Design of the Target Dump Injection Segmented (TDIS) in the framework of the High Luminosity Large Hadron Collider (HL-LHC) project

The High Luminosity Large Hadron Collider (HL-LHC) Project at CERN calls for increasing beam brightness and intensity. In this scenario, most equipment has to be redesigned and rebuilt. In particular, beam intercepting devices (such as dumps, collimators, absorbers and scrapers) have to withstand impact or scraping of the new intense HL-LHC beams without failure. Furthermore, minimizing the electromagnetic beam-device interactions is also a key design driver since they can lead to beam instabilities and excessive thermo-mechanical loading of devices. In this context, the present study assesses the conceptual design quality of the new LHC injection protection absorber, the Target Dump Injection Segmented (TDIS), from an electromagnetic and thermo-mechanical perspective. This contribution analyzes the thermo-mechanical response of the device considering two cases: an accidental beam impact scenario and another accidental scenario with complete failure of the RFcontacts. In addition, this paper presents the preliminary results from the simulation of the energy deposited by the two counter-rotating beams circulating in the device

Childhood polycythemia vera and essential thrombocythemia: Does their pathogenesis overlap with that of adult patients?

[No abstract available

Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis.

Background The MPL(Ser505Asn) mutation has been reported to be a cause of hereditary thrombocythemia. Recently, we detected this mutation in a large proportion of children with familial thrombocythemia, suggesting that in Italy the incidence of MPL(Ser505Asn) mutation could be underestimated. DESIGN AND METHODS: We extended the search for this mutation to all patients with essential thrombocythemia who had a positive family history for thrombocytosis or essential thrombocythemia. We identified eight Italian families positive for the MPL(Ser505Asn) mutation. Clinical and hematologic data were available for members of seven families, including 21 patients with a proven mutation and 20 relatives with thrombocytosis. RESULTS: Fifteen major thrombotic episodes, nine of which were fatal, were recorded among 41 patients. The thrombotic manifestation was stroke in four cases, myocardial infarction in seven cases, fetal loss in two cases, deep vein thrombosis of the leg in one case and Budd Chiari syndrome in one case. Almost all patients over 20 years old had splenomegaly and bone marrow fibrosis, while these were rarely observed in patients under 20 years old, suggesting that these manifestations are associated with aging. Finally, the life expectancy of family members with thrombocytosis was significantly shorter than that of members without thrombocytosis (P=0.003). Conclusions Patients with familial thrombocytosis caused by a MPL(Ser505Asn) mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy

Red Blood Cell Exchange as a Valid Therapeutic Approach for Pregnancy Management in Sickle Cell Disease: Three Explicative Cases and Systematic Review of Literature

Pregnancy in women with sickle cell disease (SCD) is a high-risk situation, especially during the third trimester of gestation and in the post-partum period, due to chronic hypoxia and vaso-occlusive phenomena occurring in the maternal–fetal microcirculation: as a result, unfavorable outcomes, such as intra-uterine growth restriction, prematurity or fetal loss are more frequent in SCD pregnancies. Therefore, there is a consensus on the need for a strict and multidisciplinary follow-up within specialized structures. Transfusion support remains the mainstay of treatment of SCD pregnancies, whereas more targeted modalities are still controversial: the benefit of prophylactic management, either by simple transfusions or by automated red blood cell exchange (aRBCX), is not unanimously recognized. We illustrate the cases of three SCD pregnant patients who underwent aRBCX procedures at our institution in different clinical scenarios. Moreover, we carried out a careful literature revision to investigate the management of pregnancy in SCD, with a particular focus on the viability of aRBCX. Our experience and the current literature support the use of aRBCX in pregnancy as a feasible and safe procedure, provided that specialized equipment and an experienced apheresis team is available. However, further research in this high-risk population, with appropriately powered prospective trials, is desirable to refine the indications and timing of aRBCX and to confirm the advantages of this approach on other transfusion modalities

Human amniotic mesenchymal stromal cells support the ex vivo expansion of cord blood hematopoietic stem cells

Currently over 30 000 allogeneic hematopoietic stem cell (HSC) transplantations have been performed for the treatment of hematological and nonhematological diseases using HSC from umbilical cord blood (CB). However, the wide utilization of CB as a source of HSC is limited by the low number of cells recovered. One strategy to expand ex vivo CB-HSC is represented by the use of bone marrow mesenchymal stromal cells (BM-MSCs) as a feeder to enhance HSC proliferation while maintaining HSC stemness. Indeed, BM-MSCs have been recognized as one of the most relevant players in the HSC niche. Thus, it has been hypothesized that they can support the ex vivo expansion of HSC by mimicking the physiological microenvironment present in the hematopoietic niche. Due to the role of placenta in supporting fetal hematopoiesis, MSC derived from the amniotic membrane (hAMSC) of human term placenta could represent an interesting alternative to BM-MSC as a feeder layer to enhance the proliferation and maintain HSC stemness. Therefore, in this study we investigated if hAMSC could support the ex vivo expansion of HSC and progenitor cells. The capacity of hAMSCs to support the ex vivo expansion of CB-HSC was evaluated in comparison to the control condition represented by the CB-CD34+ cells without a feeder layer. The coculture was performed at two different CD34+:MSC ratios (1:2 and 1:8) in both cell-to-cell contact and transwell setting. After 7 days, the cells were collected and analyzed for phenotype and functionality. Our results suggest that hAMSCs represent a valuable alternative to BM-MSC to support: (a) the ex vivo expansion of CB-HSC in both contact and transwell systems, (b) the colony forming unit ability, and (c) long-term culture initiating cells ability. Overall, these findings may contribute to address the unmet need of high HSC content in CB units available for transplantation

Postoperative respiratory failure in liver transplantation: Risk factors and effect on prognosis

Background :Postoperative respiratory failure (PRF, namely mechanical ventilation >48 hours) significantly affects morbidity and mortality in liver transplantation (LTx). Previous studies analyzed only one or two categories of PRF risk factors (preoperative, intraoperative or postoperative ones). The aims of this study were to identify PRF predictors, to assess the length of stay (LoS) in ICU and the 90-day survival according to the PRF in LTx patients. Methods: Two classification approaches were used: systematic classification (recipient-related preoperative factors; intraoperative factors; logistic factors; donor factors; postoperative ICU factors; postoperative surgical factors) and patient/organ classification (patient-related general factors; native-liver factors; new-liver factors; kidney factors; heart factors; brain factors; lung factors). Two hundred adult non-acute patients were included. Missing analysis was performed. The competitive role of each factor was assessed. Results: PRF occurred in 36.0% of cases. Among 28 significant PRF predictors at univariate analysis, 6 were excluded because of collinearity, 22 were investigated by ROC curves and by logistic regression analysis. Recipient age (OR = 1.05; p = 0.010), female sex (OR = 2.75; p = 0.018), Model for End-Stage Liver Disease (MELD, OR = 1.09; p<0.001), restrictive lung pattern (OR = 2.49; p = 0.027), intraoperative veno-venous bypass (VVBP, OR = 3.03; p = 0.008), pre-extubation PaCO 2 (OR = 1.11; p = 0.003) and Model for Early Allograft Function (MEAF, OR = 1.37; p<0.001) resulted independent PRF risk factors. As compared to patients without PRF, the PRF-group had longer LoS (10 days IQR 7-18 versus 5 days IQR 4-7, respectively; p<0.001) and lower day-90 survival (86.0% versus 97.6% respectively, p<0.001). Conclusion: In conclusion, MELD, restrictive lung pattern, surgical complexity as captured by VVBP, pre-extubation PaCO 2 and MEAF are the main predictors of PRF in non-acute LTx patients

Development and Validation of a Comprehensive Model to Estimate Early Allograft Failure among Patients Requiring Early Liver Retransplant

Importance: Expansion of donor acceptance criteria for liver transplant increased the risk for early allograft failure (EAF), and although EAF prediction is pivotal to optimize transplant outcomes, there is no consensus on specific EAF indicators or timing to evaluate EAF. Recently, the Liver Graft Assessment Following Transplantation (L-GrAFT) algorithm, based on aspartate transaminase, bilirubin, platelet, and international normalized ratio kinetics, was developed from a single-center database gathered from 2002 to 2015. Objective: To develop and validate a simplified comprehensive model estimating at day 10 after liver transplant the EAF risk at day 90 (the Early Allograft Failure Simplified Estimation [EASE] score) and, secondarily, to identify early those patients with unsustainable EAF risk who are suitable for retransplant. Design, Setting, and Participants: This multicenter cohort study was designed to develop a score capturing a continuum from normal graft function to nonfunction after transplant. Both parenchymal and vascular factors, which provide an indication to list for retransplant, were included among the EAF determinants. The L-GrAFT kinetic approach was adopted and modified with fewer data entries and novel variables. The population included 1609 patients in Italy for the derivation set and 538 patients in the UK for the validation set; all were patients who underwent transplant in 2016 and 2017. Main Outcomes and Measures: Early allograft failure was defined as graft failure (codified by retransplant or death) for any reason within 90 days after transplant. Results: At day 90 after transplant, the incidence of EAF was 110 of 1609 patients (6.8%) in the derivation set and 41 of 538 patients (7.6%) in the external validation set. Median (interquartile range) ages were 57 (51-62) years in the derivation data set and 56 (49-62) years in the validation data set. The EASE score was developed through 17 entries derived from 8 variables, including the Model for End-stage Liver Disease score, blood transfusion, early thrombosis of hepatic vessels, and kinetic parameters of transaminases, platelet count, and bilirubin. Donor parameters (age, donation after cardiac death, and machine perfusion) were not associated with EAF risk. Results were adjusted for transplant center volume. In receiver operating characteristic curve analyses, the EASE score outperformed L-GrAFT, Model for Early Allograft Function, Early Allograft Dysfunction, Eurotransplant Donor Risk Index, donor age × Model for End-stage Liver Disease, and Donor Risk Index scores, estimating day 90 EAF in 87% (95% CI, 83%-91%) of cases in both the derivation data set and the internal validation data set. Patients could be stratified in 5 classes, with those in the highest class exhibiting unsustainable EAF risk. Conclusions and Relevance: This study found that the developed EASE score reliably estimated EAF risk. Knowledge of contributing factors may help clinicians to mitigate risk factors and guide them through the challenging clinical decision to allocate patients to early liver retransplant. The EASE score may be used in translational research across transplant centers