New crystalline complex chlorides containing transition metal chlorides or oxychlorides as components of coordination catalysts

Novel complex chlorides have been obtained by reacting TiCl₄, VOCl₃, MoOCl₄, WOCl₄, or AlCl₃, with Be, Mg, Ca, or Sr chlorides in the presence of electron donors such as POCl₃ (L) or C₆H₅POCl₂, (L′). The resulting products, obtained with good yield, show defined stoichimetry, ionic character, and crystalline structure, and may be considered reference systems for high-yield catalysts in the low-pressure polymerization of ethylene (HDPE). Complexes (TiCl₆)MgL₆, (TiCl₅L′)₂ MgL′₆, and (Ti₂Cl₁₀)MgL₆ associated with (i-C₄H₉)₃Al were found very active in HDPE synthesis, but completely unable to polymerize propylene. This result and other evidence suggest that part of the catalytic activity of these systems is displayed by soluble species. The role played by the Mg ion in high-yield catalysts is displayed by soluble species. The role played by the Mg ion in high-yield catalysts is discussed in the light of the peculiar behavior shown by the complex chlorides containing this earth-alkali metal.     

Are hospitals becoming high reliability organizations?

High Reliability Organizations (HROs) are complex systems in which many accidents and adverse events that could occur within those systems or at the interfaces with other systems are actually avoided or prevented. Many organizations in high-risk industries have successfully implemented HRO approaches. In recent years, initiatives have been undertaken aimed at transforming hospitals into HROs. Actually, despite some improvements, these initiatives have not shown the expected results. In this paper, we discuss the possible reasons for such outcomes. We will show that, when compared with traditional HROs, hospitals are undoubtedly high-risk organizations, but have specificities and experience systemic socio-organizational barriers that make them difficult to transform into HROs.     

Genetic Variants and Tumor Immune Microenvironment: Clues for Targeted Therapies in Inflammatory Breast Cancer (IBC)

To better understand the etiology of inflammatory breast cancer (IBC) and identify potential therapies, we studied genomic alterations in IBC patients. Targeted, next-generation sequencing (NGS) was performed on cell-free DNA (cfDNA) (n = 33) and paired DNA from tumor tissues (n = 29) from 32 IBC patients. We confirmed complementarity between cfDNA and tumor tissue genetic profiles. We found a high incidence of germline variants in IBC patients that could be associated with an increased risk of developing the disease. Furthermore, 31% of IBC patients showed deficiencies in the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, PALB2, RAD51C, ATM, BARD1) making them sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We also characterized the tumor-infiltrating lymphocytes (TILs) in tumor tissue biopsies by studying several markers (CD4, CD8, FoxP3, CD20, PD-1, and PD-L1) through immunohistochemistry (IHC) staining. In 7 of 24 (29%) patients, tumor biopsies were positive for PD-L1 and PD-1 expression on TILs, making them sensitive to PD-1/PD-L1 blocking therapies. Our results provide a rationale for considering PARP inhibitors and PD-1/PDL1 blocking immunotherapy in qualifying IBC patients.     

Involvement of Alarmins in the Pathogenesis and Progression of Multiple Myeloma

Objective: Multiple Myeloma (MM) is a haematological disease resulting from the neoplastic transformation of plasma cells. The uncontrolled growth of plasma cells in the bone marrow and the delivery of several cytokines causes bone erosion that often does not regress, even in the event of disease remission. MM is characterised by a multi-step evolutionary path, which starts with an early asymptomatic stage defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease. Data Sources and Study Selection: We have selected scientific publications on the specific topics “alarmis, MGUS, and MM”, drawing from PubMed. The keywords we used were alarmines, MGUS, MM, and immune system. Results: The analysis confirms the pivotal role of molecules such as high-mobility group box-1, heat shock proteins, and S100 proteins in the induction of neoangiogenesis, which represents a milestone in the negative evolution of MM as well as other haematological and non-haematological tumours. Conclusions: Modulation of the host immune system and the inhibition of neoangiogenesis may represent the therapeutic target for the treatment of MM that is capable of promoting better survival and reducing the risk of RRMM.     

Characterizing the pollution produced by an industrial area: chemometric methods applied to the Lagoon of Venice

The industrial area of Porto Marghera discharges every year about 1.85 10(9) m(3) of waste waters in the Lagoon of Venice through its 142 discharge points, 17 of them being constantly active. The Anti-Pollution Department of Magistrato alle Acque, the Venice Water Authority, has been controlling these discharges for many years. The huge database built up during the last years could help the authorities in making choices regarding the water quality of the Venetian environment. The application of chemometric methods to the dataset obtained from chemical analyses of industrial waste water samples (almost 250, for each of them up to 57 chemical variables having been measured) is useful to answer fundamental questions related to the pollution generated by the industrial area: i) which are the main differences among the individual discharge points? ii) is there a temporal trend in global and punctual pollution? iii) which is the discharge point having the strongest relative impact on the waters? The results of the present work allow to 1) identify two different groups of discharge points, discriminated by the level of contamination and by the presence of different contaminants; 2) detect a relevant temporal trend in one of the main outfalls (the industrial and civil waste treatment plant); 3) set up a multivariate strategy to "measure" the relative modification induced on receiving lagoon waters by a single discharge. The application of such a "3-STEP multivariate analysis" to the present and future data of water quality could represent a relevant tool for monitoring industrial activities, providing at the same time a support in management decision processes.     

Design and Validation of a Custom NGS Panel Targeting a Set of Lysosomal Storage Diseases Candidate for NBS Applications

Lysosomal storage diseases (LSDs) are a heterogeneous group of approximately 70 monogenic metabolic disorders whose diagnosis represents an arduous challenge for clinicians due to their variability in phenotype penetrance, clinical manifestations, and high allelic heterogeneity. In recent years, the approval of disease-specific therapies and the rapid emergence of novel rapid diagnostic methods has opened, for a set of selected LSDs, the possibility for inclusion in extensive national newborn screening (NBS) programs. Herein, we evaluated the clinical utility and diagnostic validity of a targeted next-generation sequencing (tNGS) panel (called NBS_LSDs), designed ad hoc to scan the coding regions of six genes (GBA, GAA, SMPD1, IDUA1, GLA, GALC) relevant for a group of LSDs candidate for inclusion in national NBS programs (MPSI, Pompe, Fabry, Krabbe, Niemann Pick A-B and Gaucher diseases). A standard group of 15 samples with previously known genetic mutations was used to test and validate the entire flowchart. Analytical accuracy, sensitivity, and specificity, as well as turnaround time and costs, were assessed. Results showed that the Ion AmpliSeq and Ion Chef System-based high-throughput NBS_LSDs tNGS panel is a fast, accurate, and cost-effective process. The introduction of this technology into routine NBS procedures as a second-tier test along with primary biochemical assays will allow facilitating the identification and management of selected LSDs and reducing diagnostic delay.     

Environmental and personal determinants of support perceptions: Three generalizability studies.

The extent to which perceived social support reflects characteristics of the environment, the personality of the perceiver, and their interaction is unknown. This article shows how the methods of generalizability theory can be used to address these questions. When participants rate the same targets on the targets' supportiveness, generalizability theory provides methods for determining the extent to which support judgments are determined by effects due to targets (supporters), perceivers, and their interaction. In 3 studies, each source of variance made significant contributions to support judgments, with the Perceivers?×?Supporters interaction, characteristics of supporters, and biases of perceivers making the largest contributions, respectively. The implications for theoretical models of perceived support are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)