Novel Nanogels Loaded with Mn(II) Chelates as Effective and Biologically Stable MRI Probes.

Here it is described nanogels (NG) based on a chitosan matrix, which are covalently stabilized by a bisamide derivative of Mn-t-CDTA (t-CDTA = trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid). the Mn(II) complex acts both as a contrast medium and as a cross-linking agent. These nanogels are proposed as an alternative to the less stable paramagnetic nanogels obtained by electrostatic interactions between the polymeric matrix and paramagnetic Gd(III) chelates. The present novel nanogels show: i) relaxivity values seven times higher than that of typical monohydrated Mn(II) chelates at the clinical fields, thanks to the combination of a restricted mobility of the complex with a fast exchange of the metal-bound water molecule; ii) high stability of the formulation over time at pH 5 and under physiological conditions, thus excluding metal leaking or particles aggregation; iii) good extravasation and accumulation, with a maximum contrast achieved at 24 h post-injection in mice bearing subcutaneous breast cancer tumor; iv) high T1 contrast (1 T) in the tumor 24 h post-injection. These improved properties pave the way for the use of these paramagnetic nanogels as promising magnetic resonance imaging (MRI) probes for in vitro and in vivo preclinical applications.

Derivatives of GdAAZTA Conjugated to Amino Acids: A Multinuclear and Multifrequency NMR Study.

The GdAAZTA (AAZTA = 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) complex represents a platform of great interest for the design of innovative MRI probes due to its remarkable magnetic properties, thermodynamic stability, kinetic inertness, and high chemical versatility. Here, we detail the synthesis and characterization of new derivatives functionalized with four amino acids with different molecular weights and charges: l-serine, l-cysteine, l-lysine, and l-glutamic acid. The main reason for conjugating these moieties to the ligand AAZTA is the in-depth study of the chemical properties in aqueous solution of model compounds that mimic complex structures based on polypeptide fragments used in molecular imaging applications. The analysis of the 1H NMR spectra of the corresponding Eu(III)-complexes indicates the presence of a single isomeric species in solution, and measurements of the luminescence lifetimes show that functionalization with amino acid residues maintains the hydration state of the parent complex unaltered (q = 2). The relaxometric properties of the Gd(III) chelates were analyzed by multinuclear and multifrequency NMR techniques to evaluate the molecular parameters that determine their performance as MRI probes. The relaxivity values of all of the novel chelates are higher than that of GdAAZTA over the entire range of applied magnetic fields because of the slower rotational dynamics. Data obtained in reconstituted human serum indicate the occurrence of weak interactions with the proteins, which result in larger relaxivity values at the typical imaging fields. Finally, all of the new complexes are characterized by excellent chemical stability in biological matrices over time, by the absence of transmetallation processes, or the formation of ternary complexes with oxyanions of biological relevance. In particular, the kinetic stability of the new complexes, measured by monitoring the release of Gd3+ in the presence of a large excess of Zn2+, is ca. two orders of magnitude higher than that of the clinical MRI contrast agent GdDTPA.

High Relaxivity with No Coordinated Waters: A Seemingly Paradoxical Behavior of [Gd(DOTP)]5- Embedded in Nanogels.

Nanogels (NGs) obtained by electrostatic interactions between chitosan and hyaluronic acid and comprising paramagnetic Gd chelates are gaining increasing attention for their potential application in magnetic resonance bioimaging. Herein, the macrocyclic complexes [Gd(DOTP)]5-, lacking metal-bound water molecules (q = 0), were confined or used as a cross-linker in this type of NG. Unlike the typical behavior of Gd complexes with q = 0, a remarkable relaxivity value of 78.0 mM-1 s-1 was measured at 20 MHz and 298 K, nearly 20 times greater than that found for the free complex. A careful analysis of the relaxation data emphasizes the fundamental role of second sphere water molecules with strong and long-lived hydrogen bonding interactions with the complex. Finally, PEGylated derivatives of nanoparticles were used for the first in vivo magnetic resonance imaging study of this type of NG, revealing a fast renal excretion of paramagnetic complexes after their release from the NGs.

HeartMate 3 implantation for dextro-transposition of the great arteries after Mustard procedure: A technique of papillary muscle repositioning.

Systemic right ventricular failure after physiologic repair for dextro-transposition of the great arteries can be managed with durable mechanical circulatory support; however, the right ventricular morphology, such as intervening papillary muscles, presents challenges to inflow cannula positioning. Papillary muscle repositioning is an innovative technique to circumvent obstructive anatomy.

Venoarterial to venovenous extracorporeal life support conversion in pediatric acute respiratory distress syndrome.

In patients with pediatric acute respiratory distress syndrome (PARDS) and hemodynamic compromise who need venoarterial (VA) extracorporeal life support (ECLS), we have adopted a strategy to promote early VA-to-venovenous (VV) conversion since 2018. A single-center retrospective review was performed of all 22 patients who underwent ECLS for PARDS from 2008 to 2019. Variables were analyzed to determine factors affecting initial cannulation mode and in-hospital mortality. Outcomes were compared between before and after 2018. Of the 22 patients, 9 patients underwent initial VA-support. Small patient size and severe cardiopulmonary compromise prior to ECLS favored initial VA- over VV-support. Lactate level and vasoactive inotrope score at 24 hours post-ECLS initiation predicted in-hospital mortality. After 2018, all five patients with initial VA-support were converted to VV-support at 4.4 ± 1.3 days post-ECLS initiation without complications. In-hospital mortality decreased after 2018 (3/9) compared with before (10/13) (p = 0.041) despite longer ECLS run time (723.4 ± 384.2 vs 286.5 ± 235.1 hours, p = 0.003). The number of ECLS-related complications per ECLS 1000 run hours decreased after 2018 (7.2 ± 4.2 vs 46.9 ± 66.5, p = 0.063). Our strategy to promote early VA-to-VV conversion may be worth further evaluation in larger cohort studies.

Analysis of Signal Processing Methods to Reject the DC Offset Contribution of Static Reflectors in FMCW Radar-Based Vital Signs Monitoring.

Frequency-modulated continuous wave (FMCW) radars are currently being investigated for remote vital signs monitoring (measure of respiration and heart rates) as an innovative wireless solution for healthcare and ambient assisted living. However, static reflectors (furniture, objects, stationary body parts, etc.) within the range or range angular bin where the subject is present contribute in the Doppler signal to a direct current (DC) offset. The latter is added to the person's information, containing also a useful DC component, causing signal distortion and hence reducing the accuracy in measuring the vital sign parameters. Removing the sole contribution of the unwanted DC offset is fundamental to perform proper phase demodulation, so that accurate vital signs monitoring can be achieved. In this work, we analyzed different DC offset calibration methods to determine which one achieves the highest accuracy in measuring the physiological parameters as the transmitting frequency varies. More precisely, by using two FMCW radars, operating below 10 GHz and at millimeter wave (mmWave), we applied four DC offset calibration methods to the baseband radar signals originated by the cardiopulmonary activities. We experimentally determined the accuracy of the methods by measuring the respiration and the heart rates of different subjects in an office setting. It was found that the linear demodulation outperforms the other methods if operating below 10 GHz while the geometric fitting provides the best results at mmWave.

Modified FMCW Scheme for Improved Ultrasonic Positioning and Ranging of Unmanned Ground Vehicles at Distances < 50 mm

Unmanned ground vehicles (UGVs) find extensive use in various applications, including that within industrial environments. Efforts have been made to develop cheap, portable, and light-ranging/positioning systems to accurately locate their absolute/relative position and to automatically avoid potential obstacles and/or collisions with other drones. To this aim, a promising solution is the use of ultrasonic systems, which can be set up on UGVs and can potentially output a precise reconstruction of the drone's surroundings. In this framework, a so-called frequency-modulated continuous wave (FMCW) scheme is widely employed as a distance estimator. However, this technique suffers from low repeatability and accuracy at ranges of less than 50 mm when used in combination with low-resource hardware and commercial narrowband transducers, which is a distance range of the utmost importance to avoid potential collisions and/or imaging UGV surroundings. We hereby propose a modified FMCW-based scheme using an ad hoc time-shift of the reference signal. This was shown to improve performance at ranges below 50 mm while leaving the signal unaltered at greater distances. The capabilities of the modified FMCW were evaluated numerically and experimentally. A dramatic enhancement in performance was found for the proposed FMCW with respect to its standard counterpart, which is very close to that of the correlation approach. This work paves the way for the future use of FMCWs in applications requiring high precision.

Holey-structured tungsten metamaterials for broadband ultrasonic sub-wavelength imaging in water.

Metamaterials exhibiting Fabry-Pérot resonances are shown to achieve ultrasonic imaging of a sub-wavelength aperture in water immersion across a broad bandwidth. Holey-structured metamaterials of different thickness were additively manufactured using a tungsten substrate and selective laser melting, tungsten being chosen so as to create a significant acoustic impedance mismatch with water. Both broadband metamaterial behavior and sub-wavelength imaging in water are demonstrated experimentally and validated with finite element simulations over the 200-300 kHz range.

Ultrasonic Propagation in Highly Attenuating Insulation Materials.

Experiments have been performed to demonstrate that ultrasound in the 100-400 kHz frequency range can be used to propagate signals through various types of industrial insulation. This is despite the fact that they are highly attenuating to ultrasonic signals due to scattering and viscoelastic effects. The experiments used a combination of piezocomposite transducers and pulse compression processing. This combination allowed signal-to-noise levels to be enhanced so that signals reflected from the surface of an insulated and cladded steel pipe could be obtained.

Statistical and Proactive Analysis of an Inter-Laboratory Comparison: The Radiocarbon Dating of the Shroud of Turin.

We review the sampling and results of the radiocarbon dating of the archaeological cloth known as the Shroud of Turin, in the light of recent statistical analyses of both published and raw data. The statistical analyses highlight an inter-laboratory heterogeneity of the means and a monotone spatial variation of the ages of subsamples that suggest the presence of contaminants unevenly removed by the cleaning pretreatments. We consider the significance and overall impact of the statistical analyses on assessing the reliability of the dating results and the design of correct sampling. These analyses suggest that the 1988 radiocarbon dating does not match the current accuracy requirements. Should this be the case, it would be interesting to know the accurate age of the Shroud of Turin. Taking into account the whole body of scientific data, we discuss whether it makes sense to date the Shroud again.

Looking Through Paintings by Combining Hyper-Spectral Imaging and Pulse-Compression Thermography.

The use of different spectral bands in the inspection of artworks is highly recommended to identify the maximum number of defects/anomalies (i.e., the targets), whose presence ought to be known before any possible restoration action. Although an artwork cannot be considered as a composite material in which the zero-defect theory is usually followed by scientists, it is possible to state that the preservation of a multi-layered structure fabricated by the artist's hands is based on a methodological analysis, where the use of non-destructive testing methods is highly desirable. In this paper, the infrared thermography and hyperspectral imaging methods were applied to identify both fabricated and non-fabricated targets in a canvas painting mocking up the famous character "Venus" by Botticelli. The pulse-compression thermography technique was used to retrieve info about the inner structure of the sample and low power light-emitting diode (LED) chips, whose emission was modulated via a pseudo-noise sequence, were exploited as the heat source for minimizing the heat radiated on the sample surface. Hyper-spectral imaging was employed to detect surface and subsurface features such as pentimenti and facial contours. The results demonstrate how the application of statistical algorithms (i.e., principal component and independent component analyses) maximized the number of targets retrieved during the post-acquisition steps for both the employed techniques. Finally, the best results obtained by both techniques and post-processing methods were fused together, resulting in a clear targets map, in which both the surface, subsurface and deeper information are all shown at a glance.

Delamination Detection in Polymeric Ablative Materials Using Pulse-Compression Thermography and Air-Coupled Ultrasound.

Ablative materials are used extensively in the aerospace industry for protection against high thermal stresses and temperatures, an example being glass/silicone composites. The extreme conditions faced and the cost-risk related to the production/operating stage of such high-tech materials indicate the importance of detecting any anomaly or defect arising from the manufacturing process. In this paper, two different non-destructive testing techniques, namely active thermography and ultrasonic testing, have been used to detect a delamination in a glass/silicone composite. It is shown that a frequency modulated chirp signal and pulse-compression can successfully be used in active thermography for detecting such a delamination. Moreover, the same type of input signal and post-processing can be used to generate an image using air-coupled ultrasound, and an interesting comparison between the two can be made to further characterise the defect.

Correction to: Transposable Elements Activity is Positively Related to Rate of Speciation in Mammals.

The original version of the article unfortunately contained tagging error in Given and Surname of all the authors.

Transposable Elements Activity is Positively Related to Rate of Speciation in Mammals.

Transposable elements (TEs) play an essential role in shaping eukaryotic genomes and generating variability. Speciation and TE activity bursts could be strongly related in mammals, in which simple gradualistic models of differentiation do not account for the currently observed species variability. In order to test this hypothesis, we designed two parameters: the Density of insertion (DI) and the Relative rate of speciation (RRS). DI is the ratio between the number of TE insertions in a genome and its size, whereas the RRS is a conditional parameter designed to identify potential speciation bursts. Thus, by analyzing TE insertions in mammals, we defined the genomes as "hot" (high DI) and "cold" (low DI). Then, comparing TE activity among 29 taxonomical families of the whole Mammalia class, 16 intra-order pairs of mammalian species, and four superorders of Eutheria, we showed that taxa with high rates of speciation are associated with "hot" genomes, whereas taxa with low ones are associated with "cold" genomes. These results suggest a remarkable correlation between TE activity and speciation, also being consistent with patterns describing variable rates of differentiation and accounting for the different time frames of the speciation bursts.

Minimally Invasive Aortic Valve Replacement: Cost-Benefit Analysis of Ministernotomy Versus Minithoracotomy Approach.

BACKGROUND AND AIM OF THE STUDY: Minimally invasive aortic valve replacement via ministernotomy (ministernotomy-AVR) or minithoracotomy (minithoracotomy-AVR) is gaining popularity. To date, a direct comparison of ministernotomy-AVR versus minithoracotomy-AVR is lacking. The study aim was to compare these two procedures from a cost-benefit perspective. METHODS: Eight reports from the United States were selected from amongst 33,494 literature citations based on sample size and data completeness. Perioperative variables were collected for each surgical approach. Fixed and variable costs were estimated as cost per case in excess of full sternotomy AVR procedures. RESULTS: Ministernotomy-AVR patients were of a significantly lower mean age (59.8 years versus 67.9 years), ejection fraction (50.4-51.6% versus 56.1-57.8%), shorter cardiopulmonary bypass time (97.2 min versus 125.6 min) and cross-clamp time (69.9 min versus 87.9 min), a lower rate of blood transfusion (25.9% versus 64.4%), and a shorter length of hospital stay (5.7 versus 6.2 days). There were no significant inter-group differences in 30-day mortality, conversion to sternotomy, neurologic events, arrhythmia, wound infection, or postoperative bleeding. Assuming a volume of 50 cases per year, the added operative cost per case for a minithoracotomy-AVR was US$ 4,254 compared to US$ 290 for a ministernotomy-AVR. The added costs per case, assuming 200 cases per year, were US$ 4,209 and US$ 290, respectively. A minithoracotomy-AVR program performing 50 cases per year adds US$ 1,063,665 of operative costs over five years, compared to US$ 72,500 for a ministernotomy-AVR program. CONCLUSION: The present analysis suggested that the clinical benefits of ministernotomy-AVR are comparable or better than those of minithoracotomy-AVR, and at lower costs. Healthcare delivery organizations should consider the results of cost-benefit examinations when developing surgical valve replacement programs.