CONTRIBUTION TO THE RECOGNITION OF THE STRUCTURE OF TASSAOUT DOWNSTREAM OF TADLA BASIN THROUGH THE APPLICATION OF GEOELECTRIC METHODS

Geoelectric study is used in determining the image of the structure of the aquiferous system of the Tadla plain (Tessaout aval) through the measure of electric soundings. The treatment processing of these measures, their correlation with the data of certain drilling, the well existing in the canvassed area, and the analysis of all the results, shows that the study area of the profiles and the maps of the established electrics resistivities and clear geoelectric cups gives a general looks. This put the superimposing of several variables as evidence. Roughly speaking, grounds draws a structure of monoclonal wrinkle sometimes tectonised, which dives the Northwest towards the Southeast. This structure is affected by a series of flaws which are causing the collapse of compartments which are located in the South

GEOLOGICAL AND GEOPHYSICAL SURVEY ON THE METALLOGENIC OF THE MANGANESE MINING SITE OF BOUARFA, HIGH ATLAS, MOROCCO

The Bouarfa manganese site is located a few kilometers west of Bouarfa city on the "border chain" of North Tamlelt Moroccan High Atlas. Our Geological and geophysical investigations, helped to highlight some structural elements. It also helped to characterize the mineralized levels and point out that Bouarfa manganese is a Mississipy Valley Type (MVT). The manganese oxide beds were observed at the lower part of the banded dolomite. Manganese deposit occurs also as karsts within the massive dolomite. Mineralization is associated to the dolomite bench Middle Lias. Therefore, iron oxide and manganese forms irregular clusters and a more capricious distribution. Generally, the manganese indices are numerous and are scattered over a relatively large area allocated to Lias Medium. Manganese mineralization in the study area is in the following forms: 1. Carbonate mineralization diffuse low, but with anomalous zones of 2 to 3%, which seems to exist in the entire series of the cover to the top of the bar Hamaraouët. 2. A syngenetic manganese oxides beds mineralization with lamination (level benchmark of Hamaraouët) (several kilometers). 3. An alternative mineralization in the Hamaraouët bar, which unlike the previous one, is closely related to tectonics. 4. Epigenetic vein mineralization in the upper conglomerates. Earlier in the mineralized series, it also appears to be linked to fairly significant flaws. 5. Mineralization type "run" in Ain Beida is indeed related to a discontinuity surface that corresponds to a paleosurface emersion

Sex Hormones and Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common type of dementia and the most common neurodegenerative disorder of elderly. It is not an accelerated form of aging but it is characterized by distinct temporospatial brain pathological changes, including amyloid plaques accumulation, neurofibrillary tangles deposition, synaptic loss and neuronal death with gross brain atrophy. These changes result in persistent progressive memory and cognitive decline interfering with the usual daily activities. AD is a multifactorial disorder results from the interaction of genetic, epigenetic, environmental and lifestyle factors. Estrogen, progesterone and androgen effects are important building stones in AD pathogenesis, and their effect in brain modulation and development results in different gender susceptibility to the disease. These sex hormones whether gonadal or neurosteroids (synthesized locally in the brain) play important neuroprotective roles influencing the individual’s vulnerability to AD development, rate of mild cognitive impairment (MCI)/AD conversion and speed of AD progression. Despite the little therapeutic implications of hormonal replacement therapy in AD treatment, yet this topic still represents a challenging hopeful way to construct a strategy for the development of personalized, gender-specific AD management

Application of Geophysics for the Detection of Derangement of Phosphate Layers in the Oulad Abdoun Basin in Morocco

The phosphate series of the basin of Oulad Abdoun begins in Maastrichtian with phosphate deposits relatively very marly. It ends at the Lutetian by a calcareous slab. Derangement is any disruption of the usual succession of the phosphate series and that which disrupts the evolution of the kinematic chain, leading to a decrease in production and profitability. In this case, we have a partially disturbed series and the disturbance consists of all the elements of the series (limestone, flint, marls and phosphate). The present work has been carried out in two ways: The present work has been carried out in two ways: The first one, purely geological, consists of the identification of the different layers of the Ouled Abdoun basin in the El Halassa site and their continuity to the outcrop. At the end of these observations, the basin shows derangement of two kinds: a disturbance on the scale of the whole series known as major disturbance, and a second which affects only part of the series. Thus, it is a minor or local disturbance. The second one, geophysics, is the application of three geophysical methods: electric tomography, magnetism, and refraction seismic. The correlation of these applications should result in delineating the mineralized zone and tracking all elements that in one way or another affect this mineralization. These elements are referred to as "derangement". The combination of the results of these two methods (vertical electrical survey and tomography) used allowed us to identify and map the disturbed places in the chosen area of El Halassa. The study will be extended to other sites and the results can be compared and correlated to understand the extent and origin of these disturbances

Geophysical Characterization of Disturbances in the Phosphate Series of the OuladAbdoun, Morocco: Relationship with Atlasictectonics

The sedimentary phosphates series from the Upper Maastricht to the Lutetion of the OuladAbdoun sedimentary basin is almost identical at the basin-scale. It is made up by alternation of either phosphate or non-phosphate sub-horizontal levels. The series was characterized by rhythmic sedimentation under the form of successive elementary sequences. On the other hand, the series of SidiChennaneis distinguished by the presence of local disturbances defined by the miners under the term "dérangements". These "dérangements", which are less frequent at other mining sites (MEA Lahrech, El Hlassa, Point A), are a notable problem during extraction and remain a real obstacle at phosphate mining sites. The morphology of these "dérangements" is almost subcircular to subconical sinkholes and chaotic bodies of anarchical materials. They are fontis type paleokarsts, it is an amalgam of highly altered yellowish brecciated rusty material whose lithological nature reflects that of the surrounding series. They also reflect endokarst siliceous and ferruginous neoformedfacies in the empty spaces of the palaeokarst. The origin of the palaeokarstshasbeen linked to the presence of NE-SW trend faults that have favoured the alteration and dissolution of the gypsum and chalk facies of the Senonian. The regular spatial distribution of these fontisis well related to the regionalAtlasictectonics. This study aims to investigate these problems in its geological aspect, in order to characterize and understand their origin. The purpose of this work isto compare the results obtained by electric tomography, gravimetry and lineament mapping and match them with geological data to draw a meaningful conclusion on the existence of these disturbances and their spatial distribution in relation to tectonic

Disease Control With FOLFIRI Plus Ziv-aflibercept (zFOLFIRI) Beyond FOLFIRI Plus Bevacizumab: Case Series in Metastatic Colorectal Cancer (mCRC)

Background: The prognosis of patients with metastatic colorectal cancer (mCRC) is poor, especially after failure of initial systemic therapy. The VELOUR study showed modestly prolonged overall survival (OS) with ziv-aflibercept plus 5-fluorouracil, leucovorin, and irinotecan (zFOLFIRI) vs. placebo+FOLFIRI after progression on 5-fluoruracil, leucovorin, and oxaliplatin (FOLFOX) ± bevacizumab. The utility of zFOLFIRI after bevacizumab+FOLFIRI is unknown and not recommended in NCCN guidelines. We explored whether zFOLFIRI may be active beyond progression on bevacizumab+FOLFIRI.Methods: We undertook a retrospective analysis of patients treated in routine clinical practice. A chart review was conducted for a cohort (N = 19) of advanced cancer patients (18 mCRC) who received zFOLFIRI from 2014 to 2018 at Fox Chase Cancer Center (FCCC). Analysis included time on zFOLFIRI, PFS, OS, CEA trends and adverse events. A second mCRC cohort (N = 26) from the Flatiron Health EHR-derived database treated with zFOLFIRI after prior bevacizumab+FOLFOX and bevacizumab+FOLFIRI was analyzed for time-on-treatment and overall survival.Results: Median age of mCRC cohort at zFOLFIRI treatment was 54 (FCCC; N = 18) and 62 (Flatiron Health-cohort; N = 26). Of 18 FCCC mCRC patients, 1 patient had prior bevacizumab+FOLFOX and ramucirumab+irinotecan prior to zFOLFIRI for 8.5 months. Of 17 FCCC mCRC patients with prior bevacizumab+FOLFIRI who received zFOLFIRI, 13 had mutant-KRAS, 3 WT-KRAS, and one BRAF-V600E. The patient with BRAF-V600E mutation achieved stable disease on zFOLFIRI after multiple BRAF-targeted therapies. One patient (WT-KRAS mCRC) remained on zFOLFIRI for 14 months. Of 14 patients with mutated-KRAS, 8 remained on zFOLFIRI for >5 months including 3 for >15 months. The rate-of-change in CEA measures on zFOLFIRI was significantly different (p = 0.004) between rapid progressors and those with PFS>4 months. For mCRC patients treated with zFOLFIRI in the 3rd line or greater (N = 18), median PFS was 7.1 months (214 days) and median OS was 13.8 months (416 days). Median time-on-treatment with zFOLFIRI in the Flatiron Health cohort was 4.4 months, median OS was 7.8 months, and longest time-on-treatment with zFOLFIRI was 266 days.Conclusions: In these small real-world cohorts, clinical meaningful stable disease and overall survival on zFOLFIRI beyond progression on bevacizumab+FOLFIRI was observed in patients with mCRC. Further exploration of this approach is warranted

Pseudoprogression After Proton Therapy of Pediatric Spinal Pilocytic Astrocytoma and Myxopapillary Ependymoma

https://openworks.mdanderson.org/sumexp23/1025/thumbnail.jp

Molecular characterization and clinical outcomes of pancreatic neuroendocrine tumors (pNENs) harboring PAK4-NAMPT alterations

Background: The mTOR inhibitor, Everolimus (EVE), is FDA-approved for the treatment of advanced PNENs on the basis of delay of progression. The RADIANT-3 trial showed an increase in PFS from 4.6 to 11 months compared to placebo with an ORR of only 5%. Prior studies suggest that targeting the aberrant expression of mTOR regulators p21 activated kinase 4 (PAK4) and nicotinamide adenine dinucleotide biosynthesis enzyme nicotinamide phosphoribosyltransferase (NAMPT) in PNENs sensitizes these tumors to EVE. To further qualify these observations, we queried a large real-world dataset of PNENs, characterizing the molecular and immune landscapes, as well as the clinical outcomes associated with aberrant PAK4 and NAMPT expression. Methods: 294 cases of PNENs were analyzed using Next Generation Sequencing (NextSeq) and Whole Exome and Whole Transcriptome Sequencing (NovaSeq) at Caris Life Sciences (Phoenix, AZ). For our analyses, we stratified our study cohort into four groups based on the median expression of PAK4 and NAMPT: PAK4-low/NAMPT-low, PAK4-low/ NAMPT-high, PAK4-high/NAMPT-low and PAK4-high/NAMPT-high. Significance was determined using chi-square, Fisher-Exact or Mann-Whitney U, and p-values were adjusted for multiple comparisons (q , 0.05). Results: High prevalence of mutations in PTEN (10.71% vs 1.18%; p \u3c 0.05, q \u3e 0.05), a tumor suppressor of the mTOR pathway and high expression of genes activated in response to mTOR activation such as SLC2A1 (3.07-fold), PFKP (3.32-fold), SCD (2.70-fold), MVK (2.92-fold) and G6PD (2.58-fold) were observed in PAK4-high/NAMPT-high compared to the PAK4-low/NAMPTlow tumors (all q , 0.05). A congruent enrichment of PI3K/AKT/mTOR and glycolysis pathways by single-sample gene set enrichment analysis was observed in these tumors (all q , 0.05). When querying the immune landscape, we observed enrichment in inflammatory response, IL6/JAK/STAT3, IL2/STAT5 signaling pathways and immune checkpoint genes such as PDCD1 (5.14-fold), CD274 (2.84-fold), PDCD1LG2 (2.44-fold), CD80 (3.00-fold), CD86 (2.82-fold), IDO1 (1.92-fold), LAG3 (3.09-fold), HAVCR2 (2.66-fold) and CTLA4 (4.49-fold) in the PAK4-high/NAMPT-high tumors (all q,0.05). Immune cell infiltration estimates revealed an increase in Neutrophils, NK cells and Tregs in the PAK4-high/NAMPT-high tumors (p \u3c 0.05, q \u3e 0.05). Conclusions: Our study demonstrates that PAK4-high/NAMPT-high PNENs are associated with distinct molecular and immune profiles. While the dual blockade of PAK4 and NAMPT has been reported to enhance the efficacy of EVE in PNENs, whether such a blockade would enhance the efficacy of immunotherapeutics warrants further investigation

The Prevalence of TNFα-Induced Necrosis over Apoptosis Is Determined by TAK1-RIP1 Interplay

Death receptor-induced programmed necrosis is regarded as a secondary death mechanism dominating only in cells that cannot properly induce caspase-dependent apoptosis. Here, we show that in cells lacking TGFβ-activated Kinase-1 (TAK1) expression, catalytically active Receptor Interacting Protein 1 (RIP1)-dependent programmed necrosis overrides apoptotic processes following Tumor Necrosis Factor-α (TNFα) stimulation and results in rapid cell death. Importantly, the activation of the caspase cascade and caspase-8-mediated RIP1 cleavage in TNFα-stimulated TAK1 deficient cells is not sufficient to prevent RIP1-dependent necrosome formation and subsequent programmed necrosis. Our results demonstrate that TAK1 acts independently of its kinase activity to prevent the premature dissociation of ubiquitinated-RIP1 from TNFα-stimulated TNF-receptor I and also to inhibit the formation of TNFα-induced necrosome complex consisting of RIP1, RIP3, FADD, caspase-8 and cFLIPL. The surprising prevalence of catalytically active RIP1-dependent programmed necrosis over apoptosis despite ongoing caspase activity implicates a complex regulatory mechanism governing the decision between both cell death pathways following death receptor stimulation

Characterization of Recurrence Patterns and Outcomes of Medulloblastoma in Adults: The University of Texas MD Anderson Cancer Center Experience

BACKGROUND: Medulloblastoma in adults is rare and treatment decisions are largely driven from pediatric literature. We sought to characterize recurrent medulloblastoma in adults. METHODS: From a single-institution dataset of 200 adult patients diagnosed with medulloblastoma during 1978-2017, those with recurrence were analyzed for clinical features, treatment, and outcome. RESULTS: Of the 200 patients, 82 (41%) with median age of 29 years (18-59) had recurrence after a median follow-up time of 8.4 years (95% CI = 7.1, 10.3). Of these, 30 (37%) were standard-risk, 31 (38%) were high-risk, and 21 (26%) had unknown-risk diseases at the time of initial diagnosis. Forty-eight (58%) presented with recurrence outside the posterior fossa, of whom 35 (43%) had distant recurrence only. Median Progression-free survival (PFS) and OS from initial surgery were 33.5 and 62.4 months, respectively. Neither PFS nor OS from initial diagnosis differed between the standard-risk and high-risk groups in those who experience recurrence ( CONCLUSIONS: Recurrent medulloblastoma in adults has a poor prognosis irrespective of initial risk stratification. Recurrence commonly arises outside the posterior fossa years after initial diagnosis