Software Challenges For HL-LHC Data Analysis

The high energy physics community is discussing where investment is needed to prepare software for the HL-LHC and its unprecedented challenges. The ROOT project is one of the central software players in high energy physics since decades. From its experience and expectations, the ROOT team has distilled a comprehensive set of areas that should see research and development in the context of data analysis software, for making best use of HL-LHC's physics potential. This work shows what these areas could be, why the ROOT team believes investing in them is needed, which gains are expected, and where related work is ongoing. It can serve as an indication for future research proposals and cooperations

First-Line Support by Intra-Aortic Balloon Pump in Non-Ischaemic Cardiogenic Shock in the Era of Modern Ventricular Assist Devices

Objectives: Little is known about circulatory support in cardiogenic shock (CS) from other causes than the acute coronary syndrome or after cardiotomy. We evaluated the effects of first-line intra-aortic balloon pump (IABP) support in this subpopulation of CS patients. Methods: A retrospective study was performed in 27 patients with CS from end-stage cardiomyopathy supported firstly by IABP in the years 2011-2016. Results: At 24 h, lactate decreased from 3.2 (2.1-6.8) to 1.8 (1.2-2.2) mmol/L (p < 0.001). Eighteen patients (67%) defined as IABP responders were successfully bridged to either recovery (n = 7), left ventricular assist device (n = 5), or heart transplantation (n = 6). IABP failed in 9 patients (non-responders, 33%) who either died (n = 7) or needed support by extracorporeal membrane oxygenation (n = 2). At 24 h of IABP support, urinary output was higher (2,660 [1,835-4,440] vs. 1,200 [649-2,385] mL; p = 0.02) and fluid balance more negative (-1,564 [-2,673 to -1,086] vs. -500 [-930 to +240] mL; p < 0.001) in responders than non-responders. Overall survival at 1 year was 63%. Conclusion: In most patients, first-line support by IABP in end-stage cardiomyopathy is associated with improvement in organ perfusion and clinical stabilisation for at least 24 h allowing time for decision making on next therapies

Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases

Background: Human T cell Leukemia virus type 1 (HTLV-I) is etiologically linked to adult T cell leukemia/lymphoma (ATL) and an inflammatory neurodegenerative disease called HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP). The exact genetic or epigenetic events and/or environmental factors that influence the development of ATL, or HAM/TSP diseases are largely unknown. The tumor suppressor gene, Fragile Histidine Triad Diadenosine Triphosphatase (FHIT), is frequently lost in cancer through epigenetic modifications and/or deletion. FHIT is a tumor suppressor acting as genome caretaker by regulating cellular DNA repair. Indeed, FHIT loss leads to replicative stress and accumulation of double DNA strand breaks. Therefore, loss of FHIT expression plays a key role in cellular transformation. Methods: Here, we studied over 400 samples from HTLV-I-infected individuals with ATL, TSP/HAM, or asymptomatic carriers (AC) for FHIT loss and expression. We examined the epigenetic status of FHIT through methylation specific PCR and bisulfite sequencing; and correlated these results to FHIT expression in patient samples. Results: We found that epigenetic alteration of FHIT is specifically found in chronic and acute ATL but is absent in asymptomatic HTLV-I carriers and TSP/HAM patients' samples. Furthermore, the extent of FHIT methylation in ATL patients was quantitatively comparable in virus-infected and virus non-infected cells. We also found that longitudinal HTLV-I carriers that progressed to smoldering ATL and descendants of ATL patients harbor FHIT methylation. Conclusions: These results suggest that germinal epigenetic mutation of FHIT represents a preexisting mark predisposing to the development of ATL diseases. These findings have important clinical implications as patients with acute ATL are rarely cured. Our study suggests an alternative strategy to the current "wait and see approach" in that early screening of HTLV-I-infected individuals for germinal epimutation of FHIT and early treatment may offer significant clinical benefits

Nicoya Peninsula, Costa Rica: A single suite of Caribbean oceanic plateau magmas

The pre‐Tertiary oceanic crust exposed on the west coast of Costa Rica has been broadly referred to as the Nicoya Complex. This study was designed to determine the age of the Nicoya Complex in the Nicoya Peninsula, Playa Jacó, and the Quepos Peninsula using 40Ar‐39Ar radiometric dating and to assess the petrologic relationships between the different localities using major element, trace element, and Sr, Nd, Pb isotopic data. Radiometric ages of basalts and diabases from the Nicoya Peninsula are 88–90 Ma (with a weighted mean of 88.5 Ma), and those of two intrusive rocks (a gabbro and plagiogranite) are both 83–84 Ma. The combined geochemical data indicate that the sampled Nicoya Peninsula rocks belong to a single suite related by fractional crystallization of similar parental magmas. Nd and Pb isotopic ratios indicate a common mantle source distinct from that of mid‐ocean ridge basalts. Both the age and composition of the Nicoya rocks are consistent with the idea that they are a part of the Caribbean Cretaceous oceanic plateau [Donnelly, 1994]. The Jacó lavas are geochemically similar to the Nicoya Peninsula suite, and a single age of 84 Ma is identical to the age of the Nicoya Peninsula intrusives. The one analyzed Quepos basalt has a radiometric age of ∼64 Ma, and it is enriched in incompatible elements relative to the Nicoya rocks. Similarities in Nd and Pb isotopic ratios indicate that the Quepos and Nicoya/Jacó lavas were derived from a similar mantle source to that which produced the Nicoya rocks, possibly the Galapagos plume

Mast cells as a unique hematopoietic lineage and cell system:From Paul Ehrlich's visions to precision medicine concepts

The origin and functions of mast cells (MCs) have been debated since their description by Paul Ehrlich in 1879. MCs have long been considered 'reactive bystanders' and 'amplifiers' in inflammatory processes, allergic reactions, and host responses to infectious diseases. However, knowledge about the origin, phenotypes and functions of MCs has increased substantially over the past 50 years. MCs are now known to be derived from multipotent hematopoietic progenitors, which, through a process of differentiation and maturation, form a unique hematopoietic lineage residing in multiple organs. In particular, MCs are distinguishable from basophils and other hematopoietic cells by their unique phenotype, origin(s), and spectrum of functions, both in innate and adaptive immune responses and in other settings. The concept of a unique MC lineage is further supported by the development of a distinct group of neoplasms, collectively referred to as mastocytosis, in which MC precursors expand as clonal cells. The clinical consequences of the expansion and/or activation of MCs are best established in mastocytosis and in allergic inflammation. However, MCs have also been implicated as important participants in a number of additional pathologic conditions and physiological processes. In this article, we review concepts regarding MC development, factors controlling MC expansion and activation, and some of the fundamental roles MCs may play in both health and disease. We also discuss new concepts for suppressing MC expansion and/or activation using molecularly-targeted drugs