Designing Urban Spaces to Enhance Active and Sustainable Mobility: An Analysis of Physical and Symbolic Affordances in School Squares in the Metropolitan Area of Milan, Italy

As thresholds to cities, public spaces adjacent to schools play an important role in children’s everyday mobilities, potentially shaping their future mobility habits and affective experiences. The purpose of this paper is to investigate the urban design conditions of such spaces, defined as “school squares”, and, with the aid of affordance theory, to analyze spatial features and characteristics that might encourage or hinder active and sustainable mobility practices. In the first part of the paper, we define sustainable mobility, conduct a literature review on affective responses to the urban environment, and discuss active school travel (AST) in relation to the design of school squares. By focusing on 416 primary and lower secondary schools in the metropolitan area of Milan, we present an assessment method that is composed of on-desk and on-site surveys. In particular, Phase 1 defines the type of school squares, Phase 2 investigates physical affordances (spatial features and characteristics that directly influence active mobility practices, such as bicycle racks, protective barriers, benches, and parked cars), and Phase 3 discusses symbolic affordances (elements and characteristics that might induce different affective responses to a school square with regard to active mobility, such as bicycle racks, parked cars, greenery, and dustbins). The results indicate that in most cases school squares are characterized by typological confusion that has nothing to do with the school environment: narrow sidewalks, disorder, and low levels of safety. In order to promote active and sustainable mobility choices and enhance children’s mobile experiences, it is necessary to address the aforementioned features. The ultimate goal of this paper is to provide insights for developing an urban regeneration framework that considers school squares a safe context and a starting point from which to perform sustainable mobility practices

Social Support and Self-Efficacy on Turnover Intentions: The Mediating Role of Conflict and Commitment

Turnover intentions are a phenomenon that affects the life of organizations and causes highly negative consequences. Based on previous studies, it is possible to consider antecedents to turnover in terms of both individual and social perceived resources, which previous research does not usually examine simultaneously. The aim of this study was to explore the role of both resources (individual and social) on turnover intentions. Thus, we hypothesized that perceived social support and self-efficacy have an impact on turnover intentions and that this relationship is mediated by interpersonal conflict and Affective Commitment. A total of 392 Italian employees completed a self-report questionnaire. A structural equation model was tested. The results showed that interpersonal conflict and Affective Commitment fully mediated the relationship between social support, self-efficacy and turnover intentions. Practical implications are discussed

Blastic plasmacytoid dendritic cell neoplasm : State of the art and prospects

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare tumour, which usually a_ects elderly males and presents in the skin with frequent involvement of the bone-marrow, peripheral blood and lymph nodes. It has a dismal prognosis, with most patients dying within one year when treated by conventional chemotherapies. The diagnosis is challenging, since neoplastic cells can resemble lymphoblasts or small immunoblasts, and require the use of a large panel of antibodies, including those against CD4, CD56, CD123, CD303, TCL1, and TCF4. The morphologic and in part phenotypic ambiguity explains the uncertainties as to the histogenesis of the neoplasm that led to the use of various denominations. Recently, a series of molecular studies based on karyotyping, gene expression profiling, and next generation sequencing, have largely unveiled the pathobiology of the tumour and proposed the potentially beneficial use of new drugs. The latter include SL-401, anti-CD123 immunotherapies, venetoclax, BET-inhibitors, and demethylating agents. The epidemiologic, clinical, diagnostic, molecular, and therapeutic features of BPDCN are thoroughly revised in order to contribute to an up-to-date approach to this tumour that has remained an orphan disease for too long

Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective B therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P<0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo

Protein kinase CK2 is widely expressed in follicular, Burkitt and diffuse large B-cell lymphomas and propels malignant B-cell growth.

Serine-threonine kinase CK2 is highly expressed and pivotal for survival and proliferation in multiple myeloma, chronic lymphocytic leukemia and mantle cell lymphoma. Here, we investigated the expression of \u3b1 catalytic and \u3b2 regulatory CK2 subunits by immunohistochemistry in 57 follicular (FL), 18 Burkitt (BL), 52 diffuse large B-cell (DLBCL) non-Hodgkin lymphomas (NHL) and in normal reactive follicles. In silico evaluation of available Gene Expression Profile (GEP) data sets from patients and Western blot (WB) analysis in NHL cell-lines were also performed. Moreover, the novel, clinical-grade, ATP-competitive CK2-inhibitor CX-4945 (Silmitasertib) was assayed on lymphoma cells. CK2 was detected in 98.4% of cases with a trend towards a stronger CK2\u3b1 immunostain in BL compared to FL and DLBCL. No significant differences were observed between Germinal Center B (GCB) and non-GCB DLBCL types. GEP data and WB confirmed elevated CK2 mRNA and protein levels as well as active phosphorylation of specific targets in NHL cells. CX-4945 caused a dose-dependent growth-arresting effect on GCB, non-GCB DLBCL and BL cell-lines and it efficiently shut off phosphorylation of NF-\u3baB RelA and CDC37 on CK2 target sites. Thus, CK2 is highly expressed and could represent a suitable therapeutic target in BL, FL and DLBCL NHL

Immune-Mediated Dermatoses in Patients with Haematological Malignancies: A Comprehensive Review

Haematological malignancies induce important alterations of the immune system, which account for the high frequency of autoimmune complications observed in patients. Cutaneous immune-mediated diseases associated with haematological malignancies encompass a heterogeneous group of dermatoses, including, among others, neutrophilic and eosinophilic dermatoses, autoantibody-mediated skin diseases, vasculitis and granulomatous dermatoses. Some of these diseases, such as paraneoplastic pemphigus, are associated with an increased risk of death; others, such as eosinophilic dermatoses of haematological malignancies, run a benign clinical course but portend a significant negative impairment on a patient's quality of life. In rare cases, the skin eruption reflects immunological alterations associated with an unfavourable prognosis of the associated haematological disorder. Therapeutic management of immune-mediated skin diseases in patients with haematological malignancies is often challenging. Systemic corticosteroids and immunosuppressive drugs are considered frontline therapies but may considerably augment the risk of serious infections. Indeed, developing a specific targeted therapeutic approach is of crucial importance for this particularly fragile patient population. This review provides an up-to-date overview on the immune-mediated skin diseases most frequently encountered by patients with onco-haematological disorders, discussing new pathogenic advances and therapeutic options on the horizon

A practical algorithmic approach to mature aggressive B cell lymphoma diagnosis in the double/triple hit era. Selecting cases, matching clinical benefit. A position paper from the Italian Group of Haematopathology (G.I.E.)

An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient

Ohjelmistotyön tehostaminen automaatioympäristössä. Case: Jenkins

Tämän opinnäytetyön tarkoituksena oli toteuttaa Codecontrol Oy:lle avoimeen lähdekoodiin perustuvan web-pohjaisen Jenkins-palvelinsovelluksen asentaminen toimintakuntoon fyysiselle palvelimelle ja jakaa se usealle virtuaalipalvelimelle nykyisen yhden sijasta saaden kokonaisuus hyödyntämään master-slave -arkkitehtuurin mukaista ohjelmistoautomatisointimallia. Ennen varsinaista toteutusosuutta tämän opinnäytetyön teoriaosuudessa kerrotaan jatkuvasta integraatiosta ja jatkuvasta kehityksestä sekä niiden merkityksestä ohjelmistokehitykselle. Teoriaosuuden lopuksi esitellään toteutuksessa asennettava web-pohjainen palvelinsovellus Jenkins.The purpose of this thesis was to implement an open source web-based Jenkins server application installation into physical server for Codecontrol Oy and distribute it to multiple virtual servers instead of the existing one, thus enabling the whole utilization of the master-slave -architecture-based software automation model. Before the actual implementation part, the theoretical part of this thesis tells about continuous integration and continuous development and their significance for software development. Web-based server application Jenkins is introduced at the end of the theoretical part