Characterisation of submarine depression trails driven by upslope migrating cyclic steps: Insights from the Ceará Basin (Brazil)

Circular to elliptical topographic depressions, isolated or organized in trails, have been observed on the modern seabed in different contexts and water depths. Such features have been alternatively interpreted as pockmarks generated by fluid flow, as sediment waves generated by turbidity currents, or as a combination of both processes. In the latter case, the dip of the slope has been hypothesized to control the formation of trails of downslope migrating pockmarks. In this study, we use high-quality 3D seismic data from the offshore Ceará Basin (Equatorial Brazil) to examine vertically stacked and upslope-migrating trails of depressions visible at the seabed and in the subsurface. Seismic reflection terminations and stratal architecture indicate that these features are formed by cyclic steps generated by turbidity currents, while internal amplitude anomalies point to the presence of fluid migration. Amplitude Versus Offset analysis (AVO) performed on partial stacks shows that the investigated anomalies do not represent hydrocarbon indicators. Previous studies have suggested that the accumulation of permeable and porous sediments in the troughs of vertically stacked cyclic steps may create vertical pathways for fluid migration, and we propose that this may have facilitated the upward migration of saline pore water due to fluid buoyancy. The results of this study highlight the importance of gravity-driven processes in shaping the morphology of the Ceará Basin slope and show how non-hydrocarbon fluids may interact with vertically stacked cyclic steps

Shared and Distinctive Ultrastructural Abnormalities Expressed by Megakaryocytes in Bone Marrow and Spleen From Patients With Myelofibrosis

Numerous studies have documented ultrastructural abnormalities in malignant megakaryocytes from bone marrow (BM) of myelofibrosis patients but the morphology of these cells in spleen, an important extramedullary site in this disease, was not investigated as yet. By transmission-electron microscopy, we compared the ultrastructural features of megakaryocytes from BM and spleen of myelofibrosis patients and healthy controls. The number of megakaryocytes was markedly increased in both BM and spleen. However, while most of BM megakaryocytes are immature, those from spleen appear mature with well-developed demarcation membrane systems (DMS) and platelet territories and are surrounded by platelets. In BM megakaryocytes, paucity of DMS is associated with plasma (thick with protrusions) and nuclear (dilated with large pores) membrane abnormalities and presence of numerous glycosomes, suggesting a skewed metabolism toward insoluble polyglucosan accumulation. By contrast, the membranes of the megakaryocytes from the spleen were normal but these cells show mitochondria with reduced crests, suggesting deficient aerobic energy-metabolism. These distinctive morphological features suggest that malignant megakaryocytes from BM and spleen express distinctive metabolic impairments that may play different roles in the pathogenesis of myelofibrosis

Clinical outcomes under hydroxyurea treatment in polycythemia vera: a systematic review and meta-analysis

Hydroxyurea is the standard treatment in high risk patients with polycythemia vera. Yet, estimates of its effect in terms of clinical outcomes (thrombosis, bleeding, hematological transformations and mortality) are lacking. We performed a meta-analysis to determine the absolute risk of events in contemporary patients under hydroxyurea treatment. We searched for relevant articles or abstracts in the following databases: Medline, EMBASE, clinicaltrials.gov, WHO International Clinical Trials Registry, LILACS. Sixteen studies published from 2008 to 2018 reporting number of events using WHO diagnosis for polycythemia vera were selected. Through a random effect logistic model, incidences, study heterogeneity and confounder effects were estimated for each outcome at different follow-ups. Overall, 3,236 patients were analyzed. While incidences of thrombosis and acute myeloid leukemia were stable over time, mortality and myelofibrosis varied depending on follow-up duration. Thrombosis rates were 1.9, 3.6 and 6.8% persons/year at median ages 60, 70 and 80 respectively. Higher incidence of arterial events was predicted by previous cardiovascular complication. Leukemic transformation incidence was 0.4% persons/year. Incidence of transformation to myelofibrosis and mortality were significantly dependent on age and follow-up duration. For myelofibrosis, rates were 5.0 at 5 year and 33.7% at 10 years; overall mortality was 12.6% and 56.2% at 5 and 10 years respectively. In conclusion, we provide reliable risk estimates for the main outcomes in polycythemia vera patients under hydroxyurea treatment. These findings can help design comparative clinical trials with new cytoreductive drugs and prove the feasibility of using hard endpoints for efficacy, such as major thrombosis

Hydroxyurea prevents arterial and late venous thrombotic recurrences in patients with myeloproliferative neoplasms but fails in the splanchnic venous district. Pooled analysis of 1500 cases

We collected 1500 patients with myeloproliferative neoplasms (MPN) and arterial or venous thrombosis (935/565), pooling three independent cohorts previously reported. Long-term treatment with antiplatelet drugs or vitamin K-antagonists (VKA) was given to 1391 (92.7%) patients; 975 (65%) patients received hydroxyurea (HU). We recorded 348 recurrences (venous in 142 cases) over 6075 patient-years, with an incidence rate of 5.7 per 100 pt-years (95% CI 5.1-6.4). The site of the first thrombosis predicted the site of recurrence. Independent factors influencing the rate of novel arterial thrombosis were HU (HR 0.67, 95% CI 0.46-0.98), antiplatelet treatment (HR 0.54, 95% CI 0.35-0.82), and VKA (HR 0.58, 95% CI 0.35-0.96). On the contrary, the recurrence of venous thromboses was significantly diminished only by VKA (HR 0.60, 95% CI 0.37-0.95), while HU prevented late but not early recurrences after venous thrombosis at common sites. Of note, we failed to demonstrate a positive effect of HU in the prevention of recurrent splanchnic vein thrombosis. In conclusion, in MPN patients, HU plays a role in the prevention of arterial thrombosis, together with aspirin and VKA, whereas its action in the prevention of recurrent venous thrombosis is uncertain. Such findings call for future studies to optimize and personalize secondary prophylaxis after MPN-related thrombosis

Interferon-beta induces S phase slowing via up-regulated expression of PML in squamous carcinoma cells.

Interferon-β induces S phase slowing via up-regulated expression of PML in squamous carcinoma cell