Environmental control on the end of the Dolomia Principale/Hauptdolomit depositional system in the central Alps: Coupling sea-level and climate changes

The Norian in the Western Tethys is characterised by the deposition of early-dolomitised inner platform facies (Dolomia Principale/Hauptdolomit, DP/HD), bordered on the landward side by terrigenous coastal deposits (Keuper) and on the seaward side by calcareous backreef and reefal facies (Dachstein Limestone) passing basinward to open-sea sediments (Hallstatt facies). The inner carbonate platform is locally (Lombardy Basin, Carnic Alps, Central Austroalpine) dissected by normal faults leading to the development of intraplatform troughs. Close to the Norian-Rhaetian boundary, sedimentation records an abrupt environmental change both on platform top and basins all over the Western Tethys (e.g. Western Carpathians, Transdanubian Range, Alps, Central Apennine). The top of the Dolomia Principale locally emerged, reflecting a major eustatic sea-level fall. Emersion is recorded in favourable settings by the development of polycyclic paleosols up to 30 m thick. In the Norian intraplatform basins, the succession is capped by 4 to 8 m of thin-bedded, fine-grained limestones yielding abundant remnants of fishes and terrestrial reptiles. Fossil concentration as well as sedimentological features is indicative of reduced sedimentation rates due to decreased carbonate production, induced by the emersion of the platform top. The sea-level fall was followed by deposition of mixed fine-grained siliciclastic-carbonate successions (e.g. Riva di Solto Shale, Kossen beds, "Rhaetavicula contorta beds", Fatra Formation). Stratigraphic evidence indicates a dry climate in the Western Tethys during the Norian, as indicated by the presence of evaporites (Burano, Apennine) and arid to semi-arid coastal to playa settings (Upper Keuper, Germany). In contrast, the basal layers of the basinal shales show evidence of wet climate. The end of the Norian depositional system records two different phenomena: (1) an important sea-level fall was responsible for the emersion of the platform top and deposition of a condensed horizon in the basins: and (2) transition from dry to humid climate. The observed evolution is explained with a global cooling which caused the rapid sea-level fall responsible for the abrupt end of the DP/HD depositional system and the shift of the boundary between arid and temperate climate belts, which modified the distribution and amount of rainfall, triggering the deposition of shales along the Western Tethys margin

Effect of some disease stress on cow milk yield and features

In their review, Bertoni et al. (2003) have pointed out how in dairy cows milk yield and its characteristics are markedly modified during disease stress (general consequences of any disease). This mainly depends on secretion of cytokines, which determines anorexia, endocrine changes and diversion of some nutrients toward the immune system

Mosaic of submerged habitats in the Venice lagoon shows signs of marinization

The relationships between habitat patterns and ecosystem functioning have been widely explored in terrestrial ecosystems, but less in marine and coastal ecosystems, calling for further research in this direction. This work focuses on the mosaic of submerged habitats in the Venice lagoon, Italy. It aims to describe the habitats’ spatial patterns at multiple spatial scales, and to explore their linkages with the ecological status defined according to the EU Water Framework Directive (WFD, 2000/60/EC). The submerged habitats’ mosaic has been analysed by calculating a set of seascape metrics at different spatial scales. These metrics have been linked with the biological quality elements (BQEs) that are monitored in the lagoon in compliance to the WFD. The results show that the habitats’ spatial patterns differ between the areas of the lagoon with marine-like features and the areas which still retain more lagoon characteristics. The similarity between the pattern found in the whole lagoon and those found in marine-like areas suggests a general loss of lagoon characteristics at the lagoon scale. Regarding the ecological status, every BQE seems to be associated with a different habitat configuration at the water body scale. This does not facilitate the joint improvement of the BQEs, as required by the Directive. If we cannot achieve that, at some point we will probably have to choose what to prioritize. On a broader perspective, this calls for a reflection on what lagoon we want for the future, a vision that should be shared and account for the lagoon’s complexity, current trends and challenges

Can the new and old drugs exert an immunomodulatory effect in acute myeloid leukemia?

Acute myeloid leukemia (AML) is considered an immune-suppressive neoplasm capable of evading immune surveillance through cellular and environmental players. Increasing knowledge of the immune system (IS) status at diagnosis seems to suggest ever more attention of the crosstalk between the leukemic clone and its immunologic counterpart. During the last years, the advent of novel immunotherapeutic strategies has revealed the importance of immune dysregulation and suppression for leukemia fitness. Considering all these premises, we reviewed the “off-target” effects on the IS of different drugs used in the treatment of AML, focusing on the main advantages of this interaction. The data reported support the idea that a successful therapeutic strategy should consider tailored approaches for performing leukemia eradication by both direct blasts killing and the engagement of the IS

Inside the biology of early T-cell precursor acute lymphoblastic leukemia: the perfect trick

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare, distinct subtype of T-ALL characterized by genomic instability, a dismal prognosis and refractoriness to standard chemotherapy. Since its first description in 2009, the expanding knowledge of its intricate biology has led to the definition of a stem cell leukemia with a combined lymphoid-myeloid potential: the perfect trick. Several studies in the last decade aimed to better characterize this new disease, but it was recognized as a distinct entity only in 2016. We review current insights into the biology of ETP-ALL and discuss the pathogenesis, genomic features and their impact on the clinical course in the precision medicine era today

FLT3 mutational analysis in acute myeloid leukemia: Advantages and pitfalls with different approaches

FMS-like tyrosine kinase 3 (FLT3) is one of the most closely studied genes in blood diseases. Numerous methods have been adopted for analyses, mainly in acute myeloid leukemia (AML) diagnostic work-up. According to international recommendations, the current gold standard approach allows FLT3 canonical mutations to be investigated, providing the main information for risk assessment and treatment choice. However, the technological improvements of the last decade have permitted “black side” gene exploration, revealing numerous hidden aspects of its role in leukemogenesis. The advent of the next-generation sequencing era emphasizes lights and shadows of FLT3 conventional mutational analysis, highlighting the need for a more comprehensive study of the gene. However, more extensive analysis is opening new, unexplored questions whose impact on clinical outcomes is still unknown. The present work is focused on the main topics regarding FLT3 mutational analysis in AML, debating the strengths and weaknesses of the current gold standard approach. The rights and wrongs of NGS introduction in clinical practice will be discussed, showing that a more extensive knowledge of FLT3 mutational status could lead to reconsidering its role in AML management

Test results of the front-end system for the Silicon Drift Detectors of ALICE

The front-end system of the Silicon Drift Detectors (SDDs) of the ALICE experiment is made of two ASICs. The first chip performs the preamplification, temporary analogue storage and analogue-to-digital conversion of the detector signals. The second chip is a digital buffer that allows for a significant reduction of the connection from the front-end module to the outside world. In this paper, the results achieved on the first complete prototype of the front-end system for the SDDs of ALICE are presented

Nanopore Sequencing in Blood Diseases: A Wide Range of Opportunities

The molecular pathogenesis of hematological diseases is often driven by genetic and epigenetic alterations. Next-generation sequencing has considerably increased our genomic knowledge of these disorders becoming ever more widespread in clinical practice. In 2012 Oxford Nanopore Technologies (ONT) released the MinION, the first long-read nanopore-based sequencer, overcoming the main limits of short-reads sequences generation. In the last years, several nanopore sequencing approaches have been performed in various “-omic” sciences; this review focuses on the challenge to introduce ONT devices in the hematological field, showing advantages, disadvantages and future perspectives of this technology in the precision medicine era

A new proposal: A digital flow for the construction of a haas-inspired rapid maxillary expander (HIRME)

Maxillary expansion is a common orthodontic treatment used for the correction of posterior crossbite resulting from reduced maxillary width. Transverse maxillomandibular discrepancies are a major cause of several malocclusions and may be corrected in dierent manners; in particular, the rapid maxillary expansion (RME) performed in the early mixed dentition has now become a routine procedure in orthodontic practice. The aim of this study is to propose a procedure that reduces the patient cooperation as well as the lab work required in preparing a customized Haas-inspired rapid maxillary expander (HIRME) that can be anchored to deciduous teeth and can be utilized in mixed dentition with tubes on the molars and hooks and brackets on the canines. This article thus presents an expander that is completely digitally developed, from the first moment of taking the impression with an optical scanner to the final solidification phase by the use of a 3D printer. This digital flow takes place in a CAD environment and it starts with the creation of the appliance on the optical impression; this design is then exported as an stl extension and is sent to the print service to obtain a solid model of the device through a laser sintering process. This "rough" device goes through a post-processing procedure; finally, a commercial expansion screw is laser-welded. This expander has all the advantages of a cast-metal Haas-type RME that rests on deciduous teeth; moreover, it has the characteristic of being developed with a completely digitized and individualized process, for the mouth of the young patient, as well as being made completely of cobalt-chrome, thus ensuring greater adaptability and stability in the patient's mouth

Molecular complexity of diffuse large B-cell lymphoma: Can it be a roadmap for precision medicine?

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma; it features extreme molecular heterogeneity regardless of the classical cell-of-origin (COO) classification. Despite this, the standard therapeutic approach is still immunochemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone—R-CHOP), which allows a 60% overall survival (OS) rate, but up to 40% of patients experience relapse or refractory (R/R) disease. With the purpose of searching for new clinical parameters and biomarkers helping to make a better DLBCL patient characterization and stratification, in the last years a series of large discovery genomic and transcriptomic studies has been conducted, generating a wealth of information that needs to be put in order. We reviewed these researches, trying ultimately to understand if there are bases offering a roadmap toward personalized and precision medicine also for DLBCL