La Spazializzazione della Sicurezza delle donne attraverso la lente della Riproduzione Sociale. Il Caso Della Bolognina

Questo lavoro si inserisce nel dibattito sulle ‘geografie della paura’, che ha da tempo messo in evidenza come le percezioni di sicurezza nello spazio pubblico siano fortemente ancorate al genere. Attraverso un focus sulla spazializzazione della sicurezza delle donne nella vita quotidiana, questa ricerca contribuisce a tale dibattito proponendo l’utilizzo della riproduzione sociale come approccio, combinato a una prospettiva intersezionale, nell’intento di mostrare non solo come intervengano i processi di razzializzazione nella produzione di spazi e figure della paura, ma anche come le percezioni di sicurezza dipendano dai diversi posizionamenti dei soggetti. In termini empirici, la questione della sicurezza è stata analizzata attraverso uno studio di caso condotto in Italia in un quartiere di Bologna – la Bolognina – in cui sono state mappate: (i) le questioni di sicurezza alla luce della ristrutturazione urbana neoliberale; (ii) i discorsi di securitizzazione; (iii) l’esperienza delle donne nella vita quotidiana. In particolare, la lente della riproduzione sociale ha permesso di mostrare, in primo luogo, come il razzismo e il sessismo siano riprodotti in modo intrecciato e, in secondo luogo, come le pratiche di "fare casa" contribuiscano alla produzione dello spazio, ampliando quindi la comprensione della riproduzione sociale allo spazio urbano. Inoltre, alla luce dei risultati empirici, questo contributo adotta la lente della riproduzione sociale nel leggere la dimensione del quotidiano come strategia epistemologica per ‘provincializzare’ la teoria urbana, prendendo in considerazione l'impatto di processi più ampi di rigenerazione urbana sulle vite domestiche, e al tempo stesso gli effetti delle pratiche del ‘fare casa’ sui cambiamenti urbani, e quindi sulla teoria urbana.This dissertation contributes to the discourse on 'geographies of fear', which has highlighted how constructions of safety in public spaces are deeply gendered. By exploring women's experiences of safety in their everyday lives, this study proposes a social reproduction approach, combined with an intersectional perspective, to show how processes of racialisation are involved in producing spaces and representations of fear and how perceptions of safety depend on the different positioning of subjects. The study investigates safety through a case study conducted in Italy in a neighbourhood of Bologna (Italy) - the Bolognina - in order to map: (i) issues of safety in the context of neoliberal urban restructuring; (ii) discourses of securitisation; (iii) women's everyday experiences. The social reproduction lens extended the understanding of social reproduction to urban space by showing the intertwined reproduction of racism and sexism, and how 'home-making' practices contribute to the production of space. Therefore, based on empirical findings, the approach of social reproduction in everyday life works as an epistemological strategy to 'provincialise' urban theory by considering the impact of wider processes of urban regeneration on domestic lives, as well as the impact of women's home-making practices on urban changes

Adaptive Streaming On Heterogeneous Networks”,

ABSTRACT Specific network protocols, like MobileIP, offer seamless connectivity to mobile systems. However, the QoS requirements of streaming applications and video conferencing systems require an approach that spans across different layers of the network stack. In this paper we study how to integrate an efficient method for vertical handoff and adaptation support for multimedia streaming through heterogeneous networks. We also present experimental results obtained with our prototype on IEEE 802.11 and UMTS networks

Effect of a single intravenous zoledronic acid administration on biomarkers of acute kidney injury (AKI) in patients with osteoporosis: a pilot study

The pilot study was designed to evaluate the early effect of intravenous (iv) zoledronic acid (ZA) on renal function. METHODS: Five mg iv ZA was administered to 23 patients with osteoporosis (17 women and 6 men, mean age 73±7 SD years). Urinary NGAL, KIM-1, and MCP-1, plasma (p) MCP-1 and serum (s) IL-18, serum calcium (sCa), Creatinine clearance (CrCl), parathyroid hormone (PTH), plasma C-terminal FGF23 (pFGF23), serum (s) Klotho, calcium excretion (CaEx) and renal threshold phosphate concentration/GFR (TmPO4/GFR) were assessed at baseline, 24 hours (h) and day (d) 30 after administration. RESULTS: There was a significant decrease in sCa and CaEx at 24 h (-4.1±2.8%, p<0.01 and -28±59%, p<0.05, respectively) and d 30 (-3.9±4%, p<0.001 and 26±43%, p<0.01) and a significant increase in PTH (79.8±95.8%) at d 30 (p<0.001) compared to baseline. TmPO4/GFR significantly decreased at 24 h and d 30 (-8.6±15.9%, p<0.05 and -11.3±13.5%, p<0.001) compared to baseline. We observed no difference in the concentration of pFGF23, sKlotho and urinary AKI biomarkers at any time occasions. Mean levels of sIL-18 and pMCP-1 significantly increased at 24 h (44±88%; p<0.01 and 198±237%; p<0.001) and returned to baseline at d 30. CONCLUSIONS: Our pilot study suggests that there is no direct acute effect of ZA on kidney function. The increase in plasma MCP-1 and serum IL-18 concentration could be associated with the stimulation of immunity mechanisms occurring soon after the administration of the drug. Secondary hyperparathyroidism develops shortly after the infusion of ZA and maintained even after one month

Acute effect of zoledronic acid on the risk of cardiac dysrhythmias.

There have been recent concerns regarding the risk of serious adverse events, such as cardiac dysrhythmia and atrial fibrillation (AF), associated with bisphosphonate use in osteoporosis. This open-label, non-randomized, crossover pilot study evaluated short-term effects of zoledronic acid and placebo on the occurrence of cardiac dysrhythmias and prodysrhythmic profile in postmenopausal women with osteoporosis and low risk of cardiac dysrhythmias. Fifteen postmenopausal women (mean age 70.7 ± 6.9 years) with osteoporosis received placebo infusion on day 1 and zoledronic acid 5 mg on day 7. Standard 12-lead resting EKG measured QT parameters at baseline and up to 24 h after infusion. Continuous 24-h EKG assessed dysrhythmic events and heart rate variability (HRV) for 24 h after infusion. There were no statistically significant differences in resting EKG parameters between placebo and zoledronic acid: QTc (404.28 ± 9.28 and 410.63 ± 18.43 ms), no significant differences in mean serum electrolytes at baseline and after infusion, and no significant association between QT/QTc parameters and serum electrolytes before and after each infusion (QTc: 401.83 ± 17.73 for zoledronic acid and 404.65 ± 16.79 for placebo). There was no significant difference in HRV parameters between placebo and zoledronic acid, and no dysrhythmias were recorded at rest or with 24 h EKG monitoring. Zoledronic acid does not produce dysrhythmia or prodysrhythmic effects in the short term. Among possible mechanisms proposed for cardiac dysrhythmias with zoledronic acid, no serum electrolyte or autonomous nervous system balance perturbations have been reported

Harnessing a Novel Dyrk1a-Ablim2-MKL1 Regulatory Module in Megakaryocyte Morphogenesis to Enable Scalable Platelet "Pharming"

International audienceGrowing clinical demands for platelet transfusions combined with supply limitations have created shortages which are trending toward a global crisis. Major efforts have been taken to address key issues of platelet sources, storage, and utilization. Recent progress in ex vivo culture-based production of megakaryocytes (Mk) and platelets, "pharming," has highlighted the potential for novel, donor-independent sources amenable to antigenic editing and cryo-stockpiling. Such cultures can be easily initiated from umbilical cord blood (CB) progenitors, induced pluripotent stem cells (iPSC), or directly re-programmed somatic cells. The major roadblock associated with these Mk sources consists of their fetal ontogenic status, which is beneficial for expansion but severely limits platelet production. The ability to elicit in pre-expanded Mk an adult program of morphogenesis (polyploidization, enlargement, and proplatelet formation) would enable circumvention of this scalability barrier. A master regulator of adult Mk morphogenesis consists of the transcriptional coactivator MKL1 which undergoes nuclear translocation in response to RhoA-mediated actin polymerization, stimulated by thrombopoietin and environmental mechano-sensing. Nuclear MKL1 associates with the transcription factor SRF1 to upregulate cytoskeletal remodeling factors, including filamin A and Hic-5, that act as morphogenesis effectors. Our previous studies identified in infantile CB Mk a failure in MKL1 upregulation resulting from repression by the oncofetal RNA-binding factor IGF2BP3. Pharmacologic suppression of IGF2BP3 with BET inhibitors rescued MKL1 expression and improved platelet production but caused cycle arrest preventing polyploidization. As an alternative approach to abrogate the fetal blockade in Mk morphogenesis, we sought to promote MKL1 activity by targeting a kinase, Dyrk1a, which had been shown to restrain MKL1 from nuclear translocation. Treatment of infantile CB Mk with a variety of Dyrk1-selective inhibitors including harmine and EHT 1610 strongly enhanced polyploidization (p = 0.015 and 0.009 respectively), enlargement (p < 0.005) , and in vitro platelet release (2 fold each, p = 0.001 and 0.007 respectively), attaining levels seen with adult Mk. When xenotransplanted into NSG mice, harmine-treated CB Mk demonstrated enhanced capability for in vivo platelet release (about 5 fold, p = 0.016). CB stem cells expanded with the AHR antagonist SR1 and an iPSC-Mk cell line also responded to Dyrk1 inhibition with robustly increased morphogenesis. Several findings implicated MKL1 in this response: 1) induction of nuclear translocation by the inhibitors, 2) induction of target genes (filamin A and Hic-5) by the inhibitors, and 3) loss of response to inhibitors in Mkl1-ko murine progenitors. Supporting Dyrk1a as a relevant target, mice with Mk-specific loss of one Dyrk1a allele (Dyrk1aflox/wt;Pf4-Cre) displayed increases in platelet counts (p = 0.037) and marrow Mk polyploidization (p = 0.02). In addition, retroviral expression in human progenitors of a dominant negative Dyrk1a mutant K188R promoted Mk enlargement (p = 0.014). shRNA knockdowns could not be obtained due to toxicity of > ~60% loss of Dyrk1a. To determine mechanisms for Dyrk1a control of morphogenesis, we analyzed the actin cytoskeleton, a key regulator of MKL1. Dyrk1 inhibition in all types of Mk progenitors (adult, infantile, and iPSC) induced assembly of cortical filamentous actin (F-actin), as detected by Alexa594-phalloidin staining. Prior studies showed cytoskeletal binding by Dyrk1a and direct phosphorylation of F-actin regulators N-WASP and Ablim1. A survey of human marrow expression patterns for candidate Dyrk1a substrates (The Human Protein Atlas) identified Ablim2, as showing a Mk-specific, cortical staining pattern. Dyrk1 inhibition increased Ablim2 levels ~5-fold in CB Mk (p < 0.005), and immunofluorescence displayed a cortical distribution similar to F-actin. Lentiviral shRNA knockdown of Ablim2 abrogated all effects of Dyrk1 inhibition, blocking: F-actin formation, MKL1 nuclear translocation, activation of the MKL1 targets, and Mk morphogenesis. These findings thus delineate a novel Dyrk1a-Ablim2-MKL1 regulatory module in Mk morphogenesis that can be manipulated to address the problem of scaling ex vivo production and might also serve as a future in vivo therapeutic target for thrombocytopenia

Parathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidism, as evaluated by exercise test

Objective: To investigate whether parathyroidectomy (PTx) reverses risk factors for arrhythmias related to the QT dynamic changes evaluated during bicycle ergometry exercise test (ET). Methods: Twenty-four postmenopausal women with primary hyperparathyroidism (PHPT) (mean age 60.0 +/- 8.4 years) and 30 sex- and age-matched controls underwent ET, echocardiography, and biochemical evaluation. The following stages were considered during ET: rest, peak exercise, and recovery. The patients were randomized to two groups: 12 underwent PTx (group A) and 12 were followed-up conservatively (group B). After 6 months, the patients were studied again. Results: Groups A and B showed no differences in mean baseline biochemical values, echocardiographic parameters, and QTc interval. PHPT patients showed an increased occurrence of ventricular premature beats (VPBs) during ET compared with controls (37.0 vs 6.6%, P=0.03). Serum calcium level was a predictor of VPBs (P=0.05). Mean value of QTc was in the normal range at baseline (group A: 401 +/- 16.9; group B: 402.25 +/- 13.5 ms) but significantly lower than controls (417.8 +/- 25.1 ms, P < 0.01). A negative correlation was found between QTc and calcium values (P=0.03). Physiological reduction of QTc interval from rest to peak exercise was not observed in PHPT patients before surgery. After PTx, group A had a significant reduction in VPBs compared with baseline (at baseline, 5 of 12 vs none of 12 patients after PTx, P=0.03) and a restored normal QT adaptation during ET. Group B showed no significant changes after a 6-month period. Conclusions: PTx reduces the occurrence of VPBs and restored the QTc adaptation during ET