Decoding DarkMatter

Decoding DarkMatter is a documentary film about two Asian transgender poetry performance artists: Alok Vaid-Menon and Janani Balasubramanian. It documents their journey from Stanford University to their first large theater production; It Gets Bitter, at Joe’s Pub in New York City

Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review

The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies

Characterisation of the guinea pig model of osteoarthritis by in vivo three-dimensional magnetic resonance imaging

AbstractObjective: To characterise longitudinal changes in joint integrity and cartilage volume in vivo in the guinea pig spontaneous osteoarthritis (OA) model by magnetic resonance imaging (MRI).Methods: Guinea pigs knee were imaged in vivo by high-resolution three-dimensional (3D) MRI between the ages of 3 and 12 months. Image analysis was performed to assess qualitative knee joint changes between 3 and 12 months (n=16) and quantitative volumetric changes of the medial tibial cartilage between 9 and 12 months (n=7). After imaging, animals were killed and knees were assessed macroscopically and histologically.Results: From 3 to 6 months qualitative observation by MRI and histopathology indicated localised cartilage swelling on the medial tibial plateau. At 6 months, bone cysts had developed in the epiphysis. At 9 months, we observed by MRI and histopathology, fragmentation of the medial tibial cartilage in areas not protected by the meniscus. Cartilage degeneration had intensified at 12 months with evidence of widespread loss of cartilage throughout the tibial plateau. Segmentation of the MR cartilage images showed a 36% loss of volume between 9 and 12 months.Conclusions: We have achieved 3D image acquisition and segmentation of knee cartilage in a guinea pig model of chronic OA, which permits measurements previously only possible in man. High resolution and short acquisition time allowed qualitative longitudinal characterisation of the entire knee joint and enabled us to quantify for the first time longitudinal tibial cartilage volume loss associated with disease progression

Bone area provides a responsive outcome measure for bone changes in short-term knee osteoarthritis studies

Objective: This post-hoc study analyzed 3D bone area from an osteoarthritis (OA) cohort demonstrating no change in cartilage thickness. Methods: 27 women with painful medial knee OA had MRI at 0, 3 and 6 months. Images were analysed using active appearance models. Results: At 3 and 6 months the mean change in medial femoral bone area was 0.34% [95% CI 0.04, 0.64] and 0.61% [CI 0.32, 0.90]. 40% of subjects had progression > SDD at 6 months. Conclusion: In this small cohort at high risk of OA progression, bone area changed at 3 and 6 months when cartilage morphometric measures did not

Stirred not shaken; critical evaluation of a proposed Archean meteorite impact in West Greenland

Funding Information: The Ministry of Mineral Resources and Labour, Greenland Government supported field and analytical work.Large meteorite impacts have a profound effect on the Earth's geosphere, atmosphere, hydrosphere and biosphere. It is widely accepted that the early Earth was subject to intense bombardment from 4.5 to 3.8 Ga, yet evidence for subsequent bolide impacts during the Archean Eon (4.0 to 2.5 Ga) is sparse. However, understanding the timing and magnitude of these early events is important, as they may have triggered significant change points to global geochemical cycles. The Maniitsoq region of southern West Greenland has been proposed to record a ∼3.0 Ga meteorite impact, which, if confirmed, would be the oldest and only known impact structure to have survived from the Archean. Such an ancient structure would provide the first insight into the style, setting, and possible environmental effects of impact bombardment continuing into the late Archean. Here, using field mapping, geochronology, isotope geochemistry, and electron backscatter diffraction mapping of 5,587 zircon grains from the Maniitsoq region (rock and fluvial sediment samples), we test the hypothesis that the Maniitsoq structure represents Earth's earliest known impact structure. Our comprehensive survey shows that previously proposed impact-related geological features, ranging from microscopic structures at the mineral scale to macroscopic structures at the terrane scale, as well as the age and geochemistry of the rocks in the Maniitsoq region, can be explained through endogenic (non-impact) processes. Despite the higher impact flux, intact craters from the Archean Eon remain elusive on Earth.Publisher PDFPeer reviewe

Can cartilage loss be detected in knee osteoarthritis (OA) patients with 3–6 months' observation using advanced image analysis of 3T MRI?

SummaryPurposePrior investigations of magnetic resonance imaging (MRI) biomarkers of cartilage loss in knee osteoarthritis (OA) suggest that trials of interventions which affect this biomarker with adequate statistical power would require large clinical studies of 1–2 years duration. We hypothesized that smaller, shorter duration, “Proof of Concept” (PoC) studies might be achievable by: (1) selecting a population at high risk of rapid medial tibio-femoral (TF) progression, in conjunction with; (2) high-field MRI (3T), and; (3) using advanced image analysis. The primary outcome was the cartilage thickness in the central medial femur.MethodsMulti-centre, non-randomized, observational cohort study at four sites in the US. Eligible participants were females with knee pain, a body mass index (BMI)≥25kg/m2, symptomatic radiographic evidence of medial TF OA, and varus mal-alignment. The 29 participants had a mean age of 62 years, mean BMI of 36kg/m2, with eight index knees graded as Kellgren–Lawrence (K&L)=2 and 21 as K&L=3. Eligible participants had four MRI scans of one knee: two MRIs (1 week apart) were acquired as a baseline with follow-up MRI at 3 and 6 months. A trained operator, blind to time-point but not subject, manually segmented the cartilage from the Dual Echo Steady State water excitation MR images. Anatomically corresponding regions of interest were identified on each image by using a three-dimensional statistical shape model of the endosteal bone surface, and the cartilage thickness (with areas denuded of cartilage included as having zero thickness – ThCtAB) within each region was calculated. The percentage change from baseline at 3 and 6 months was assessed using a log-scale analysis of variance (ANOVA) model including baseline as a covariate. The primary outcome was the change in cartilage thickness within the aspect of central medial femoral condyle exposed within the meniscal window (w) during articulation, neglecting cartilage edges [nuclear (n)] (nwcMF·ThCtAB), with changes in other regions considered as secondary endpoints.ResultsAnatomical mal-alignment ranged from −1.9° to 6.3°, with mean 0.9°. With one exception, no changes in ThCtAB were detected at the 5% level for any of the regions of interest on the TF joint at 3 or 6 months of follow-up. The change in the primary variable (nwcMF·ThCtAB) from (mean) baseline at 3 months from the log-scale ANOVA model was −2.1% [95% confidence interval (CI) (−4.4%, +0.2%)]. The change over 6 months was 0.0% [95% CI (−2.7%, +2.8%)]. The 95% CI for the change from baseline did not include zero for the cartilage thickness within the meniscal window of the lateral tibia (wLT·ThCtAB) at 6 month follow-up (−1.5%, 95% CI [−2.9, −0.2]), but was not significant at the 5% level after correction for multiple comparisons.ConclusionsThe small inconsistent compartment changes, and the relatively high variabilities in cartilage thickness changes seen over time in this study, provide no additional confidence for a 3- or 6-month PoC study using a patient population selected on the basis of risk for rapid progression with the MRI acquisition and analyses employed

The Mesoarchaean Akia terrane, West Greenland, revisited : new insights based on spatial integration of geophysics, field observation, geochemistry and geochronology

NJG thanks Australian Research Council grant FL160100168 for financial support.The northern part of the North Atlantic Craton (NAC) in southern West Greenland comprises a large tract of exposed Meso-Neoarchaean continental crust, divided into the ca 3300–2900 Ma Akia and ca 2900–2500 Ma Tuno terranes. We combine aeromagnetic, stream sediment geochemical, new litho-chemical and zircon geochronological data with previously published data to re-evaluate the crustal architecture and evolution of the Akia terrane and its boundary towards the Tuno terrane. The previously recognised, but overlooked, Alanngua complex, situated between the Akia and Tuno terranes is bounded by aeromagnetic lineaments interpreted as Neoarchaean shear zones and has a distinct spectrum of Neoarchaean magmatic and metamorphic zircon ages that are rare in the Akia terrane. The Alanngua complex comprises components derived from both the Akia and Tuno terranes and is interpreted as a tectonic melange created during the Neoarchaean assembly of the NAC. Within the Akia terrane, the chemistry of orthogneiss samples indicate that a large percentage is too mafic to classify as TTG s.s., implying that not only partial melting of mafic crust, but also some yet unaddressed mantle involvement is necessary in their formation. Previous models for the generation of the ca. 3015–2990 Ma quartz-dioritic Finnefjeld and Taserssuaq complexes conflict with their geochemical variation. The complexes are spatially associated with strong aeromagnetic responses that are interpreted to reflect a large gabbro-diorite intrusion, and we propose that the protoliths of the Finnefjeld and Taserssuaq complexes are genetically linked to such intrusion. Formed at same time are carbonatite, high-Mg gabbro and tonalite-trondhjemite, and we propose that this wide spectrum of rocks could have formed by lithospheric and crustal melting in response to asthenospheric upwelling possibly in an extensional setting. Periods of extensive magmatism in the Akia terrane were previously recognised at ca. 3220-3180 Ma and 3070-2970 Ma. We now subdivide the latter period into three episodes: juvenile basaltic-andesitic volcanism at 3070–3050 Ma; tonalitic and dioritic plutonism at 3050–3020 Ma, and gabbroic-dioritic plus tonalitic-trondhjemitic plutonism at 3020–2985 Ma. This last episode was immediately followed by crustal reworking during collision at 2980–2950 Ma.Publisher PDFPeer reviewe

Regional zircon U-Pb geochronology for the Maniitsoq region, southwest Greenland

The Ministry of Mineral Resources, Government of Greenland, funded this project. Analyses in the JdLC GeoHistory Facility were enabled by instrumentation supported by AuScope (auscope.org.au) and the Australian Government via the National Collaborative Research Infrastructure Strategy. The Tescan Mira3 FEG-SEM was funded through the Australian Research Council LIEF program.Zircon U-Pb geochronology places high-temperature geological events into temporal context. Here, we present a comprehensive zircon U-Pb geochronology dataset for the Meso- to Neoarchean Maniitsoq region in southwest Greenland, which includes the Akia Terrane, Tuno Terrane, and the intervening Alanngua Complex. The magmatic and metamorphic processes recorded in these terranes straddle a key change-point in early Earth geodynamics. This dataset comprises zircon U-Pb ages for 121 samples, including 46 that are newly dated. A principal crystallization peak occurs across all three terranes at ca. 3000 Ma, with subordinate crystallization age peaks at 3200 Ma (Akia Terrane and Alanngua Complex only), 2720 Ma and 2540 Ma. Metamorphic age peaks occur at 2990 Ma, 2820-2700 Ma, 2670-2600 Ma and 2540 Ma. Except for one sample, all dated metamorphic zircon growth after the Neoarchean occurred in the Alanngua Complex or within 20 km of its boundaries. This U-Pb dataset provides an important resource for addressing Earth Science topics as diverse as crustal evolution, fluid-rock interaction and mineral deposit genesis.Publisher PDFPeer reviewe

Imaging biomarkers of lung ventilation in interstitial lung disease from ¹²⁹Xe and oxygen enhanced ¹H MRI

PURPOSE: To compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. STUDY TYPE: Prospective longitudinal. POPULATION: Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. FIELD STRENGTH/SEQUENCE: MRI performed at 1.5 T. Inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. ASSESSMENT: Five 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. STATISTICAL TEST: To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. RESULTS: The global PFT tests could not distinguish ILD subtypes. Ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. DATA CONCLUSION: Neither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF