Trace element and stable isotope dispersion halo around a high sulfidation epithermal Au-Ag deposit emplaced in Quarzitic Sandstone: The Lagunas Norte Deposit, Northern Peru

The Lagunas Norte high sulfidation epithermal Au-Ag deposit is, with 11.2 Moz of total resources, the most important ore deposit discovered recently in Peru. It is largely hosted by folded, Cretaceous quartzitic sandstone of the Chimu Formation, but ~30% of the ore was emplaced in the Miocene Calipuy Group volcanic rocks overlying the quartzites, as well as in two phreatomagmatic diatreme breccia bodies cutting the Cretaceous units. Due to the low reactivity of the quartzites, the alteration halo around the deposit is obscure so that the deposit eluded discovery until 2001. However, stable-oxygen isotope geochemistry combined with multi element data can vector to ore. The oxygen isotopic composition of quartz reflects hydrothermal alteration beyond the halo visible in the relatively pure (mostly >95% SiO2) sandstones. Regional background δ18O values of unaltered sandstones are between 13.2‰ and 13.8‰ whereas much higher v18O values between 16.5‰ and 16.8‰ in finegrained yellowish quartz veins in the sandstones (silice parda) and vuggy quartz in the volcanic rocks record the influence of the mineralizing fluid. The quartzitic sandstones affected by hydrothermal fluids near the deposit show δ18O values between 14‰ and 15‰ and similar elevated values are observed near faults to the north of the deposit. The highest δ18O values in the silica parda correlate with high Ti and Te contents but low Ga and Pb contents relative to those of the unaltered quartzites. Mobile elements like Na and K are commonly below detection limit (ALS Chemex - ICP-MS ME-ICP06 & ME-MS61), even in the unaltered sandstones. We conclude that stable isotope geochemistry is a potentially powerful tool when defining the extent of hydrothermal fluid flow in non-reactive host rocks

NEW EVIDENCES ABOUT THE MIOCENIC MAGMATISM IN THE VETASCALIFORNIAMINING DISTRICT (SANTANDER MASSIF, EASTERNCORDILLERA, COLOMBIA)

En el distrito Minero de Vetas-California (DMVC) afloran rocas ígneas tanto de textura porfirítica-afanítica, como de textura porfirítica-fanerítica, relacionadas con el evento magmático más reciente conocido hasta el momento para el Macizo de Santander, de edad Mioceno. Estas rocas, al parecer se confinan hacia las zonas de influencia de fallas NNW (similares en su dirección a la Falla Bucaramanga-Santa Marta) y un sistema de fallas NE. Las rocas con textura porfirítica-fanerítica y de composiciones entre cuarzo monzodioritas y granodioritas, por ahora solo han sido observadas al Éste del área de estudio, mientras que las rocas de textura porfirítica afanítica, de composiciones entre andesitas porfiríticas y riodacitas porfiríticas, son más frecuentes al Oeste. Dos tipos de rocas datadas en el presente estudio; una de variedad andesita porfirítica, localizada en el lado Oeste del área de estudio y otra de una granodiorita de textura porfirítica-fanerítica, localizada al Éste del área; arrojaron edades de 10.1±0.2 y 10.9±0.2 Ma, respectivamente (utilizando el método U-Pb en circones, mediante la técnicaLA-MC-ICPMS: laser ablation multicollector inductively coupled plasma mass spectrometry). En este sentido, y apoyados en las aún limitadas edades conocidas, se infiere que este sector del Macizo de Santander fue afectado por un pulso ígneo de por lo menos 2.5 Ma de duración. La presencia de rocas ígneas de edad Mioceno afectadas por procesos de alteración hidrotermal y con estilos de mineralización epitermal y porfirítica, y la falta de evidencias de rocas ígneas más jóvenes que 8.4 Ma, permiten sugerir que en algún(os) momento(s) de la evolución del magmatismo Miocenico, pudieron tener lugar procesos magmático-hidrotermales asociados a eventos mineralizantes en el DMVC. Palabras clave: Distrito Minero Vetas-California (DMVC), Mioceno, Fallas, Edades U-Pb, Macizo de Santander.      In The Vetas-California Mining District (DMVC), igneous rocks with porphyritic-aphanitic and porphyriticphaneritic textures crop out, which are related to the Miocene and most recent magmatic event known for the Santander Massif. The emplacement of these rocks is apparently controlled by the intersections of NNW faults(similar in direction to the Bucaramanga-Santa Marta fault) and the NE fault systems. Porphyritic-phaneriticquartz’ monzodiorites and granodiorite rocks are confined to the eastern part of the studied area; mean while the porphyritic-aphanitic andesite and rhyodacitic rocks are confined to the western part. The two types ofigneous rocks dated in this study; a porphyritic andesite variety (located to the western part of the studied area)and a granodiorite with prophyritic-phaneritic texture (located to the eastern part); yielded ages of 10.1 ± 0.2and 10.9 ± 0.2 Ma, respectively (U-Pb method on zircons, using the LA-MC-ICPMS technique: laser ablation inductively coupled plasma multicollector mass spectrometry). These ages, together with previously published data, indicate that magmatic pulse lasted up to 2.5 Ma. The presence of Miocene igneous rocks affected by hydrothermal alteration and with epithermal and porphyry style mineralization, and the absence of igneous rocks younger than 8.4 m.y. (at least currently not known), allow to propose that during some time(s) of the Miocenic magmatic pulse,could take place magmatic-hydrothermal processes related to mineralizing events inthe DMVC. Keywords: Vetas-California Mining District, Miocene, Faults, U-Pb ages, Santander Massif

NEW EVIDENCES ABOUT THE MIOCENIC MAGMATISM IN THE VETASCALIFORNIAMINING DISTRICT (SANTANDER MASSIF, EASTERNCORDILLERA, COLOMBIA)

En el distrito Minero de Vetas-California (DMVC) afloran rocas ígneas tanto de textura porfirítica-afanítica, como de textura porfirítica-fanerítica, relacionadas con el evento magmático más reciente conocido hasta el momento para el Macizo de Santander, de edad Mioceno. Estas rocas, al parecer se confinan hacia las zonas de influencia de fallas NNW (similares en su dirección a la Falla Bucaramanga-Santa Marta) y un sistema de fallas NE. Las rocas con textura porfirítica-fanerítica y de composiciones entre cuarzo monzodioritas y granodioritas, por ahora solo han sido observadas al Éste del área de estudio, mientras que las rocas de textura porfirítica afanítica, de composiciones entre andesitas porfiríticas y riodacitas porfiríticas, son más frecuentes al Oeste. Dos tipos de rocas datadas en el presente estudio; una de variedad andesita porfirítica, localizada en el lado Oeste del área de estudio y otra de una granodiorita de textura porfirítica-fanerítica, localizada al Éste del área; arrojaron edades de 10.1±0.2 y 10.9±0.2 Ma, respectivamente (utilizando el método U-Pb en circones, mediante la técnicaLA-MC-ICPMS: laser ablation multicollector inductively coupled plasma mass spectrometry). En este sentido, y apoyados en las aún limitadas edades conocidas, se infiere que este sector del Macizo de Santander fue afectado por un pulso ígneo de por lo menos 2.5 Ma de duración. La presencia de rocas ígneas de edad Mioceno afectadas por procesos de alteración hidrotermal y con estilos de mineralización epitermal y porfirítica, y la falta de evidencias de rocas ígneas más jóvenes que 8.4 Ma, permiten sugerir que en algún(os) momento(s) de la evolución del magmatismo Miocenico, pudieron tener lugar procesos magmático-hidrotermales asociados a eventos mineralizantes en el DMVC. Palabras clave: Distrito Minero Vetas-California (DMVC), Mioceno, Fallas, Edades U-Pb, Macizo de Santander.      In The Vetas-California Mining District (DMVC), igneous rocks with porphyritic-aphanitic and porphyriticphaneritic textures crop out, which are related to the Miocene and most recent magmatic event known for the Santander Massif. The emplacement of these rocks is apparently controlled by the intersections of NNW faults(similar in direction to the Bucaramanga-Santa Marta fault) and the NE fault systems. Porphyritic-phaneriticquartz’ monzodiorites and granodiorite rocks are confined to the eastern part of the studied area; mean while the porphyritic-aphanitic andesite and rhyodacitic rocks are confined to the western part. The two types ofigneous rocks dated in this study; a porphyritic andesite variety (located to the western part of the studied area)and a granodiorite with prophyritic-phaneritic texture (located to the eastern part); yielded ages of 10.1 ± 0.2and 10.9 ± 0.2 Ma, respectively (U-Pb method on zircons, using the LA-MC-ICPMS technique: laser ablation inductively coupled plasma multicollector mass spectrometry). These ages, together with previously published data, indicate that magmatic pulse lasted up to 2.5 Ma. The presence of Miocene igneous rocks affected by hydrothermal alteration and with epithermal and porphyry style mineralization, and the absence of igneous rocks younger than 8.4 m.y. (at least currently not known), allow to propose that during some time(s) of the Miocenic magmatic pulse,could take place magmatic-hydrothermal processes related to mineralizing events inthe DMVC. Keywords: Vetas-California Mining District, Miocene, Faults, U-Pb ages, Santander Massif

Prostate cancer detection rate in men undergoing transperineal template-guided saturation and targeted prostate biopsy

OBJECTIVES To compare prostate cancer (PCa) detection rate of transperineal template-guided saturation prostate biopsy (SBx) and multiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound fusion guided targeted biopsy (TBx). MATERIALS AND METHODS: We prospectively enrolled 392 men who underwent SBx and TBx in case of suspicious lesions from November 2016 to October 2019. Triggers for a biopsy were an elevated prostate-specific antigen (PSA) and/or positive digital rectal examination and only treatment naïve patients without a previous diagnosis of PCa were included. Study inclusion occurred before biopsy and a prebiopsy mpMRI was available in all men. SBx were taken from 20 different locations according to the modified Barzell zones. The primary endpoint was the detection rate of clinically significant PCa (csPCa) and insignificant PCa (ciPCa) by SBx and/or TBx by comparing the two methods alone and in combination. Additional TBx were taken for any prostate imaging-reporting and data system (PI-RADS) lesion ≥3 seen on the mpMRI. csPCa was defined as any Gleason score ≥7 and ciPCa as Gleason score 6. RESULTS A total of 392 men with a median age of 64 years (interquartile range [IQR]: 58-69), a median PSA of 7.0 ng/ml (IQR: 4.8-10.1) were enrolled. Overall, PCa was found in 200 (51%) of all biopsied men, with 158 (79%) being csPCa and 42 (21%) ciPCa. A total of 268 (68%) men with a suspicious mpMRI and underwent a combined TBx and SBx, of whom csPCa was found in 139 (52%). In this subgroup, 116/139 (83%) csPCa would have been detected by TBx alone, and an additional 23 (17%) were found by SBx. Men with a negative mpMRI (PI-RADS < 3, n = 124, 32%) were found to have csPCa in 19 (15%) cases. In patients with a negative mpMRI in combination with a PSA density <0.1 ng/ml$^{2}$ , only 8% (3/36) had csPCa. If only TBx would have been performed and all men with a negative mpMRI would not have been biopsed, 42/158 (27%) of csPCa would have been missed, and 38/42 (90%) ciPCa would have not been detected. On multivariable analysis, significant predictors of csPCa were increasing PSA (odds ratio, OR: 1.07 [95% confidence interval, CI: 1.03-1.11]), increasing age (OR: 1.07 [95% CI: 1.03-1.11]), PI-RADS score ≥ 3 (OR: 6.49 [95% CI: 3.55-11.89]), and smaller prostate volume (OR: 0.96 [95% CI: 0.95 -0.97] (p < 0.05 for all parameters). CONCLUSION In comparison to SBx, TBx alone detects csPCa in only ¾ of all men with a positive mpMRI lesion. Thus, systematic biopsies in addition to TBx have to be considered at least in some who undergo a prostate biopsy. In men with a negative mpMRI, SBx still detects 15% csPCa, but similarly overdetecting ciPCa. According to our results, low PSA density and negative mpMRI findings could be used to decide which men can safely avoid biopsy

KDR Identifies a Conserved Human and Murine Hepatic Progenitor and Instructs Early Liver Development

SummaryUnderstanding the fetal hepatic niche is essential for optimizing the generation of functional hepatocyte-like cells (hepatic cells) from human embryonic stem cells (hESCs). Here, we show that KDR (VEGFR2/FLK-1), previously assumed to be mostly restricted to mesodermal lineages, marks a hESC-derived hepatic progenitor. hESC-derived endoderm cells do not express KDR but, when cultured in media supporting hepatic differentiation, generate KDR+ hepatic progenitors and KDR− hepatic cells. KDR+ progenitors require active KDR signaling both to instruct their own differentiation into hepatic cells and to non-cell-autonomously support the functional maturation of cocultured KDR− hepatic cells. Analysis of human fetal livers suggests that similar progenitors are present in human livers. Lineage tracing in mice provides in vivo evidence of a KDR+ hepatic progenitor for fetal hepatoblasts, adult hepatocytes, and adult cholangiocytes. Altogether, our findings reveal that KDR is a conserved marker for endoderm-derived hepatic progenitors and a functional receptor instructing early liver development

Swiss Survey on current practices and opinions on clinical constellations triggering the search for PNH clones.

UNLABELLED This national survey investigated the current practice in Switzerland by collecting participants' opinions on paroxysmal nocturnal hemoglobinuria (PNH) clone assessment and clinical practice. AIM This study aimed to investigate clinical indications prompting PNH clones' assessment and physician's accessibility of a flow cytometry facility, and also to understand clinical attitudes on the follow-up (FU) of patients with PNH clones. METHODS The survey includes 16 multiple-choice questions related to PNH and targets physicians with a definite level of experience in the topic using two screener questions. Opinion on clinical management was collected using hypothetical clinical situations. Each participant had the option of being contacted to further discuss the survey results. This was an online survey, and 264 physicians were contacted through email once a week for 5 weeks from September 2020. RESULTS In total, 64 physicians (24.2%) from 23 institutions participated (81.3% hematologists and 67.2% from university hospitals). All had access to flow cytometry for PNH clone testing, with 76.6% having access within their own institution. The main reasons to assess for PNH clones were unexplained thrombosis and/or hemolysis, and/or aplastic anemia (AA). Patients in FU for PNH clones were more likely to be aplastic anemia (AA) and symptomatic PNH. In total, 61% of the participants investigated PNH clones repetitively during FU in AA/myelodysplastic syndromes patients, even when there was no PNH clone found at diagnosis, and 75% of the participants tested at least once a year during FU. Opinions related to clinical management were scattered. CONCLUSION The need to adhere to guidelines for the assessment, interpretation, and reporting of PNH clones emerges as the most important finding, as well as consensus for the management of less well-defined clinical situations. Even though there are several international guidelines, clear information addressing specific topics such as the type of anticoagulant to use and its duration, as well as the indication for treatment with complement inhibitors in some borderline situations are needed. The analysis and the discussion of this survey provide the basis for understanding the unmet needs of PNH clone assessment and clinical practice in Switzerland

The role of changing geodynamics in the progressive contamination of Late Cretaceous to Late Miocene arc magmas in the southern Central Andes

The tectonic and geodynamic setting of the southern Central Andean convergent margin changed significantly between the Late Cretaceous and the Late Miocene, influencing magmatic activity and its geochemical composition. Here we investigate how these changes, which include changing slab-dip angle and convergence angles and rates, have influenced the contamination of the arc magmas with crustal material. Whole rock geochemical data for a suite of Late Cretaceous to Late Miocene arc rocks from the Pampean flat-slab segment (29–31 °S) of the southern Central Andes is presented alongside petrographic observations and high resolution age dating. In-situ U–Pb dating of magmatic zircon, combined with Ar–Ar dating of plagioclase, has led to an improved regional stratigraphy and provides an accurate temporal constraint for the geochemical data. A generally higher content of incompatible trace elements (e.g. Nb/Zr ratios from 0.019 to 0.083 and Nb/Yb from 1.5 to 16.4) is observed between the Late Cretaceous (~ 72 Ma), when the southern Central Andean margin is suggested to have been in extension, and the Miocene when the thickness of the continental crust increased and the angle of the subducting Nazca plate shallowed. Trace and rare earth element compositions obtained for the Late Cretaceous to Late Eocene arc magmatic rocks from the Principal Cordillera of Chile, combined with a lack of zircon inheritance, suggest limited assimilation of the overlying continental crust by arc magmas derived from the mantle wedge. A general increase in incompatible, fluid-mobile/immobile (e.g., Ba/Nb) and fluid-immobile/immobile (e.g., Nb/Zr) trace element ratios is attributed to the influence of the subducting slab on the melt source region and/or the influx of asthenospheric mantle. The Late Oligocene (~ 26 Ma) to Early Miocene (~ 17 Ma), and Late Miocene (~ 6 Ma) arc magmatic rocks present in the Frontal Cordillera show evidence for the bulk assimilation of the Permian–Triassic (P–T) basement, both on the basis of their trace and rare earth element compositions and the presence of P–T inherited zircon cores. Crustal reworking is also identified in the Argentinean Precordillera; Late Miocene (12–9 Ma) arc magmatic rocks display distinct trace element signatures (specifically low Th, U and REE concentrations) and contain inherited zircon cores with Proterozoic and P–T ages, suggesting the assimilation of both the P–T basement and a Grenville-aged basement. We conclude that changing geodynamics play an important role in determining the geochemical evolution of magmatic rocks at convergent margins and should be given due consideration when evaluating the petrogenesis of arc magmas.</p

Productive Hepatitis C Virus Infection of Stem Cell-Derived Hepatocytes Reveals a Critical Transition to Viral Permissiveness during Differentiation

Primary human hepatocytes isolated from patient biopsies represent the most physiologically relevant cell culture model for hepatitis C virus (HCV) infection, but these primary cells are not readily accessible, display individual variability, and are largely refractory to genetic manipulation. Hepatocyte-like cells differentiated from pluripotent stem cells provide an attractive alternative as they not only overcome these shortcomings but can also provide an unlimited source of noncancer cells for both research and cell therapy. Despite its promise, the permissiveness to HCV infection of differentiated human hepatocyte-like cells (DHHs) has not been explored. Here we report a novel infection model based on DHHs derived from human embryonic (hESCs) and induced pluripotent stem cells (iPSCs). DHHs generated in chemically defined media under feeder-free conditions were subjected to infection by both HCV derived in cell culture (HCVcc) and patient-derived virus (HCVser). Pluripotent stem cells and definitive endoderm were not permissive for HCV infection whereas hepatic progenitor cells were persistently infected and secreted infectious particles into culture medium. Permissiveness to infection was correlated with induction of the liver-specific microRNA-122 and modulation of cellular factors that affect HCV replication. RNA interference directed toward essential cellular cofactors in stem cells resulted in HCV-resistant hepatocyte-like cells after differentiation. The ability to infect cultured cells directly with HCV patient serum, to study defined stages of viral permissiveness, and to produce genetically modified cells with desired phenotypes all have broad significance for host-pathogen interactions and cell therapy