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The IQ Consortium NHP Reuse Working Group (WG) comprises members from 15 pharmaceutical and biotechnology companies. In 2020, the WG developed and distributed a detailed questionnaire on protein non-naïve NHP reuse to the WG member companies. The WG received responses from key stakeholders including principal investigators, facility managers, animal welfare officers and research scientists. This paper’s content reflects the consolidated opinion of the WG members and the questionnaire responses on the subject of NHP reuse within nonclinical programs at all stages of research and development. Many of the pharmaceutical companies represented in the working group or participating in the questionnaire have already achieved some level of NHP reuse in their nonclinical programs, but the survey results suggested that there is significant potential to increase NHP reuse further and a need to understand the considerations involved in reuse more clearly. The WG has also focused carefully on the inherent concerns and risks of implementing protein non-naive NHP reuse and has evaluated the best methods of risk assessment and decision-making. This paper presents a discussion on the challenges and opportunities surrounding protein non-naïve NHP reuse and aims to stimulate further industry dialogue on the subject and provide guidance for pharmaceutical companies to establish roadmaps and decision trees enabling increased protein non-naïve NHP reuse. In addition, this paper represents a solid basis for collaborative engagement between pharmaceutical and biotechnology companies with contract research organizations (CROs) to discuss how the availability of protein non-naïve NHP within CROs can be better leveraged for their use within nonclinical studies.

Deep incised glacial valleys surrounded by high peaks form the modern topography of the Southern Patagonian Andes. Two Miocene plutonic complexes in the Andean retroarc, the cores of the Fitz Roy (49°S) and Torres del Paine (51°S) massifs, were emplaced at 16.7±0.3 Ma and 12.5±0.1 Ma, respectively. Subduction of ocean ridge segments initiated at 54°S, generating northward opening of an asthenospheric window with associated mantle upwelling and orogenic shortening since 16 Ma. Subsequently, the onset of major glaciations at 7 Ma caused drastic changes in the regional topographic evolution. To constrain the respective contributions of tectonic convergence, mantle upwelling and fluvio-glacial erosion to rock exhumation, we present inverse thermal modeling of a new dataset of zircon and apatite (U-Th)/He from the two massifs, complemented by apatite 4He/3He data for Torres del Paine. Our results show rapid rock exhumation recorded in the Fitz Roy massif between 10.5 and 9 Ma, which we ascribe to mantle upwelling and/or crustal shortening due to ridge subduction at 49°S. Both massifs record a pulse of rock exhumation between 6.5 and 4.5 Ma, which we interpret as the result of the onset of Patagonian glaciations. After a period of erosional quiescence during the Miocene/Pliocene transition, increased rock exhumation since 3-2 Ma to present day is interpreted as the result of alpine glacial valley carving promoted by reinforced glacial-interglacial cycles. This study demonstrates that along-strike thermochronological studies provide us with the means to assess the spatio-temporal variations in tectonic, mantle, and surface processes forcing on rock exhumation.

Alpine landscapes form in mountain belts that likely experienced tectonic uplift during plate’s convergence, and efficient erosion dominated by glacial carving and circle retreat. In southern Patagonia N-S oriented late Miocene plutonic complexes are exposed in deep incised valleys with summits topographically above the glacial equilibrium line altitude. Two of the most emblematic ones are the Fitz Roy (Chaltén, latitude 49°S) and the Torres del Paine (latitude 51°S) plutonic complexes, ~2 km higher than the mostly flat bottom valley that is partially covered by the Southern Patagonian Icefield. This continental region is located above an asthenospheric window that opens and migrates from the latitude 54 °S towards the latitude 46 °S since ~16 Ma, and experienced dynamic uplift during episodes of spreading ridge collision with the continental margin. Here we present a new dataset of combined low-temperature thermochronometers from the Chaltén and Torres del Paine plutonic complexes, and their thermal history inversion numerical modeling, to identify the geodynamic processes forcing on the exhumation of the mountain belt. These complexes are separated by 200 km along the strike of the belt, and share a pulse of rapid exhumation at ca. 6 Ma, likely showing that glaciation was regionally starting at this moment. After a period of quiescence, in Torres del Paine the exhumation rate is accelerated from ~2 Ma to the present, interpreted as a signal of the Pleistocene climatic transition creating incise valleys. Only in the Fitz Roy a pulse of rapid exhumation is present at ca. 10 Ma, approximately coincident with the time range in which the ridge was subducting beneath the continent at that latitude. This allows us to separate the climatic from the tectonic/mantle forcing to the exhumation in southern Patagonia, and represents the first in-situ observation of the passage of the asthenospheric window in the low-temperature thermochronometric record of the region.

Late Miocene calc-alkaline intrusions in the back-arc of Southern Patagonia mark an eastward migration of the arc due to accelerated subduction velocity of the Nazca plate or slab flattening preceding active ridge subduction. Amongst these intrusions are the emblematic Torres del Paine (51°S) and Fitz Roy (49°S) plutonic complexes, crystalised at ca. 12.5 and ca. 16.5 Ma, respectively (Leuthold et al., 2012; Ramírez de Arellano et al., 2012). Both intrusions are located at the eastern boundary of the Southern Patagonian Icefield and form prominent peaks with steep slopes that are ~3 km higher in elevation than the surrounding low-relief foreland. Their exhumation has been proposed as a response to glacial erosion and associated glacial rebound since ca. 7 Ma (Fosdick et al., 2013), and/or by regional dynamic uplift between 14 and 6 Ma due to the northward migration of subducting spreading ridges (Guillaume et al., 2009). Here we present a new data set of apatite and zircon (U-Th)/He from both plutonic complexes, numerically modelled to unravel their late-Neogene to Quaternary thermal histories. Our results show three rapid cooling periods for the Fitz Roy intrusion: at ca. 9.5 Ma, at ca. 7.5 Ma, and since ca. 1 Ma. For Torres del Paine, inverse thermal modelling reveals short and rapid cooling at ca. 6.5 Ma followed by late-Quaternary final cooling. The 10 Ma cooling signal only evidenced in the northern plutonic complex (Fitz Roy) may represent an exhumation response to the northward migrating subduction of spreading ridge segments, causing localized dynamic uplift. Thus, the absence of exhumation signal before 6.5 Ma in the southern part (Torres del Paine) suggest that the spreading ridge subduction must have occurred before its 12.5 Ma emplacement. On the other hand, rapid cooling by similar magnitude in both plutonic complexes between ca. 7.5–6.5 Ma, likely reflects the onset of late-Cenozoic glaciations in Southern Patagonia. Finally, the late-stage Quaternary cooling signals differ between Torres del Paine and Fitz Roy, likely highlighting different exhumation responses (i.e. relief development vs. uniform exhumation) to mid-Pleistocene climate cooling. We thus identify and distinguish the causes of rapid exhumation periods in the Southern Patagonian Andes, and propose a first Late Miocene exhumation pulse due to subduction of spreading ridge dynamics, and two Late Cenozoic exhumation episodes due to regional climate changes that have shaped alpine landscapes in this region.References:Leuthold J., et al. 2012. Time resolved construction of a bimodal laccolith (Torres del Paine, Patagonia). EPSL.Ramírez de Arellano C., et al. 2012. High precision U/Pb zircon dating of the Chaltén Plutonic Complex (Cerro Fitz Roy, Patagonia) and its relationship to arc migration in the southernmost Andes. Tectonics.Fosdick J. C., et al. 2013. Retroarc deformation and exhumation near the end of the Andes, southern Patagonia. EPSL.Guillaume B. 2009. Neogene uplift of central eastern Patagonia: Dynamic response to active spreading ridge subduction? Tectonics.

The NASA Mars 2020 Perseverance rover mission will collect a suite of scientifically compelling samples for return to Earth. On the basis of orbital data, the Mars 2020 science team identified two notional sample caches to study (1) the geology of Jezero crater, collected during the prime mission and (2) the ancient crust outside of Jezero crater, collected during a possible extended mission. Jezero crater geology consists of well-preserved, Early Hesperian to Late Noachian deltaic and lacustrine deposits sourced from a river system that drained Noachian terrain. The crater floor comprises at least two distinct units of sedimentary or volcanic origin whose relationship to the deltaic deposits is presently unclear. Remotely-sensed data reveal signatures of carbonate+olivine and clay minerals within crater floor and crater margin units. Samples from within Jezero that comprise the prime mission notional sample collection thus include: crater floor units; fine- and coarse-grained delta facies, the former with potential to preserve organic matter and/or biosignatures, the latter to possibly constrain the type and timing of sediment deposition; chemical sediments with the potential to preserve biosignatures; a sample of crater rim bedrock; and at least one sample of regolith. The region of southern Nili Planum, directly outside the western rim of Jezero crater, is geologically distinct from Jezero crater and contains diverse Early or even Pre-Noachian lithologies, that may contain records of early planetary differentiation, magnetism, paleoclimate and habitability. The notional sample collection from this region will include: layered and other basement rocks; megabreccias, which may represent blocks of (pre-)Noachian crust; basement-hosted hydrothermal fracture fill; olivine+carbonate rocks that are regionally significant and may be related to units within Jezero crater; and mafic cap unit rocks. The samples described are notional and may change with ongoing surface investigations. However, the samples we anticipate collecting align well with community priorities for Mars exploration, addressing geologic diversity, potential ancient biologic activity on Mars, planetary evolution, volatiles, and human health hazards. Many other Mars 2020 team members were involved in this planning.

The origin of the phenomenon known as the Great Unconformity has been a fundamental yet unresolved problem in the geosciences for over a century. Recent hypotheses advocate either global continental exhumation of more than 3–4 km during Cryogenian (717–635 Ma) snowball Earth glaciations, or alternatively, diachronous episodic exhumation throughout the Neoproterozoic (1000–540 Ma) due to plate tectonic reorganization from supercontinent Rodinia assembly and breakup. To test these hypotheses, the temporal pattern of Neoproterozoic thermal histories were evaluated for four North American locations using previously published medium-to-low temperature thermochronology and geologic information. We present inverse time-temperature simulations within a Bayesian modelling framework that record a consistent signal of relatively rapid, high magnitude cooling of ~120–200°C interpreted as erosional exhumation of upper crustal basement during the Cryogenian. These models imply widespread, synchronous cooling consistent with at least ~3–5 km of unroofing during snowball Earth glaciations, but also demonstrate that plate tectonic drivers, with the potential to cause both exhumation and burial, may have significantly influenced the thermal history in regions that were undergoing deformation concomitant with glaciation. In the cratonic interior, however, glaciation remains the only plausible mechanism that satisfies the required timing, magnitude, and broad spatial pattern of continental erosion revealed by our thermochronological inversions. To obtain a full picture of the extent and synchroneity of such erosional exhumation, studies on stable cratonic crust below the Great Unconformity must be repeated on all continents.

A case of spontaneous splenic rupture is reported in which accordion-like compression of a calcified splenic artery is demonstrated roentgenologically, representing an additional sign in the diagnosis of splenic enlargement on plain film roentgenograms of the abdomen.