Addressing Load Sensitivity of Rational Macromodels

Behavioral models are effective tools used to relieve the computational burden of large-scale system-level simulations. In electrical and electronic applications, the Vector Fitting (VF) iteration often represents the algorithm of choice for generating low order equivalent circuits for complex multiport components in a data-driven setting. Although accurate and reliable in general, macromodels generated via VF are inherently represented in terms of a rational approximation of one specific input-output transfer function of the structure under modeling, e.g., its scattering matrix. However, accuracy in the scattering representation does not necessarily imply a good accuracy when solving the macromodel in a system-level setting, under different termination conditions. In fact, the sensitivity of the macromodel with respect to its loading conditions may be large and needs to be addressed and controlled. In this work, we present a modified VF scheme that overcomes this issue, by introducing in the rational approximation algorithm the requirement that the macromodel remains accurate when interconnected with a known class of admissible networks. The proposed formulation is based on an augmentation of the cost function minimized at each VF iteration; further, it does not require additional expensive data gathering steps when compared to standard approaches. The effectiveness of the scheme is tested over a set of relevant examples, in particular for Power Integrity applications

Towards Accelerated Transient Solvers for Full System Power Integrity Verification

This paper proposes a novel framework for power integrity verification of multicore systems, including voltage stabilization provided by multiple integrated voltage regulators at the core interfaces. The proposed framework adopts a two-stage macromodeling strategy to derive a compact representation of the full system dynamics as observed from each core. These dynamics are parameterized by the time-varying duty cycle provided by dedicated feedback controllers to each voltage regulator, here implemented through an averaged model. We show that the proposed simulation framework has the potential to outperform direct transient analysis based on SPICE engines

A Compressed Multivariate Macromodeling Framework for Fast Transient Verification of System-Level Power Delivery Networks

This paper discusses a reduced-order modeling and simulation approach for fast transient power integrity verifi- cation at full system level. The reference structure is a com- plete power distribution network (PDN) from platform voltage regulator module (VRM) to multiple cores, including board, package, decoupling capacitors, and per-core fully integrated voltage regulators (FIVR). All blocks are characterized and known through high-fidelity models derived from first-principle solvers (full-wave electromagnetic and circuit-level extractions). The complexity of such detailed characterization grows very large and becomes intractable, especially for power integrity verification of massive multicore platforms subjected to real workload scenarios. We approach this problem by exploiting a multi-stage macromodeling and compression process, leading to a compact representation of the system dynamics in terms of a linearized state-space structure with multiple feedback loops from the FIVR controllers. The PDN macromodel is obtained through a data-driven approach starting from reference small- signal frequency responses, obtaining a sparse and structured representation specifically designed to match the behavior of the reference system. The resulting compact model is then solved in time-domain very efficiently. Results on mobile and enterprise server benchmarks demonstrate a speedup in runtime up to 50× with respect to HSPICE, with negligible loss of accuracy

Behavioral Pattern of Risso’s Dolphin (Grampus griseus) in the Gulf of Taranto (Northern Ionian Sea, Central-Eastern Mediterranean Sea)

Relatively scant information is available on the Risso’s dolphin in comparison to the other species regularly present in the Mediterranean Sea. Recently, its conservation status has been updated to Endangered by the International Union for Conservation of Nature (IUCN) in this Sea. Therefore, the need to increase information on its biology and ecology is even more urgent. This study reports the first preliminary information on the behavioral traits of the species occurring in the Gulf of Taranto (Northern Ionian Sea). Data on predominant behavioral activity states and on a set of group composition variables (group formation, cruising speed, dive duration and interaction between individuals) were collected from April 2019 to September 2021, applying the focal-group protocol with instantaneous scan sampling. Group size, depth and group composition variables were compared between activity states. Results highlight that both the group size and the several variables considered varied significantly depending on activity state. The group size was significantly smaller during feeding than resting and traveling and a characterization in terms of group formation, cruise speed, dive duration and interaction between animals is provided for the different activity states. Moreover, a list of behavioral events which occurred, as well as their relative frequency of distribution among activity states, is reported. Finally, details on the sympatric occurrences between Risso’s and striped dolphins, as well as the repetitive interaction observed between adult individuals and plastic bags floating on the sea surface, are reported and discussed

Hysteroscopic Removal of Intrauterine Device in Pregnancy: A Scoping Review to Guide Personalized Care

Background and objectives: Pregnancies that occur with an intrauterine device (IUD) in situ are at increased risk for developing severe conditions which may affect the fetus and the mother. The incidence of such adverse consequences significantly drops after device removal. A scoping review of the literature was performed to highlight the risks, benefits, and outcomes of hysteroscopic removal of intrauterine devices in early pregnancy. Materials and Methods: PubMed, Scopus, and Web of Science were searched. The review included all reports from 1990 to October 2022. The research strategy adopted included different combinations of the following terms: (“hysteroscopy”) AND (“pregnancy”) AND (“intrauterine device” or “IUD”) AND (“intrauterine system” or “IUS”). A scoping review of the hysteroscopic removal of IUDs during pregnancy was performed. All studies identified were listed by citation, title, authors, and abstract. Duplicates were identified by an independent manual screening performed by two researchers and then removed. For the eligibility process, two authors independently screened the titles and abstracts of all non-duplicated papers and excluded those not pertinent to the topic. Results: PRISMA guidelines were followed. Nine manuscripts were detected, accounting for 153 patients. Most IUD removals occurred during the first trimester of pregnancy. Most of the time, the procedure was safe and without consequences. Conclusions: This review highlights the safety and efficacy of operative hysteroscopy as a method of IUD removal in early pregnancy. We recommend using a 3 to 5 mm hysteroscope, avoiding cervical dilation, and maintaining low infusion pressure during the procedure to avoid potential damage to the gestational sac and IUD fragment displacement. Heating the distension media to 30 ◦C should be considered

Dual-fuel injection fundamentals: experimental – numerical analysis into a constant-volume vessel

Abstract Dual-fuel combustion mode in compression ignition engines has been tested thoroughly, showing high potential for the reduction of emissions (especially nitric oxides and particulate matter) while keeping unchanged the fuel conversion efficiency compared with conventional Diesel engines. Controlling the reactivity of the secondary fuel is crucial for this kind of application. To this aim, a combined experimental/numerical approach is proposed in this study to provide, on one side, experimental data in controlled conditions for the calibration of the numerical models; on the other side, a numerical framework for the accurate simulation of the dual-fuel injection in engine-like operating conditions. More in detail, a constant-volume combustion vessel has been used to simulate and analyze the injection process varying the characteristic control parameters. Detailed high-resolution images of the injection and combustion processes were acquired for the validation of the numerical framework. Numerical simulations, carried out by means of the CONVERGE CFD code using a Reynolds Average Navier Stokes (RANS) approach allow for understanding the key differences between the nominal and off-design settings. Results have been compared with the experimental data in terms of liquid spray penetration. A comparison with high resolution images has also been done to prove the accuracy of the model to describe the spray evolution in terms of spray characteristics. In the provided picture, this contribution aims at demonstrating the robustness of the experimental/numerical framework that is essential for further development of such engine solution

NTRK Gene Fusions in Solid Tumors and TRK Inhibitors: A Systematic Review of Case Reports and Case Series

The approval of larotrectinib and entrectinib for cancer patients harboring an NTRK gene fusion has represented a milestone in the era of "histology-agnostic" drugs. Among the clinical trials that led to the approval of these two drugs, most of the enrolled patients were affected by soft tissue sarcomas, lung, and salivary gland cancer. However, as next-generation sequencing assays are increasingly available in the clinical setting, health care professionals may be able to detect NTRK gene fusions in patients affected by tumor types under or not represented in the clinical trials. To this aim, we systematically reviewed MEDLINE from its inception to 31 August 2022 for case reports and case series on patients with NTRK gene fusion-positive tumors treated with TRK inhibitors. A virtual cohort of 43 patients was created, excluding those enrolled in the above-mentioned clinical trials. Although our results align with those existing in the literature, various cases of central nervous system tumors were registered in our cohort, confirming the benefit of these agents in this subgroup of patients. Large, multi-institutional registries are needed to provide more information about the efficacy of TRK inhibitors in cancer patients affected by tumor types under or not represented in the clinical trials

Huge Tracheal Diverticulum in a Patient with Mounier-Kuhn Syndrome

Tracheal diverticulum is a rare benign entity. Tracheobronchomegaly (TBM), also known as Mounier-Kuhn syndrome, is a rare disorder characterized by marked dilation of the trachea and main bronchi, associated with thinning or atrophy of the elastic tissue. Because of the weakened trachea and increased intraluminal pressure related to chronic cough, some patients may develop mucosal herniation leading to tracheal diverticulosis. We report the case of a patient with TBM with a huge tracheal diverticulum, diagnosed by bronchoscopy and computed tomography with three-dimensional reconstruction. To our knowledge this is the largest tracheal diameter described in a patient affected by this syndrome

Relationship between retinal microvascular impairment and subclinical atherosclerosis in SLE

objectives: patients with SLE have higher cardiovascular (CV) risk compared with healthy controls (HC) and are characterised by accelerated atherosclerosis; intima media thickness (IMT), marker of subclinical atherosclerosis, is higher in patients with SLE than in HCs. Retinal microvascular impairment detected through optical coherence tomography angiography (OCTA) was investigated as a marker of systemic vascular involvement in SLE.the aim of the study was to evaluate the relationship between retinal vascular impairment and IMT in SLE. methods: cross-sectional study recruiting patients with SLE and HCs. Data of the study population were collected. CV risk was evaluated through the american college of cardiology/american heart association (ACC/AHA) guidelines, framingham and QRESEARCH risk estimator V.3 (QRISK3) scores. Both groups underwent OCTA and carotid ultrasound with IMT assessment.Statistical analysis was accomplished using Pearson/Spearman, t-test/Mann-Whitney or χ2 test. Variables statistically significant at univariate regression analysis were tested in an age-corrected and sex-corrected multivariate regression model. results: 43 patients with SLE and 34 HCs were recruited.patients with SLE showed higher triglycerides (p=0.019), triglycerides-glucose (TyG) Index (p=0.035), ACC/AHA guidelines (p=0.001), Framingham Risk Scores (p=0.008) and a reduced superficial (p<0.001) and deep (p=0.005) whole retinal vessel density (VD) compared with HCs.In SLE univariate analysis, deep whole VD showed a negative correlation with IMT (p=0.027), age (p=0.001), systolic blood pressure (p=0.011), QRISK3 Score (p<0.001), systemic lupus international collaborating clinics damage index (p=0.006) and apolipoprotein B (p=0.021), while a positive correlation was found with female sex (p=0.029). Age-adjusted and sex-adjusted multivariate analysis confirmed QRISK3 score (p=0.049) and IMT (p=0.039) to be independent risk factors for reduced retinal VD. conclusions: patients with SLE showed lower retinal VD and higher CV risk indicators compared with HCs. Among patients with SLE, QRISK3 Score and IMT were found to be independent risk factors for retinal vascular impairment, suggesting a role of OCTA in evaluating preclinical CV involvement in SLE. moreover, TyG index could represent a biomarker of CV risk in patients with SLE compared with HCs

LFA-1 Controls Th1 and Th17 Motility Behavior in the Inflamed Central Nervous System

Leukocyte trafficking is a key event during autoimmune and inflammatory responses. The subarachnoid space (SAS) and cerebrospinal fluid are major routes for the migration of encephalitogenic T cells into the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, and are sites of T cell activation before the invasion of CNS parenchyma. In particular, autoreactive Th1 and Th17 cell trafficking and reactivation in the CNS are required for the pathogenesis of EAE. However, the molecular mechanisms controlling T cell dynamics during EAE are unclear. We used two-photon laser microscopy to show that autoreactive Th1 and Th17 cells display distinct motility behavior within the SAS in the spinal cords of mice immunized with the myelin oligodendrocyte glycoprotein peptide MOG(35-55). Th1 cells showed a strong directional bias at the disease peak, moving in a straight line and covering long distances, whereas Th17 cells exhibited more constrained motility. The dynamics of both Th1 and Th17 cells were strongly affected by blocking the integrin LFA-1, which interfered with the deformability and biomechanics of Th1 but not Th17 cells. The intrathecal injection of a blocking anti-LFA-1 antibody at the onset of disease significantly inhibited EAE progression and also strongly reduced neuro-inflammation in the immunized mice. Our results show that LFA-1 plays a pivotal role in T cell motility during EAE and suggest that interfering with the molecular mechanisms controlling T cell motility can help to reduce the pathogenic potential of autoreactive lymphocytes