Pressure—Temperature—Time Paths of Regional Metamorphism II. Their Inference and Interpretation using Mineral Assemblages in Metamorphic Rocks

A companion paper (England & Thompson, 1984a) investigates the pressure-temperature-time (PTt) paths followed by rocks undergoing burial metamorphism in continental thickening events. This paper discusses problems involved in inferring such paths from the petrological data available in metamorphic rocks and—once such paths are determined—how they may be interpreted in terms of the thermal budgets of metamorphism. Each of the principal facies series (glaucophane-jadeite, andalusite- sillimanite and kyanite-sillimanite) may be encountered by rocks involved in the thickening and erosion of continental crust in a regime of average continental heat flow. The inference of a minimum thermal budget required for a given metamorphism depends strongly on a knowledge of the PTt paths followed by rocks during the metamorphism. Discrimination between possible thermal regimes is greatly enhanced if portions of PTt paths, rather than single PT points, are available, and additional constraint is possible if these paths are supplemented by geochronological, structural and heat flow dat

Pressure—Temperature—Time Paths of Regional Metamorphism I. Heat Transfer during the Evolution of Regions of Thickened Continental Crust

The development of regional metamorphism in areas of thickened continental crust is investigated in terms of the major controls on regional-scale thermal regimes. These are: the total radiogenic heat supply within the thickened crust, the supply of heat from the mantle, the thermal conductivity of the medium and the length and time scales of erosion of the continental crust. The orogenic episode is regarded as consisting of a relatively rapid phase of crustal thickening, during which little temperature change occurs in individual rocks, followed by a lengthier phase of erosion, at the end of which the crust is at its original thickness. The principal features of pressure—temperature—time (PTt) paths followed by rocks in this environment are a period of thermal relaxation, during which the temperature rises towards the higher geotherm that would be supported by the thickened crust, followed by a period of cooling as the rock approaches the cold land surface. The temperature increase that occurs is governed by the degree of thickening of the crust, its conductivity and the time that elapses before the rock is exhumed sufficiently to be affected by the proximity of the cold upper boundary. For much of the parameter range considered, the heating phase encompasses a considerable portion of the exhumation (decompression) part of the PTt path. In addition to the detailed calculation of PTt paths we present an idealized model of the thickening and exhumation process, which may be used to make simple calculations of the amount of heating to be expected during a given thickening and exhumation episode and of the depth at which a rock will start to cool on its ascent path. An important feature of these PTt paths is that most of them lie within 50 °C of the maximum temperature attained for one third or more of the total duration of their burial and uplift, and for a geologically plausible range of erosion rates the rocks do not begin to cool until they have completed 20 to 40 per cent of the total uplift they experience. Considerable melting of the continental crust is a likely consequence of thickening of crust with an average continental geotherm. A companion paper discusses these results in the context of attempts to use metamorphic petrology data to give information on tectonic processe

Effects of a temperature-dependent rheology on large scale continental extension

The effects of a temperature-dependent rheology on large-scale continental extension are investigated using a thin viscous sheet model. A vertically-averaged rheology is used that is consistent with laboratory experiments on power-law creep of olivine and that depends exponentially on temperature. Results of the calculations depend principally on two parameters: the Peclet number, which describes the relative rates of advection and diffusion of heat, and a dimensionless activation energy, which controls the temperature dependence of the rheology. At short times following the beginning of extension, deformation occurs with negligible change in temperature, so that only small changes in lithospheric strength occur due to attenuation of the lithosphere. However, after a certain critical time interval, thermal diffusion lowers temperatures in the lithosphere, strongly increasing lithospheric strength and slowing the rate of extension. This critical time depends principally on the Peclet number and is short compared with the thermal time constant of the lithosphere. The strength changes cause the locus of high extensional strain rates to shift with time from regions of high strain to regions of low strain. Results of the calculations are compared with observations from the Aegean, where maximum extensional strains are found in the south, near Crete, but maximum present-day strain rates are largest about 300 km further north

Remote assessment of platelet function in patients with acute stroke or transient ischaemic attack

Background: Antiplatelets reduce recurrence after cerebral ischaemia. The international TARDIS trial assessed the safety and efficacy of intensive (combined aspirin, dipyridamole and clopidogrel) versus guideline (aspirin and dipyridamole, or clopidogrel alone) antiplatelet agents given for one month in patients with acute stroke or TIA. The aim of this substudy was to assess the effect of antiplatelet agents taken at baseline on platelet function reactivity and activation. Methods: In a substudy, platelet function, assessed by remotely measured surface expression of P-selectin (CD62P, Platelet Solutions Ltd), was assessed at baseline in patients who were and were not taking antiplatelet agents at the time of randomisation. Data are Median Fluorescence values (MF). Results: The aspirin P-selectin test demonstrated that platelet expression was lower in 485 patients taking aspirin than in 171 patients taking no aspirin: mean 209 (SD 188) vs. 552 (431), difference 343 (95% confidence intervals, CI 295.3, 390.7) (2p<0.001). Aspirin did not suppress P-selectin levels below 500 units in 22 (4.5%) patients. The clopidogrel P-selectin test showed that platelet reactivity was lower in 96 patients taking clopidogrel than in 586 patients taking no clopidogrel: 653 (297) vs. 969 (315), difference 316.1 (95% CI 248.6, 383.6) (2p<0.001). However, clopidogrel did not suppress P selectin level below 860 units in 24 (24.7%) patients. Conclusions: Aspirin and clopidogrel each suppress stimulated platelet P-selectin although one quarter of patients on clopidogrel have high on-treatment platelet reactivity. Platelet function testing, assessed as platelet P-selectin expression, may be performed remotely in the context of a large multicentre trial

Preliminary effects and acceptability of a co-produced physical activity referral intervention

Objectives: To explore the preliminary effects and acceptability of a co-produced physical activity referral intervention. Study Design: Longitudinal design with data collected at baseline and post a 12-week physical activity referral intervention. Setting. Community leisure centre. Methods: 32 adults with controlled lifestyle-related health conditions took part in a physical activity referral intervention (co-produced by a multidisciplinary stakeholder group) comprising 12 weeks’ subsidised fitness centre access plus four behaviour change consultations. A complete case analysis (t-tests and magnitude-based inferences) was conducted to assess baseline-to-12-week change in physical activity, cardiometabolic, and psychological measures. Semi-structured interviews were conducted (n=12) to explore experiences of the intervention. Results: Mean improvements were observed in cardiorespiratory fitness-2 (3.6 ml.kg.-1min-1 (95% confidence interval 1.9 to 5.4) P<0.001) and moderate-to-vigorous physical activity (12.6 min.day (95% CI 4.3 to 29.6) P=0.013). Participants were positive about the support from exercise referral practitioners, but experienced some challenges in a busy and under staffed gym environment. Conclusions: A co-produced physical activity referral intervention elicited short-term improvements in physical activity and cardiometabolic health. Further refinements may be required, via ongoing feedback between stakeholders, researchers and service users, to achieve the intended holistic physical activity focus of the intervention, prior to a definitive trial

Perfusion Imaging for Endovascular Thrombectomy in Acute Ischemic Stroke Is Associated With Improved Functional Outcomes in the Early and Late Time Windows

Background: The impact on clinical outcomes of patient selection using perfusion imaging for endovascular thrombectomy (EVT) in patients with acute ischemic stroke presenting beyond 6 hours from onset remains undetermined in routine clinical practice. Methods: Patients from a national stroke registry that underwent EVT selected with or without perfusion imaging (noncontrast computed tomography/computed tomography angiography) in the early (&lt;6 hours) and late (6-24 hours) time windows, between October 2015 and March 2020, were compared. The primary outcome was the ordinal shift in the modified Rankin Scale score at hospital discharge. Other outcomes included functional independence (modified Rankin Scale score ≤2) and in-hospital mortality, symptomatic intracerebral hemorrhage, successful reperfusion (Thrombolysis in Cerebral Infarction score 2b-3), early neurological deterioration, futile recanalization (modified Rankin Scale score 4-6 despite successful reperfusion) and procedural time metrics. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, prestroke disability, intravenous thrombolysis, mode of anesthesia (Model 1) and including EVT technique, balloon guide catheter, and center (Model 2). Results: We included 4249 patients, 3203 in the early window (593 with perfusion versus 2610 without perfusion) and 1046 in the late window (378 with perfusion versus 668 without perfusion). Within the late window, patients with perfusion imaging had a shift towards better functional outcome at discharge compared with those without perfusion imaging (adjusted common odds ratio [OR], 1.45 [95% CI, 1.16-1.83]; P=0.001). There was no significant difference in functional independence (29.3% with perfusion versus 24.8% without; P=0.210) or in the safety outcome measures of symptomatic intracerebral hemorrhage (P=0.53) and in-hospital mortality (10.6% with perfusion versus 14.3% without; P=0.053). In the early time window, patients with perfusion imaging had significantly improved odds of functional outcome (adjusted common OR, 1.51 [95% CI, 1.28-1.78]; P=0.0001) and functional independence (41.6% versus 33.6%, adjusted OR, 1.31 [95% CI, 1.08-1.59]; P=0.006). Perfusion imaging was associated with lower odds of futile recanalization in both time windows (late: adjusted OR, 0.70 [95% CI, 0.50-0.97]; P=0.034; early: adjusted OR, 0.80 [95% CI, 0.65-0.99]; P=0.047). Conclusions: In this real-world study, acquisition of perfusion imaging for EVT was associated with improvement in functional disability in the early and late time windows compared with nonperfusion neuroimaging. These indirect comparisons should be interpreted with caution while awaiting confirmatory data from prospective randomized trials.</p

Perfusion Imaging for Endovascular Thrombectomy in Acute Ischemic Stroke Is Associated With Improved Functional Outcomes in the Early and Late Time Windows

Background: The impact on clinical outcomes of patient selection using perfusion imaging for endovascular thrombectomy (EVT) in patients with acute ischemic stroke presenting beyond 6 hours from onset remains undetermined in routine clinical practice. Methods: Patients from a national stroke registry that underwent EVT selected with or without perfusion imaging (noncontrast computed tomography/computed tomography angiography) in the early (&lt;6 hours) and late (6-24 hours) time windows, between October 2015 and March 2020, were compared. The primary outcome was the ordinal shift in the modified Rankin Scale score at hospital discharge. Other outcomes included functional independence (modified Rankin Scale score ≤2) and in-hospital mortality, symptomatic intracerebral hemorrhage, successful reperfusion (Thrombolysis in Cerebral Infarction score 2b-3), early neurological deterioration, futile recanalization (modified Rankin Scale score 4-6 despite successful reperfusion) and procedural time metrics. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, prestroke disability, intravenous thrombolysis, mode of anesthesia (Model 1) and including EVT technique, balloon guide catheter, and center (Model 2). Results: We included 4249 patients, 3203 in the early window (593 with perfusion versus 2610 without perfusion) and 1046 in the late window (378 with perfusion versus 668 without perfusion). Within the late window, patients with perfusion imaging had a shift towards better functional outcome at discharge compared with those without perfusion imaging (adjusted common odds ratio [OR], 1.45 [95% CI, 1.16-1.83]; P=0.001). There was no significant difference in functional independence (29.3% with perfusion versus 24.8% without; P=0.210) or in the safety outcome measures of symptomatic intracerebral hemorrhage (P=0.53) and in-hospital mortality (10.6% with perfusion versus 14.3% without; P=0.053). In the early time window, patients with perfusion imaging had significantly improved odds of functional outcome (adjusted common OR, 1.51 [95% CI, 1.28-1.78]; P=0.0001) and functional independence (41.6% versus 33.6%, adjusted OR, 1.31 [95% CI, 1.08-1.59]; P=0.006). Perfusion imaging was associated with lower odds of futile recanalization in both time windows (late: adjusted OR, 0.70 [95% CI, 0.50-0.97]; P=0.034; early: adjusted OR, 0.80 [95% CI, 0.65-0.99]; P=0.047). Conclusions: In this real-world study, acquisition of perfusion imaging for EVT was associated with improvement in functional disability in the early and late time windows compared with nonperfusion neuroimaging. These indirect comparisons should be interpreted with caution while awaiting confirmatory data from prospective randomized trials.</p

Preconception maternal iodine status is associated with IQ but not with measures of executive function in childhood

Background: adverse effects of severe maternal iodine deficiency in pregnancy on fetal brain development are wellestablished, but the effects of milder deficiency are uncertain. Most studies examine iodine status in pregnancy; less is known about iodine nutrition before conception. Objective: we examined relations between maternal preconception iodine status and offspring cognitive function, within a prospective mother-offspring cohort. Methods: maternal iodine status was assessed through the use of the ratio of iodine:creatinine concentrations (I/Cr) in spot urine samples [median (IQR) period before conception 3.3 y (2.2-4.7 y)]. Childhood cognitive function was assessed at age 6-7 y. Full-scale IQ was assessed via the Wechsler Abbreviated Scale of Intelligence, and executive function through the use of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses (n = 654 mother-child dyads) were adjusted for potential confounders including maternal intelligence, education, and breastfeeding duration. Results: the median (IQR) urinary iodine concentration was 108.4 μg/L (62.2-167.8 μg/L) and the I/Cr ratio 114 μg/g (76- 164 μg/g). The preconception I/Cr ratio was positively associated with child IQ, before and after adjustment for potential confounding influences [β = 0.13 (95% CI: 0.04, 0.21)/SD, P = 0.003]. 8.9% of women had a preconception urinary I/Cr ratio &lt; 50 μg/g; compared with those with an I/Cr ratio ≥150 μg/g, the IQ of their offspring was 0.49 (95% CI: 0.79, 0.18) SD lower. There were no associations with the executive function outcomes assessed via CANTAB, before or after adjustment for confounders. Conclusions: the positive association between iodine status before conception and child IQ provides some support for demonstrated links between low maternal iodine status in pregnancy and poorer cognitive function reported in other studies. However, given the negative effects on school performance previously observed in children born to iodine-deficient mothers, the lack of associations with measures of executive function in the present study was unexpected. Further data are needed to establish the public health importance of low preconception iodine status.</p