In 2023, Princeton University Press published Richard Langlois’s The Corporation and the Twentieth Century: The History of American Business Enterprise. It is a book of comparable mass to Alfred Chandler’s 1977 The Visible Hand and equally ambitious.1 The erudition is vast. (The bibliography alone runs 78 closely-printed pages. There are 122 pages of equally closely-printed footnotes to the 522-page main text whose own font is not large.) A production such as this seemed worth more than the usual traditional-form reviews, and in the September following its publication, the Penn Economic History Forum put on a symposium to discuss it. Interest was widespread: attendance in the room was agreeably substantial and came from far beyond the seminar’s usual catchment area, and there were requests for the Zoom link to the proceedings from around the world. (The expense was not vast and the ratio of impact to expense was almost certainly favorable relative to ordinary seminars. The economic history community might not suffer from putting on more such events when suitable occasions arise.)

The circadian timing system regulates many aspects of metabolic physiology, including the postprandial response to meals(1). Experimental inversion of circadian and behavioural rhythms by 12 hours adversely effects markers of metabolic health(2). We investigated effects of a more modest 5hour delay in behavioural cycles.

Fourteen participants completed an 8-day in-patient laboratory protocol, with controlled sleepwake opportunities, light-dark cycles, and diet. The 5-hour delay in behavioural cycles was induced by delaying sleep opportunity. We measured: melatonin to confirm central circadian phase; fasting markers and postprandial metabolism; energy expenditure; subjective sleepiness; and appetite, throughout the waking period.

After the phase delay, there was slower gastric emptying at breakfast, lower fasting plasma glucose, higher postprandial plasma glucose and triglycerides, and lower thermic effect of feeding. Any changes were abolished or attenuated within 48-72 hours. Further, we show no difference in 16 h waking energy expenditure.

These data extend our previous findings, which showed no time-of-day effect on energy expenditure in healthy adults.

Depression is a common prenatal psychological complication. We aimed to investigate if maternal pre-pregnancy diet can impact prenatal depressive symptoms and the mediating role of pre-pregnancy BMI and inflammation. We used data (N 1141) from the Alberta Pregnancy Outcomes and Nutrition cohort study. We calculated Mediterranean diet adherence (MED) and dietary inflammatory index (DII) scores using data from pre-pregnancy FFQ. In the third-trimester, we assessed depressive symptoms using Edinburgh Postpartum Depression Scale (EPDS) and inflammation through serum C-reactive protein (CRP) levels. BMI was calculated from self-reported pre-pregnancy weight. Race-stratified analyses (white and people of colour) were run. We observed no association between MED or DII tertiles and depressive symptoms. However, white participants in the MED tertile-3 had lower risk of depression (EPDS < 10) compared with tertile-1 (OR = 0·56, 95 % CI, 0·33, 0·95). White individuals in MED tertile-3 had lower BMI (MD = –1·08; 95 % CI, −1·77, −0·39) and CRP (MD = –0·53; 95 % CI, −0·95, −0·11) than tertile-1, and those in DII tertile-2 (MD = 0·44; 95 % CI, 0·03, 0·84) and tertile-3 (MD = 0·42; 95 % CI, 0·01, 0·83) had higher CRP than tertile-1. Among people of colour, neither MED nor DII was associated with BMI or CRP, but BMI was negatively associated with depressive symptoms (β = –0·25, 95 % CI, −0·43, −0·06). We found no association between diet and depressive symptoms through BMI or CRP, in either race. Pre-pregnancy diet might affect the risk of prenatal depression in a race-specific way. Further research is required to explore the racial differences in the association between maternal diet and prenatal depressive symptoms/depression risk.

Background: Cerebral venous thrombosis (CVT) is a rare cause of stroke, with 10–15% of patients experiencing dependence or death. The role of endovascular therapy (EVT) in the management of CVT remains controversial and practice patterns are not well-known. Methods: We distributed a comprehensive 53-question survey to neurologists, neuro-interventionalists, neurosurgeons and other relevant clinicians globally from May 2023 to October 2023. The survey asked about practice patterns and perspectives on EVT for CVT and assessed opinions regarding future clinical trials. Results: The overall response rate was 31% (863 respondents from 2744 invited participants) across 61 countries. A majority (74%) supported use of EVT for certain CVT cases. Key considerations for EVT included worsening level of consciousness (86%) and other clinical deficits (76%). Mechanical thrombectomy with aspiration (22%) and stent retriever (19%) were the most utilized techniques, with regional variations. Post-procedurally, low molecular weight heparin was the predominant anticoagulant administered (40%), although North American respondents favored unfractionated heparin. Most respondents supported future trials of EVT (90%). Conclusions: Our survey reveals significant heterogeneity in approaches to EVT for CVT, highlighting the necessity for adequately powered clinical trials to guide standard-of-care practices.

Background: Cerebral venous thrombosis (CVT)most commonly affects younger women. Diagnosis may be delayed due to its distinct presentation and demographic profile compared to other stroke types. Methods: We examined delays to diagnosis of CVT in the SECRET randomized trial and TOP-SECRET parallel registry. Adults diagnosed with symptomatic CVT within <14 days were included. We examined time to diagnosis and number of health care encounters prior to diagnosis and associations with demographics, clinical and radiologic features and functional and patient-reported outcomes (PROMS) at days 180&365. Results: Of 103 participants, 68.9% were female; median age was 45 (IQR 31.0-61.0). Median time from symptom onset to diagnosis was 4 (1-8) days. Diagnosis on first presentation to medical attention was made in 60.2%. The difference in time to diagnosis for single versus multiple presentations was on the order of days (3[1-7] vs. 5[2-11.75], p=0.16). Women were likelier to have multiple presentations (OR 2.53; 95% CI1.00-6.39; p=0.05) and longer median times to diagnosis (5[2-8]days vs. 2[1-4.5] days; p=0.005). However, this was not associated with absolute or change in functional, or any patient reported, outcome measures (PROMs) at days 180&365. Conclusions: Diagnosis of CVT was commonly delayed; women were likelier to have multiple presentations. We found no association between delayed diagnosis and outcomes.

Background: Adults with congenital heart disease (ACHD) are at risk for stroke and dementia. We report baseline and Year 1 results from an ongoing study assessing brain health in people with moderate- and great-complexity ACHD. Methods: Participants aged ≥18 undergo baseline and Year-3 brain MRI/MRA and annual cognitive assessment (MoCA, NIH Toolbox-Cognitive Battery (NIH-TB)). Results: Of 93 participants to date, 79 (85%) have completed Year 1 follow-up. At baseline, the great-complexity group had lower MoCA (26.32 vs. 27.38; p=0.04) and NIH-TB scores (total composite 45.63 vs. 52.80; p=0.002) than the moderate-complexity group. Year-1 testing showed numerical improvements across cognitive batteries in both groups. More participants with great-complexity ACHD had white matter hyperintensities (WMH; 72% vs. 55%; p=0.21) and cerebral microbleeds (CMBs; 72% vs. 54%; p=0.17) on baseline neuroimaging, but differences were not significant. Conclusions: Baseline neuroimaging shows a greater-than-expected burden for age of CMB and WMH in the context of previous cardiac surgery. Baseline cognitive performance was worse with great-complexity ACHD. Improved cognitive battery performance across both subgroups at Year-1 suggests a practice effect. Repeat neuroimaging will be performed in Year-3 and cognitive performance is reassessed annually.

The modern marine megafauna is known to play important ecological roles and includes many charismatic species that have drawn the attention of both the scientific community and the public. However, the extinct marine megafauna has never been assessed as a whole, nor has it been defined in deep time. Here, we review the literature to define and list the species that constitute the extinct marine megafauna, and to explore biological and ecological patterns throughout the Phanerozoic. We propose a size cut-off of 1 m of length to define the extinct marine megafauna. Based on this definition, we list 706 taxa belonging to eight main groups. We found that the extinct marine megafauna was conspicuous over the Phanerozoic and ubiquitous across all geological eras and periods, with the Mesozoic, especially the Cretaceous, having the greatest number of taxa. Marine reptiles include the largest size recorded (21 m; Shonisaurus sikanniensis) and contain the highest number of extinct marine megafaunal taxa. This contrasts with today’s assemblage, where marine animals achieve sizes of >30 m. The extinct marine megafaunal taxa were found to be well-represented in the Paleobiology Database, but not better sampled than their smaller counterparts. Among the extinct marine megafauna, there appears to be an overall increase in body size through time. Most extinct megafaunal taxa were inferred to be macropredators preferentially living in coastal environments. Across the Phanerozoic, megafaunal species had similar extinction risks as smaller species, in stark contrast to modern oceans where the large species are most affected by human perturbations. Our work represents a first step towards a better understanding of the marine megafauna that lived in the geological past. However, more work is required to expand our list of taxa and their traits so that we can obtain a more complete picture of their ecology and evolution.

For centuries, fossils from the Maastrichtian type locality and adjacent quarries have provided key evidence of vertebrate diversity during the latest Cretaceous, yet until recently the Maastrichtian type area had revealed no important insights into the evolutionary history of birds, one of the world’s most conspicuous groups of extant tetrapods. With the benefit of high-resolution micro-CT scanning, two important avian fossils from the Maastrichtian type area have now been examined in detail, offering profound, complementary insights into the evolutionary history of birds. The holotype specimens of these new taxa, Janavis finalidens Benito, Kuo, Widrig, Jagt and Field, 2022, and Asteriornis maastrichtensis Field, Benito, Chen, Jagt and Ksepka, 2020, were originally collected in the late 1990s, but were only investigated in detail more than twenty years later. Collectively, Janavis and Asteriornis provide some of the best evidence worldwide regarding the factors that influenced stem bird extinction and crown bird survivorship through the Cretaceous-Palaeogene transition, as well as insights into the origins of key anatomical features of birds such as an extensively pneumatised postcranial skeleton, a kinetic palate, and a toothless beak. Asteriornis also provides scarce evidence of a Cretaceous-aged divergence time calibration within the avian crown group, while together, Janavis and Asteriornis constitute the only documented co-occurrence of crown birds and non-neornithine avialans. Here, we review key insights into avian evolutionary history provided by these discoveries from the Maastrichtian stratotype, document undescribed and newly discovered Maastrichtian fossils potentially attributable to Avialae and provide the first histological data for the holotype of Asteriornis, illustrating its skeletal maturity at the time of its death.

We evaluated a digital learning programme for non-specialists to develop knowledge-based competencies in a problem-solving intervention for adolescents to examine the overall impact of training on knowledge-based competencies among learners; and to compare the effects of two training conditions (self-guided digital training with or without coaching) in a nested parallel, two-arm, individually randomised controlled trial. Eligible participants were 18 or older; fluent in Hindi or English; able to access digital training; and had no prior experience of delivering structured psychotherapies. 277 participants were enrolled from 31 March 2022 to 19 June 2022 of which 230 (83%) completed the study. There was a significant increase in competency score from pre-training (Mean = 7.01, SD = 3.29) to post-training (Mean = 8.88, SD = 3.80), 6 weeks after the pre-training assessment. Knowledge competency scores showed larger increase among participants randomised to the coaching arm (AMD = 1.09, 95% CI 0.26–1.92, p = 0.01) with an effect size (d) of 0.33 (95% CI 0.08–0.58). More participants completed training in the coaching arm (n = 96, 69.6%) compared to the self-guided training arm (n = 56, 40.3%). In conclusion, a coach-supported remote digital training intervention is associated with enhanced participation by learners and increased psychotherapeutic knowledge competencies.

In the first half of the twentieth century, deaths from infectious disease, especially among the very young, fell dramatically in American cities. However, as infant mortality fell and life expectancy rose, racial inequality in urban infectious disease mortality grew. In this paper, we show that the fall in mortality and the rise in racial inequality in mortality reflected two countervailing processes. The dramatic decline in infant mortality from waterborne diseases drastically reduced the total urban infectious disease mortality rate of both Black and white Americans while having a comparatively small effect on the total racial disparity in urban infectious disease mortality. In contrast, the unequal fall in tuberculosis mortality, particularly in the prime of life, widened racial inequality in infectious disease mortality in US cities.

Background: Women are reported to have worse outcomes than men following ischemic stroke despite similar treatment effects for thrombolysis and endovascular treatment. Methods: We performed a post-hoc analysis of patients with acute ischemic stroke and intracranial occlusion enrolled in INTERRSeCT, an international prospective cohort study. We compared workflow times, reperfusion therapy choices, and 90-day modified Rankin scale (mRS) scores. Results: We included 575 patients, mean age 70.2 years (SD: 13.1) and 48.5% female. There were no significant sex differences in onset-to-CT (males: 115 minutes [IQR: 72-171], females: 114 minutes [IQR: 75-196] ) or CT-to-thrombolysis time (males: 24 minutes [IQR: 17-32], females: 23 minutes [IQR: 18-36]). However, female participants had a 12-minute faster CT-to-groin-puncture time, p=0.001. Reperfusion therapies did not significantly differ by sex. Reperfusion therapies included thrombolysis alone (males: 46%, females: 49%), EVT alone (males: 34%, females: 34%), thrombolysis plus EVT (males: 8%, females 9%) and conservative management (males: 12%, females: 8%). Median 90-day mRS was 2 (IQR: 1-4) in both males and females, p=0.1. Conclusions: In the INTERRSeCT cohort, rates of reperfusion therapy, workflow times and 90-day outcomes were similar between sexes, suggesting that women are not subject to any poorer performance in key quality indicators for reperfusion treatment for acute stroke.

Background: Sex differences in treatment response to intravenous thrombolysis (IVT) are poorly characterized. We compared sex-disaggregated outcomes in patients receiving IVT for acute ischemic stroke in the Alteplase compared to Tenecteplase (AcT) trial, a Canadian multicentre, randomised trial. Methods: In this post-hoc analysis, the primary outcome was excellent functional outcome (modified Rankin Score [mRS] 0-1) at 90 days. Secondary and safety outcomes included return to baseline function, successful reperfusion (eTICI≥2b), death and symptomatic intracerebral hemorrhage. Results: Of 1577 patients, there were 755 women and 822 men (median age 77 [68-86]; 70 [59-79]). There were no differences in rates of mRS 0-1 (aRR 0.95 [0.86-1.06]), return to baseline function (aRR 0.94 [0.84-1.06]), reperfusion (aRR 0.98 [0.80-1.19]) and death (aRR 0.91 [0.79-1.18]). There was no effect modification by treatment type on the association between sex and outcomes. The probability of excellent functional outcome decreased with increasing onset-to-needle time. This relation did not vary by sex (pinteraction 0.42). Conclusions: The AcT trial demonstrated comparable functional, safety and angiographic outcomes by sex. This effect did not differ between alteplase and tenecteplase. The pragmatic enrolment and broad national participation in AcT provide reassurance that there do not appear to be sex differences in outcomes amongst Canadians receiving IVT.