Multigap RPC time resolution to 511 keV annihilation photons

The time resolution of Multigap Resistive Plate Counters (MRPCs) to $511$ keV gamma rays has been investigated using a $^{22}$Na source and four detectors. The MRPCs time resolution has been derived from the Time-of-Flight information, measured from pairs of space correlated triggered events. A GEANT4 simulation has been performed to analyze possible setup contributions and to support experimental results. A time resolution (FWHM) of $376$ ps and $312$ ps has been measured for a single MRPC with four $250$ $\mu$m gas gaps by considering respectively one and two independent pairs of detectors.Comment: 25 pages, 14 figure

Folates in Trypanosoma brucei: achievements and opportunities

Trypanosoma brucei is the agent of human African trypanosomiasis (HAT), a neglected disease that threatens the lives of 65 million people in sub-Saharan Africa every year. Unfortunately, available therapies are unsatisfactory, due primarily to safety issues and development of drug resistance. Over the last decades significant effort has been made in the discovery of new potential anti-HAT agents, with help from the World Health Organization (WHO) and private\u2013public partnerships such as the Drugs for Neglected Diseases Initiative (DNDi). Whereas antifolates have been a valuable source of drugs against bacterial infections and malaria, compounds effective against T. brucei have not yet been identified. Considering the relatively simple folate metabolic pathway in T. brucei, along with results obtained in this research field so far, we believe that further investigations might lead to effective chemotherapeutic agents. Herein we present a selection of the more promising results obtained so far in this field, underlining the opportunities that could lead to successful therapeutic approaches in the future

Which role for a European Minister of Economy and Finance in a European Fiscal Union?

The European Commission has proposed to inaugurate a European Minister of Economy and Finance with the broad purpose of streamlining the complex and fragmented decision-making processes within the European Monetary Union. The Minister would jointly serve as Vice-President of the Commission and President of the Eurogroup, and have the tasks of coordinating budgetary instruments and structural reforms, designing and implementing adequate fiscal policies for the euro area, coordinating the enforcement of the Stability and Growth Pact, among others. This policy report discusses the potential role the Minister could play in the development of the European Fiscal Union. The report lays out the main challenges along the current institutional solutions facing several dimensions of the Fiscal Union, in particular related to fiscal sustainability, macroeconomic shocks, incentives of structural reforms, and the optimum provision of European public goods. The report then discusses whether and to what degree the new European Minister of Economy and Finance can provide appropriate solutions to these challenges for the Fiscal Union

The expression of MDM2/CDK4 gene product in the differential diagnosis of well differentiated liposarcoma and large deep-seated lipoma

Ordinary lipomas are cytogenetically characterized by a variety of balanced rearrangements involving chromosome segment 12q13–15, whereas well differentiated liposarcomas (WDL) show supernumerary ring and giant marker chromosomes, known to contain amplified 12q sequences. The tight correlation between the presence of ring chromosomes and both amplification and overexpression of MDM2 and CDK4 genes suggests the exploration of the possibility that immunocytochemistry (ICC) might assist in the differential diagnosis of lipoma-like well differentiated liposarcomas (LL-WDL) and large deep-seated lipomas (LDSL). For this purpose, 21 cases of the former and 19 cases of the latter tumours were analysed by ICC and, according to the availability of material, by molecular and cytogenetic approaches. All lipomas displayed a null MDM2/CDK4 phenotype, whereas all LL-WDL showed MDM2/CDK4 or CDK4 phenotypes. Southern blot analysis performed on 16 suitable cases, complemented by fluorescence in situ hybridization and classical cytogenetic analysis in 11 cases, was consistent with, and further supported the immunophenotyping data. In conclusion, MDM2/CDK4 product-based immunophenotyping appears to represent a valuable method for the categorization of arguable LDSL. © 2000 Cancer Research Campaig

Machine learning prediction models for mitral valve repairability and mitral regurgitation recurrence in patients undergoing surgical mitral valve repair

Background: Mitral valve regurgitation (MR) is the most common valvular heart disease and current variables associated with MR recurrence are still controversial. We aim to develop a machine learning-based prognostic model to predict causes of mitral valve (MV) repair failure and MR recurrence. Methods: 1000 patients who underwent MV repair at our institution between 2008 and 2018 were enrolled. Patients were followed longitudinally for up to three years. Clinical and echocardiographic data were included in the analysis. Endpoints were MV repair surgical failure with consequent MV replacement or moderate/severe MR (>2+) recurrence at one-month and mod-erate/severe MR recurrence after three years. Results: 817 patients (DS1) had an echocardiographic examination at one-month while 295 (DS2) also had one at three years. Data were randomly divided into training (DS1: n = 654; DS2: n = 206) and validation (DS1: n = 164; DS2 n = 89) cohorts. For intra-operative or early MV repair failure assessment, the best area under the curve (AUC) was 0.75 and the complexity of mitral valve prolapse was the main predictor. In predicting moderate/severe recurrent MR at three years, the best AUC was 0.92 and residual MR at six months was the most important predictor. Conclusions: Machine learning algorithms may improve prognosis after MV repair procedure, thus improving indications for correct candidate selection for MV surgical repair

Immunoglobulin A Nephropathy. Recurrence After Renal Transplantation

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. The disease generally runs an indolent course but may lead to ESRD in 20-30% of patients in 20 years or more after diagnosis. Patients with IgA nephropathy are ideal candidates for renal transplant because they are generally relatively young and with few comorbidities. Their graft survival is better or comparable to that of controls at 10 years, though few data are available after 10 years of follow-up. Recurrence of the original disease in the graft is a well-known complication of transplant in IgAN and is a significant cause of deterioration of graft function. Recurrent IgAN rarely manifests clinically before 3 years post transplantation. Recurrence rate is estimated to be around 30% with considerable differences among different series. Despite these factors there is no certain recurrence predictor, young age at renal transplant, rapid progression of the original disease and higher levels of circulating galactose-deficient IgA1 and IgA-IgG immune complexes are all associated with a higher rate of recurrence. Which pathogenetic mechanisms are responsible for the progression of the recurrence to graft function deterioration, and what therapy can prevent or slow down the progression of the disease in the graft, are open questions. The aim of this review is to describe the clinical outcome of renal transplantation in IgA patients with attention to the rate and the predictors of recurrence and to discuss the available therapeutic options for the management of recurrence

Identification of a novel spliced variant of the SYT gene expressed in normal tissues and in synovial sarcoma

Synovial sarcoma (SS) is cytogenetically characterized by the translocation t(X;18)(p11.2-q11.2) generating a fusion between the SYT gene on chromosome 18 and one member of the SSX family gene (SSX1; SSX2; SSX4) on chromosome X. Here, we report for the first time that 2 forms of SYT mRNA are present in both normal tissues and SSs. By amplifying the full-length SYT cDNA of two SSs, we detected 2 bands, here designated N-SYT and I-SYT. The latter, previously undescribed, contains an in-frame insertion of 93 bp. Its sequencing revealed a 100% homology with the mouse SYT gene. These two SYT forms were present, although in different amounts, in all human normal tissues examined, including kidney, stomach, lung, colon, liver and synovia. Coexistence of N-SYT and I-SYT (both fused with SSX) was detected in a series of 59 SSs (35 monophasic and 24 biphasic) and in a SS cell line. A preliminary analysis of the differential expression levels of N-SYT and I-SYT in SSs revealed that the latter was consistently overexpressed, suggesting a role in SS pathogenesis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Usefulness of multimodality imaging approach in the diagnosis of mechanical prosthetic valve dysfunction

Background Although the long-term outcome of mechanical mitral and aortic prosthetic valve (M-PV, Ao-PV), PV dysfunction (PVD) remains a very serious complication associated with high morbidity and mortality. Thrombosis/pannus and paravalvular leak are the 2 main mechanisms of PVD. The diagnosis of PVD, based on clinical presentation may be challenging, but it is essential for referring the patient to the optimal treatment (clinical follow-up, thrombolysis, surgery). An integrated multimodality imaging approach, comprising several parameters by transthoracic echocardiography (TTE) and fluoroscopy (F), is mandatory to pursue the correct therapeutic pathway. Purpose This study aims to evaluate the incremental diagnostic value of combined TTE+F over each imaging modality alone in symptomatic pts with Ao-PV or M-PV and high suspicion of PVD. Methods 387 consecutive pts (63\ub111y, 213 Ao-PV, 173 M-PV) suspected for PVD, symptomatic for dyspnea, embolic events, fever or haemolysis were enrolled. All patients were imaged by TTE and F within 2 days after the admission to the hospital. TTE was defined positive for PVD in presence of intra/para-prosthetic regurgitation or high transprosthetic gradient (>20mmHg in Ao-PV, >8mmHg in M-PV) together with altered Doppler parameters (for Ao-PV: DVI <0.25, AT>95ms; for M-PV: Peak Mitral Velocity>2m/sec, VTIPrMV/VTILVO>2.5, PHT>130ms). F was defined positive for PVD when leaflet/s restriction occurs. PVD was confirmed by transoesophageal echocardiography (TOE) or positive response of thrombolysis (T), or surgical inspection (S). Results PVD was found in 46% (99/213) of Ao-PV and in 53% (91/173) of M-PV at TOE/T/S. Sensitivity (SE), specificity (SP), negative predictive value (NPV), positive predictive value (PPV) and diagnostic accuracy (ACC) for TTE, F and combined TTE+F are reported in Table. The integration of TTE+F data significantly improved ACC both for Ao-PV and M-PV. At ROC analysis, the combined model of TTE+F showed the highest AUC for the detection of PVD compared with TTE and F alone (Figure). Table 1. Comparison of diagnostic accuracy between TTE, F, and TTE+F TTE-Ao-PV (n=211) F-Ao_PV (n=204) TTE+F-Ao-PV (n=202) TTE-M-PV (n=172) F-M-PV (n=158) TTE+F-M-PV (n=157) SE / SP / NPV / PPV / ACC (%) 86 / 89 / 88 / 88 / 88 59 / 99 / 72 / 98 / 79 94 / 88 / 94 / 88 / 91 74 / 90 / 75 / 89 / 81 49 / 96 / 60 / 93 / 70 81 / 86 / 78 / 88 / 83 Figure 1. ROC curves Conclusions In patients with clinical suspicion of PVD, TTE and F are both valid tools to evaluate the PV performance. However, the combined model of TTE+F had a significant incremental value over TTE or F alone to diagnose the presence of PVD. This multimodality imaging approach allows to overcome several weaknesses of the TTE or F alone and consequently provides a prompt recognition of PVD even though TOE remains the gold standard to diagnose paravalvular Leak and non-obstructive thrombosis

Prolonged remission of disseminated atypical adenomatous hyperplasia under gefitinib.

Abstract:Atypical adenomatous hyperplasia (AAH) is a putative precursor of bronchioloalveolar carcinoma (BAC) and adenocarcinoma of the lung, developing from terminal respiratory unit cells. AAH and BAC lesions typically present as ground-glass opacities at spiral chest computed tomography. Epidermal growth factor receptor polysomy/mutations, conferring higher sensitivity to Gefitinib, are frequent in BAC but less common in AAH. We describe an interesting case of disseminated AAH showing a sustained remission under Gefitinib therapy