Search

BACKGROUND: Pulmonary thromboendarterectomy (PTE) is the gold standard treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, the results are poorly quantified outside a few registry reports and several individual centers. METHODS: A systematic review was performed searching five electronic databases assessing the outcomes for adult patients undergoing PTE for CTEPH. All articles that reported mortality data were included. Primary outcome measures were early/inpatient mortality; secondary outcomes were survival, pulmonary haemodynamics, morbidity and functional status following PTE for CTEPH. Results were pooled via a meta-analysis of proportions and meta-regression. RESULTS: A total of 5,717 studies were identified, yielding sixty-one relevant papers. Thirty-day mortality ranged from 0.8% to 24.4%, and on meta-analysis was 8.4% [95% confidence interval (CI): 7.2–9.6%]. Mortality was noted to decrease with increasing center volume of PTE cases (P

Fentanyl is an anesthetic/analgesic commonly used in surgical and recovery settings. CYP3A4 and CYP3A5 encode enzymes, which metabolize fentanyl; genetic variants in these genes impact fentanyl pharmacokinetics in adults. Pharmacokinetic (PK) studies are difficult to replicate in children due to the burden of additional blood taken solely for research purposes. The aim of this study is to test the effect of CYP3A5 and CYP3A4 genetic variants on fentanyl PKs in children using opportunistically collected samples. Fentanyl concentrations were measured from remnant blood specimens and dosing data were extracted from electronic health records. Variant data defining CYP3A4*1G and CYP3A5*3 and *6 alleles were available from prior genotyping; alleles with no variant were defined as *1. The study cohort included 434 individuals (median age 9 months, 52% male subjects) and 1,937 fentanyl concentrations were available. A two-compartment model was selected as the base model, and the final covariate model included age, weight, and surgical severity score. Clearance was significantly associated with either CYP3A5*3 or CYP3A5*6 alleles, but not the CYP3A4*1G allele. A genotype of CYP3A5*1/*3 or CYP3A5*1/*6 (i.e., intermediate metabolizer status) was associated with a 0.84-fold (95% confidence interval (CI): 0.71-1.00) reduction in clearance vs. CYP3A5*1/*1 (i.e., normal metabolizer status). CYP3A5*3/*3, CYP3A5*3/*6, or CYP3A5*6/*6 (i.e., poor metabolizer status) was associated with a 0.76-fold (95% CI: 0.58-0.99) reduction in clearance. In the final model, expected clearance was 8.9 and 6.8 L/hour for a normal and poor metabolizer, respectively, with median population covariates (9 months old, 7.7 kg, low surgical severity).

BACKGROUND: At present, the optimal management strategy for chronic type B aortic dissection (CTBAD) remains unknown, as equipoise remains regarding medical management versus endovascular treatment versus open surgery. However, the results over recent years of thoracic endovascular aortic repair (TEVAR) in CTBAD appear promising. The aim of this systematic review was to provide a comprehensive analysis of the available data reporting outcomes and survival rates for TEVAR in CTBAD. METHODS: Electronic searches of six databases were performed from inception to April 2021. All studies reporting outcomes, specifically 30-day mortality rates, for endovascular repair of CTBAD were identified. Relevant data were extracted, and a random-effects meta-analysis of proportions or means was performed to aggregate the data. Survival data were pooled using data derived from original Kaplan-Meier curves, which allows reconstruction of individual patient data. RESULTS: Forty-eight studies with 2,641 patients were identified. Early (

The North American continent has a rich record of the tectonic environments and processes that occur throughout much of Earth history. This Memoir focuses on seven “turning points” that had specific and lasting impacts on the evolution of Laurentia: (1) The Neoarchean, characterized by cratonization; (2) the Paleoproterozoic and the initial assembly of Laurentia; (3) the Mesoproterozoic southern margin of Laurentia; (4) the Midcontinent rift and the Grenville orogeny; (5) the Neoproterozoic breakup of Rodinia; (6) the mid-Paleozoic phases of the Appalachian-Caledonian orogen; and (7) the Jurassic–Paleogene assembly of the North American Cordillera. The chapters in this Memoir provide syntheses of current understanding of the geologic evolution of Laurentia and North America, as well as new hypotheses for testing.

The North American continent has a rich geologic record that preserves evidence for tectonic processes throughout much of Earth’s history. Within this long history, however, particular times—e.g., “turning points”—have had specific and lasting impact on the evolution of Laurentia (ancestral North America). This volume is focused on seven of these “turning points”: (1) The Neoarchean (2.7–2.5 Ga), characterized by cratonization and the Kenoran orogen(s); (2) the Paleoproterozoic (1.9–1.7 Ga) and the initial assembly of Laurentia; (3) the Mesoproterozoic (1.5–1.4 Ga) Andean-style margin on the southern edge of Laurentia with the Pinware-Baraboo-Picuris orogeny; (4) the 1.2–1.0 Ga Midcontinent rift, and the Grenville orogeny and assembly of Rodinia; (5) the 700–500 Ma Neoproterozoic breakup of Rodinia; (6) the mid-Paleozoic (420–340 Ma) closure of the Iapetus and Rheic oceans and the development of the Appalachian-Caledonian orogen; and (7) the Jurassic–Paleogene (200–50 Ma) assembly of the North American Cordilleran margin by terrane accretion and subduction. The assembled chapters provide syntheses of current understanding of the geologic evolution of Laurentia and North America, as well as new hypotheses for testing. The inclusion of work from different geological time periods within a single volume provides continent-wide perspectives on the evolution of tectonic events and processes that acted on and within Laurentia.

The Appalachian Mountains were formed through multiple phases of Paleozoic orogenesis associated with terrane accretion. The timing, tempo, and significance of each event in New England are obscured by overprinting, the limits of geochronologic tools, and differences between lithotectonic domains. We present new monazite and xenotime geochronology, 40Ar/39Ar thermochronology, and major- and trace-element thermobarometry from major tectonic domains in southern New England and across multiple structural levels. These data show contrasting pressure-temperature-time (P-T-t) paths across tectonic domains and highlight eastward metamorphic overprinting associated with younger tectonic events. Our data and geochemical proxies suggest two major periods of crustal thickening, ca. 455–440 Ma and 400–380 Ma, and a heterogeneous record of thinning/exhumation. Ordovician (Taconic) crustal thickening postdates the interpreted accretion of the Moretown terrane by ~20 m.y. and may have been related to shallow subduction after subduction polarity reversal. Subsequent cooling and exhumation (440–430 Ma) may have been related to the end of the Taconic orogeny and opening of the Connecticut Valley basin. (Neo)Acadian tectono-metamorphism is recognized in accreted terranes of New England and is absent in the Taconic block. Amphibolite- to (high-pressure) granulite-facies metamorphism, slow cooling, and protracted anatexis ca. 400–340 Ma support the existence of a long-lived orogenic plateau in southern New England. Exhumation, which began at 340–330 Ma, may have involved ductile (channel) flow. The boundary between continental Laurentia and accreted terranes has been reactivated at multiple times and is presently manifested as a 12–15 km Moho step. At the latitude of our samples, Alleghanian-age tectonism (ca. 310–285 Ma) was limited to retrograde metamorphism, and relatively minor loading and exhumation in the vicinity of the Pelham dome. Our results highlight the sensitivity of the integrative petrochronologic approach and the transition of the eastern margin of Laurentia from terrane accretion to the formation of a high-elevation plateau.

Aortic valve infective endocarditis is a life-threatening condition. Patients frequently present profoundly unwell and extensive surgery may be required to correct the underlying anatomical deficits and control sepsis. Periannular involvement occurs in more than 10% of patients with aortic valve endocarditis. Complex aortic valve endocarditis has a mortality rate of 10 to 40%. Longstanding surgical dogma suggests homografts represent the optimal replacement option in complex aortic valve endocarditis; however, there is a paucity of evidence and lack of consensus on the optimal replacement choice. A systematic review and meta-analysis was performed utilizing EMBASE, PubMed, and the Cochrane databases to review articles describing homografts versus aortic valve replacement and/or valved conduit graft implantation for complex aortic valve endocarditis. The outcomes of interest were mortality, reinfection, and reoperation. Eleven studies were included in this meta-analysis, contributing 810 episodes of complex aortic valve endocarditis. All included reports were cohort studies. There was no statistically significant difference in overall mortality (risk ratio [RR] 0.99; 95% confidence interval [CI], 0.61–1.59; p = 0.95), reinfection (RR 0.89; 95% CI, 0.45–1.78; p = 0.74), or reoperation (RR 0.91; 95% CI, 0.38–2.14; p = 0.87) between the homograft and valve replacement/valved conduit graft groups. Overall, there was no difference in mortality, reinfection, or reoperation rates between homografts and other valve or valved conduits in management of complex aortic endocarditis. However, there is a paucity of high-quality evidence in the area, and comparison of valve types warrants further investigation.

Over the past two decades surgical approaches for mitral valve (MV) disease have evolved with the advent of minimally invasive techniques. Robotic mitral valve repair (RMVr) safety and efficacy has been well documented, however, mid- to long-term data are limited. The aim of this review was to provide a comprehensive analysis of the available mid- to long-term data for RMVr.Electronic searches of five databases were performed to identify all relevant studies reporting minimum five-year data on RMVr. Pre-defined primary outcomes of interest were overall survival, freedom from MV reoperation and from moderate or worse mitral regurgitation (MR) at five years or more post-RMVr. A meta-analysis of proportions or means was performed, utilizing a random effects model, to present the data. Kaplan-Meier curves were aggregated using reconstructed individual patient data.Nine studies totaling 3,300 patients undergoing RMVr were identified. Rates of overall survival at 1-, 5- and 10-year were 99.2%, 97.4% and 92.3%, respectively. Freedom from MV reoperation at eight-years post RMVr was 95.0%. Freedom from moderate or worse MR at seven years was 86.0%. Rates of early post-operative complications were low with only 0.2% all-cause mortality and 1.0% cerebrovascular accident. Reoperation for bleeding was low at 2.2% and successful RMVr was 99.8%. Mean intensive care unit and hospital stay were 22.4 hours and 5.2 days, respectively.RMVr is a safe procedure with low rates of early mortality and other complications. It can be performed with low complication rates in high volume, experienced centers. Evaluation of available mid-term data post-RMVr suggests favorable rates of overall survival, freedom from MV reoperation and from moderate or worse MR recurrence.

Robotic-assisted mitral valve surgery (RMVS) is becoming an increasingly performed procedure in cardiac surgery, however, its true safety and efficacy compared to the gold standard conventional sternotomy approach [conventional sternotomy mitral valve surgery (CSMVS)] remains debated. The aim of this meta-analysis was to provide a comprehensive analysis of all available literature comparing RMVS to CSMVS.An electronic search of five databases was performed to identify all relevant studies comparing RMVS to CSMVS. Pre-defined primary outcomes of interest included all-cause mortality, cerebrovascular accidents (CVA) and re-operation for bleeding. Secondary outcomes of interest included cross clamp time, cardiopulmonary bypass (CPB) time, intensive care unit (ICU) and hospital length of stay (LOS), post-operative atrial fibrillation (POAF) and red blood cell (RBC) transfusion.The search strategy identified fourteen studies qualifying for inclusion in this meta-analysis comparing RMVS to CSMVS. The outcomes of 6,341 patients (2,804 RMVS and 3,537 CSMVS) were included. RMVS had significantly lower mortality when compared to CSMVS group in both the unmatched [odds ratio (OR) 0.33; 95% confidence interval (CI): 0.19-0.57; P0.001] and matched cohorts (OR 0.35; 95% CI: 0.15-0.80; P=0.01). There was no significant difference in rates of CVA or re-operation for bleeding between the two groups in either the entire included cohort or matched patients. CSMVS had significantly shorter cross clamp time by 28 minutes (95% CI: 19.30-37.32; P0.001) and CPB time by 49 minutes (95% CI: 36.16-61.01; P0.001) which remained significantly shorter in the matched cohorts. RMVS had shorter ICU [mean difference (MD) 26 hours; 95% CI: -34.31 to -18.52; P0.001] and hospital LOS (MD 2 days; 95% CI: -2.66 to -1.37; P0.001), which were again both significantly shorter in the matched cohort. RMVS group also had fewer RBC transfusions (OR 0.44; 95% CI: 0.28-0.70; P0.001).Current evidence on comparative outcomes of RMVS and CSMVS is limited with only low-quality studies currently available. This present meta-analysis suggests that RMVS may have lower mortality and shorter ICU and hospital LOS, however CSMVS may be associated with significantly shorter cross clamp and CPB times. Further analysis of high-quality studies with randomized data is required to verify these results.

Recognition of fundamental tectonic boundaries has been extremely diffi-cult in the (>1000-km-wide) Proterozoic accretionary orogen of south western North America, where the main rock types are similar over large areas, and where the region has experienced multiple postaccretionary deformation events. Discrete ultramafic bodies are present in a number of areas that may mark important boundaries, especially if they can be shown to represent tectonic fragments of ophiolite complexes. However, most ultramafic bodies are small and intensely altered, precluding petrogenetic analysis. The 91-Mile peridotite in the Grand Canyon is the largest and best preserved ultramafic body known in the southwest United States. It presents a special opportunity for tectonic analysis that may illuminate the significance of ultramafic rocks in other parts of the orogen. The 91-Mile peridotite exhibits spectacular cumulate layering. Contacts with the surrounding Vishnu Schist are interpreted to be tectonic, except along one margin, where intrusive relations have been interpreted. Assemblages include olivine, clinopyroxene, orthopyroxene, magnetite, and phlogopite, with very rare plagioclase. Textures suggest that phlogopite is the result of late intercumulus crystallization. Whole-rock compositions and especially mineral modes and compositions support derivation from an arc-related mafic magma. K-enriched subduction-related fluid in the mantle wedge is interpreted to have given rise to a K-rich, hydrous, high-pressure partial melt that produced early magnetite, Al-rich diopside, and primary phlogopite. The modes of silicate minerals, all with high Mg#, the sequence of crystallization, and the lack of early plagioclase are all consistent with crystallization at relatively high pressures. Thus, the 91-Mile peridotite body is not an ophiolite fragment that represents the closure of a former ocean basin. It does, however, mark a significant tectonic boundary where lower-crustal arc cumulates have been juxtaposed against middle-crustal schists and granitoids.

The true incidence of bicuspid valve-related aortic dissection (AD) is extremely difficult to ascertain. This review aimed to provide the reported cumulative incidence of bicuspid aortic valve (BAV)-related AD in actively monitored study populations.Four electronic databases were used to perform literature searches. A meta-analysis of proportions or means were performed for categorical and continuous variables, as appropriate. Survival data was calculated from the aggregation of Kaplan-Meier (KM) curves from the included studies, where reported.A total of 4,330 patients were identified in eleven studies. A cumulative incidence of bicuspid valve-related AD of 0.6% across a median follow-up time of 9 years was identified. Actuarial survival across this monitored population at 1, 3, 5 and 10 years was 97.2%, 96.7%, 92.45%, and 81.1%, respectively.This systematic review and meta-analysis identified a low incidence of AD across the examined follow-up period. Large, prospective studies involving early identification of bicuspid valve pathology, recruitment, and follow-up of BAV cohorts with comparison to the baseline population are required to most accurately determine the outcomes of these patients.

Background: The treatment of aortic valve disease is the most common valvular surgery in industrialized nations, with 3–9% of the population over the age of eighty having at least moderate aortic stenosis. As transcatheter aortic valve replacement (TAVR) has become more established, newer surgical prostheses have been developed with a variety of anchoring systems that do not rely solely on sutures to hold the valve in an appropriate position. The Edwards Intuity valve is a bovine pericardial prosthesis that is modelled on the widely implanted Perimount MagnaEase aortic prosthesis. The Perceval valve is a bovine pericardial valve attached to a self-expanding nitinol stent, which uses the radial force exerted on the patient’s aortic annulus and aortic root by the stent portion to hold the valve in position. This meta-analysis compares the outcomes of comparative studies of these two valve systems. Methods: This systematic review and meta-analysis compares the outcomes of rapid deployment valves (RDV) and sutureless valves (SURD) and was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and guidance. The search strategy interrogated six electronic databases. Outcomes measured included all-cause mortality at latest follow up, stroke, cross-clamp and cardiopulmonary bypass (CPB) times, pacemaker implantation rates, paravalvular leak and post-operative transvalvular gradient Results: The search strategy identified 407 unique papers for initial assessment with seven studies qualifying for inclusion in the analysis. The outcomes of 4,076 patients (1,650 RDV, 2,426 SURD) were included. There was no difference in mortality, stroke or moderate or worse paravalvular regurgitation between the two groups. SURD had significantly shorter CPB time by 15.7 minutes [95% confidence interval (CI): 4.2–27.1; P=0.007] and a shorter cross-clamp time by 11.3 minutes (95% CI: 6.3–16.3; P

Post-marketing population pharmacokinetic (PK) and pharmacodynamic (PD) studies can be useful to capture patient characteristics affecting PK or PD in real-world settings. These studies require longitudinally measured dose, outcomes, and covariates in large numbers of patients; however, prospective data collection is cost-prohibitive. Electronic health records (EHRs) can be an excellent source for such data, but there are challenges, including accurate ascertainment of drug dose. We developed a standardized system to prepare datasets from EHRs for population PK/PD studies. Our system handles a variety of tasks involving data extraction from clinical text using a natural language processing algorithm, data processing, and data building. Applying this system, we performed a fentanyl population PK analysis, resulting in comparable parameter estimates to a prior study. This new system makes the EHR data extraction and preparation process more efficient and accurate, and provides a powerful tool to facilitate post-marketing population PK/PD studies using information available in EHRs.

Use of electronic health record (EHR) data to estimate population pharmacokinetic (PK) profiles necessitates several assumptions. We sought to investigate sensitivity to some of these assumptions about dose timing and absorption rates.A population PK study with 363 subjects was performed using real-world data extracted from EHRs to estimate the tacrolimus population PK profile. Data were extracted and built using our automated system, EHR2PKPD, suitable for quickly constructing large PK datasets from the EHR. Population PK studies for oral medications performed using EHR data often assume a regular dosing schedule as prescribed without incorporating exact dosing time. We assessed the sensitivity of the PK parameter estimates to assumptions about dose timing using last-dose times extracted by our own natural language processing system, medExtractR. We also investigated the sensitivity of estimates to absorption rate constants that are often fixed at a published value in tacrolimus population PK analyses. We conducted simulation studies to investigate how drug PK profiles and experimental designs such as concentration measurements design affect sensitivity to incorrect assumptions about dose timing and absorption rates.There was no appreciable difference in parameter estimates with assumed versus extracted last-dose time, and our sensitivity analysis revealed little difference between parameters estimated across a range of assumed absorption rate constants.Our findings suggest that drugs with a slower elimination rate (or a longer half-life) are less sensitive to dose timing errors and that experimental designs which only allow for trough blood concentrations are usually insensitive to deviation in absorption rate.

Migmatites are common in the hinterland of orogenic belts. The timing and mechanism (in situ vs. external, P-T conditions, reactions, etc.) of melting are important for understanding crustal rheology, tectonic history, and orogenic processes. The Adirondack Highlands has been used as an analog for mid/deep crustal continental collisional tectonism. Migmatites are abundant, and previous workers have interpreted melting during several different events, but questions remain about the timing, tectonic setting, and even the number of melting events. We use multiscale compositional mapping combined with in situ geochronology and geochemistry of monazite to constrain the nature, timing, and character of melting reaction(s) in one locality from the eastern Adirondack Highlands. Three gray migmatitic gneisses, studied here, come from close proximity and are very similar in microscopic and macroscopic (outcrop) appearance. Each of the rocks is interpreted to have undergone biotite dehydration melting (i.e., Bt + Pl + Als + Qz = Grt + Kfs + melt). Full-section compositional maps show the location of reactants and products of the melting reaction, especially prograde and retrograde biotite, peritectic K-feldspar, and leucosome, in addition to all monazite and zircon in context. In addition, the maps provide constraints on kinematics during melting and a context for interpretation of accessory phase composition and geochronology. More so than zircon, monazite serves as a monitor of melting and melt loss. The growth of garnet during melting leaves monazite depleted in Y and HREEs while melt loss from the system leaves monazite depleted in U. Results show that in all three localities, partial melting occurred during at ca. 1160–1150 Ma (Shawinigan orogeny), but the samples show high variability in the location and degree of removal of the melt phase, from near complete to segregated into layers to dispersed. All three localities experienced a second high-T event at ca. 1050 Ma, but only the third (non-segregated) sample experienced further melting. Thus, in addition to bulk composition, the fertility for melting is an important function of the previous history and the degree of mobility of earlier melt and fluids. Monazite is also a sensitive monitor of retrogression; garnet breakdown leads to increased Y and HREE in monazite. Results here suggest that all three samples remained at depth between the two melting events but were rapidly exhumed after the second event.

The western Chipman domain of the east Athabasca mylonite triangle in northern Saskatchewan, Canada, displays a large positive aeromagnetic anomaly that is the result of retrograde magnetite production during exhumation. Petrologic, magnetic coercivity, and hysteresis analyses indicate that multidomain magnetite is the primary magnetic phase in rocks of the region. Measurements of magnetic susceptibility from the western Chipman domain document five orders of magnitude variation, while rocks from the eastern Chipman domain are paramagnetic. The distribution of Koenigsberger ratios is approximately a mixed bimodal lognormal distribution with peak ratios at 0.039 and 0.73, suggesting that magnetic susceptibility is more significant than remanent magnetization. However, remanent magnetization is an important contributor to total magnetization. Petrographic observations indicate that magnetite is primarily produced from the breakdown of hornblende. The consumption of hornblende is also texturally associated with the production of actinolite and the hydration-related breakdown of granulite facies mineral phases such as garnet and clinopyroxene. Based on the proximity of the positive aeromagnetic anomaly to the Cora Lake shear zone, late-stage deformation along the shear zone during exhumation of the east Athabasca mylonite triangle may have structurally controlled the infiltration of fluids resulting in the heterogeneous production of magnetite. These results document the utility of integrating aeromagnetic, petrologic, and rock magnetic data to transcend observational scales and better understand regional tectonometamorphic history.

Electron microprobe trace element analysis is a significant challenge. Due to the low net intensity of peak measurements, the accuracy and precision of such analyses relies critically on background measurements, and on the accuracy of any pertinent peak interference corrections. A linear regression between two points selected at appropriate background positions is a classical approach for electron probe microanalysis (EPMA). However, this approach neglects the accurate assessment of background curvature (exponential or polynomial), and the presence of background interferences, a hole in the background, or an absorption edge can dramatically affect the results if underestimated or ignored. The acquisition of a quantitative wavelength-dispersive spectrometry (WDS) scan over the spectral region of interest remains a reasonable option to determine the background intensity and curvature from a fitted regression of background portions of the scan, but this technique can be time consuming and retains an element of subjectivity, as the analyst has to select areas in the scan which appear to represent background. This paper presents a new multi-point background (MPB) method whereby the background intensity is determined from up to 24 background measurements from wavelength positions on either side of analytical lines. This method improves the accuracy and precision of trace element analysis in a complex matrix through careful regression of the background shape, and can be used to characterize the background over a large spectral region covering several elements to be analyzed. The overall efficiency improves as systematic WDS scanning is not required to assess background interferences. The method is less subjective compared to methods that rely on WDS scanning, including selection of two interpolation points based on WDS scans, because “true” backgrounds are selected through an exclusion method of possible erroneous backgrounds. The first validation of the MPB method involves blank testing to ensure the method can accurately measure the absence of an element. The second validation involves the analysis of U-Th-Pb in several monazite reference materials of known isotopic age. The impetus for the MPB method came from efforts to refine EPMA monazite U-Th-Pb dating, where it was recognized that background errors resulting from interference or strong background curvature could result in errors of several tens of millions of years on the calculated date. Results obtained on monazite reference materials using two different microprobes, a Cameca SX-100 Ultrachron and a JEOL JXA-8230, yield excellent agreement with ages obtained by isotopic methods (Thermal Ionization Mass Spectrometry [TIMS], Sensitive High-Resolution Ion MicroProbe [SHRIMP], or Secondary Ion Mass Spectrometry [SIMS]). Finally, the MPB method can be used to model the background over a large spectrometer range to improve the accuracy of background measurement of minor and trace elements acquired on a same spectrometer, a method called the shared background measurement. This latter significantly improves the accuracy of minor and trace element analysis in complex matrices, as demonstrated by the analysis of Rare Earth Elements (REE) in REE-silicates and phosphates and of trace elements in scheelite.

The Acadian and Neoacadian orogenies are widely recognized, yet poorly understood, tectono-thermal events in the New England Appalachian Mountains (USA). We quantified two phases of Paleozoic crustal thickening using geochemical proxies. Acadian (425–400 Ma) crustal thickening to 40 km progressed from southeast to northwest. Neoacadian (400–380 Ma) crustal thickening was widely distributed and varied by 30 km (40–70 km) from north to south. Doubly thickened crust and paleoelevations of 5 km or more support the presence of an orogenic plateau at ca. 380–330 Ma in southern New England. Neoacadian crustal thicknesses show a strong correlation with metamorphic isograds, where higher metamorphic grade corresponds to greater paleo-crustal thickness. We suggest that the present metamorphic field gradient was exposed through erosion and orogenic collapse influenced by thermal, isostatic, and gravitational properties related to Neoacadian crustal thickness. Geobarometry in southern New England underestimates crustal thickness and exhumation, suggesting the crust was thinned by tectonic as well as erosional processes.

Summary Net starch synthesis by isolated chloroplasts of the intertidal alga Codium fragile (Suringar) Hariot was determined by enzymic hydrolysis (amyloglucosidase/α-amylase) of solubilized chloroplast samples followed by the measurement of the resultant glucose yields by hexokinase/glucose-6-phosphate dehydrogenase-coupled reactions. Net starch synthesis was only observed between 100 and 375 μmol m−2 s−1 (PAR) corresponding to irradiance values which supported saturating or super-saturating rates of photosynthesis. Light filter inactivation of the light-harvesting complex carotenoids siphonoxanthin and siphonein reduced net starch synthesis by 68 %. These findings are discussed in relation to photosynthesis in an intertidal zone environment.

SUMMARY Net starch synthesis isolated chloroplasts of Codium fragile appears to be regulated in a similar manner to that of vascular plants. Exogenous 10 mol m−3 PGA stimulated net starch synthesis at 200 μmol m−2 s −1 (PPFD) by approx. 69%, whilst 10 mol m−3 P1 not only inhibited synthesis but also promoted net starch degradation. However, unlike vascular plant chloroplasts, 10 mol m−3 G6P was found to stimulate net starch synthesis by approx. 52% under the same conditions. This apparent difference in response to exogenous G6P is discussed in relation to the operation of the P1-G6P translocator in chloroplasts of this species

Geochemical and isotopic data, detailed descriptions of methods, and Figures S1–S4.