Study and design of topologies and components for high power density DC-DC converters

Size reduction of low power electronic DC–DC converters is a topic of major interest for power electronics which requires the study and design of circuits and components working under redefined requirements. For this purpose, novel circuital topologies provide advantages in terms of power density increment, especially where a single chip design is feasible. These concepts have been applied to design and implement an integrated high step-down multiphase buck converter and to study the miniaturization of a stackable fiflyback architecture. Particular attention has been dedicated to power inductors, focusing on the modeling and measurement of magnetic materials’ hysteresis and core losses

Instantaneous Stereo Depth Estimation of Real-World Stimuli with a Neuromorphic Stereo-Vision Setup

The stereo-matching problem, i.e., matching corresponding features in two different views to reconstruct depth, is efficiently solved in biology. Yet, it remains the computational bottleneck for classical machine vision approaches. By exploiting the properties of event cameras, recently proposed Spiking Neural Network (SNN) architectures for stereo vision have the potential of simplifying the stereo-matching problem. Several solutions that combine event cameras with spike-based neuromorphic processors already exist. However, they are either simulated on digital hardware or tested on simplified stimuli. In this work, we use the Dynamic Vision Sensor 3D Human Pose Dataset (DHP19) to validate a brain-inspired event-based stereo-matching architecture implemented on a mixed-signal neuromorphic processor with real-world data. Our experiments show that this SNN architecture, composed of coincidence detectors and disparity sensitive neurons, is able to provide a coarse estimate of the input disparity instantaneously, thereby detecting the presence of a stimulus moving in depth in real-time

Serotonin drives striatal synaptic plasticity in a sex-related manner.

Abstract Introduction Plasticity at corticostriatal synapses is a key substrate for a variety of brain functions – including motor control, learning and reward processing – and is often disrupted in disease conditions. Despite intense research pointing toward a dynamic interplay between glutamate, dopamine (DA), and serotonin (5-HT) neurotransmission, their precise circuit and synaptic mechanisms regulating their role in striatal plasticity are still unclear. Here, we analyze the role of serotonergic raphe-striatal innervation in the regulation of DA-dependent corticostriatal plasticity. Methods Mice (males and females, 2–6 months of age) were housed in standard plexiglass cages at constant temperature (22 ± 1 °C) and maintained on a 12/12 h light/dark cycle with food and demineralized water ad libitum. In the present study, we used a knock-in mouse line in which the green fluorescent protein reporter gene (GFP) replaced the I Tph2 exon (Tph2GFP mice), allowing selective expression of GFP in the whole 5-HT system, highlighting both somata and neuritis of serotonergic neurons. Heterozygous, Tph2+/GFP, mice were intercrossed to obtain experimental cohorts, which included Wild-type (Tph2+/+), Heterozygous (Tph2+/GFP), and Mutant serotonin-depleted (Tph2GFP/GFP) animals. Results Using male and female mice, carrying on different Tph2 gene dosages, we show that Tph2 gene modulation results in sex-specific corticostriatal abnormalities, encompassing the abnormal amplitude of spontaneous glutamatergic transmission and the loss of Long Term Potentiation (LTP) in Tph2GFP/GFP mice of both sexes, while this form of plasticity is normally expressed in control mice (Tph2+/+). Once LTP is induced, only the Tph2+/GFP female mice present a loss of synaptic depotentiation. Conclusion We showed a relevant role of the interaction between dopaminergic and serotonergic systems in controlling striatal synaptic plasticity. Overall, our data unveil that 5-HT plays a primary role in regulating DA-dependent corticostriatal plasticity in a sex-related manner and propose altered 5-HT levels as a critical determinant of disease-associated plasticity defects

Enhancing identification and treatment of patients with concomitant chronic venous insufficiency and diabetes mellitus A modified Delphi study from the CODAC (ChrOnic venous disease and Diabetes Advisory Council) group

Background: Chronic venous insufficiency (CVI) and diabetes mellitus (DM) pose significant burdens to patients and healthcare systems. While the two diseases share a number of commonalities in risk factors and pathophysiology, they are often assessed and managed separately. This can lead to a worsening of comorbidities and limitations in a patient’s quality of life. This project aims to develop recommendations to enhance the identification and treatment of patients with concomitant CVI and DM. Methods: Using a modified Delphi method, a panel of experts developed 38 Likert Scale and two multiple choice questions across six key themes. These were used to form an online survey which was disseminated through a convenience sampling approach to CVI and DM healthcare professionals across Europe, Central America, South America, and the Middle East. The threshold for consensus was set at ≥75%.Results: A total of 238 responses were received. 27/38 statements attained &gt;90% agreement, nine of 38 attained between 75-90%, and two failed to meet the threshold (&lt;75%). The awareness around the impact of the two diseases was high, but a gap was highlighted in the identification of patients with concomitant CVI and DM. Conclusions: The high level of agreement shows that healthcare professionals are aware of the gaps in identification and treatment of patients with concomitant CVI and DM, and of the need to approach this as a combined therapy area. An algorithm is proposed to help the identification of at-risk patients and to provide recommendations on the management of patients with concomitant disease. (Cite this article as: Bozkurt AK, van Rijn MJ, Bouskela E, Gastaldi G, Glauser F, Haller H, et al. Enhancing identification and treatment of patients with concomitant chronic venous insufficiency and diabetes mellitus. A modified Delphi study from the CODAC (ChrOnic venous disease and Diabetes Advisory Council) group. Int Angiol 2023;42:427-35. DOI: 10.23736/S0392-9590.23.05061-7)</p

Preservation of positional identity in fetus-derived neural stem (NS) cells from different mouse central nervous system compartments

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The Role of Non-Covalent Interactions on Cluster Formation: Pentamer, Hexamers and Heptamer of Difluoromethane

The role of non-covalent interactions (NCIs) has broadened with the inclusion of new types of interactions and a plethora of weak donor/acceptor partners. This work illustrates the potential of chirped-pulse Fourier transform microwave technique, which has revolutionized the field of rotational spectroscopy. In particular, it has been exploited to reveal the role of NCIs' in the molecular self-aggregation of difluoromethane where a pentamer, two hexamers and a heptamer were detected. The development of a new automated assignment program and a sophisticated computational screening protocol was essential for identifying the homoclusters in conditions of spectral congestion. The major role of dispersion forces leads to less directional interactions and more distorted structures than those found in polar clusters, although a detailed analysis demonstrates that the dominant interaction energy is the pairwise interaction. The tetramer cluster is identified as a structural unit in larger clusters, representing the maximum expression of bond between dimers.We thank MINECO (CTQ2017-89150-R), Basque Government (IT1162-19 and PIBA2018-11), the UPV/EHU (PPG17/10, GIU18/207), CSIC (2018FR0036, LINKA20249), University of Bologna (RFO), Fondazione CARISBO (2018/0353) and NSF (CHE-1903871 and CHE-2018427) for the financial support. C.C thanks MINECO for a Juan de la Cierva contract. L.E. was supported by Marie Curie fellowship PIOF-GA-2012-32840

The emerging role of cancer nanotechnology in the panorama of sarcoma

In the field of nanomedicine a multitude of nanovectors have been developed for cancer application. In this regard, a less exploited target is represented by connective tissue. Sarcoma lesions encompass a wide range of rare entities of mesenchymal origin affecting connective tissues. The extraordinary diversity and rarity of these mesenchymal tumors is reflected in their classification, grading and management which are still challenging. Although they include more than 70 histologic subtypes, the first line-treatment for advanced and metastatic sarcoma has remained unchanged in the last fifty years, excluding specific histotypes in which targeted therapy has emerged. The role of chemotherapy has not been completely elucidated and the outcomes are still very limited. At the beginning of the century, nano-sized particles clinically approved for other solid lesions were tested in these neoplasms but the results were anecdotal and the clinical benefit was not substantial. Recently, a new nanosystem formulation NBTXR3 for the treatment of sarcoma has landed in a phase 2-3 trial. The preliminary results are encouraging and could open new avenues for research in nanotechnology. This review provides an update on the recent advancements in the field of nanomedicine for sarcoma. In this regard, preclinical evidence especially focusing on the development of smart materials and drug delivery systems will be summarized. Moreover, the sarcoma patient management exploiting nanotechnology products will be summed up. Finally, an overlook on future perspectives will be provided

Exploratory findings from a prematurely closed international, multicentre, academic trial: RAVELLO, a phase III study of regorafenib versus placebo as maintenance therapy after first-line treatment in RAS wild-type metastatic colorectal cancer

Background In patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the role of maintenance therapy after first-line treatment with chemotherapy plus antiepidermal growth factor receptor (EGFR) monoclonal antibodies (MoAb) is still an object of debate. Methods We assessed the efficacy and safety of regorafenib as a switch maintenance strategy after upfront 5-fluorouracil-based chemotherapy plus an anti- EGFR MoAb in patients with RAS WT mCRC. RAVELLO was a phase III, international, double-blind, placebocontrolled, academic trial. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival and toxicity. Regorafenib or placebo were administered daily for 3 weeks of 4-week cycle until disease progression or unacceptable toxicity, up to 24 months. Results The study was stopped prematurely due to slow accrual and lack of funding after the randomisation of 21 patients: 11 in the regorafenib arm and 10 in the placebo arm. The small sample size precludes any statistical analysis. Toxicity was acceptable and consistent with the known regorafenib safety profile. Median PFS was similar in the two arms. However, a subgroup of patients treated with regorafenib experienced a remarkably long PFS. Three patients were progression free at 9 months in the regorafenib arm versus one patient in the placebo arm, whereas at 12 months two regorafenib-treated patients were still progression free versus none in the placebo arm. Conclusion RAVELLO trial demonstrated that growing financial and bureaucratic hurdles affect the feasibility of independent academic research. Although stopped prematurely and within the limited sample size, RAVELLO suggests that regorafenib has not a major activity in maintenance setting after upfront chemotherapy and anti-EGFR MoAb. However, a subgroup of patients experienced a remarkable long PFS, indicating that a better refinement of the patient population would help to identify subjects that might benefit from a regorafenib personalised approach in the switch maintenance settin

Consensus based recommendations for diagnosis and medical management of Poland syndrome (sequence)

Background Poland syndrome (OMIM: 173800) is a disorder in which affected individuals are born with missing or underdeveloped muscles on one side of the body, resulting in abnormalities that can affect the chest, breast, shoulder, arm, and hand. The extent and severity of the abnormalities vary among affected individuals. Main body The aim of this work is to provide recommendations for the diagnosis and management of people affected by Poland syndrome based on evidence from literature and experience of health professionals from different medical backgrounds who have followed for several years affected subjects. The literature search was performed in the second half of 2019. Original papers, meta-analyses, reviews, books and guidelines were reviewed and final recommendations were reached by consensus. Conclusion Being Poland syndrome a rare syndrome most recommendations here presented are good clinical practice based on the consensus of the participant experts