Tectonic evolution of the Bernárdides between 44°30´S and 46°S

En esta Tesis se presenta una descripción de la evolución tectónica Mesozoica a Cenozoica del sistema de los Bernárdides o como se lo conoce más recientemente, faja plegada y corrida de San Bernardo entre los 44°30‘S y los 46°S. Esta área constituye el sector central de una zona de deformación de intraplaca recientemente definida como antepaís fragmentado Patagónico. En esta disertación se presentan datos estructurales de campo, sísmicos, geocronológicos y resultados de modelamiento análogo que en conjunto permiten caracterizar las fases de alzamiento y los mecanismos de deformación que afectaron el interior Patagónico. Un análisis integrado de datos estructurales y sísmicos (2-D y 3-D) en la faja plegada y corrida de San Bernardo y la Sub-cuenca de Río Mayo con foco en los depósitos continentales del Grupo Chubut (Cretácico Inferior tardío-Cretácico Superior) permitió inferir un carácter sinorogénico para las diferentes unidades que lo componen. Esto sugeriría el desarrollo temprano de un sistema de antepaís fragmentado asociado al crecimiento de la faja plegada y corrida de San Bernardo, sugiriendo un levantamiento inicial del mismo durante el Cretácico Inferior tardío a Cretácico Superior. Estos resultados implican la coexistencia de campos de esfuerzos contrastantes donde la compresión andina E-O actuó coetáneamente con una reactivación extensional transversal en sentido aproximado N-S en el sector oriental de la cuenca del Golfo de San Jorge. Aquí se propone una relación causal entre ambos fenómenos donde la compresión gatilló una reactivación de rifting sinorogénico en estructuras extensionales previas. El origen de los esfuerzos compresivos se discuten en relación a múltiples procesos que abarcan desde estadios de alta convergencia de placas y alta velocidad de la placa Sudamericana, colisión de dorsales oceánicas hasta cambios en el ángulo de subducción, como lo evidencia la migración hacia el este del frente volcánico durante el Cretácico Inferior tardío y el posterior cese del volcanismo de arco durante el Paleoceno. El estudio del registro sedimentario Terciario en la faja plegada y corrida de San Bernardo, la Sub-cuenca de Río Mayo y La Meseta de Chalía en el pié de monte andino, permitió desentrañar una serie de eventos de deformación contraccional en el Paleoceno a Eoceno que afectaron el sector de intraplaca patagónico en el Cenozoico temprano. Luego, en el Eoceno terminal el frente de deformación se habría retraído desde el antepaís fragmentado hacia los Andes Nordpatagónicos como lo indican, el cese de la compresión en el sector de la faja plegada y corrida de San Bernardo y la detección de estratos de crecimiento datados en ~40 Ma en la Meseta de Chalía. En el Oligoceno superior a Mioceno inferior, el sector del antepaís fragmentado fue afectado por un episodio extensional como lo revelan la depositación sinextensional de rocas volcánicas máficas. Este escenario cambió a un régimen compresivo en el Mioceno medio basado en la presencia de plateaus volcánicos cenozoicos plegados y la datación de secuencias sinorogénicas marinas. Finalmente, la actividad tectónica se habría reinstaurado recientemente en el área precordillerana como lo indica la presencia de depósitos cuaternarios fallados y plegados en el área de estudio. Un análisis integrando la historia de deformación cretácica y cenozoica revela que la deformación se propagó de manera rápida (~2 Ma) desde los Andes hacia el sector de intraplaca en el antepaís fragmentado (~200 km) en dos oportunidades, a los ~120 Ma y ~17-16 Ma. En este sentido, los resultados del modelamiento análogo, indican que la rápida propagación de la deformación hacia el interior patagónico pudo haber estado favorecida por una variación lateral en la resistencia cortical, donde zonas de debilidad vinculadas a la presencia de cuencas de rift mesozoicas en la Patagonia, actuaron como focalizadores efectivos de la deformación durante la orogenia Andina. Otro aspecto a destacar en la evolución general del área de estudio es la falta de correlación entre el ángulo de subducción y el estado de esfuerzos de la placa superior. Se considera en esta Tesis que el amplio registro de procesos de intraplaca en el área de estudio podría contribuir al entendimiento, aún escaso, de la orogénesis de intraplaca en márgenes de subducción tipo-Andino. Finalmente, una revisión de la evolución tectónica de las cuencas del Golfo de San Jorge, Grupo Salta y Taubaté en el sureste de Brasil; y la comparación con la historia de alzamiento de los Andes Nordpatagónicos y Centrales, permiten plantear la posibilidad de procesos de rifting y/o transtensionales en el antepaís de sistemas orogénicos directamente inducidos por compresión regional en un margen tipo-Andino.This dissertation describes the Meso-Cenozoic tectonic evolution between 44°30‘S and 46°S of the Bernárdides system, also known as the San Bernardo fold and thrust belt. This area is located in the central zone of the Patagonian broken foreland, a broad morphostructural unit characterized by intense intraplate deformation. This Thesis presents field structural, seismic, geochronological data, as well as results of analog modeling that allowed the characterization of uplift phases and deformational mechanics in the Patagonian interior. An integrated analysis of structural and seismic (2-D and 3-D) data in the San Bernardo fold and thrust belt and the Río Mayo Sub-basin, focused in the continental beds of the Chubut Group (late Early to Late Cretaceous), allowed the recognition of a synorogenic character in all units belonging to this group, suggesting the early development of a broken foreland system related to the initial uplift of the San Bernardo fold and thrust belt since late Early Cretaceous times. These results imply the coexistence between contrasting stress-fields, where E-O-directed compression took place in concert with transversal N-S- directed extension further east in the San Jorge Gulf Basin. A causal relation between both processes is here proposed, where regional compression may have triggered a synorogenic foreland rift reactivation of an earlier extensional fabric. The origin of the compressional stress-field is then discussed in relation to multiple factors that go from changes in plate dynamics to subduction of mid-ocean ridges that converged to induce a shallow angle to the subducting slab, as evidenced by an eastward migration of the arc front in late Early Cretaceous and a volcanic arc gap until Paleocene times. The study of the Cenozoic sedimentary record in the San Bernardo fold and thrust belt, Río Mayo Sub-basin and the Meseta de Chalía in the Andean foothills, unraveled a series of intraplate deformational events spanning the Paleocene to Eocene periods. In the latest Eocene the orogenic front retracted westwards to the North Patagonian Andes as indicated by the cessation of intraplate deformation in the San Bernardo fold and thrust belt and the local U-Pb zircon dating of synorogenic deposits in the Meseta de Chalía over the eastern Andean front. In the Oligocene to early Miocene, the broken foreland sector was subjected to intraplate extension as revealed by the eruption of widespread within-plate magmatism over the entire area and field description of sinextensional deposits. This scenario changed to generalized compression in middle Miocene as suggested by the presence of folded and thrust volcanic rocks and U-Pb zircon dating of marine synorogenic deposits. Then, tectonic activity in the San Bernardo fold and thrust belt resumed as evidenced by faulting of Quaternary fluvial deposits in the study area. An integrated analysis of the Mesozoic to Cenozoic deformational record reveals a rapid propagation of the deformational front (~2 Ma) from the Andes to the broken foreland sector (~200 km) in two opportunities, at ~120 Ma and ~17-16 Ma. In this sense, analog modeling results indicate that fast migration of the orogenic front could be facilitated by the presence of weak zones located in the intraplate sector related to Early Mesozoic rift basins, acting as stress focalizers during Andean orogeny. Another aspect to highlight from the presented Meso-Cenozoic evolution is that there seems to be no clear correlation between slab angle and the stress state in the upper plate. As a whole, the complete record of intraplate tectonic processes unraveled in the study area may contribute to the understanding of intraplate orogenesis in Andean-type tectonic settings. Finally, a revision of the tectonic evolution of the San Jorge Gulf Basin, Grupo Salta and Taubaté Basin in southeast Brazil and its comparison with the main uplift phases of the Central and North Patagonian Andes, allow considering the possibility of a rifting event or a transtensional reactivation of the foreland sectors in orogenic systems directly related to regional compression related to Andean-type margins.Fil: Gianni, Guido M.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Ghost-arc geochemical anomaly at a spreading ridge caused by supersized flat subduction

The Southern Atlantic-Southwest Indian ridges (SASWIR) host mid-ocean ridge basalts with a residual subduction-related geochemical fingerprint (i.e., a ghost-arc signature) of unclear origin. Here, we show through an analysis of plate kinematic reconstructions and seismic tomography models that the SASWIR subduction-modified mantle source formed in the Jurassic close to the Georgia Islands slab (GI) and remained near-stationary in the mantle reference frame. In this analysis, the GI lies far inboard the Jurassic Patagonian-Antarctic Peninsula active margin. This was formerly attributed to a large-scale flat subduction event in the Late Triassic-Early Jurassic. We propose that during this flat slab stage, the subduction-modified mantle areas beneath the Mesozoic active margin and surrounding sutures zones may have been bulldozed inland by >2280 km. After the demise of the flat slab, this mantle anomaly remained near-stationary and was sampled by the Karoo mantle plume 183 Million years (Myr) ago and again since 55 Myr ago by the SASWIR. We refer to this process as asthenospheric anomaly telescoping. This study provides a hitherto unrecognized geodynamic effect of flat subduction, the viability of which we support through numerical modeling.G. M. G. and C. R. N. recognize the support given by CONICET and the funding given by the Universidad Nacional de la Patagonia San Juan Bosco (Grant number: CIUNPAT no. 1399). S. Z. and J. L. acknowledge the funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 777778. S.Z. acknowledges the funding of Project PID2020-113463RB-C32 funded by MCIN/AEI /10.13039/501100011033 and the funding of Generalitat de Catalunya via the 2021 SGR 01049.Peer ReviewedPostprint (published version

Cretaceous deformation of the southern Central Andes: synorogenic growth strata in the Neuquén Group (35° 300–37° S)

The Neuquén Group is an Upper Cretaceous continental sedimentary unit exhumed during the latest Miocene contractional phase occurred in the southern Central Andes, allowing a direct field observation and study of the depositional geometries. The identification of growth strata on these units surrounding the structures of the frontal parts of the Andes, sedimentological analyses and U–Pb dating of detrital components, allowed the definition of a synorogenic unit that coexisted with the uplift of the early Andean orogen since ca. 100 Ma, maximum age obtained in this work, compatible with previous assignments and constrained in the top by the deposition of the Malarg€ue Group, in the Maastrichtian (ca. 72 Ma). The definition of a wedge top area in this foreland basin system, where growth strata were described, permitted to identify a Late Cretaceous orogenic front and foredeep area, whose location and amplitude contrast with previous hypotheses. This wedge top area was mostly fed from the paleo-Andes with small populations coming from sources in the cratonic area that are interpreted as a recycling in Jurassic and Lower Cretaceous sections, which contrasts with other analyses performed at the foredeep zone that have mixed sources. In particular, Permian sources are interpreted as coming directly from the cores of the basement structures, where Neopaleozoic sections are exposed, next to the synorogenic sedimentation, implying a strong incision in Late Cretaceous times with an exhumation structural level similar to the present. The maximum recognised advance for this Late Cretaceous deformation in the study area is approximately 500 km east of the Pacific trench, which constitutes an anomaly compared with neighbour segments where Late Cretaceous deformations were found considerably retracted. The geodynamic context of the sedimentation of this unit is interpreted as produced under the westward fast moving of South America, colliding with two consecutive mid-ocean ridges during a period of important plate reorganisation. The subduction of young, anhydrous, buoyant lithosphere would have produced changes in the subduction geometry, reflected first by an arc waning/gap and subsequently by an arc migration that coexisted with synorogenic sedimentation. These magmatic and deformational processes would be the product of a shallow subduction regime, following previous proposals, which occurred in Late Cretaceous times, synchronous to the sedimentation of the Neuqu en Group.Facultad de Ciencias Naturales y Muse

Thermal Suppression of Strong Pinning

We study vortex pinning in layered type-II superconductors in the presence of uncorrelated disorder for decoupled layers. Introducing the new concept of variable-range thermal smoothing, we describe the interplay between strong pinning and thermal fluctuations. We discuss the appearance and analyze the evolution in temperature of two distinct non-linear features in the current-voltage characteristics. We show how the combination of layering and electromagnetic interactions leads to a sharp jump in the critical current for the onset of glassy response as a function of temperature.Comment: LaTeX 2.09, 4 pages, 2 figures, submitted to Phys. Rev. Let

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

<div><p>Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in <i>Cftr^F508del</i> homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the <i>F508del-CFTR</i> mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from <i>F508del</i> homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both <i>in vivo</i>, in mice, and <i>in vitro</i>, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 <i>F508del-CFTR</i> homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells <i>in vivo</i>, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of <i>TNF/TNF-alpha (tumor necrosis factor)</i> and <i>CXCL8</i> (<i>chemokine [C-X-C motif] ligand 8</i>) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the <i>F508del-CFTR</i> mutation.</p></div

Conversion gastrectomy for stage IV unresectable gastric cancer: a GIRCG retrospective cohort study

Background: The aim of this study is to report the experience with conversion surgery from six Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers, focusing our analysis on factors affecting survival and the risk of recurrence. Methods: A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. Results: Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI &gt; 6) (n = 38, 84.4%), distant metastatic nodes (n = 3, 6.6%) and extensive liver involvement (n = 4, 8.8%). Median follow-up was 25&nbsp;months (IQR 9-50). Median overall survival from surgery was 15&nbsp;months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12&nbsp;months with 1- and 3-year survival of 46.4 and 33.9%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 4.41, 95% CI 1.72\u201311.3, p = 0.002). A positive microscopic resection margin was the only risk factor for recurrence (HR 5.72, 95% CI 1.04\u201331.4, p = 0.045). Conclusions: Unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survivals. The main prognostic factor for these patients was the presence of more than one type of extra-gastric metastatic involvement

The neutrophil to lymphocyte ratio (NLR) and the presence of large nodal mass are independent predictors of early response: A subanalysis of the prospective phase II PET-2-adapted HD0607 trial

The neutrophil to lymphocyte ratio (NLR) and the lymphocyte to monocyte ratio (LMR) can reflect both the myeloid dysfunction and T-cell immune suppression and have prognostic significance

Structured and shared CT radiological report of gastric cancer: a consensus proposal by the Italian Research Group for Gastric Cancer (GIRCG) and the Italian Society of Medical and Interventional Radiology (SIRM)

Objectives Written radiological report remains the most important means of communication between radiologist and referring medical/surgical doctor, even though CT reports are frequently just descriptive, unclear, and unstructured. The Italian Society of Medical and Interventional Radiology (SIRM) and the Italian Research Group for Gastric Cancer (GIRCG) promoted a critical shared discussion between 10 skilled radiologists and 10 surgical oncologists, by means of multi-round consensus-building Delphi survey, to develop a structured reporting template for CT of GC patients. Methods Twenty-four items were organized according to the broad categories of a structured report as suggested by the European Society of Radiology (clinical referral, technique, findings, conclusion, and advice) and grouped into three "CT report sections" depending on the diagnostic phase of the radiological assessment for the oncologic patient (staging, restaging, and follow-up). Results In the final round, 23 out of 24 items obtained agreement ( >= 8) and consensus ( 0.05). Conclusions The structured report obtained, shared by surgical and medical oncologists and radiologists, allows an appropriate, clearer, and focused CT report essential to high-quality patient care in GC, avoiding the exclusion of key radiological information useful for multidisciplinary decision-making

Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis

<p>Abstract</p> <p>Purpose</p> <p>to investigate the factors affecting survival and toxicity in patients treated with stereotactic radiosurgery (SRS), with special attention to volumes of brain receiving a specific dose (V10 - V16 Gy) as predictors for brain radionecrosis.</p> <p>Patients and Methods</p> <p>Two hundred six consecutive patients with 310 cerebral metastases less than 3.5 cm were treated with SRS as primary treatment and followed prospectively at University of Rome La Sapienza Sant'Andrea Hospital. Overall survival, brain control, and local control were estimated using the Kaplan-Meier method calculated from the time of SRS. Univariate and multivariate analysis using a Cox proportional hazards regression model were performed to determine the predictive value of prognostic factors for treatment outcome and SRS-related complications.</p> <p>Results</p> <p>Median overall survival and brain control were 14.1 months and 10 months, respectively. The 1-year and 2-year survival rates were 58% and 24%, and respective brain control were 43% and 22%. Sixteen patients recurred locally after SRS, with 1-year and 2-year local control rates of 92% and 84%, respectively. On multivariate analysis, stable extracranial disease and KPS >70 were associated with the most significant survival benefit. Neurological complications were recorded in 27 (13%) patients. Severe neurological complications (RTOG Grade 3 and 4) occurred in 5.8% of patients. Brain radionecrosis occurred in 24% of treated lesions, being symptomatic in 10% and asymptomatic in 14%. On multivariate analysis, V10 through V16 Gy were independent risk factors for radionecrosis, with V10 Gy and V12 Gy being the most predictive (p = 0.0001). For V10 Gy >12.6 cm³and V12 Gy >10.9 cm³the risk of radionecrosis was 47%.</p> <p>Conclusions</p> <p>SRS alone represents a feasible option as initial treatment for patients with brain metastases, however a significant subset of patients may develop neurological complications. Lesions with V12 Gy >8.5 cm³carries a risk of radionecrosis >10% and should be considered for hypofractionated stereotactic radiotherapy especially when located in/near eloquent areas.</p

Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukemia

Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2DBCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.This work was supported in part by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital; by a Stand Up to Cancer Innovative Research Grant and St. Baldrick’s Foundation Scholar Award (to C.G.M.); by a St. Baldrick’s Consortium Award (S.P.H.), by a Leukemia and Lymphoma Society Specialized Center of Research grant (S.P.H. and C.G.M.), by a Lady Tata Memorial Trust Award (I.I.), by a Leukemia and Lymphoma Society Special Fellow Award and Alex’s Lemonade Stand Foundation Young Investigator Awards (K.R.), by an Alex’s Lemonade Stand Foundation Award (M.L.) and by National Cancer Institute Grants CA21765 (St Jude Cancer Center Support Grant), U01 CA157937 (C.L.W. and S.P.H.), U24 CA114737 (to Dr Gastier-Foster), NCI Contract HHSN261200800001E (to Dr Gastier-Foster), U10 CA180820 (ECOG-ACRIN Operations) and CA180827 (E.P.); U10 CA180861 (C.D.B. and G.M.); U24 CA196171 (The Alliance NCTN Biorepository and Biospecimen Resource); CA145707 (C.L.W. and C.G.M.); and grants to the COG: U10 CA98543 (Chair’s grant and supplement to support the COG ALL TARGET project), U10 CA98413 (Statistical Center) and U24 CA114766 (Specimen Banking). This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract Number HHSN261200800001E