Krumped control: Constructing the L.A.P.D. interface

What is at stake in this thesis are the ways in which we approach policing and controlling the cityscape, and, more importantly, architecture's role in this authoritative and institutional apparatuses. Looking at the Watts neighborhood of South Central Los Angeles as both example and test site, this project analyzes how and why the policing apparatus of a city fails to operate effectively, especially in contested urban environments. Existing architectural precedents here, and in other dense cities, have been reduced to emblematic fortresses, where the station and the police are rendered inactive and inaccessible. Responding to this crisis, this thesis re-imagines the police station as a piece of city infrastructure that situates itself as an interface between police and populus. Borrowing from vernacular models of spatial organization and local public phenomenon, the traditionally invisible policing processes get invaded by the surrounding neighborhood, rendering those processes visible and accessible

Healthcare workers training courses on vaccinations: A flexible format easily adaptable to different healthcare settings.

Since 2017, Italy has expanded the compulsory vaccination from 4 to 10 for those aged 0 to 16 years. Because of the great organizational effort required for the immunization services, minor attention was given to the vaccinations not included among the mandatory ones. This situation led to a real difficulty in harmonizing the vaccination procedures even inside a single region. In the Lazio region, the Laboratory of Vaccinology of the University of Rome Tor Vergata established a working group to create a new training model for healthcare professionals. The course program proposed an update of three vaccinations which are not mandatory but actively offered. It included the same part of scientific updating and a variable part based on local experiences. A specific anonymous questionnaire on knowledge and attitude was administered. The study aimed to propose a general format of training courses for vaccination centers adaptable to the individual local health units (ASLs) and to evaluate through questionnaires. The results show differences in knowledge and attitudes toward non‐mandatory vaccinations among the ASLs of Lazio, confirming the usefulness of a support to make knowledge and procedures homogeneous. This model could be adapted to any healthcare setting and exported to other services

Taking screenshots of the invisible: A study on bacterial contamination of mobile phones from university students of healthcare professions in Rome, Italy

Mobile phones (MPs) are commonly used both in the personal and professional life. We assessed microbiological contamination of MPs from 108 students in healthcare professions (HPs), in relation to their demographic characteristics and MPs handling habits, collected by means of a questionnaire. Cultural and biochemical tests were performed, and statistical analyses were carried out. Staphylococci were present in 85% of MPs, Enterococci in 37%, Coliforms in 6.5%; E. coli was never detected. Staphylococcus epidermidis was the most frequently isolated staphylococcal species (72% of MPs), followed by S. capitis (14%), S. saprophyticus, S. warneri, S. xylosus (6%), and by S. aureus (4%). Heterotrophic Plate Counts (HPC) at 37◦C, ranged from 0 to 1.2 × 104 CFU/dm2 (mean = 362 CFU/dm2). In univariate analysis, the male gender only was significantly associated with higher HPCs and enterococcal contamination. Multiple linear regression models explained only 17% and 16% of the HPC 37◦C and staphylococcal load variability, respectively. Developing specific guidelines for a hygienic use of MPs in clinical settings, for preventing cross-infection risks, is advisable, as well as introducing specific training programs to HP students. MPs decontamination procedures could also be implemented in the community

Anopheline mosquito saliva contains bacteria that are transferred to a mammalian host through blood feeding

Introduction: Malaria transmission occurs when Plasmodium sporozoites are transferred from the salivary glands of anopheline mosquitoes to a human host through the injection of saliva. The need for better understanding, as well as novel modes of inhibiting, this key event in transmission has driven intense study of the protein and miRNA content of saliva. Until now the possibility that mosquito saliva may also contain bacteria has remained an open question despite the well documented presence of a rich microbiome in salivary glands. MethodsUsing both 16S rRNA sequencing and MALDI-TOF approaches, we characterized the composition of the saliva microbiome of An. gambiae and An. stephensi mosquitoes which respectively represent two of the most important vectors for the major malaria-causing parasites P. falciparum and P. vivax. ResultsTo eliminate the possible detection of non-mosquito-derived bacteria, we used a transgenic, fluorescent strain of one of the identified bacteria, Serratiamarcescens, to infect mosquitoes and detect its presence in mosquito salivary glands as well as its transfer to, and colonization of, mammalian host tissues following a mosquito bite. We also showed that Plasmodium infection modified the mosquito microbiota, increasing the presence of Serratia while diminishing the presence of Elizabethkingia and that both P. berghei and Serratia were transferred to, and colonized mammalian tissues. DiscussionThese data thus document the presence of bacteria in mosquito saliva, their transfer to, and growth in a mammalian host as well as possible interactions with Plasmodium transmission. Together they raise the possible role of mosquitoes as vectors of bacterial infection and the utility of commensal mosquito bacteria for the development of transmission-blocking strategies within a mammalian host

Microbiology and Clinical Outcome of Hospital-Acquired Respiratory Infections in an Italian Teaching Hospital: A Retrospective Study

The burden, microbial etiology and clinical impact of hospital-acquired respiratory infections (HARIs) were determined at an Italian teaching hospital over a 12-month period. For this purpose, overall ordinary hospitalizations >= 2 days of subjects over 18 years old with discharge from 1 January 2018 to 31 December 2018 were examined by cross-referencing demographic and clinical data from hospital discharge forms with microbiological data from the computer system of the Microbiology Unit. We identified 329 individuals with HARIs (96 females and 233 males; median age 70 years, range 18-93), who represented 1/4 of the total hospital-acquired infections (HAIs) in the period. The inpatient setting was medical and surgical in similar proportions (169 vs. 160, respectively) and the mean hospital stay was 38.9 +/- 33.6 days. One hundred and forty patients (42.6% of the total sample) were suffering from one or more chronic diseases. A total of 581 microorganisms (82 antibiotic-resistant and 499 non-resistant) were detected in HARI patients. The most common isolated species were Staphylococcus aureus (16.7%), Klebsiella pneumoniae (13.3%), Pseudomonas spp. (12.6%) and Acinetobacter baumannii (10.5%), followed by Enterobacter spp. (5.3%), Escherichia coli (5.2%) and Enterococcus spp. (4.8%). One hundred and sixty-seven individuals (49.0% of the total) had polymicrobial infections. One hundred thirty-one patients (39.8% of the total) underwent endotracheal intubation and mechanical ventilation and 62.6% of them died, compared to 17.7% of the non-intubated patients. Multivariable analysis confirmed a positive correlation between death and increased age (p = 0.05), surgical MDC (p = 0.007), number of microorganisms over the sample mean (p = 0.001), the presence of chronic diseases (p = 0.046), and intubation and mechanical ventilation (p < 0.0001). A positive correlation between intubation and antibiotic-resistant organisms (p = 0.003) was also found. HARIs are still a major public health problem and require constant surveillance due to their severe clinical outcome

Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab

Background: Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade. Methods: Data from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015–December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan–Meier method, landmark-analyses and Cox regressions. Results: Patients, mostly males (63%, n = 84) with a median age of 35 years (range, 15–82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1–9), received a median of 18 nivolumab doses (range, 1–57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI. Conclusions: In patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic ‘equalizers’ counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL

The role of the Bcl-2 family of proteins in the pathogenesis of B-cell chronic lymphocytic leukaemia

B-cell chronic lymphocytic leukaemia (B-CLL) is an acquired neoplastic disease characterised by a clonal accumulation of long-lived, functionally immature and CD5+ B-lymphocytes, which particularly accumulate in the lymphatic system, peripheral blood, bone marrow, spleen and liver. Symptoms include lymphocytosis, immune system dysfunction and autoimmune disease, but transformation to more aggressive forms of neoplastic disease occur and development of a second malignancy is not uncommon. The disease is one of later years being unusual before 50 years of age, the rates of incidence vary on a racial basis, and it has a highly variable prognosis. Some patients die within months of diagnosis despite intensive treatment, whilst others survive for 30-plus years without any form of medical intervention and die of unrelated causes. The principal causes of death in patients whose deaths are directly related to the disease are opportunistic infection due to the impairment of immune system function and bleeding disorders. No treatment has been shown to cure the disease or consistently extend life expectancy. It has been recognised for more than 30 years that the accumulation of malignant cells in B-CLL is at least as important in the pathogenesis of the disease as their neoplastic proliferation. With the discoveries that Bcl-2 extended the life of follicular lymphoma cells by conferring resistance to apoptosis and was commonly expressed in B-CLL cells, it was extrapolated that Bcl-2 might play a similar role in the development of the disease by extending the life span of B-CLL cells. Bcl-2 has frequently been shown to be over expressed in B-CLL cells and genetic translocations and/or malfunction of Bcl-2 family regulating molecular entities may play a part in this. However, since its discovery, Bcl-2 has been shown to be part of a large family of genes which is highly and evolutionarily conserved. Members of the bcl-2 family are defined by sequence homology in four Bcl-2 homology (BH) regions and a hydrophobic membrane-spanning domain, with the possession of specific BH domains determining whether individual proteins have pro- or anti-apoptotic activity. Family members such as Bcl-2 and Bcl-XL extend the life span of cells, whilst others such as Bax and Bak shorten it. Oltvai, Milliman and Korsmeyer have proposed a general model of apoptosis, in which the cell's apoptotic fate is determined by the cellular balance between pro- and anti-apoptotic bcl-2 family members. The effect of unregulated expression of Bcl-2 family members in B-CLL cells conforms to this paradigm and resistance to apoptosis appears to be conferred through a cellular imbalance of power between pro- and anti-apoptotic bcl-2 family members, particularly Bcl-2 and Bax, which is tilted in favour of cell survival. However, the apoptotic fate of B-CLL cells, and hence the neoplasm, may be influenced by other family members, with Mcl-1, Bcl-XL, Bak, with the non-family but Bcl-2-associated protein, Bag-1, also found expressed in B-CLL cells. Similarities between the structure of the more conserved family members and other pore-forming proteins, along with the ability of Bcl-2, Bcl-XL, and Bax to form pores in synthetic membranes, suggest that they may exert their influence through pore-forming activities in intracellular membranes, particularly mitochondrial membranes. Bcl-2 family members may regulate apoptosis by changing the permeability of membranes to ions and apoptosis-inducing molecules, and physical interactions between Bcl-2 family proteins mediated by the BH domains may be important in both pore-forming and pore-inhibiting activities. Research findings suggest that the levels of Bcl-2 family members in B-CLL cells may be modulated by a wide range of largely extracellular influences, including the cytokines interleukin-4 (IL-4), IL-8, IL-10, interferon-a (IFN-?), IFN-?, and basic fibroblast growth factor (bPGF). Levels of Bcl-2 family members may also be modulated by contact between B-CLL cells and bone marrow (BM) stromal cells, activation of lgM, CD95, CD40 or CD6, the p53 gene product, and co-cultivation with CDw32-transfected murine fibroblasts. Such modulation may offer some insight into the pathogenesis of the disease, an explanation for the higher level expression of Bcl-2 family members in B-CLL, and an explanation for the highly variable prognosis. Additionally, if Bcl-2 family members can be shown unequivocally to be controlled by any of these molecular entities, the existence of these influences may offer the opportunity to reduce the neoplastic cells' apoptotic threshold by manipulating the relative levels of pro- and anti-apoptotic Bcl-2 family members as a treatment regime, or prior to more conventional treatment regimes

Venous Thromboembolism in Lymphoma: Risk Stratification and Antithrombotic Prophylaxis

Lymphoma is listed among the neoplasias with a high risk of venous thromboembolism (VTE). Risk factors for VTE appear to differ from risk factors in solid tumors. We review the literature of the last 20 years for reports identifying these risk factors in cohorts consisting exclusively of lymphoma patients. We selected 25 publications. The most frequent studies were analyses of retrospective single-center cohorts. We also included two reports of pooled analyses of clinical trials, two meta-analyses, two analyses of patient registries, and three analyses of population-based databases. The VTE risk is the highest upfront during the first two months after lymphoma diagnosis and decreases over time. This upfront risk may be related to tumor burden and the start of chemotherapy as contributing factors. Factors consistently reported as VTE risk factors are aggressive histology, a performance status ECOG 65 2 leading to increased immobility, more extensive disease, and localization to particular sites, such as central nervous system (CNS) and mediastinal mass. Association between laboratory values that are part of risk assessment models in solid tumors and VTE risk in lymphomas are very inconsistent. Recently, VTE risk scores for lymphoma were developed that need further validation, before they can be used for risk stratification and primary prophylaxis. Knowledge of VTE risk factors in lymphomas may help in the evaluation of the individual risk-benefit ratio of prophylaxis and help to design prospective studies on primary prophylaxis in lymphoma

Treatment with Idelalisib in Patients with Relapsed or Refractory Follicular Lymphoma: The Observational Italian Multicenter FolIdela Study

Follicular lymphoma (FL) is an indolent hematological disease, often responsive to the first line of treatment, but characterized by repeated relapses. The therapeutic algorithm for relapsed/refractory FL patients comprises phosphatidylinositol 3-kinase inhibitors. Idelalisib showed anticancer activity, while inducing a significant rate of toxicities. Since the evidence in the literature on its use in normal clinical practice is scarce, a retrospective multicenter study was conducted to evaluate effectiveness and tolerability in a real-life context. Seventy-two patients with a median age at diagnosis of 57.2 years—mostly with an advanced stage (88.9%) and relapsed to the most recent therapy (79.1%)—were enrolled. The median number of prior therapies was three (20.8% refractory to the last therapy before idelalisib). With a median number of 4 months of treatment, the overall response rate was 41.7% (20.8% complete responses). Median disease-free survival and overall survival were achieved at 8.4 months and at 4 years, respectively. Forty-four percent of patients experienced at least one drug-related toxicity: 6.9% hematological ones and 43% non-hematological. The study confirmed that idelalisib has anticancer effectiveness and an acceptable safety profile in relapsed/refractory FL with unfavorable prognostic characteristics, even in the context of normal clinical practice