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Distributed acoustic sensing (DAS) technology enables the detection of waves generated by seismic events, generally as uniaxial strain/strain rate time-series observed for dense, subsequent, portions of a Fibre Optic Cable (FOC). Despite the advantages in measurement density, data quality is often affected by uniaxial signal polarization, site effects and cable coupling, beyond the physical energy decay with distance. To better understand the relative importance of these factors for data inversion, we attempt a first modelling of noise patterns affecting DAS arrival times for a set of seismic events. The focus is on assessing the impact of noise statistics, together with the geometry of the problem, on epicentral location uncertainties. For this goal, we consider 15 'real-world' cases of DAS arrays with different geometry, each associated with a seismic event of known location. We compute synthetic P -wave arrival times and contaminate them with four statistical distributions of the noise. We also estimate P -wave arrival times on real waveforms using a standard seismological picker. Eventually, these five data sets are inverted using a Markov chain Monte Carlo method, which offers the evaluation of the relative event location differences in terms of posterior probability density (PPD). Results highlight how cable geometry influences the shape, extent and directionality of the PPDs. However, synthetic tests demonstrate how noise assumptions on arrival times often have important effects on location uncertainties. Moreover, for half of the analysed case studies, the observed and synthetic locations are more similar when considering noise sources that are independent of the geometrical characteristics of the arrays. Thus, the results indicate that axial polarization, site conditions and cable coupling, beyond other intrinsic features (e.g. optical noise), are likely responsible for the complex distribution of DAS arrival times. Overall, the noise sensitivity of DAS suggests caution when applying geometry-only-based approaches for the a priori evaluation of novel monitoring systems. [ABSTRACT FROM AUTHOR]

Background and aims: There is still limited knowledge regarding the clinical profile and appropriateness of treatment in patients with hypothyroidism hospitalized in Internal Medicine (IM) Departments in Italy. The aim of this study is to evaluate: 1) the characteristics of patients and possible deviations from national and international clinical practice recommendations (CPRs) in evidence-based guidelines (EBGs); 2) the improvement of patient management by means of a standardized educational programme (EP). Methods: A nationwide multicentre study, comprising two replications of a retrospective survey (phases 1 and 3) with an intervening EP (phase 2) in half of the centres and no EP in the other half, was conducted. The EP was based on outreach visits. Centres were assigned to the two arms of the study, labelled the training group (TG) and control group (CG) respectively, by cluster randomization. Four EBGs and 39 CPRs provided the basis on which 22 treatment management indicators were identified (7 referring to the time of hospital admission, 15 to post-admission). Results: The 21 participating centres recruited 587 hospitalized patients with hypothyroidism, 421 of which were females (71.7%, mean age 74.1 + 14.4 yrs): 318 in phase 1 and 269 in phase 3. The cause of hypothyroidism was unknown in 282 patients (48%). Evaluation at the time of admission identified satisfactory adherence to CPRs (>50%) for 63.6% of the indicators. In the phase 3, TG centres showed significant improvement vs CG in 4 of the 15 post-admission indicators, while 1 out of 15 was significantly worse. Conclusions: The EP based on outreach visits significantly improved some indicators in the management of patients with hypothyroidism, with specific reference to appropriateness of TSH dosage and levothyroxine (LT4) treatment modality. Clinical Trial Registration: ClinicalTrials.gov , identifier NCT05314790. [ABSTRACT FROM AUTHOR]

This paper deals with the combination of a proline-based moiety with biologically active gold centers in the oxidation states +1 and +3. In particular, six Au(I)/(III)–proline dithiocarbamato (DTC) complexes with general formulae [Au I2 (DTC)2] and [AuIIIX2(DTC)] (X = Cl, Br) are reported here. After the synthesis of the ligand and the complexes, all derivatives were characterized via several techniques and tested for their stability in DMSO/water media. This study was focused on the demonstration of a peculiar behavior of Au(III)–DTC species in solution. Finally, the complexes were screened for their antiproliferative activity against 2 human cancer cell lines, namely HepG2 and HepG2/SB3, taken as models of hepatocellular carcinoma. The latter, chosen for its aggressiveness due to the upregulation of the anti-apoptotic protein SerpinB3, was selectively inhibited in terms of growth by some Au(III)–DTC complexes. [ABSTRACT FROM AUTHOR]

Structural imaging and event location require an accurate estimation of the seismic velocity. However, active seismic surveys used to estimate it are expensive and time‐consuming. During the last decade, fiber‐optic‐based distributed acoustic sensing has emerged as a reliable, enduring, and high‐resolution seismic sensing technology. We show how downhole distributed acoustic sensing passive records from the San Andreas Fault Observatory at Depth can be used for seismic velocity estimation. Using data recorded from earthquakes propagating near‐vertically, we compute seismic velocities using first‐break picking as well as slant stack decomposition. This methodology allows for the estimation of both P and S wave velocity models. We also use records of the ambient seismic field for interferometry and P wave velocity model extraction. Results are compared to a regional model obtained from surface seismic as well as a conventional downhole geophone survey. We find that using recorded earthquakes, we obtain the highest P wave model resolution. In addition, it is the only method that allows for S wave velocity estimation. Computed P and S models unravel three distinct areas at the depth range of 50‐750 m, which were not present in the regional model. In addition, we find high VP/VS values near the surface and a possible VP/VS anomaly about 500 m deep. We confirm its existence by observing a strong S‐P mode conversion at that depth. Key Points: A seismically active area is recorded using distributed acoustic sensing of a downhole fiberWe estimate P‐ and S‐ wave velocities using fiber data and compare them with conventional surveysVelocity analysis unveils a geological structure at the San Andreas Fault Observatory at Depth location [ABSTRACT FROM AUTHOR]

The study of the process of HIV entry into the host cell and the creation of biomimetic nanosystems that are able to selectively bind viral particles and proteins is a high priority research area for the development of novel diagnostic tools and treatment of HIV infection. Recently, we described multilayer nanoparticles (nanotraps) with heparin surface and cationic peptides comprising the N‐terminal tail (Nt) and the second extracellular loop (ECL2) of CCR5 receptor, which could bind with high affinity some inflammatory chemokines, in particular, Rantes. Because of the similarity of the binding determinants in CCR5 structure, both for chemokines and gp120 HIV protein, here we expand this approach to the study of the interactions of these biomimetic nanosystems and their components with the peptide representing the V3 loop of the activated form of gp120. According to surface plasmon resonance results, a conformational rearrangement is involved in the process of V3 and CCR5 fragments binding. As in the case of Rantes, ECL2 peptide showed much higher affinity to V3 peptide than Nt (KD = 3.72 × 10−8 and 1.10 × 10−6 M, respectively). Heparin‐covered nanoparticles bearing CCR5 peptides effectively bound V3 as well. The presence of both heparin and the peptides in the structure of the nanotraps was shown to be crucial for the interaction with the V3 loop. Thus, short cationic peptides ECL2 and Nt proved to be excellent candidates for the design of CCR5 receptor mimetics. Cationic peptides comprising N‐terminal tail (Nt) and second extracellular loop (ECL2) of CCR5 receptor, bind with high affinity the peptide representing V3 loop of HIV gp120 (KD = 0.04 μM and 1.10 μM, respectively). Heparin‐covered nanoparticles (nanotraps) bearing these CCR5 peptides effectively bind V3 as well. The presence of both heparin and peptides in the structure of the nanotraps is shown to be crucial for the interaction with V3 peptide. [ABSTRACT FROM AUTHOR]

The number of elderly people, mostly aged over 85 years (the 'oldest old'), is increasing worldwide. As a consequence, accompanying morbidity and disability have been increasing, and frailty, defined as an age-related condition of decline of physiological reserves and vulnerability, represents an emerging problem. Caring for older frail people may represent a challenge, since the elderly differ significantly from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions. Specific criteria of therapeutic appropriateness and modified goals of care are needed in such patients, also in endocrine care settings. Indeed, thyroid dysfunctions are among the most common conditions in older, multimorbid populations. The prevalence of overt and subclinical hypothyroidism is as high as 20% and thyroid hormone prescription is common in the elderly, with a trend toward levothyroxine treatment of more marginal degrees of hypothyroidism. In addition, older patients have the highest rate of overtreatment during replacement therapy and are more susceptible to developing adverse effects from thyroid hormone excess. Recently, results of a multicentric randomized controlled trial, the TRUST-IEMO collaboration trial, added further insights to the debated question of whether and when levothyroxine treatment is required and if it is beneficial in the elderly. With this in mind, we revised the relevant literature on the impact of thyroid dysfunction and replacement therapy among older people, with the aim to better define indications, benefits and risks of L-T4 replacement therapy in the frail elderly. [ABSTRACT FROM AUTHOR]

Objective In our Pathology Department, fine needle aspiration ( FNA) of palpable thyroid nodules is performed by cytopathologists who ensure correct sample management and rapid on-site evaluation ( ROSE). Conversely, ultrasound ( US)-guided FNAs have traditionally been carried out by endocrinologists and radiologists in outside clinics, where the presence of a cytopathologist is not always feasible. To overcome this limitation, cytopathologists have started to perform US-guided FNAs themselves. This study retrospectively evaluates 1 year of this novel practice. Methods A total of 2225 US-guided FNAs were performed in our clinic by cytopathologists, whereas 1490 aspirates were taken by a group of non-cytopathologists. Among these, 756 FNAs were taken by a single experienced endocrinologist. The distribution of the Bethesda classification categories was evaluated in each of these groups. Results FNAs performed by cytopathologists were more often diagnostic and better prepared than those taken by non-cytopathologists, including those taken by the experienced endocrinologist ( P < 0.01). The latter operator yielded a higher rate of suspicious and malignant FNAs, reflecting a more appropriate clinical triage of worrisome nodules. Conclusion Although the endocrinologist's evaluation is crucial to select clinically relevant thyroid nodules, cytopathologists can reliably perform US guidance in addition to their traditional expertise in sampling, specimen preparation and ROSE. [ABSTRACT FROM AUTHOR]

The X band PELDOR spectroscopy was used to investigate the magnetic dipole-dipole interactions in glassy solutions of nitroxide mono-labeled tylopeptin B and heptaibin peptaibiotics at 77 K. Specifically, a study was performed of the tylopeptin B peptides labeled at either position 3, 8, or 13, denoted as T3, T8, and T13, respectively. The heptaibin analogs labeled at either position 2 or 14, denoted as H2 and H14, respectively, were also investigated. It was shown that in frozen glassy peptide solutions in methanol, the spin labels are randomly distributed over the solvent volume. This result points to the absence of specific dipolar interactions between the peptides under these conditions. However, peptide aggregation was detected in weakly polar methanol/toluene environments. To study the properties of the resulting aggregates, we examined the depth of modulation for the PELDOR traces as a function of the concentration of the peptides in solution and the distances between the spin labels in the aggregates. Based on the concentration dependencies, the number of peptide molecules in the aggregates was estimated. We find that this value ranges from 2 to 3, depending on the position of the spin label in the peptide sequence. The combined analysis of the distance spectra and the number of peptide molecules in the aggregates allows us to suggest that dimer formation is the prevailing mode of self-association. In the case of spin-labeled tylopeptin B, the molecules in the dimer are head-to-head oriented. In addition, the distance spectra of the aggregates show that the C-termini of the molecules in the tylopeptin B dimer are more mobile than the Ntermini. This phenomenon leads to an increase in the spread of the distances between the nitroxides as the label position is approaching the peptide C-terminus. For heptaibin, we show that two forms of dimerization (head-to-head and head-to-tail) occur. Finally, in addition to dimers, aggregates containing 3 or 4 peptide molecules, which give broad lines in the distance spectra, are seen in solution. [ABSTRACT FROM AUTHOR]

We present a migration velocity analysis (MVA) method based on wavefield extrapolation. Similarly to conventional MVA, our method aims at iteratively improving the quality of the migrated image, as measured by the flatness of angle-domain common-image gathers (ADCIGs) over the aperture-angle axis. However, instead of inverting the depth errors measured in ADCIGs using ray-based tomography, we invert‘image perturbations’ using a linearized wave-equation operator. This operator relates perturbations of the migrated image to perturbations of the migration velocity. We use prestack Stolt residual migration to define the image perturbations that maximize the focusing and flatness of ADCIGs.Our linearized operator relates slowness perturbations to image perturbations, based on a truncation of the Born scattering series to the first-order term. To avoid divergence of the inversion procedure when the velocity perturbations are too large for Born linearization of the wave equation, we do not invert directly the image perturbations obtained by residual migration, but a linearized version of the image perturbations. Thelinearized image perturbationsare computed by a linearized prestack residual migration operator applied to the background image. We use numerical examples to illustrate how the backprojection of the linearized image perturbations, i.e. the gradient of our objective function, is well behaved, even in cases when backprojection of the original image perturbations would mislead the inversion and take it in the wrong direction.We demonstrate with simple synthetic examples that our method converges even when the initial velocity model is far from correct. In a companion paper, we illustrate the full potential of our method for estimating velocity anomalies under complex salt bodies. [ABSTRACT FROM AUTHOR]

Angle-domain common-image gathers (ADCIGs) are an essential tool for migration velocity analysis (MVA). We present a method for computing ADCIGs in 3D from the results of wavefield-continuation migration. The proposed methodology can be applied before or after the imaging step in a migration procedure. When computed before imaging, 3D ADCIGs are functions of the offset ray parameters; we derive the geometric relationship that links the offset ray parameters to the aperture angleγ and the reflection azimuthφ. When computed after imaging, 3D ADCIGs are directly produced as functions ofγ andφ.The mapping of the offset ray parametersinto the angles (γ,φ) depends on both the local dips and the local interval velocity; therefore, the transformation of ADCIGs computed before imaging into ADCIGs that are functions of the actual angles is difficult in complex structure. By contrast, the computation of ADCIGs after imaging is efficient and accurate even in the presence of complex structure and a heterogeneous velocity function. On the other hand, the estimation of the offset ray parametersis less sensitive to velocity errors than the estimation of the angles (γ,φ). When ADCIGs that are functions of the offset ray parametersare adequate for the application of interest (e.g. ray-based tomography), the computation of ADCIGs before imaging might be preferable.Errors in the migration velocity cause the image point in the angle domain to shift along the normal to the apparent geological dip. By assuming stationary rays (i.e. small velocity errors), we derive a quantitative relationship between this normal shift and the traveltime perturbation caused by velocity errors. This relationship can be directly used in an MVA procedure to invert depth errors measured from ADCIGs into migration velocity updates. In this paper, we use it to derive an approximate 3D residual moveout (RMO) function for measuring inconsistencies between the migrated images at differentγ andφ. We tested the accuracy of our kinematic analysis on a 3D synthetic data set with steeply dipping reflectors and a vertically varying propagation velocity. The tests confirm the accuracy of our analysis and illustrate the limitations of the straight-ray approximation underlying our derivation of the 3D RMO function. [ABSTRACT FROM AUTHOR]

Subsalt imaging is strongly dependent on the quality of the velocity model. However, rugose salt bodies complicate wavefield propagation and lead to subsalt multipathing, illumination gaps and shadow zones, which cannot be handled correctly by conventional traveltime-based migration velocity analysis (MVA). We overcome these limitations by the wave-equation MVA technique, introduced in a companion paper, and demonstrate the methodology on a realistic synthetic data set simulating a salt-dome environment and a Gulf of Mexico data set. We model subsalt propagation using wave paths created by one-way wavefield extrapolation. Those wave paths are much more accurate and robust than broadband rays, since they inherit the frequency dependence and multipathing of the underlying wavefield. We formulate an objective function for optimization in the image space by relating an image perturbation to a perturbation of the velocity model. The image perturbations are defined using linearized prestack residual migration, thus ensuring stability, relative to the first-order Born approximation assumptions. Synthetic and real data examples demonstrate that wave-equation MVA is an effective tool for subsalt velocity analysis, even when shadows and illumination gaps are present. [ABSTRACT FROM AUTHOR]

Abstract: In order to investigate the antiproliferative properties of antamanide, we have synthesized and studied two antamanide analogs where the phenylalanine residue in positions 6 or 9 is substituted by tyrosine, their corresponding linear forms and the cyclic and linear des Phe[sup 5],Phe[sup 6]–Tyr[sup 9]–analogs. Antamanide and its biologically active synthetic analogs are able to form highly stable complexes with metal ions, particularly Na[sup +], K[sup +] and Ca[sup 2+]. We studied the ion‐binding properties of the Tyr–antamanide analogs by CD and Tb[sup 3+]‐mediated fluorescence in acetonitrile. In this medium the far‐and near‐UV CD spectra of the neat Tyr[sup 6]–antamanide analog are very similar to that of the parent cyclic decapeptide. Substantial differences occur on the contrary in the CD spectra of the neat Tyr[sup 9]–antamanide, particularly in the regions at 220 nm and 270–290 nm. In acetonitrile, as already found for antamanide, the interaction with the above‐mentioned metal ions always produces evident changes in the far‐ and near‐UV CD spectra of both analogs. On the contrary, the CD spectra of the linear deca‐ and octa‐ and of the cyclic octa‐analogs are affected by the presence of metal ions only in the near‐UV region. In the same solvent the Tb[sup 3+]‐mediated fluorescence spectra of all the synthetic peptides are remarkably affected by the addition of ions. On the basis of the spectral total changes, by using either or both the spectroscopic techniques, it has been possible to determine the ion binding constants for all the linear and cyclic Tyr–antamanide analogs and to compare them with that of the parent peptide. The antitoxic and antiproliferative activities of these antamanide analogs have been tentatively correlated to their ion‐binding properties. A preliminary account of this work was given in ( 1). [ABSTRACT FROM AUTHOR]

Objectives This study was designed to assess systolic wall stress and ventricular function in patients with deranged growth hormone secretion, in an attempt to elucidate the mechanisms of growth hormone interaction with heart performance. Design A case-control study. Subjects Thirty patients with active acromegaly, free of diabetes mellitus and coronary artery disease, and 25 subjects with congenital growth hormone deficiency were studied. Twelve growth hormone-deficient subjects were reevaluated after 12 months of recombinant human growth hormone therapy. Two groups of 30 normal subjects each were used as controls for the acromegalic and growth hormone-deficient patients, respectively. Results In the acromegalics, end-systolic wall stress was reduced (−20%; P<0·01) due to ventricular wall thickening (+26%; P<0·001), whereas cardiac output was significantly increased (+20%; P<0·01). The velocity of fibre shortening was unchanged. In growth hormone-deficient subjects, end-systolic wall stress was markedly increased (+38%; P<0·001) due to a significant reduction of ventricular wall thickness (−28%; P<0·001), whereas cardiac output was significantly decreased (−44%; P<0·001) Replacement therapy with recombinant human growth hormone produced a partial correction of wall thickness and stress. Consequently, systolic performance and cardiac output improved significantly. Conclusion This study demonstrates that growth hormone plays a role in the control of cardiac wall stress and performance through a mechanism mediated by the effect of growth hormone on myocardial tissue growth. The data may have therapeutic implications in cardiac diseases that lead to heart failure. [ABSTRACT FROM PUBLISHER]

To investigate left and right ventricular involvement in acromegaly, 20 patients were studied by Doppler echocardiography. Nine of them had systemic hypertension. Right ventricular free wall thickness was significantly increased in acromegalic patients (8 ± 2 vs 4 ± 1 mm; P <0.001). Left ventricular mass index was augmented both in the whole group and in the subgroup of normotensive acromegalics, as compared with normals (134 ± 33 and 115 ± 20 vs 80 ± 18 g.m,. P <0.01). Ejection phase indices were normal in the patient group, while impaired left and right ventricular diastolic filling was found. In fact, isovolumic relaxation time was prolonged (118 ± 21 vs 78 ± 12 ms; P <0.001), ratio of early to late mitral (0. ± 0.3 vs 1.8±0.5 P<0.001) and tricuspid (1.0±0.2 vs 1.4±0.3 P<0.001 flow velocities were significantly decreased as compared with controls. Superior vena cava flowmetry was also abnormal showing a marked decrease of diastolic filling wave and, consequently, of the ratio between peak diastolic and peak systolic flow velocity. No significant differences observed between normotensive and hypertensive acromegalics, except for left ventricular mass index (115 ± 20 vs 156 ± 31 g.m; P <0.01). These findings indicate that abnormal diastolic filling patterns of transmitral, transtricuspid, and superior vena cava flowmetry suggesting ‘impaired relaxation’ associated with increased left and right ventricular mass, frequently occur in acromegaly. [ABSTRACT FROM PUBLISHER]