A laser probe ⁴⁰Ar /³⁹Ar and INAA investigation of four Apollo granulitic breccias

Infrared laser probe 40Ar/39Ar geochronology, instrumental neutron activation analysis (INAA) and analytical electron microscopy have been performed on four 0.5 x 1.0 x 0.3 cm polished rock tiles of Apollo 16 and 17 granulitic breccias (60035, 77017, 78155, and 79215). Pyroxene thermometry indicates that these samples were re-equilibrated and underwent peak metamorphic sub-solidus recrystallization at 1000 – 1100°C, which resulted in homogeneous mineral compositions and granoblastic textures. 40Ar/39Ar data from this study reveal that three samples (60035, 77017, and 78155) have peak metamorphic ages of ~4.1 Ga. Sample 79215 has a peak metamorphic age of 3.9 Ga, which may be related to Serenitatis basin formation. All four samples contain moderately high concentrations of meteoritic siderophiles. Enhanced siderophile contents in three of the samples provide evidence for projectile contamination of their target lithologies occurring prior to peak metamorphism. Post-peak metamorphism, low-temperature (<300ºC) events caused the partial resetting of argon in the two finer-grained granulites (60035 and 77017). These later events did not alter the mineralogy or texture of the rocks, but caused minor brecciation and the partial release of argon from plagioclase. Interpretation of the low-temperature data indicates partial resetting of the argon systematics to as young as 3.2 Ga for 60035 and 2.3 Ga for 77017. Cosmic ray exposure ages range from 6.4 to ~339 Ma. Our results increase the amount of high-precision data available for the granulitic breccias and lunar highlands crustal samples. The results demonstrate the survival of pre-Nectarian material on the lunar surface and document the effects of contact metamorphic and impact processes during the pre-Nectarian Epoch, as well as the low-temperature partial resetting of ages by smaller impact events after 3.9 Ga. The mineralogy and chemical composition of these rocks, as well as exhumation constraints, indicate that the source of heat for metamorphism was within kilometres of the surface via burial beneath impact melt sheets or hot ejecta blankets

Observation of centimetre-scale argon diffusion in alkali feldspars: implications for ⁴⁰Ar/³⁹Ar thermochronology

New data from a gem-quality feldspar from Itrongay, Madagascar, record naturally occurring 40Ar/39Ar age profiles which can be numerically modelled by invoking a single diffusion mechanism and show that microtexturally simple crystals are capable of recording complex thermal histories. We present the longest directly measured, naturally produced 40Ar*-closure profiles from a single, homogeneous orthoclase feldspar. These data appear to confirm the assumption that laboratory derived diffusion parameters are valid in nature and over geological timescales. Diffusion domains are defined by crystal faces and ancient cracks, thus in gem-quality feldspars the diffusion domain size equates to the physical grain size. The data also illustrate the potential of large, gem-quality feldspars to record detailed thermal histories over tens of millions of years and such samples should be considered for future studies on the slow cooling of continental crust

Textural characterization, major and volatile element quantification and Ar-Ar systematics of spherulites in the Rocche Rosse obsidian flow, Lipari, Aeolian Islands:A temperature continuum growth model.

Spherulitic textures in the Rocche Rosse obsidian flow (Lipari, Aeolian Islands, Italy) have been characterized through petrographic, crystal size distribution (CSD) and in situ major and volatile elemental analyses to assess the mode, temperature and timescales of spherulite formation. Bulk glass chemistry and spherulite chemistry analyzed along transects across the spherulite growth front/glass boundary reveal major-oxide and volatile (H2O, CO2, F, Cl and S) chemical variations and heterogeneities at a ≤5 μm scale. Numerous bulk volatile data in non-vesicular glass (spatially removed from spherulitic textures) reveal homogenous distributions of volatile concentrations: H2O (0.089 ± 0.012 wt%), F (950 ± 40 ppm) and Cl (4,100 ± 330 ppm), with CO2 and S consistently below detection limits suggesting either complete degassing of these volatiles or an originally volatile-poor melt. Volatile concentrations across the spherulite boundary and within the spherulitic textures are highly variable. These observations are consistent with diffusive expulsion of volatiles into melt, leaving a volatile-poor rim advancing ahead of anhydrous crystallite growth, which is envisaged to have had a pronounced effect on spherulite crystallization dynamics. Argon concentrations dissolved in the glass and spherulites differ by a factor of ~20, with Ar sequestered preferentially in the glass phase. Petrographic observation, CSD analysis, volatile and Ar data as well as diffusion modeling support continuous spherulite nucleation and growth starting at magmatic (emplacement) temperatures of ~790–825 °C and progressing through the glass transition temperature range (T g ~ 750–620 °C), being further modified in the solid state. We propose that nucleation and growth rate are isothermally constant, but vary between differing stages of spherulite growth with continued cooling from magmatic temperatures, such that there is an evolution from a high to a low rate of crystallization and low to high crystal nucleation. Based on the diffusion of H2O across these temperature ranges (~800–300 °C), timescales of spherulite crystallization occur on a timescale of ~4 days with further modification up to ~400 years (growth is prohibitively slow <400 °C and would become diffusion reliant). Selective deformation of spherulites supports a down-temperature continuum of spherulite formation in the Rocche Rosse obsidian; indeed, petrographic evidence suggests that high-strain zones may have catalyzed progressive nucleation and growth of further generations of spherulites during syn- and post-emplacement cooling

Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy

We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks. Treatment effects on DXA measures for domagrozumab versus placebo were assessed at Week 49. At Week 49, domagrozumab statistically significantly increased lean body mass versus placebo in the appendicular skeleton (p = 0.050) and arms (p < 0.001). The relationship between lean body mass at Week 49 and functional endpoints at Week 97 was evaluated. Changes in lean body mass at Week 49 in all regions except arms were significantly correlated with percent change from baseline in 4-stair climb (4SC) at Week 97. DXA-derived percent lean mass at Week 49 also correlated with 4SC and North Star Ambulatory Assessment at Week 97. These data indicate that whole-body DXA measures can be used as biomarkers for treatment effects and disease progression in patients with DMD, and warrant further investigation.Trial registration: ClinicalTrials.gov, NCT02310763; registered 8 December 2014

New ⁴⁰Ar/³⁹Ar dating of the Antrim Plateau Volcanics, Australia: clarifying an age for the eruptive phase of the Kalkarindji continental flood basalt province

The Kalkarindji flood basalt province of northern Australia erupted in the mid-Cambrian. Today the province consists of scattered volcanic and intrusive suites, the largest being the Antrim Plateau Volcanics (APV) in Northern Territory. Accurate dating of Kalkarindji has proved challenging with previous studies focused on minor volcanics and intrusive dykes in Northern Territory and Western Australia. These previously published data, corrected to the same decay constants, range from 512.8 to 509.6 ± 2.5 Ma [2σ], placing Kalkarindji in apparent synchronicity with the Cambrian Stage 4–5 biotic crisis at 510 ± 1 Ma. This study utilises 40Ar/39Ar dating of basalts from the APV to accurately date the major volcanic eruptions in this province. Results yield an age of 508.0–498.3 ± 5.5 Ma [2σ], indicating the APV is younger than the intrusives. These dates allude to a relative timing discrepancy, where intrusive activity in the North Australian Craton preceded the eruption of the APV as the last magmatic activity in the region. The determination of these largest eruptions to be later than 510 Ma, effectively disassociates Kalkarindji lavas from being a major cause of the 510 Ma biotic crisis, but cannot definitively discount any deleterious effects on the fragile Cambrian ecosystem

Recycling Argon through Metamorphic Reactions: the Record in Symplectites

The 40Ar/39Ar ages of metamorphic micas that crystallized at high temperatures are commonly interpreted as cooling ages, with grains considered to have lost 40Ar via thermally-driven diffusion into the grain boundary network. Recently reported laser-ablation data suggest that the spatial distribution of Ar in metamorphic micas does not always conform to the patterns predicted by diffusion theory and that despite high metamorphic temperatures, argon was not removed efficiently from the local system during metamorphic evolution. In the Western Gneiss Region (WGR), Norway, felsic gneisses preserve microtextural evidence for the breakdown of phengite to biotite and plagioclase symplectites during near isothermal decompression from c. 20–25 to c. 8–12 kbar at ~700°C. These samples provide an ideal natural laboratory to assess whether the complete replacement of one K-bearing mineral by another at high temperatures completely ‘resets’ the Ar clock, or whether there is some inheritance of 40Ar in the neo-crystallized phase. The timing of the high-temperature portion of the WGR metamorphic cycle has been well constrained in previous studies. However, the timing of cooling following the overprint is still much debated. In-situ laser ablation spot dating in phengite, biotite-plagioclase symplectites and coarser, texturally later biotite yielded 40Ar/39Ar ages that span much of the metamorphic cycle. Together these data show that despite residence at temperatures of ~700°C, Ar is not completely removed by diffusive loss or during metamorphic recrystallization. Instead, Ar released during phengite breakdown appears to be partially reincorporated into the newly crystallizing biotite and plagioclase (or is trapped in fluid inclusions in those phases) within a close system. Our data show that the microtextural and petrographic evolution of the sample being dated provides a critical framework in which local 40Ar recycling can be tracked, thus potentially allowing 40Ar/39Ar dates to be linked more accurately to metamorphic history

Argon redistribution during a metamorphic cycle: Consequences for determining cooling rates

40Ar/39Ar thermochronology is commonly used to constrain the rates and times of cooling in exhumed metamorphic terranes, with ages usually linked to temperature via Dodson's closure temperature (TC) formulation. Whilst many metamorphic 40Ar/39Ar data are consistent with the timing of crystallisation or cooling within a chronological framework defined by other, higher temperature, chronometers, other 40Ar/39Ar data are more difficult to interpret. We report white mica and biotite single grain fusion and laser ablation 40Ar/39Ar ages from felsic gneisses from the Western Gneiss Region, Norway. The rocks record isothermal decompression from peak eclogite-facies conditions (white mica stable) to amphibolite-facies conditions (biotite stable) at c. 700 °C. White mica and biotite yield dispersed single grain fusion dates from 416 to 373 Ma and 437 to 360 Ma respectively. In-situ laser ablation analyses provide a similar range, with white mica spot ages ranging from 424 to 370 Ma and biotite spot ages ranging from 437 to 370 Ma. The dates span the duration of the metamorphic cycle suggested by previous studies, and cannot be reconciled with the results of simple models of Ar loss by diffusion during cooling. Samples that show evidence for different physical processes, such as the chemical breakdown of white mica, partial melting, and fluid ingress, generated different age populations to samples that did not experience or record obvious petrological evidence for these processes. Samples that record significant recrystallization and deformation yielded younger white mica (but older biotite) single grain fusion ages than more pristine samples. Amphibolite-facies gneisses that preserve evidence for significant partial melting generated younger biotite ages than samples that recorded evidence for significant hydration. Our data support other reported observations that high-temperature metamorphic mica 40Ar/39Ar dates cannot be assumed to record the timing of cooling through a specific temperature window. Careful assessment of the petrographic context of the dated minerals and consideration of their post-crystallisation history may provide a more robust insight into whether ‘age’ links to ‘stage’ in a temporally meaningful way

Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab

Duchenne muscular dystrophy (DMD) is a progressive, neuromuscular disorder caused by mutations in the DMD gene that results in a lack of functional dystrophin protein. Herein, we report the use of quantitative magnetic resonance imaging (MRI) measures as biomarkers in the context of a multicenter phase 2, randomized, placebo-controlled clinical trial evaluating the myostatin inhibitor domagrozumab in ambulatory boys with DMD (n = 120 aged 6 to < 16 years). MRI scans of the thigh to measure muscle volume, muscle volume index (MVI), fat fraction, and T2 relaxation time were obtained at baseline and at weeks 17, 33, 49, and 97 as per protocol. These quantitative MRI measurements appeared to be sensitive and objective biomarkers for evaluating disease progression, with significant changes observed in muscle volume, MVI, and T2 mapping measures over time. To further explore the utility of quantitative MRI measures as biomarkers to inform longer term functional changes in this cohort, a regression analysis was performed and demonstrated that muscle volume, MVI, T2 mapping measures, and fat fraction assessment were significantly correlated with longer term changes in four-stair climb times and North Star Ambulatory Assessment functional scores. Finally, less favorable baseline measures of MVI, fat fraction of the muscle bundle, and fat fraction of lean muscle were significant risk factors for loss of ambulation over a 2-year monitoring period. These analyses suggest that MRI can be a valuable tool for use in clinical trials and may help inform future functional changes in DMD.Trial registration: ClinicalTrials.gov identifier, NCT02310763; registered December 2014

Priority strategies to improve gender equity in Canadian emergency medicine: proceedings from the CAEP 2021 Academic Symposium on leadership

Objectives: Gender inequities are deeply rooted in our society and have significant negative consequences. Female physicians experience numerous gender-related inequities (e.g., microaggressions, harassment, violence). These inequities have far-reaching consequences on health, well-being and career longevity and may result in the devaluing of various strengths that female emergency physicians bring to the table. This, in turn, has an impact on patient healthcare experience and outcomes. During the 2021 Canadian Association of Emergency Physicians (CAEP) Academic Symposium, a national collaborative sought to understand gender inequities in emergency medicine in Canada. Methods: We used a multistep stakeholder-engagement-based approach (harnessing both quantitative and qualitative methods) to identify and prioritize problems with gender equity in emergency medicine in Canada. Based on expert consultation and literature review, we developed recommendations to effect change for the higher priority problems. We then conducted a nationwide consultation with the Canadian emergency medicine community via online engagement and the CAEP Academic Symposium to ensure that these priority problems and solutions were appropriate for the Canadian context. Conclusion: Via the above process, 15 recommendations were developed to address five unique problem areas. There is a dearth of research in this important area and we hope this preliminary work will serve as a starting point to fuel further research. To facilitate these scholarly endeavors, we have appended additional documents identifying other key problems with gender equity in emergency medicine in Canada as well as proposed next steps for future research

Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy.

We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to \u3c16 \u3eyears) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49. Secondary endpoints included other functional tests, pharmacokinetics, and pharmacodynamics. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in domagrozumab- and placebo-treated patients, respectively. Difference in mean (95% CI) change from baseline in 4SC at week 49 for domagrozumab vs placebo was 0.27 (-7.4 to 7.9) seconds (p = 0.94). There were no significant between-group differences in any secondary clinical endpoints. Most patients had ≥1 adverse event in the first 48 weeks; most were mild and not treatment-related. Median serum concentrations of domagrozumab increased with administered dose within each dose level. Non-significant increases in muscle volume were observed in domagrozumab- vs placebo-treated patients. Domagrozumab was generally safe and well tolerated in patients with DMD. Efficacy measures did not support a significant treatment effect. Clinicaltrials.gov identifiers: NCT02310763 and NCT02907619