential for applications in sensing, photovoltaics or optoelectronics, among other fields. We present here a scalable approach to engineer plasmonic supercrystal arrays, based on the template-assisted assembly of gold nanospheres with topographically patterned polydimethylsiloxane molds. Regular square arrays of hexagonally packed supercrystals were achieved, reaching periodicities down to 400 nm and feature sizes around 200 nm, over areas up to 0.5 cm2. These two-dimensional supercrystals exhibit well-defined collective plasmon modes that can be tuned from the visible through the near-infrared by simple variation of the lattice parameter. We present electromagnetic modeling of the physical origin of the underlying hybrid modes and demonstrate the application of superlattice arrays as surface-enhanced Raman scattering (SERS) spectroscopy substrates which can be tailored for a specific probe laser. We therefore investigated the influence of the lattice parameter, local degree of order, and cluster architecture to identify the optimal configuration for highly efficient SERS of a nonresonant Raman probe with 785 nm excitation.

Data from hyperspectral infrared sounders are routinely ingested worldwide by the National Weather Centers. The cloud‐free fraction of this data is used for initializing forecasts which include temperature, water vapor, water cloud, and ice cloud profiles on a global grid. Although the data from these sounders are sensitive to the vertical distribution of ice and liquid water in clouds, this information is not fully utilized. In the future, this information could be used for validating clouds in National Weather Center models and for initializing forecasts. We evaluate how well the calculated radiances from hyperspectral Radiative Transfer Models (RTMs) compare to cloudy radiances observed by AIRS and to one another. Vertical profiles of the clouds, temperature, and water vapor from the European Center for Medium‐Range Weather Forecasting were used as input for the RTMs. For nonfrozen ocean day and night data, the histograms derived from the calculations by several RTMs at 900 cm−1have a better than 0.95 correlation with the histogram derived from the AIRS observations, with a bias relative to AIRS of typically less than 2 K. Differences in the cloud physics and cloud overlap assumptions result in little bias between the RTMs, but the standard deviation of the differences ranges from 6 to 12 K. Results at 2,616 cm−1at night are reasonably consistent with results at 900 cm−1. Except for RTMs which use full scattering calculations, the bias and histogram correlations at 2,616 cm−1are inferior to those at 900 cm−1for daytime calculations. Getting the right clouds of the right type, at the right time and location in Global Circulation Models, is key to getting the local energy balance right. This is key to an accurate forecast. If the clouds are of the wrong type or at the wrong location or time, the accuracy of the forecast is degraded. We evaluate the accuracy of the best currently available cloud description (produced by the European Center for Medium‐Range Weather Forecasting) by comparing the radiances calculated using Radiative Transfer Models (RTMs) from six major development teams to cloudy radiances observed by the Atmospheric Infrared Sounder at the same location and time. The better RTMs fit statistically reasonably well in the 11‐μm atmospheric window area, with little latitude (zonal) and day/night cloud‐type related bias. None of the RTMs fit well in the 4‐μm atmospheric window area during daytime, unless the calculations use full scattering. With the current state of art, all major RTMs would be suitable to start the validation of cloud effects in the National Weather Center models using just one 11‐μm atmospheric window channel. In the 900‐cm−1atmospheric window channel several Radiative Transfer Models have a better than 0.95 correlation between the histogram derived from the observations and those derived from the calculationsDifferences in the bias between observations and calculations for the 2,616‐cm−1atmospheric window channel are not inconsistent with results at 900 cm−1if the daytime calculations use full scatteringDifferences in the cloud physics and cloud overlap assumptions between Radiative Transfer Models result in a standard deviation of the pairwise difference of between 6 and 12 K; differences due to the cloud overlap assumption alone result in a 3‐K standard deviation

The direct assimilation in 4D‐Var of principal component (PC) scores derived from Infrared Atmospheric Sounding Interferometer (IASI) spectra has recently been demonstrated. To maximize the exploitation of the IASI instrument, a future step is to consider the extension of the PC approach to the extraction of information from the 4.3‐μm CO2‐absorbing region. Shortwave IASI channels are currently underused compared to similar longwave channels because of day‐night variations in data usability due to departures from local thermodynamic equilibrium (LTE). In this paper, we document the introduction of non‐LTE (NLTE) effects in the PC‐based version of the radiative transfer for TIROS operational vertical sounder (RTTOV) fast radiative transfer model (PC‐RTTOV). The inclusion of NLTE effects in PC‐RTTOV has required the development of a parameterized scheme that allows the fast computation of a NLTE correction to LTE radiances. The fast NLTE model is general enough to be applied to any sensor and can be utilized to add a fast and accurate NLTE correction to polychromatic LTE spectra computed by any general radiative transfer model, including RTTOV, which now incorporates the fast NLTE model developed in this study. The accuracy of the NLTE correction is such that daytime and nighttime radiances can be simulated to almost the same degree of accuracy. The comparison with IASI observations shows that the fast NLTE model presented here performs significantly better than the fast NLTE model incorporated in the previous version of RTTOV and also that improvements have to be made to the simulation of NLTE effects at winter high latitudes. Development of a fast NLTE model for satellite nadir‐sounding applicationsExtension of a principal component‐based fast radiative transfer model to the simulation of NLTE effectsThe fast NLTE model can accurately simulate daytime shortwave satellite radiances but performs somewhat lesser at winter high latitudes

As contamination and environmental degradation increase, there is a huge demand for new eco-friendly materials. Despite its use for thousands of years, cellulose and its derivatives have gained renewed interest as favourable alternatives to conventional plastics, due to their abundance and lower environmental impact. Here, we report the fabrication of photonic and plasmonic structures by moulding hydroxypropyl cellulose into submicrometric periodic lattices, using soft lithography. This is an alternative way to achieve structural colour in this material, which is usually obtained by exploiting its chiral nematic phase. Cellulose-based photonic crystals are biocompatible and can be dissolved in water or not depending on the derivative employed. Patterned cellulose membranes exhibit tunable colours and may be used to boost the photoluminescence of a host organic dye. Furthermore, we show how metal coating these cellulose photonic architectures leads to plasmonic crystals with excellent optical properties acting as disposable surface-enhanced Raman spectroscopy substrates. Biodegradable cellulose-based photonic and plasmonic architectures are fabricated via soft nanoimprinting lithography, and are used for structural colour generation, photoluminescence enhancement and as disposable surface-enhanced Raman scattering substrates.

This paper reports on the clinical aspects, electroencephalographic (EEG) features, and neuroimaging findings in children with full trisomy 18 and associated epilepsy, and compares the evolution and outcome of their neurological phenotype. We retrospectively studied 18 patients (10 males and 8 females; aged 14 months to 9 years) with full trisomy 18 and epilepsy. All patients underwent comprehensive assessment including neuroimaging studies of the brain. We divided patients into two groups according to neuroimaging findings: (Group 1) 10 patients harboring structural brain malformations, and (Group 2) 8 patients with normal brain images. Group 1 had a significantly earlier age at seizure onset (2 months) compared to Group 2 (21 months). The seizure semiology was more severe in Group 1, who presented multiple seizure types, need for polytherapy (80% of patients), multifocal EEG abnormalities and poorer outcome (drug resistant epilepsy in 90% of patients) than Group 2 who presented a single seizure type, generalized or focal, and non‐specific EEG pattern; these patients were successfully treated with monotherapy with good outcome. Imaging revealed a wide and complex spectrum of structural brain abnormalities including anomalies of the commissures, cerebellar malformations, cortical abnormalities, and various degrees of cortical atrophy. Epilepsy in full trisomy 18 may develop during the first months of life and can be associated with structural brain malformations. Patients with brain malformations can show multiple seizure types and can frequently be resistant to therapy with antiepileptic drugs. © 2016 Wiley Periodicals, Inc.

This overview follows the evolution of the studies carried out, mainly during last years, on polysaccharide hydrogels, with particular attention on the researches carried out in our department, often in collaboration with other groups in our country and abroad. The review points out the importance of this type of networks for the optimization of drug delivery and targeting in the various forms of macro, micro and nano systems. It is also shown that these materials are suitable for the culture of different types of cells. Release mechanisms are reported and explained by different physico-chemical approaches and by means of molecular dynamics simulations and the anomalous swelling behavior of a scleroglucan/borax hydrogel is thoroughly discussed. The role of polymer combinations forming interpenetrated structures is explained in terms of specific properties which significantly differ from those of the constituent polymers, thus allowing appropriate tailoring of the delivery rates. Finally the wide possibilities of applications of nanogel structures which allow combination therapies for cancer treatment and can be suitable for intracellular targeting are reported. The studies on polysaccharide hydrogels are still in progress and it is underlined that future researches, more focused on the passage from lab to market, should be further stimulated.

Symptoms are recorded by obtaining a clinical history. Allergen sensitization is demonstrated by skin prick test or allergen-specific IgE serology. IgE sensitizations to allergen sources can be identified knowing the relationship between major aeroallergens and homologous allergen families. Some develop allergic sensitization to pan-allergens. Allergen extracts do not allow definitive separation of the sources. IgE antibody analysis of the major allergenic molecules facilitates differentiation of sensitizing allergen sources. IgE sensitizations to inhalant allergens are only relevant in the case of corresponding symptoms. In questionable cases, conjunctival or nasal provocation tests help induce confirmatory symptoms and identify relevant allergens for immunotherapy.

The aim of this overview is to review the evolution of the studies carried out, during more than 25 years, on nanohydrogels obtained by self-assembling of pullulan (PUL) using several hydrophobization strategies. After the first publications, mainly devoted to the preparation and characterization of PUL nanogels, a remarkable number of studies demonstrated how wide can be the field of applications within the main topic of biopharmaceutics. Numerous hydrophilic and lipophilic drugs were entrapped in the nanogel networks, consequently PUL nanogels have been proposed as delivery systems for single drugs and for combination therapies which allowed improvements of pharmacological activities and patient compliance. Furthermore, the large amount of water content allowed loading also proteins which could maintain their native structure and properties. Stimuli-sensitive and stealth PUL nanogel formulations allowed improving the performances of antitumor drugs. These nanohydrogels have also been studied for imaging techniques and for vaccines to be administered by injection and by mucosal application. The studies on PUL nanogels are still in progress and the perspectives for future researches are also addressed.

Aim. Paroxysmal eyelid movements (PEM) are non‐epileptic episodes characterized by eyelid closure, upturning of the eyes, and rapid eyelid flutter. The aim of this study was to report clinical and EEG data of patients with PEM and its relationship with visual sensitivity. Methods. We studied 26 patients with epilepsy (12 males and 14 females; mean age: 14.0±6.9 years) who presented PEM. The epilepsy was idiopathic generalized (eight cases), idiopathic focal (six cases), symptomatic focal (five cases), and reflex epilepsy (seven cases). PEM and blinking were analysed by video‐EEG recordings at rest and during intermittent photic stimulation, pattern stimulation, and TV watching. Blink rate was evaluated during three different conditions: at rest, during a TV‐viewing period, and at the occurrence of PEM. Analysis of variance (ANOVA) was used for statistical comparisons. Results. Repeated episodes of PEM were recorded in all patients. The frequency of PEM ranged from 8 to 12.5 Hz (average: 9.6±1.5). PEM were accompanied by a significant increase in blinking compared to the rest condition and TV watching (blink rate: 56.5±21.1 vs25.0±16.2 vs11.3±11.8, respectively; p<0.0001). Photoparoxysmal EEG responses (measured as sensitivity to photic stimulation) were found in 25 cases, associated with pattern sensitivity in 22; only one patient was sensitive to pattern but not photic stimulation. Visually‐induced seizures were recorded in 20 cases, triggered by both stimuli (photic and pattern stimulation) in 11 patients; seizures were triggered by pattern stimulation (but not photic stimulation) in five, photic stimulation (but not pattern stimulation) in three, and TV watching (but not photic or pattern stimulation) in one. Epileptic eyelid myoclonia was noted in 17 patients. Conclusion. The coexistence of PEM, photoparoxysmal EEG responses, increased blinking, and epileptic eyelid myoclonia suggests an underlying dysfunction involving cortical‐subcortical neural networks, according to the recent concept of system epilepsies. [Published with video sequences] Content available: Video

The importance of growth factor delivery in cartilage tissue engineering is nowadays widely recognized. However, when growth factors are administered by a bolus injection, they undergo rapid clearance before they could stimulate the cells of interest at promoting cartilage repair. Their short half-lives make growth factors ineffective, unless administered at supraphysiological doses, with potentially harmful consequences on patient safety. Recently, new tissue engineering strategies relying on the combination of biodegradable scaffolds and specific biological cues, such as growth or adhesive factors or genetic material, have demonstrated that controlled release is the key factor for achieving effective cartilage repair at lower drug doses. Among all biomaterials, hydrogels have emerged as promising cartilage tissue engineering scaffolds for simultaneous cell growth and drug delivery. In fact, hydrogels can be easily loaded with cells and drugs, that are subsequently released in a controlled fashion. The success of hydrogels in controlled drug delivery for tissue engineering originates from their biocompatibility and capacity to integrate well with the host tissue. This review overviews the hydrogels technologies now available for the regeneration of cartilage that base their efficacy on the controlled release of bioactive substances able to modulate cellular behavior and to eventually lead to successful tissue repair.