Procurement in a crisis: how to mitigate the risk of corruption, collusion, abuse and incompetence

During the pandemic, public procurement often had to be done at speed. A new ebook by Oriana Bandiera (LSE), Erica Bosio (World Bank) and Giancarlo Spagnolo (University of Rome II) looks at how a balance between rules and discretion can be maintained during emergency situations

Differential expression of long non-coding RNAs are related to proliferation and histological diversity in follicular lymphomas

"This is the peer reviewed version of the following article: Roisman, Alejandro, et al. "Differential expression of long non‐coding RNA s are related to proliferation and histological diversity in follicular lymphomas." British journal of haematology (2018), which has been published in final form at https://doi.org/10.1111/bjh.15656. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."Long non-coding RNAs (lncRNAs) comprise a family of non-coding transcripts that are emerging as relevant gene expression regulators of different processes, including tumour development. To determine the possible contribution of lncRNA to the pathogenesis of follicular lymphoma (FL) we performed RNA-sequencing at high depth sequencing in primary FL samples ranging from grade 1-3A to aggressive grade 3B variants using unpurified (n = 16) and purified (n = 12) tumour cell suspensions from nodal samples. FL grade 3B had a significantly higher number of differentially expressed lncRNAs (dif-lncRNAs) with potential target coding genes related to cell cycle regulation. Nine out of the 18 selected dif-lncRNAs were validated by quantitative real time polymerase chain reaction in an independent series (n = 43) of FL. RP4-694A7.2 was identified as the top deregulated lncRNA potentially involved in cell proliferation. RP4-694A7.2 silencing in the WSU-FSCCL FL cell line reduced cell proliferation due to a block in the G1/S phase. The relationship between RP4-694A7.2 and proliferation was confirmed in primary samples as its expression levels positively related to the Ki-67 proliferation index. In summary, lncRNAs are differentially expressed across the clinico-biological spectrum of FL and a subset of them, related to cell cycle, may participate in cell proliferation regulation in these tumours.Peer ReviewedPostprint (author's final draft

COVID-19 : high-resolution computed tomography findings in the first 64 patients admitted to the Hospital of Cremona, the epicentre of the pandemic in Europe

Purpose: In December 2019, a new coronavirus (SARS-CoV-2) was identified as being responsible for the pulmonary infection called COVID-19. On 21 February 2020, the first autochthonous case of COVID-19 was detected in Italy. Our goal is to report the most common chest computed tomography (CT) findings identified in 64 patients, in the initial phase of COVID-19. Methods: Sixty-four chest high-resolution computed tomography (HRCT) examinations performed at the Radiology Unit of the Hospital of Cremona, from 22 to 29 February 2020, of 64 patients during first week of hospitalization for COVID-19 were retrospectively evaluated. All cases were confirmed by real-time RT-PCR for SARS-CoV-2. Image analysis was independently conducted by 2 radiologists with 10 years and 1 year of experience in chest imaging. The inter-observer agreement was obtained by applying a Cohen’s κ test. Results: The average age of patients was 67.1 years (± 12.2); men 42 (66%). HRCT was performed on the 5th (± 1.5) day of hospitalization. More frequently, the initial CT changes of the lung show more or less extensive areas of ground-glass, as single pattern or with parenchymal consolidations. Coronavirus lung involvement appears very frequently multi-lobar, bilateral, and it concerns both subpleural and central regions. An excellent agreement (κ: 0.88-1, CI: 0.79-1.01, p < 0.05) concerning CT findings between the 2 operators was reached. Conclusions: Our data suggest that detection of the most frequent pulmonary CT-scan changes, in the early stages of COVID-19, can be performed, with excellent agreement, among readers with different experience, and consequently attribute their exact diagnostic value, in an appropriate clinical and environmental exposure setting

Differential expression of long non-coding RNAs are related to proliferation and histological diversity in follicular lymphomas

Long non‐coding RNAs (lncRNAs) comprise a family of non‐coding transcripts that are emerging as relevant gene expression regulators of different processes, including tumour development. To determine the possible contribution of lncRNA to the pathogenesis of follicular lymphoma (FL) we performed RNA‐sequencing at high depth sequencing in primary FL samples ranging from grade 1‐3A to aggressive grade 3B variants using unpurified (n = 16) and purified (n = 12) tumour cell suspensions from nodal samples. FL grade 3B had a significantly higher number of differentially expressed lncRNAs (dif‐lncRNAs) with potential target coding genes related to cell cycle regulation. Nine out of the 18 selected dif‐lncRNAs were validated by quantitative real time polymerase chain reaction in an independent series (n = 43) of FL. RP4‐694A7.2 was identified as the top deregulated lncRNA potentially involved in cell proliferation. RP4‐694A7.2 silencing in the WSU‐FSCCL FL cell line reduced cell proliferation due to a block in the G1/S phase. The relationship between RP4‐694A7.2 and proliferation was confirmed in primary samples as its expression levels positively related to the Ki‐67 proliferation index. In summary, lncRNAs are differentially expressed across the clinico‐biological spectrum of FL and a subset of them, related to cell cycle, may participate in cell proliferation regulation in these tumours

Microscopic dynamics in liquid metals: the experimental point of view

The experimental results relevant for the understanding of the microscopic dynamics in liquid metals are reviewed, with special regards to the ones achieved in the last two decades. Inelastic Neutron Scattering played a major role since the development of neutron facilities in the sixties. The last ten years, however, saw the development of third generation radiation sources, which opened the possibility of performing Inelastic Scattering with X rays, thus disclosing previously unaccessible energy-momentum regions. The purely coherent response of X rays, moreover, combined with the mixed coherent/incoherent response typical of neutron scattering, provides enormous potentialities to disentangle aspects related to the collectivity of motion from the single particle dynamics. If the last twenty years saw major experimental developments, on the theoretical side fresh ideas came up to the side of the most traditional and established theories. Beside the raw experimental results, therefore, we review models and theoretical approaches for the description of microscopic dynamics over different length-scales, from the hydrodynamic region down to the single particle regime, walking the perilous and sometimes uncharted path of the generalized hydrodynamics extension. Approaches peculiar of conductive systems, based on the ionic plasma theory, are also considered, as well as kinetic and mode coupling theory applied to hard sphere systems, which turn out to mimic with remarkable detail the atomic dynamics of liquid metals. Finally, cutting edges issues and open problems, such as the ultimate origin of the anomalous acoustic dispersion or the relevance of transport properties of a conductive systems in ruling the ionic dynamic structure factor are discussed.Comment: 53 pages, 41 figures, to appear in "The Review of Modern Physics". Tentatively scheduled for July issu

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Terre e rocce da scavo tra decreto Ronchi, "riforma ambientale" e Commissione CE

Le terre e le rocce derivanti da scavi interessano vari settori dell'industria delle costruzioni sia sotto il profilo economico sia sotto il profilo giuridico. L'eventuale riutilizzo dello smarino può essere talora difficoltoso o impossibile in relazione anche alla definizione comunitaria -in generale ed in particolare - di rifiuto, di rifiuto pericoloso ed alla disputa sui cd sottoprodotti. Questa ultima definizione viene qui opportunamente sviluppata sotto il profilo giuridico ed operativo con l'obiettivo di condurre ad una soluzione ragionevole del problema nel rispetto del diritto comunitario, dell'ambiente e delle esigenze dei settori economici coinvolt