The Late Carboniferous to Permian continental successions of the Southern Alps can be subdivided into two main tectono-sedimentary Cycles, separated by a marked unconformity sealing a Middle Permian ...time gap, generally estimated at over 10 Ma. The lower cycle (1), between the Variscan crystalline basement and the Early Permian, is mainly characterised by fluvio-lacustrine and volcanic deposits of calc-alkaline acidic-to-intermediate composition, which range up to a maximum thickness of more than 2,000 m. The upper cycle (2), which is devoid of volcanics, is mostly dominated through the Mid?–Late Permian by alluvial sedimentation which covered the previous basins and the surrounding highs, giving rise to the subaerial Verrucano Lombardo-Val Gardena (Gröden) red-beds, up to about 800 m thick. The palaeontological record from the terrigenous deposits of both the above cycles consists mainly of macro- and microfloras and tetrapod footprints. The age of the continental deposits is widely discussed because of the poor chronological significance of a large number of fossils which do not allow reliable datings; however, some sections are also controlled by radiometric calibrations. The comparison with some selected continental successions in southern Europe allows to determine their evolution and set up correlations. A marked stratigraphic gap shows everywhere between the above-mentioned Cycles 1 and 2. As in the Southern Alps, the gap reaches the greatest extent during the Mid-Permian, near the Illawarra Reversal geomagnetic event (265 Ma). In western Europe, however, such as in Provence and Sardinia, the discussed gap persists upwardly to Late Permian and Early Triassic or slightly younger times, i.e. to the onset of the “Alpine sedimentary Cycle”, even though in northeastern Spain (Iberian Ranges, Balearic Islands) this gap results clearly interrupted by late Guadalupian–Lopingian deposits. The above two major tectonosedimentary cycles reflect, in our view, two main geodynamic events that affected the southern Europe after the Variscan orogenesis: the Late Carboniferous–Early Permian transformation of the Gondwana–Eurasia collisional margin into a diffuse dextral transform margin and the Middle–Late Permian opening of the Neotethys Ocean, with the onset of a generalised extensional tectonic regime and the progressive westward marine ingression.
A stability investigation based on Digital Outcrop Models (DOMs) acquired in emergency conditions by photogrammetric surveys based on Remote Piloted Aerial System (RPAS) was conducted on an unstable ...rock slope near Gallivaggio (Western Alps, Italy). The predicted mechanism of failure and volume of the unstable portion of the slope were successively verified on the DOMs acquired after the rockfall that effectively collapsed the May 29th, 2018. The comparison of the pre- and post-landslide 3D models shows that the estimated mode of failure was substantially correct. At the same time, the predicted volume of rock involved in the landslide was overestimated by around 10%. To verify if this error was due to the limited accuracy of the models georeferenced in emergency considering only the Global Navigation Satellite System/Inertial Measurement Unit (GNSS/IMU)-information of RPAS, several Ground Control Points (GCPs) were acquired after the failure. The analyses indicate that the instrumental error in the volume calculation due to the direct-georeferencing method is only of the 1.7%. In contrast, the significant part is due to the geological uncertainty in the reconstruction of the real irregular geometry of the invisible part of the failure surface. The results, however, confirm the satisfying relative accuracy of the direct-georeferenced DOMs, compatible with most geological and geoengineering purposes.
Objective:
Aim of this trial was to compare efficacy of activated platelet-rich plasma against hyaluronic acid as intra-articular injections to people with osteoarthritis of the knee.
Design:
Phase-2 ...randomized controlled trial, with blind patients and outcome assessors.
Setting:
Outpatient rehabilitation service; years 2011–2013.
Subjects:
Patients with knee osteoarthritis grades 2–3 at magnetic resonance imaging (MRI) were included after consent and randomized. Target sample size was 25 patients per group.
Interventions:
Patients received three activated platelet-rich plasma (intervention group) or hyaluronic acid (controls) intra-articular injections at 4-week intervals.
Main measures:
Main outcome measure was proportion of patients with >1 grade improvement at six months from last injection, as assessed by a radiologist blind to study group. Patients were evaluated over time clinically and with functional scales (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lysholm, Tegner, American Knee Society Score (AKSS), Lequesne, visual analogue scale (VAS) for pain).
Results:
Overall, 30 patients were randomized to intervention and 28 to control group. For primary outcome, 28 patients (29 knees) in the intervention and 22 (25 knees) in the control group were available. Patients with at least 1 grade improvement at repeat MRI were 14 (48.3%) in the intervention and 2 (8%) in the control group (P < 0.003). Improvement in symptoms and functional scales was consistently higher in the intervention group. No side-effects were observed in either group.
Conclusion:
Activated platelet-rich plasma reduces articular damage as evident at MRI, as soon as six months after treatment; it reduces pain and improves patient’s function and overall quality of life.
Within the context of erythropoiesis and the possibility of producing artificial red blood cells (RBCs)
, a most critical step is the final differentiation of enucleated erythroblasts, or ...reticulocytes, to a fully mature biconcave discocyte, the RBC. Reviewed here is the current knowledge about this fundamental maturational process. By combining literature data with our own experimental evidence we propose that the early phase in the maturation of reticulocytes to RBCs is driven by a membrane raft-based mechanism for the sorting of disposable membrane proteins, mostly the no longer needed transferrin receptor (TfR), to the multivesicular endosome (MVE) as cargo of intraluminal vesicles that are subsequently exocytosed as exosomes, consistently with the seminal and original observation of Johnstone and collaborators of more than 30 years ago (Pan BT, Johnstone RM. Cell. 1983;33:967-978). According to a strikingly selective sorting process, the TfR becomes cargo destined to exocytosis while other molecules, including the most abundant RBC transmembrane protein, band 3, are completely retained in the cell membrane. It is also proposed that while this process could be operating in the early maturational steps in the bone marrow, additional mechanism(s) must be at play for the final removal of the excess reticulocyte membrane that is observed to occur in the circulation. This processing will most likely require the intervention of the spleen, whose function is also necessary for the continuous remodeling of the RBC membrane all along this cell's circulatory life.
Field surveys, well data and a detailed interpretation of a depth‐converted seismic line, reveal that the Romanengo High, an isolated low relief that interrupts the morphological continuity of the Po ...Plain (N Italy) west of the Oglio River, coincides with a partially buried anticline, still active in recent times (Romanengo anticline). The Pliocene to Holocene evolution of the structure has been reconstructed by sequential restoration based on combined decompaction and unfolding methods, from the early Pliocene to Holocene. The analysis shows that from the beginning of the Pliocene onward, periods of tectonic activity have alternated with periods of quiescence. The more significant tectonic uplift rates are recorded during the late Pliocene (0.33 ± 0.06 mm/yr) and the beginning of Calabrian (0.284 ± 0.12 mm/yr), while at the end of Calabrian the structure was virtually inactive. During the early Pleistocene the reversal in the vergence of the structure indicates the onset of interaction with the Apennines deformational front in the area. From middle Pleistocene to Holocene, a marked increase in the tectonic uplift has been recorded, with an uplift rate of about 0.12 ± 0.05 mm/yr. A preliminary evaluation of the seismic hazards connected to blind thrusts affecting this active frontal sector of the Alpine chain, where it collides with the Apennines buried deformation fronts, is finally discussed.
Key Points
An active anticline in the Po Plain in Italy
Background
Although many trials are currently investigating the safety and efficacy of convalescent plasma (CP) in critically ill COVID‐19 patients, there is a paucity of ongoing and published ...studies evaluating the CP donors' side. This retrospective study reports the first Italian experience on CP donors' selection and donations.
Methods
Patients aged 18‐68 years who had recovered from COVID‐19 at least 2 weeks previously were recruited between March 18 and June 30, 2020 in a study protocol at the Italian hospitals of Pavia and Mantova.
Results
During the study period, 494 of 512 donors recruited were judged eligible and underwent 504 plasmapheresis procedures. Eighty‐five percent (437/512) of the CP donors were males. The average time between symptom recovery and CP donation was 36.6 (±20.0) days. Four hundred and eighty‐eight plasmapheresis procedures (96.8%) were concluded and each unit was divided into two subunits (total 976) with an average volume of 316.2 (±22.7) mL. Ninety‐three percent (460/494) of CP donors at the time of plasma donation had a neutralizing IgG titer ≥1:80. Plasmapheresis‐related adverse reactions occurred in 2.6% (13/504) of cases; all the reactions were mild and none required therapeutic intervention. Donors' age and COVID‐19 severity were positively associated with greater antibody responses.
Conclusion
This study demonstrates the feasibility and safety of a pilot CP program conducted in Italy. The identification of factors (ie, age and severity of COVID‐19) positively associated with higher neutralizing antibody titers at the time of donation may help to optimize the selection of CP donors.
An open-source MATLAB application (app) named Discontinuity Intensity Calculator and Estimator (DICE) was developed in order to quantitatively characterize the fractures, or in more general, ...discontinuities within a rocky outcrop in three-dimensional (3D) digital data, such as digital outcrop model (DOM). The workflow proposed for the parametrization of the discontinuities consists of the following steps: (1) Analysis and mapping of the fractures detected within the 3D DOMs; (2) Calculation of the orientation, position and dimensions of discontinuities that are represented by best-fit circular planes; (3) Determining the discontinuity parameters (dimension, distribution, spacing and intensity) by the DICE algorithm using different 3D oriented sampling techniques (3D oriented scanline, 3D oriented circular scan window and spherical scan volume). Different sampling methods were bench tested with a synthetic, as well as a natural case study, and compared in order to understand the advantages and limitations of each technique. The 3D oriented circular scan window appears to be the most effective method for fracture intensity estimation with high accuracy (error 0.4%) and stability with variations in scan radius.
Red blood cells (RBCs) begin their circulatory life as reticulocytes (Retics) after their egress from the bone marrow where, as R1 Retics, they undergo significant rearrangements in their membrane ...and intracellular components, via autophagic, proteolytic, and vesicle-based mechanisms. Circulating, R2 Retics must complete this maturational process, which involves additional loss of significant amounts of membrane and selected membrane proteins. Little is known about the mechanism(s) at the basis of this terminal differentiation in the circulation, which culminates with the production of a stable biconcave discocyte. The membrane of R1 Retics undergoes a selective remodeling through the release of exosomes that are enriched in transferrin receptor and membrane raft proteins and lipids, but are devoid of Band 3, glycophorin A, and membrane skeletal proteins. We wondered whether a similar selective remodeling occurred also in the maturation of R2 Retics. Peripheral blood R2 Retics, isolated by an immunomagnetic method, were compared with mature circulating RBCs from the same donor and their membrane protein and lipid content was analyzed. Results show that both Band 3 and spectrin decrease from R2 Retics to RBCs on a "per cell" basis. Looking at membrane proteins that are considered as markers of membrane rafts, flotillin-2 appears to decrease in a disproportionate manner with respect to Band 3. Stomatin also decreases but in a more proportionate manner with respect to Band 3, hinting at a heterogeneous nature of membrane rafts. High resolution lipidomics analysis, on the contrary, revealed that those lipids that are typically representative of the membrane raft phase, sphingomyelin and cholesterol, are enriched in mature RBCs with respct to Retics, relative to total cell lipids, strongly arguing in favor of the selective retention of at least certain subclasses of membrane rafts in RBCs as they mature from Retics. Our hypothesis that rafts serve as additional anchoring sites for the lipid bilayer to the underlying membrane-skeleton is corroborated by the present results. It is becoming ever more clear that a proper lipid composition of the reticulocyte is necessary for the production of a normal mature RBC.
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