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Abstract  A general method for the solution of dual integral-equation systems is discussed in the context of applications in engineering electromagnetics. The approach follows a formulation based on a Fourier-series expansion of the unknown function and a successive expansion in a Neumann series of the Fourier-series coefficients. It is characterized by better convergence properties than classical numerical techniques usually adopted to solve the same class of problems and low computational costs. The efficiency and the performance of the proposed method are illustrated using the example of a typical electrostatic problem: the evaluation of the charge distribution of a hollow conducting cylinder, starting from the knowledge of the potential on the surface. [ABSTRACT FROM AUTHOR]

Cardiogenic shock (CS) is a serious complication of heart attack and constitutes one of its main causes of death. To date, there is no data on its treatment and evolution in Latin America., Objectives: To know the clinical characteristics, treatment strategies, evolution and in-hospital mortality of CS in Latin America., Materials and Methods: This is a prospective, multicenter registry of patients hospitalized with CS in the context of acute coronary syndromes (ACS) with and without ST segment elevation for 24 months., Results: 41 Latin American centers participated incorporating patients during the period between October 2021 and September 2023. 278 patients were included. Age: 66 (59-75) years, 70.1 % men. 74.8 % of the cases correspond to ACS with ST elevation, 14.4 % to ACS without ST elevation, 5.7 % to right ventricular infarction and 5.1 % to mechanical complications. CS was present from admission in 60 % of cases. Revascularization: 81.3 %, inotropic use: 97.8 %, ARM: 52.5 %, Swan Ganz: 17 %, intra-aortic balloon pump: 22.2 %. Overall in-hospital mortality was 52.7 %, with no differences between ACS with or without ST., Conclusions: Morbidity and mortality is very high despite the high reperfusion used., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Swan Ganz Catheter (SGC) allows us to diagnose different types of cardiogenic shock (CS)., Objectives: 1) Determine the frequency of use of SGC, 2) Analyze the clinical characteristics and mortality according to its use and 3) Analyze the prevalence, clinical characteristics and mortality according to the type of Shock., Methods: The 114 patients (p) from the ARGEN SHOCK registry were analyzed. A "classic" pattern was defined as PCP > 15 mm Hg, CI < 2.2 L/min/ m2, SVR > 1,200 dynes × sec × cm-5. A "vasoplegic/mixed" pattern was defined when p did not meet the classic definition. CS due to right ventricle (RV) was excluded., Results: SGC was used in 35 % (n:37). There were no differences in clinical characteristics according to SGC use, but those with SGC were more likely to receive dobutamine, levosimendan, and intra aortic balloon pump (IABP). Mortality was similar (59.4 % vs 61.3 %). The pattern was "classic" in 70.2 %. There were no differences in clinical characteristics according to the type of pattern or the drugs used. Mortality was 54 % in patients with the classic pattern and 73 % with the mixed/vasoplegic pattern, but the difference did not reach statistical significance (p:0.23)., Conclusions: SGC is used in one third of patients with CS. Its use does not imply differences in the drugs used or in mortality. Most patients have a classic hemodynamic pattern. There are no differences in mortality or in the type of vasoactive agents used according to the CS pattern found., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Currently the patient is defined as an older adult (OA) when the age is at least 60 years. Given the long life expectancy, it is interesting to evaluate whether all OAs with acute myocardial infarction (AMI) are equal. The objectives were to know the prevalence of OA in AMI and within them, that of those ≥75 years of age and to analyze characteristics, reperfusion treatments and in-hospital mortality according to whether they are < or ≥ 75 years of age., Methods: OA patients admitted to the National Registry of Infarction with ST segment elevation (ARGENIAM-ST) were analyzed. They were divided into group 1: 60-74 years old and group 2: ≥ 75 years old and compared with each other., Results: 3626 AM, 75.9% from Group 1, the rest from Group 2. In group 2 there were more women, hypertensive and with a history of coronary arteries. There was a similar percentage of diabetes and dyslipidemia, but fewer of smokers. In Group 2, less reperfusion treatment was used (although more primary angioplasty), with similar door-to-balloon time. Patients in Group 2 received fewer medications of proven efficacy and in the hospital course, they had more bleeding (although not major), more heart failure and more mortality: 18.3% vs. 9.4%, p<0.001. Age ≥75 years was an independent predictor of mortality., Conclusions: one in four patients with AMI is over 75 years old; they receive less reperfusion, have more heart failure, bleeding and twice the mortality rate than patients between 60 and 74 years.

Cardiogenic Shock is one of the main causes of death in ST segment Elevation Myocardial Infarction. To know the clinical characteristics, in-hospital evolution and mortality of patients with Cardiogenic Shock. Patients enrolled in the ARGEN-IAM-ST Registry were analyzed. Predictors of Cardiogenic Shock and death during hospital stay were established. A total of 6122 patients were admitted between 2015 and 2022. Cardiogenic Shock was present in 10.75% of cases. Patients with CS were older (64.5 vs 60 years), more females (41% vs 36%), with more antecedents of infarction and a higher prevalence of anterior location of infarction and multivessel disease. They were also less revascularized (88.5% vs 91.5%) and had a higher incidence of failed angioplasty (15.7% vs 2.7%). They also evidenced a higher occurrence of mechanical complications (6.8% vs 0.4%), ischemic recurrence (7.4% vs 3.4%) and cardiac arrest on admission (44.8% vs 2.6%). All the differences described showed statistical significance with P < 0.05. Overall mortality was 58% in contrast to 2.77% in patients without Cardiogenic Shock (P < 0.001). Only age, DBT, and early cardiac arrest were independent predictors of shock on admission whereas age, female gender, cardiac arrest on admission and failed angioplasty were independent predictors of death. One out of 10 patients with ST Elevation Myocardial Infarction presented cardiogenic shock. Its clinical characteristics were similar to those described more than 20 years ago. Despite a high use of reperfusion strategy cardiogenic shock continues to have a very high mortality Argentina., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Autologous chimeric antigen receptor (CAR) αβ T-cell therapies have demonstrated remarkable antitumor efficacy in patients with haematological malignancies; however, not all eligible cancer patients receive clinical benefit. Emerging strategies to improve patient access and clinical responses include using premanufactured products from healthy donors and alternative cytotoxic effectors possessing intrinsic tumoricidal activity as sources of CAR cell therapies. γδ T cells, which combine innate and adaptive mechanisms to recognise and kill malignant cells, are an attractive candidate platform for allogeneic CAR T-cell therapy. Here, we evaluated the manufacturability and functionality of allogeneic peripheral blood-derived CAR + Vδ1 γδ T cells expressing a second-generation CAR targeting the B-cell-restricted CD20 antigen., Methods: Donor-derived Vδ1 γδ T cells from peripheral blood were ex vivo -activated, expanded and engineered to express a novel anti-CD20 CAR. In vitro and in vivo assays were used to evaluate CAR-dependent and CAR-independent antitumor activities of CD20 CAR + Vδ1 γδ T cells against B-cell tumors., Results: Anti-CD20 CAR + Vδ1 γδ T cells exhibited innate and adaptive antitumor activities, such as in vitro tumor cell killing and proinflammatory cytokine production, in addition to in vivo tumor growth inhibition of B-cell lymphoma xenografts in immunodeficient mice. Furthermore, CD20 CAR + Vδ1 γδ T cells did not induce xenogeneic graft-versus-host disease in immunodeficient mice., Conclusion: These preclinical data support the clinical evaluation of ADI-001, an allogeneic CD20 CAR + Vδ1 γδ T cell, and a phase 1 study has been initiated in patients with B-cell malignancies (NCT04735471)., Competing Interests: KPN, TB, AA, AM, JMR, LB, MMB, JK‐W, HS, SP, AD, CM, NTH, HT, VDR, AG‐R, M Hoopes, DS, RS, M Herrman, SEA, BTA, ZA, SP and SMH are, or were, employees of Adicet Bio, Inc., and FD, KS and KB are employees of Regeneron Pharmaceuticals, Inc., (© 2022 Adicet Bio Inc. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Glucocorticoids (GCs) are widely used to treat a variety of autoimmune and inflammatory diseases; however, systemic delivery of GCs is associated with side effects that affect essentially every organ system, reflecting the nearly ubiquitous expression of the glucocorticoid receptor (GR). Targeted delivery of GCs to diseased tissues using antibody-glucocorticoid conjugates (GC-ADCs) offers a therapeutic alternative to overcome these adverse effects. Herein, we describe novel classes of GCs that exhibited greater potency than dexamethasone and budesonide, a 100-fold selectivity toward the GR over other nuclear receptors, and no in vitro safety liability in pharmacology assays (hERG, AMES) and that demonstrated a substantial reduction in tumor necrosis factor-α (TNF-α) release in mice challenged with lipopolysaccharide (LPS). The site-specific conjugated GC-ADCs via cathepsin-cleavable linkers were highly stable in plasma and specifically released GCs in antigen-positive cells, suggesting that these novel GCs can serve as ADC payloads to treat autoimmune and inflammatory diseases.

T-cell-redirecting bispecific antibodies have emerged as a new class of therapeutic agents designed to simultaneously bind to T cells via CD3 and to tumor cells via tumor-cell-specific antigens (TSA), inducing T-cell-mediated killing of tumor cells. The promising preclinical and clinical efficacy of TSAxCD3 antibodies is often accompanied by toxicities such as cytokine release syndrome due to T-cell activation. How the efficacy and toxicity profile of the TSAxCD3 bispecific antibodies depends on the binding affinity to CD3 remains unclear. Here, we evaluate bispecific antibodies that were engineered to have a range of CD3 affinities, while retaining the same binding affinity for the selected tumor antigen. These agents were tested for their ability to kill tumor cells in vitro, and their biodistribution, serum half-life, and anti-tumor activity in vivo. Remarkably, by altering the binding affinity for CD3 alone, we can generate bispecific antibodies that maintain potent killing of TSA + tumor cells but display differential patterns of cytokine release, pharmacokinetics, and biodistribution. Therefore, tuning CD3 affinity is a promising method to improve the therapeutic index of T-cell-engaging bispecific antibodies., (© 2021. The Author(s).)

CD3-engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells are potent therapeutic approaches for redirecting patient T cells to recognize and kill tumors. Here we describe a fully human bsAb (REGN5458) that binds to B-cell maturation antigen (BCMA) and CD3, and compare its antitumor activities vs those of anti-BCMA CAR T cells to identify differences in efficacy and mechanism of action. In vitro, BCMAxCD3 bsAb efficiently induced polyclonal T-cell killing of primary human plasma cells and multiple myeloma (MM) cell lines expressing a range of BCMA cell surface densities. In vivo, BCMAxCD3 bsAb suppressed the growth of human MM tumors in murine xenogeneic models and showed potent combinatorial efficacy with programmed cell death protein 1 blockade. BCMAxCD3 bsAb administration to cynomolgus monkeys was well tolerated, resulting in the depletion of BCMA+ cells and mild inflammatory responses characterized by transient increases in C-reactive protein and serum cytokines. The antitumor efficacy of BCMAxCD3 bsAb was compared with BCMA-specific CAR T cells containing a BCMA-binding single-chain variable fragment derived from REGN5458. Both BCMAxCD3 bsAb and anti-BCMA CAR T cells showed similar targeted cytotoxicity of MM cell lines and primary MM cells in vitro. In head-to-head in vivo studies, BCMAxCD3 bsAb rapidly cleared established systemic MM tumors, whereas CAR T cells cleared tumors with slower kinetics. Thus, using the same BCMA-binding domain, these results suggest that BCMAxCD3 bsAb rapidly exerts its therapeutic effects by engaging T cells already in place at the tumor site, whereas anti-BCMA CAR T cells require time to traffic to the tumor site, activate, and numerically expand before exerting antitumor effects., (© 2021 by The American Society of Hematology.)

Diabetes and heart failure are closely interdependent, but its significance in decompensated heart failure (DHF) is not uniformly accepted., Objective: To compare mortality between diabetics and nondiabetics with DHF., Methods and Results: In-hospital and 1-year mortality of 1004 consecutive patients with DHF: 25.6% diabetics; median age was 81, 53% male. Diabetics were younger, more often male, with higher prevalence of ischemic etiology and reduced ejection fraction. Congestion was the most prevalent finding in both groups. In hospital mortality was 6.3% vs 6.6 % in nondiabetics and diabetics respectively and 1-year mortality was 35.77% in nondiabetics and 29.3% in diabetics. There were no significant differences in mortality at univariate and multivariate analyses. We applied a propensity score restricted to 378 patients, 189 (50%) diabetics and 189 (50%) and no significant differences were found., Conclusion: Diabetes had no impact on prognosis in DHF. Advanced age may played a major role in outcomes i thus making less relevant the presence of diabetes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Graphene-based nano-porous materials (GNM) are potentially useful for all those applications needing a large specific surface area (SSA), typical of the bidimensional graphene, yet realized in the bulk dimensionality. Such applications include for instance gas storage and sorting, catalysis and electrochemical energy storage. While a reasonable control of the structure is achieved in micro-porous materials by using nano-micro particles as templates, the controlled production or even characterization of GNMs with porosity strictly at the nano-scale still raises issues. These are usually produced using dispersion of nano-flakes as precursors resulting in little control on the final structure, which in turn reflects in problems in the structural model building for computer simulations. In this work, we describe a strategy to build models for these materials with predetermined structural properties (SSA, density, porosity), which exploits molecular dynamics simulations, Monte Carlo methods and machine learning algorithms. Our strategy is inspired by the real synthesis process: starting from randomly distributed flakes, we include defects, perforation, structure deformation and edge saturation on the fly, and, after structural refinement, we obtain realistic models, with given structural features. We find relationships between the structural characteristics and size distributions of the starting flake suspension and the final structure, which can give indications for more efficient synthesis routes. We subsequently give a full characterization of the models versus H 2 adsorption, from which we extract quantitative relationship between the structural parameters and the gravimetric density. Our results quantitatively clarify the role of surfaces and edges relative amount in determining the H 2 adsorption, and suggest strategies to overcome the inherent physical limitations of these materials as adsorbers. We implemented the model building and analysis procedures in software tools, freely available upon request.

ADCs based on the natural product maytansine have been successfully employed clinically. In a previous report, ADCs based on hydrophilic non-cell permeable maytansinoids was presented. The authors in this report further explore the maytansine scaffold to develop tubulin inhibitors capable of cell permeation. The research resulted in amino-benzoyl-maytansinoid payloads that were further elaborated with linkers for conjugating to antibodies. This approach was applied to MUC16 tumor targeting antibodies for ovarian cancers. A positive control ADC was evaluated alongside the amino-benzoyl-maytansinoid ADC and the efficacy observed was equivalent while the isotype control ADCs had no effect., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Nowadays, Distribution System Operators are increasing the digitalization of their smart grids, making it possible to measure and manage their state at any time. However, with the massive eruption of change-distributed generation (e.g., renewable resources, electric vehicles), the grid operation have become more complex, requiring specific technologies to balance it. In this sense, the demand-side management is one of its techniques; the demand response is a promising approach for providing Flexibility Services (FSs) and complying with the regulatory directives of the energy market. As a solution, this paper proposes the use of the OpenADR (Open Automated Demand Response) standard protocol in combination with a Decentralized Permissioned Market Place (DPMP) based on Blockchain. On one hand, OpenADR hierarchical architecture based on distributed nodes provides communication between stakeholders, adding monitoring and management services. Further, this architecture is compatible with an aggregator schema that guarantees the compliance with the strictest regulatory framework (i.e., European market). On the other hand, DPMP is included at different levels of this architecture, providing a global solution to Flexibility Service Providers (FSP) that can be adapted depending on the regulation of a specific country. As a proof of concept, this paper shows the result of a real experimental case, which implements a Capacity Bidding Program where the OpenADR protocol is used as a communication method to control and monitor energy consumption. In parallel, the proposed DPMP based on Blockchain makes it possible to manage the incentives of FSs, enabling the integration of local and global markets.

Background and Aim: According to the World Health Organization (WHO), falls represent the second main cause of accidental and involuntary deaths worldwide, which led to define them as one of the "four giants of the geriatrician" that particularly affect the elderly aged ≥ 65 years. The study's aim is to evaluate whether the Traffic Crash scale is valid in identifying patients at risk of falling by comparing it to the Conley scale currently used., Methods: Prospective observational study evaluating the fall risk using TC on a sample of patients aged ≥ 65 years, hospitalized in General Medicine Ward and Gastroenterology, after informed consent and favorable opinion of the AVEN Ethics Committee. The results are compared with those obtained from the Conley scale, and with those obtained from the indications of the Business Operating Instruction. The method of administration occurred concurrently and distinctly on the same patient by two researchers in order to demonstrate the scale inter-rater reliability., Results: The final sample was made up of 88 patients. Data shows that 46 out of 55 patients (84%) are medium / high risk for both scales. According to the indications of the Company Operating Instruction, the entire sample is at risk. The inter-rater reliability was confirmed with Cohen's K which is equal to p = 1., Conclusions: The TC scale is comparable to Conley scale, for the fall risk identification but specifically the stratification is low-medium-high. Therefore, in future, this will make it possible to implement personalized prevention interventions in care planning.