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Introduction: In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients. Methods: A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age =15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria. Results: Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01). Conclusions: A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity. [ABSTRACT FROM AUTHOR]

Maria Bova,1 Anna Valerieva,2 Maddalena Alessandra Wu,3 Riccardo Senter,4 Francesca Perego5 1Department of Translational Medical Sciences and Interdepartmental Center for Research in Basic and Clinical Immunology Sciences, University of Naples Federico II, Naples, Italy; 2Clinical Centre of Allergology, Medical University of Sofia, Sofia, Bulgaria; 3Department of Biomedical Science, University of Milan, Milan, Italy; 4Department of Medicine, University of Padova, Padova, Italy; 5Department of Cure Subacute, Istituti Clinici Scientifici Maugeri, IRCCS, Milan, ItalyCorrespondence: Francesca PeregoDepartment of Cure Subacute, Istituti Clinici Scientifici Maugeri, IRCCS, via Camaldoli 64, Milan 20138, ItalyTel +39 3489050440Email francesca.perego@icsmaugeri.itAbstract: Despite the efficacy of the on-demand treatment for the control of acute attacks of Hereditary Angioedema due to C1-Inhibitor Deficiency (C1-INH-HAE), the number and severity of attacks and the impairment in the quality of life of the affected patients have led to the development of a new monoclonal antibody, lanadelumab, directly addressed to the blockage of bradykinin, the principal mediator of vasodilation during angioedema attacks. It is indicated for the prophylactic treatment, it is easy to administer, highly effective and with known limited side effects. The current review summarizes the development of the drug, its clinical background and its perspectives.Keywords: C1-inhibitor hereditary angioedema, long-term prophylaxis, lanadelumab, monoclonal antibody, rare disease

We report measurements of the fracture energies of hexagonal honeycomb structured silica/polymer composite films that were produced through an evaporation induced self-assembly process. These films exhibit large anisotropy with their hexagonal pore axes aligned with the dip-coating direction. The experimental strategy included depositing films onto a flexible Kapton substrate and then straining them, in situ, under a microscope. To study the effect of the anisotropic microstructure on the fracture energy, cracks were propagated both parallel and perpendicular to the cylindrical pore axis directions. For both cases, the geometries of the evolving crack patterns with loading were micrographically recorded and the desired energy release rates were calculated using a two-dimensional steady-state channeling crack model. The model was implemented using the ANSYS finite element program. The experimental observations showed significant inelastic film deformation prior to crack propagation. These deformations were fully captured in the model, with properties obtained directly from the experiments. The calculated energy release rates were 12.3±0.5 J/m2 for the parallel direction and 6.7±0.5 J/m2 for the perpendicular direction. These numbers are significantly larger than the bulk silica value of roughly 4 J/m2, indicating the role of the local nanostructure in blunting and deflecting the crack tips. Experimental validation of the highly anisotropic energy release rates was obtained through transmission electron microscopy images of fractured films. [ABSTRACT FROM AUTHOR]

Femtosecond pump–probe absorption spectroscopy is used to investigate the role of Er3+ dopants in the early relaxation pathways of photoexcited Si nanocrystals. The fate of photoexcited electrons in three different Si nanostructures was studied and correlated with the effect of Er-doping and the nature of the dopant architecture. In Si nanocrystals without Er3+ dopant, a trapping component was identified to be a major electron relaxation mechanism. Addition of Er3+ ions into the core or surface shell of the nanocrystals was found to open up additional nonradiative relaxation pathways, which is attributed to Er-induced trap states in the Si host. Analysis of the photodynamics of the Si nanocrystal samples reveals an electron trapping mechanism involving trap-to-trap hopping in the doped nanocrystals, whereby the density of deep traps seem to increase with the presence of erbium. To gain additional insights on the relative depths of the trapping sites on the investigated nanostructures, benzoquinone was used as a surface adsorbed electron acceptor to facilitate photoinduced electron transfer across the nanocrystal surface and subsequently assist in back electron transfer. The established reduction potential (-0.45 V versus SCE) of the electron acceptor helped reveal that the erbium-doped nanocrystal samples have deeper trapping sites than the undoped Si. Furthermore, the measurements indicate that internally Er-doped Si have relatively deeper trapping sites than the erbium surface-enriched nanocrystals. The electron-shuttling experiment also reveals that the back electron transfer seems not to recover completely to the ground state in the doped Si nanocrystals, which is explained by a mechanism whereby the electrons are captured by deep trapping sites induced by erbium addition in the Si lattice. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The problem addressed concerns the conditions that foster productivity among natural scientists in a large research laboratory. We take several variables identified as important in two major perspectives in the literature on productivity, and use these variables to construct a causal model. Using path analysis, we test the model by employing data from a sample of 295 scientists working at an atomic research facility in West Germany. In general, educational level of the scientists has an important, positive impact on productivity; years of service has a varying and more modest positive effect. Rank of the scientist has an intermediate positive impact on productivity; psychological factors have a negligible effect. Finally, the influence the scientist has on his research endeavors has a modest positive impact on productivity. [ABSTRACT FROM AUTHOR]

* This report covers a portion of the applied research program of the Technical Training Branch, Training Research Division of Behavioral Sciences Laboratory. The research was conducted in part under Contract AF 33(657)‐10234 by the University of Cincinnati in support of Project 1710, “ Training, Personnel and Psychological Stress Aspects of Bioastro‐nautics,” Task 171007, “ Automated Training and Programmed Instruction.” The Technical Training Branch planned and directed the research, and prepared the report. The research was begun in March 1963 and was completed in July 1963. [ABSTRACT FROM PUBLISHER]